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Index

Page numbers in italic refer to figures/tablesGreek letters are spelled out (e.g., alpha)

AAG (alpha-acid glycoprotein) 578

ABC drug transporters 92–95;see also efflux drugtransporters; P-glycoprotein

B1 transporters 92–93,94, 99

C transporters 92, 93–94G2 transporters 92, 94–95

ABC (awakening breathingcontrolled) trial 1046–1048

absence seizures 596

absolute drug potency 14

absorption; see also specificagents by name

pediatric pharmacology1129–1130, 1132

pharmacogeriatrics 1139systemic 580–581

acamprosate 1107

acceleromyography 1032–1034

ACCP guidelines 775

accumulation factors/index 66

ACE (angiotensin-convertingenzyme) inhibitors 731,735–736, 1096

acetaminophen see paracetamol

acetazolamide 790, 792

acetylcholine 330, 333–334chemical structure 612preclinical pharmacology 667synaptic transmission 200

acetylcholine receptors 374–375;see also muscarinicacetylcholine receptors;nicotinic acetylcholinereceptors

channel block 611desensitization block 611increased expression 622–624neuromuscular blockingdrugs 613, 624–625

non-competitive block609–611

perioperative medication 995postsynaptic transmission 609presynaptic transmission 608volatile anesthetics 371

acetylcholinesterase 79, 611–612,633–634, 635–636

acetylcholinesterase inhibition266–267, 634;see also neuromuscularblockade reversal

drug interactions 636–637paralysis reversal 1035pharmacokinetics 637side effects 637

acetylcysteine 997

acetylsalicylic acid 1099–1100;see also aspirin

acid-sensing ion channels 236

acquired cholinesterasedeficiency 617–618

acquired immunity 349–353

acronyms, non-ionotropic/non-Gprotein-coupled receptors 53

ACS see acute coronarysyndromes

ACTH see adrenocorticotropichormone

actin filaments 199, 278

action potentials 248, 259abnormal impulse activity257–258

active ion pumps 253amplitude 257, 258balance of currents , 250–251capacitance, cell 253,254–255, 258

cardiac action potential294, 295

cardiac cycle 316channel gating 251–253

channel selectivity 249–250, 251epicardial/endocardial 296factors affecting conductionvelocity 258–259

inactivation 252, 257–258membrane reaction time254–255

nerve impulse 253, 254neuromuscular function262–263, 265

Ohm’s Law 248–249propagation 256subthreshold responses255–256, 257

thresholds 256–257transmembrane currents/ionchannels 249

transmembrane proteins 253variable conductances 251

acupressure, for postoperativenausea and vomiting 1030

acute coronary syndromes 1091,1101–1102;see also myocardial ischemia

antiplatelet therapy,perioperative 1099–1100

definition/diagnosis1091–1092

pharmacologic/interventionalmanagement 1092,1093, 1094

acute kidney injury 783–784;see also kidney function

classification stages 785pharmacotherapy 794, 795risk factors 784

acute lung injury 814;see also lung function

acute myocardial infarction 886

acute respiratory distresssyndrome 814

adamantanes 980–982

adaptive immunity 349–353

addiction 486, 536; see also drug/alcohol users

definition 1106heroin 542opioid agonist-antagonists 540

additive interactions 147–148,1011–1012

adenomatous polyp preventionon vioxx (APPROVe)Trial 556

adenosine 294, 692, 694,700–701, 795

adenosine triphosphate (ATP)36, 625

adenylate cyclase 502

ADME (absorption, distribution,metabolism, elimination)85, 133

ADMET (absorption,distribution, metabolism,elimination, toxicity) 85

administration see drugadministration routes

adrenal insufficiency 816–817,1017–1018

adrenaline see epinephrine

adrenergic neurons 330

adrenoceptor antagonists 676,684–685; see also alpha-adrenoceptor agonists;beta-blockers

adverse drug reactions698, 700

antiarrhythmic agents693, 699–700

atenolol 682–683bisoprolol 683cardiovascular patients989, 999

carvedilol 680, 684celiprolol 683clinical pharmacology 681–682

1163

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Cambridge University Press978-0-521-89666-5 - Anesthetic Pharmacology, Second EditionEdited by Alex S. Evers, Mervyn Maze and Evan D. KharaschIndexMore information

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adrenoceptor antagonists (cont.)esmolol 683future study directions684

labetalol 684mechanisms of drug action676–677, 678

metoprolol 683–684nebivolol 681, 684preclinical pharmacology680–681

propranolol 682receptor signaling 677–680sotalol 682

adrenocorticotropic hormone815, 818–819

feedback inhibition 819stimulation test 820, 826

adverse drug reactions 15, 1117;see also allergic reactions;drug interactions;neurotoxicity

aminoglycosides 972–973anesthetic myopathysyndrome 137–139, 138

anti-neoplastics 988aprotonin 936argatroban 922aspirin 927autonomic nervous system 411azoles 978, 979calcium channel blockers 988carbepenems 969, 970cephalosporins 968–969circulatory effects, inhaledanesthetics 409–411

dantrolene 988dipyridamole 928direct thrombin inhibitors 924drug choice 1028–1029echinocandins 978, 980epsilon-aminocaproic acid/tranexamic acid 935

fluoroquinolones 976–977glycoprotein receptorinhibitors 930

gut motility/secretioninhibitors 848, 849, 850, 851

heparin 917–918histamine receptor antagonists843–844

inhaled anesthetics 407–409lincosamides 975–976lipopeptides 970, 971local anesthetics 582–583macrolides 973monobactams 969nitroimidazoles 978opioids 1061oxazolidinones 974–975penicillins 966, 967pharmacogenetics 132, 133polyenes 978, 980

polymyxins 971–972propofol 426–427, 450proton pump inhibitors 845sodium channel blockers,intermediate binding kinetics694, 695

sodium channel blockers, rapidbinding kinetics 695, 696

sodium channel blockers,slow binding kinetics696, 697

streptogramins 974, 975tetracyclines/glycylcyclines973, 974

thienopyridines 929thrombolytic agents 932trimethoprim/sulfamethoxazole976, 977–978

vancomycin 970, 971warfarin 925–926

AEDs see antiepileptics

aging, definition 1139;see also pharmacogeriatrics

agitation 533, 1041

agonists 6, 15; see also specificagents by name

allosteric receptor activationmodels 12

catalytic receptor model 9drug action targets,neurotransmitters 206

efficacy 7indirect 8multiple agonist sites 7–8, 8

AICD (automatic implantablecardiac defibrillator) 1096

AKI see acute kidney injury

AKIN (Acute Kidney InjuryNetwork) criteria784, 785

albumin 578, 807–808, 1131

albuterol 658

alcohol users 486, 998, 1001,1107–1109; see also drug/alcohol users

aldosterone 786

aldosterone antagonists 1096

alfentanilbioavailability 93bolus dosing 510–513closed-loop drugadministration 115–116

dose equivalence calculation67–68

open-loop TCI 112properties 538speed of onset 1007–1010transdermal administration124–125

ALI (acute lung injury) 814;see also lung function

A-Line AEP 180

alkaloids, opium 493–494

allergic reactions 1117, 1124;see also anaphylacticreactions

definitions/conceptualisations1117

antibacterial therapy 965antibiotics 1118antihistamines 1121aprotinin 1120blood products 1119drug additives/preservatives1119

FDA reporting mechanisms1121–1124

heparin 1119intravenous anesthetics458–460

latex 1120local anesthetics 582management strategies1120–1121

neuromuscular blockingagents 1119–1120

patient evaluation 1121polypeptides 1120protamine 1120treatment plan 1122–1123

allopregnalone 368

allosteric agonists 12

allosteric drug binding sites 4

allosteric enhancers 11

allosteric receptor activationmodels 11–12, 15, 12

alosetron 850

alpha-acid glycoprotein 578alpha-adrenoceptors 651–652,653, 654, 680

alpha-adrenoceptoragonists 478, 488, 648, 653,654–657, 658–659;see also specific agents byname

amnestic effects 482, 484anesthetic-sparing effects 483,486–487

anti-inflammatory effects484–485

cardioprotection 485cardiovascular patients –perioperative medication989, 999

cerebral circulation 481, 485clinical pharmacology 482,567, 656, 661–662

critical care applications 487critical care sedation 484

dosage/administration486–487, 567, 735–736

endocrine effects 481–482gastrointestinal effects 486hemodynamic effects 480–481hemodynamic stability 485mechanisms of drug action478–479, 567–568

neuroprotection 481pharmacodynamics 482–483pharmacokinetics 482preclinical pharmacology479–480, 567

renal effects 482renoprotection 485respiratory effects 486shivering 485vasodilators 730–731

alpha-adrenoceptor antagonists989, 999; see alsoadrenoceptor antagonists

alpha-glucosinade inhibitors879, 880

alpha-glutathione-S-transferase(GST) 80, 402

alpha-methylopa 656, 657

alphaxalone 368

alteplase 932;see also thrombolytic agents

althesin 456–457

alveolar-arterial gradient 393

alvimopan 543

Alzheimer’s disease 222, 995, 1157

ambulatory analgesia 1070

American Academy ofNeurology 590

American College of Critical CareMedicine guidelines 627

amino acids 890, 893–900,894–897

aminoglycosides 971, 972–973

aminopenicillins 966, 967

amiodarone 692, 693, 697–698, 702

amnesia 217–218, 220, 361, 478,488; see also alpha-adrenoceptor agonists;memory; sedatives

alpha-adrenoceptor agonists482, 484

anesthetic action mechanisms378

benzodiazepines 467chloral hydrate 487inhaled anesthetics 400–401muscarinic antagonists487–488

sedation 1041

Index

1164






AMPA receptors 37, 367–368, 375

amphetamine 660–661, 1112

amphoceterin B 977, 978, 979–980

amplification, signal 12–13, 17

amplification response,sympathetic nervoussystem 330

amplitude, action potentials257, 258

amputation, phantom limb pain1069–1070

analgesia 361; see also novelanalgesics; pain;postoperative analgesia;regional analgesia; and seespecific agents by name

action mechanisms 378,496–498

closed-loop drugadministration 117

efficiency, Oxford LeagueTable 555

maintenance of/emergencefrom anesthesia 1031

obstetrics 952–953open-loop TCI 110perioperative medication997–998, 1000

analytical validity,pharmacogenetics 133–134

anaphylactic reactions1117–1118, 1124;see also allergic reactions

agents causing 1118clinical manifestations 1118definitions/conceptualisations1117–1118

management strategies1120–1121

neuromuscular blocking drugs613, 614

patient evaluation 1121therapy 1121treatment plan 1122–1123

Andersen syndrome 307

anesthetic action mechanisms359, 374, 377–378

barbiturates 367–368brainstem/hypothalamus/thalamus 376

cerebral cortex 377defining anesthesia 361deviations from Meyer–Overton rule 359–360

drug action targets 361etomidate 362–364, 366hypothalamic–pituitary–adrenal axis 819–820

ketamine 374–375

Meyer–Overton correlation/unitary theory 359, 360, 361,378

neuroanatomy 375neurosteroids 368–369nitrous oxide 375propofol 367proteins as targets 360–361, 378spinal cord 374, 375–376structure–activity relationships362

volatile anesthetics 369–374xenon 375

anesthetic degradation 413

anesthetic myopathy syndrome137–139, 138

angina 742–743

angiogenesis 280, 283

angiotensin-converting enzyme(ACE) inhibitors 731,735–736, 1096

angiotensin II 284–285

angiotensin receptor blockers(ARBs) 732, 735–736, 1096

angiotensinogen 786

animal studiesacute kidney injury 795hemorrhagic shock 1016plasma volume expansioncalculation 801–802

relevance to humans1156–1157

anisoylated plasminogenactivator complex (APSAC)931–932

anorexia 890

ANP (atrial natriuretic peptide)786, 795

ANS see autonomic nervoussystem

antagonists 8–10, 15;see also specific agents byname

buprenorphine/nalbuphine 540catalytic receptor model 9drug action targets,neurotransmitters 206

drug interactions 147–148

anteretrovirals 979, 980

anterograde amnesia 467

antiarrhythmics see arrhythmia

antibacterialsallergic reactions 965aminoglycosides 971, 972–973carbepenems 969, 970cell membrane active agents964, 971–972

cell wall active agents 964,966–971

cephalosporins 966–969DNA synthesis targeting drugs964, 976–978

fluoroquinolones 964, 975,976–977

glycopeptides 964,970–971

lincosamides 964, 974, 975–976lipopeptides 964, 970, 971macrolides 964, 972, 973major antibacterial targets964

monobactams 969nitroimidazoles 964, 978oxazolidinones 964,974–975

penicillins 964, 966, 967,1118

polymyxins 964, 971–972predictors of antimicrobialeffect 963

ribosomal protein synthesisinhibitors 964, 972–976

streptogramins 964, 974,975

tetracyclines/glycylcyclines964, 972, 973–974

trimethoprim/sulfamethoxazole975, 976, 977–978

antibiotics; see also antibacterials;antifungals; antimicrobials

allergic reactions 1118prophylaxis issues 982

anticholinergics/anticholinesterases 672–673;see also parasympatholyticdrugs

antiemetics 860antipsychotics 601, 604asthma treatments 754–755motion sickness 856neostigmine pyrostigmineedrophonium 1146

paralysis reversal 1035pharmacogeriatrics 1146

anticoagulants 915, 919;see also platelet functionagents

non-ST-elevation myocardialinfarction/unstable anginamanagement 1095

perioperative medication992, 1000

ST elevation myocardialinfarction management1094–1095

anticonvulsants 564benzodiazepines 467clinical pharmacology565–566

dosage/administration 566mechanisms of drug action564, 565

obstetrics 954perioperative medication 994,1000

preclinical pharmacology564–565

antidepressants 206, 993, 1000;see also MAO inhibitors;tricyclics; SSRIs

antiemetics 855, 868–869;see also postoperative nauseaand vomiting

anesthesia 865–866benzamides 860–861corticosteroids 860, 865definitions 855management strategies 865neurokinin type 1 receptorantagonists 860, 864–865

neuroleptics 860, 861–862pharmacology 859–860premedication 865risk-adapted prophylaxis867–868

serotonin type 3 receptorantagonists 860, 862–864

antiepileptics (AEDs) 589–592,591–592, 605

adverse drug reactions 447,590, 592–595, 598

carbamazepine 593, 594,595, 596

clonazepam 593, 596disease interactions 589–590drug interactions 594ethosuxamide 593, 594,595, 596

felbamate 591–592, 593, 598fosphenytoin 598–599gabapentin 591–592, 593, 594,595, 598

lamotrigine 591–592, 593, 594,595, 597

levetiracetam 591–592, 593,594, 595–598

oxcarbazepine 591–592, 593,594, 595, 597

pharmacokinetics 589, 592,593, 595–598

phenobarbital 593, 594,595, 596

phenytoin 592–595pregabalin 594, 598primidone 594, 595, 596tiagabine 591–592, 593, 594,595, 597

topiramate 591–592, 593, 594,595, 597

valproate 593, 594, 595, 596zonisamide 591–592, 593, 594,595, 597

Index

1165






antifolates 964

antifungalsazoles 977, 978–979cell membrane active agents978–980

cell wall active agents 980echinocandins 977, 978, 980mechanism of drug action 978polyenes 977, 978, 979–980

antigens 349, 350, 830–831

antiherpes agents 980, 981

antihistamines 860, 1121, 1122

anti-inflammatories,perioperative medication997–998, 1000

anti-inflammatory agents forasthma

leukotriene antagonists/5-lipoxygenase inhibitors758–760

nedocromil sodium/sodiumcromoglycate 757–758

omalizumab 760–761

anti-influenza agents 980–982

antilipemic agents 990, 999

antimicrobials 963, 966, 983–984;see also antibacterials;antifungals; antivirals

allergic reactions 965anesthesia, surgicalprophylaxis 982

antibiotic prophylaxis issues 982major antimicrobial targets 963perioperative medication995, 1000

predictors of antimicrobialeffect 963–965

antimuscarinics 849–850

antineoplastics 988, 995, 996, 1000

antioxidants 794–795,901–902, 907

antiparkinsonian agents 994, 1000

antiplatelet agentssee anticoagulants; plateletfunction agents

antipseudomonal penicillins966, 967

antipsychotics 599, 605–606;see also lithium

adverse drug reactions600–601, 602, 603, 604, 605

chlorpromazine 599, 600,601, 604

delirium prevention/management 1052

disease interactions 604drug interactions 601–604

haloperidol 599, 600, 601,604–605

mechanisms of drug action599–600


pharmacokinetics 600, 601,604–605

quetiapine 600, 602, 605

antipsychotics, atypical 599, 605adverse drug reactions 600–601drug interactions 603–604

anti-rejection drugssee immunosuppressants

antistaphylococcal penicillins966, 967

antitussive effects, opioids 499

antiviralsanteretrovirals 979, 980anti-herpes virus agents 980, 981anti-influenza agents 980–982,981

anxiety, postoperative nauseaand vomiting 858

anxiolytics 1041benzodiazepines 467, 468metabotropic glutamatereceptor agonists 242

midazolam 453propofol 448–449

Aplysia (sea slug), memory/learning 210, 226

apneic threshold 407;see also respiratorydepression

apoptosis 48, 53, 1152, 1157

APPROVe (adenomatous polypprevention on vioxx) trial 556

aprepitant 860, 865

aprotonin 935–936adverse drug reactions 936allergic reactions 1120clinical pharmacology935–936

mechanism of drug action 935monitoring 936

APSAC (anisoylatedplasminogen activatorcomplex) 931–932

ARBs (angiotensin receptorblockers) 732, 735–736, 1096

ARDS (acute respiratory distresssyndrome) 814

area under the curve (AUC) 963

arecholine 668

argatroban 915, 921–922

adverse drug reactions 922clinical pharmacology 922dosage/administration 922mechanism of drug action 922new/emerging concepts 922preclinical pharmacology 922

arginine, nutritionalpharmacology 900, 901

arginine vasopressin (AVP)285, 786, 788–790, 957,1029, 1121

aripiprazole 599, 600, 601

aromatic ring 577–578, 585

arrhythmias/antiarrhythmicagents 296–297, 298, 299,689, 701–703; see also cardiacrhythm

administration 701alcohol users 1108amiodarone 692, 693,697–698, 702

beta-blockers 693, 699–700calcium channel blockers693–694, 700, 742, 745–746

cardiac rhythm 296cardiovascular patients,perioperative medication989–990, 999

disopyramide 691–693,695, 702

dofetilide 692, 693, 699, 702dosage 701–702flecainide 692, 693, 696, 702ibutilide 692, 693, 698–699, 702inhaled anestheticspharmacology 409–410

ion channels 689, 690–691, 690lidocaine 692, 693, 695, 702mechanisms of drug action 689mexiletine 692, 693,695–696, 702

moricizine 692, 693, 697, 702multiple channel blockers 693other antiarrythmic agents 694potassium channel blockers 693preclinical pharmacology691–692

procainamide 691–693, 694, 702propafenone 692, 693,696–697, 702

quinidine 691–693,694–695, 702

sodium channel blockers691–693

sotalol 692, 693, 698, 702STEMI/UA/NSTEMIadjunctive therapies 1096

tocainide 692, 693, 696, 702

arthritis 501

ascending pathways, paintransmission 229–230

ascending reticular activatingsystem 180–182

ASICs (acid sensing ionchannels) 236

aspiration pneumonitis 848

aspirin 548, 926–928adverse drug reactions 927analgesia, postoperative 1063clinical pharmacology926–927

dosage/administration 927mechanism of drug action 926monitoring 927new/emerging concepts 927–928Oxford League Table of NNT555

pharmacokinetic parameters553–550

sensitivity 557surgery 927

associativity 202

asthma treatments 751, 761–762administration 753, 754, 755,757, 758, 759–760, 760–761

anticholinergic agents 754–755beta adrenoceptor agonists751–753

clinical pharmacology752–753, 754, 755, 756–757,758, 759, 760

corticosteroids 756–757, 825induction of anesthesia 1017leukotriene antagonists/5-lipoxygenase inhibitors758–760

mechanisms of drug action751–752, 754–755, 756,757–758, 759, 760

methylxanthines 753–754nedocromil sodium/sodiumcromoglycate 757–758

new/emerging therapies 761non-steroidal anti-inflammatory drugs 557

omalizumab 760–761preclinical pharmacology752, 753–754, 755, 756,758, 759, 760

volatile anesthetics 755–756

atenolol 682–683, 700, 702

ATP (adenosine triphosphate)36, 625

ATP-binding cassette (ABC)transporters see ABC drugtransporters

atracurium blockade reversal 635

atrial natriuretic peptide (ANP)786, 795

atropine 668–669, 692

Index

1166






adverse drug reactions ofoverdose 672

clinical pharmacology669–672

gut motility/secretioninhibitors 851–852

heart rate 671paralysis reversal 1036psychedelics/party drugs1112–1113

AUC (area under the curve) 963

autobiographical memory 212

autoimmune diseases 353–354, 501

automatic implantable cardiacdefibrillator (AICD) 1096

automaticity 296–297, 298, 299;see also arrhythmias/antiarrhythmic agents;cardiac rhythm

autonomic nervous system(ANS) 330, 341–342

anesthetic action mechanisms361, 378

biochemical/molecularmechanisms 337–338

blood pressure control/vascular tone 1077–1078,1079, 1080

cell physiology 335–336cholinergic physiology336–337

failure/dysfunction 338–339functional assessment 338, 339inhaled anestheticspharmacology 411

neuromuscular blockingdrugs 613

organ physiology 333–335pharmacological modulation340–341

second messengers 338succinylcholine 618, 619sympathetic hyperactivity339–340

systems physiology 330–333

autoregulation of blood flow 319,320, 406

AVP (arginine vasopressin)285, 786, 788–790, 957,1029, 1121

awakening see emergence fromanesthesia

awakening breathing controlled(ABC) trial 1046–1048

awareness 177; see also sleep/consciousness

and anesthetic-inducedunconsciousness 179

brain/cell physiology 177

clinical context 179–180cognitive context 177–179during general anesthesia179–180, 400–401

axillary blocks 1067

axonsfunctional anatomy 574–575size 258–259

azathioprine 835

AZD3043 458

azimilide 692, 693

azoles 977, 978–979

B cells 352

bacterial infectionsee antibacterial therapy

bactericidal effects 963

bacteriostatic effects 963

balanced anesthesia 147, 513

ball-and-chain model 300

barbiturates, anesthetic 420;see also methohexital;thiamylal; thiopental

adverse drug reactions 447allergic reactions 459anesthetic action mechanisms374, 367–368

cerebral ischemia andanesthetic neuroprotection1152–1153

drug/alcohol users 1111immunosuppression 838postoperative nausea andvomiting 859

structure–activityrelationships 362

baroreflex 334–335, 649–651

basal autonomic tone 648

Bayesian optimization 115

BBB see blood–brain barrier

BChE (butyryl-cholinesterase)deficiency 134–135

BCRP (breast cancer resistanceprotein) 92, 94–95

BDNF (brain-derivedneurotrophic factor)1154

beach-chair position 1035

belladonna 1112–1113

benzamides 860–861

benzodiazepines 466, 475;see also specific agentsby name

adverse drug reactions 473anticonvulsant activity 467

anxiolytic effects 467, 468for awake fiberoptic intubation1053

calcium channel blockers-druginteractions 747

clinical pharmacology 468–469CNS7056X 458delirium prevention/management 1051

dosage/administration 473–475drug actions on memory 215,216, 217, 467

drug/alcohol users 1111glucocorticoids secretion 819hypnotic activity 468induction of anesthesia 1008mechanisms of drug action466–467

myorelaxant activity 468perioperative medication 994,1000

pharmodynamic differences470, 471–473

pharmokinetic differences469–471, 469, 470


sedation 467, 1043, 1047

benzothiazepines 742, 743

benztropine 673

beraprost 774

BET (bolus, elimination,transfer) 104

beta-adrenoceptors 651–652,657–658, 677–680

figures 23, 653, 654, 678,679

beta-adrenoceptor agonists 648,657–658, 658–659

clinical pharmacology 737,752–753

dosage/administration735–736, 753

history/background 751mechanisms of drug action751–752

perioperative medication 997preclinical pharmacology 752preterm labor 954vasodilators 731

beta-blockers (beta-adrenoceptorantagonists);see also adrenoceptorantagonists

cardiovascular patients-perioperative medication987–988, 999

myocardial ischemia1097–1099

STEMI/UA/NSTEMIadjunctive therapies 1096

beta-lactams 964carbepenems 969, 970cephalosporins 966–969monobactams 969penicillins 966, 967

bethanechol 667–668

binding cooperativity 5;see also protein binding;receptor binding

bioavailability 63; see also specificagents by name

biologics 833

biotransformation, drug 72, 85;see also clearance; enzymes

basic drug metabolismconcepts 74

consequences of anestheticmetabolism 72–73

disease states 84–85drug interactions 82–83, 84geriatrics 82neurotransmitters 206pediatrics 81, 82pharmacogenetics 83–84pregnancy 81role of brain 81role of intestine 80role of kidney 80–81role of lung 81variation between patients82–85

bisoprolol 683

Bispectral Index (BIS) 114,179, 180

central nervous systemmonitoring 1046

depth of anesthesia 1032, 1033obstetrics 951

bleeding, calcium channelblockers 746

Bliss independence 149

blood–brain barrier 93, 95, 96drug transporters 95modulation for clinicalpurposes 93, 99

pediatric pharmacology 1131

blood–cerebrospinal fluidbarrier 97

blood gas solubility coeffcient386, 387, 388

blood hemoglobin concentration801

blood pressure 114, 1078–1079,1080; see also hemodynamics;hypertension; hypotension;vascular tone

blood products, allergic reactions1119

Index

1167






blood–retinal barrier (BRB) 96–97

blood volume status 791–793

body composition,pharmacogeriatrics1139–1140, 1147

body temperaturesee thermoregulation

BOLD (blood oxygenation level)response 211

bolus dosing of opioids 510–513

bone healthimmunosuppressants/anti-rejection drugs 838

non-steroidal anti-inflammatory drugs 557–558

bottom-up costing 168–169

bottom-up pathways of sleep/consciousness 177, 188

bowel sounds 890, 907

bowel surgery 399

brachial plexus blocks 1066–1067

bradychardia see cardiovasculareffects

brainbiotransformation, drug 81derived neurotrophic factor(BDNF) 1154

injury, crystalloid fluids 805

brainstem, anesthetic actionmechanisms 376

brainweb 210, 219

BRB (blood–retinal barrier) 96–97

breakpoint 963

breakthrough cancer pain 123,126, 509

breast cancer, and antipsychoticdrugs 604

breast cancer resistance protein(BCRP) 92, 94–95

breast milk transfer 950–951

breast surgery, chronic pain 1069breathing systems;see also respiratorydepression

inhaled anestheticspharmokinetics 392–393

spontaneous ventilationmaintenance 1018–1019

bronchial smooth musclerelaxants 614

bronchoconstriction 408, 409

bronchodilation 755–756;see also asthma treatments

Brugada syndrome 296, 298,301, 302

bubbles, inhaled anestheticspharmokinetics 393

buccal fentanyl 126

bupivacaine 566, 578, 584–585clinical pharmacology566–567

dosage/administration 567mechanisms of drug action566

preclinical pharmacology 566

buprenorphine 537antagonist effects 540;see also opioid agonist-antagonists

maintenance therapy540–542

burn injuries 624, 901, 907

butorphanol 537; see also opioidagonist-antagonists

butyrophenones 599;see also antipsychotic drugs

adverse drug reactions600–601

drug interactions 603postoperative nausea andvomiting 861–862

butyryl cholinesterase (BChE)deficiency 134–135

C channels see calcium ionchannels

C-reactive protein (CRP) 347

CABG (coronary artery bipassgraft) 1094

cachexin see tumor necrosisfactor

CACI (computer-assistedcontinuous infusion) 104

calcium ionsheart failure-positive inotropicdrugs for 707, 708

local anesthetics 239–240neuromuscular function263–264

regulation of neurosecretion197, 237, 743–745

role in long-term potentiation204

second messengers 24–26, 25vascular smooth muscle 278,278, 279

calcium ion channels 31–32,564–565, 747

calcium regulation 743–745dysfunction/disease states 304regulation 303–304structure and function 303

calcium ion channel blockers741, 744, 748–749, 988;see also ziconotide

adverse drug reactions 700,745–746

angina 742–743antiarrhythmic agents693–694, 700

arrhythmias 742calcium regulation 743–745cardiovascular effects 742, 999dantrolene 748drug interactions 746–747drug metabolism 745hemodynamic action 741for hypertension 741–742mechanisms of drug action743–745

perioperative cardioprotection743, 743

pharmacogenetics 747pharmacokinetics 746–745preterm labor 954–955pulmonary vasodilators770–771

regression of left ventricularhypertrophy 742

renal effects 747renal failure 743STEMI/UA/NSTEMIadjunctive therapies 1096

vasodilators 733–734,735–736, 737, 741

calcium sensitizers 734, 735–736

calcium/calmodulin/calcineurin-induced nuclear factor 832

CAM-ICU (ConfusionAssessment Method for theICU) 1049

cAMP 20, 24, 325, 625

CAN (central autonomicnetwork) 648

Canadian Critical Care Nutritionguidelines 903

cancer 53calcium channel blockers 746cytotoxic resistance 91–92, 93;see also efflux drugtransporters

immunology 354–355opioids in prevention ofmetastases 501

pain control 123, 124;see also pain transmission/transduction

subcutaneous administration124

cannabinoids 569, 1110–1111

can’t intubate can’t ventilatescenarios 620–621, 620–621

capacitance, cell 253, 254, 258

capases 786

capillary membrane 800

CAPRIE study 929

carbachol 667–668

carbamazepine 593, 594, 595, 596

carbepenems 969, 970

carbohydrates 892, 894–897

carbon monoxide 17, 405

carbonic anhydrase inhibitors 790

carboxylesterases 78–79

cardiac cell physiology 322–323

cardiac cycle 316–317

cardiac rhythm 293, 310;see also arrhythmias/antiarrhythmic agents

calcium ion channels 303–304cardiac action potential 294, 295cardiac inward rectifiers 307cell-to-cell coupling/gapjunctions 297–298

conduction pathways 293–294delayed rectifier Kþ currents304–306

disease states 302–303, 304,305, 306–307

drug action targets 308–310ion channels-generalstructure/function 299–301

ion channels-special features297, 300–301

layer-specificelectrophysiology/arrhythmias 296

neural control 293pacemaker current 307–308reentrant arrhythmias294–295

sodium ion channels 301–303transient outward currentITO 304

ultra-rapid delayed rectifier306–307

cardiac surgery/cardiologyepsilon-aminocaproic acid/tranexamic acid 934

infusion fluids 806sedation 1055

cardioplegia 1100–1101

cardiovascular depression 473

cardiovascular effects;see also heart function

acetylcholinesterase inhibition637


crystalloid fluids 805

Index

1168






dexmedetomidine 1044drug interactions 1012, 1013immunosuppressants/anti-rejection drugs 836

inhaled anestheticspharmacology 412

induction of anesthesia1012–1014

local anesthetics 584non-steroidal anti-inflammatory drugs 555–556

opioid agonist-antagonists 540opioid clinical pharmacology534–535

opioids 499pharmacogeriatrics 1140propofol 449thiopental 1007

cardiovascular patients,perioperative medication987, 988, 991, 999–1000

alpha-adrenoceptorantagonists 989, 999

antidysrhythmics 989–990, 999antilipemic agents 990, 999beta-adrenoceptor antagonists987–988, 999

calcium channel blockers988, 999

diuretics 990, 1000nitrates 989, 999pulmonary vasodilators989, 999

renin angiotensin systemantagonists 988–989, 999

caregiver controlled analgesia(CCA) 1062–1063

carotid body relaxants 613–614

carvedilol 680, 684

caspases 52–53

CAT (computed axialtomography) scanning1054–1055

catabolism 890, 897, 900, 907

catalytic receptors 3–4, 9

catecholaminesanaphylaxis therapy 1122–1123clinical pharmacology 737dobutamine 713dopamine 712dopexamine 712–713dosage 719ephedrine 714epinephrine 710–711isoproterenol 713–714norepinephrine 711–712preclinical pharmacology709–710

receptor pharmacology729–730

catechol-O-methyltransferase(COMT) 336

CATIA (computer-assisted totalintravenous anesthesia) 104

cauda equina syndrome (CES) 582

CBF see cerebral blood flow

CCA (caregiver controlledanalgesia) 1062–1063

CCIP (computer-controlledinfusion pump) 104

CDAD (Clostridium difficile-associated diarrhea) 843

celecoxib long-term arthritissafety study (CLASS) 557

celiprolol 683

cell mediated immunity 349;see also T cells

cell membranes see membranes

cell signaling 17, 18, 18

cell surface receptors 18

cell-to-cell coupling 297–298

cell wall active agents 964,966–971, 980

central autonomic network(CAN) 648

central nervous systemantipsychotic drugs 603, 604drug barriers 93, 95, 96local anesthetics 583–584perioperative medication 993,995, 1000

propofol 449sedation 1045–1046

central sensitization 235

cephalosporins 966–969

cerebral blood flow (CBF)alpha-adrenoceptor agonists481, 485

inhaled anestheticspharmacology 406

response to hyper/hypocarbia407

cerebral cortex 377

cerebral injury 405–407, 413

cerebral ischemia 1158–1159anesthetic neuroprotection 1151excitotoxicity 1154influence of specificanesthetics 1152–1154

mechanism of drug action1152, 1154–1155

neurogenesis effects 1154–1155pathophysiology 1151–1152reconciliation of opposing effectsof anesthetics 1157–1158

cerebral metabolic rate (CMR)405–406

cerebral protection, inhaledanesthetics pharmacology 412

cerebral state index 1032

Cerebral State monitor 180

cerebrospinal fluid (CSF) 407

certain safety factor 15

CES (cauda equina syndrome) 582

chemical partition 90–91

chemical synapses 192–193, 194;see also synaptictransmission

chemotherapy drugs, perioperativemedication 995, 996, 1000

chest wall rigidity 534

children see pediatricpharmacology

chiralitylocal anesthetics 579–580, 585non-steroidal anti-inflammatory drugs 551

chloral hydrate 487, 488

chloroprocaine 578, 582

chlorpromazine 599, 600, 601, 604

choline esters 667–668

cholinergic neurons 330, 336–337

cholinesterases 78–79acquired cholinesterasedeficiency 617–618

inhibitors, perioperativemedication 995, 1000

neuromuscular blockingdrugs 617–618

cholinomimetic alkaloids 668

choroid plexus 97

chronic congestive heartfailure 337

chronic kidney disease (CKD)783, 784, 794; see also kidneyfunction

chronic medication users,anesthesia forsee perioperative medication

chronic obstructive pulmonarydisease (COPD) 452

chronic painaddiction to opioides 1107analgesia, postoperative1069–1070

opioid clinical pharmacology536

cigarette smoking see smoking

cimetidine 843–844

CIN (contrast-inducednephropathy) 794–795

circadian rhythm 815

circle systems, inhaledanesthetics 393

cirrhosis, liver 428

CLASS (celecoxib long-termarthritis safety study) 557

classificationdrug receptors 2–4, 18peripheral nerves 575

clearance 57–58, 74, 82, 83;see also biotransformation;enzymes

basic concepts 73–74pediatric pharmacology1131–1132

clinical pharmacology,information technology 160

clonazepam 593, 596

clonidine 567, 656analgesia, postoperative 1064clinical pharmacology 567dosage/administration 567mechanisms of drug action567–568

preclinical pharmacology 567preemptive analgesia 1068

clopidogrel 1099–1100

closed-loop control systems 1078

closed-loop drug administration103–104, 112, 116–118;see also target controlledinfusion

control algorithm 115, 116future study directions 116hypnotics 115–116opioids 116, 117pharmokinetic closed-loop113–114

pharmokinetic-dynamicclosed-loop 103, 114–115

prototype examples 115, 117set-point 115

Clostridium difficile-associateddiarrhea (CDAD) 843

clozapine 599, 600, 601

CMR (cerebral metabolic rate)405–406

CNG (cyclic nucleotide gated)ion channels 40–41

CNS see central nervous system

CNS7056X 458

coagulation 282–283, 912–915,1108; see also platelet function

Index

1169






cocaine 335, 340, 1111

Cockcroft–Gault equation 1140

codeineCYP2D6 84lactation 526Oxford League Table ofNNT 555

pharmacogenetics 519

cognitive outcomesanesthetic neurotoxicity1155–1156

post-operative dysfunction140, 212, 221–222, 1157

sedation complications 1042

coincidence detector 203

coinduction 1011

colchicine 997

collectins 347–348

colloid fluids 800, 805, 807–809blood volume status 793comparison with crystalloids809

monitoring 1034

colonoscopy, sedation 1055

COMMIT trial 929, 1097

compartment models 62, 63pharmacokinetics 58–61special 57thiopental 422

competitive inhibition 15, 9, 10,10, 609

complement system 346–347

compound A 403–404

computed axial tomography(CAT) scanning 1054–1055

computer-assisted continuousinfusion (CACI) 104

computer-assisted totalintravenous anesthesia(CATIA) 104

computer-controlled infusionpump (CCIP) 104

computer modeling,pharmacoeconomics 172, 173

COMT (catechol-O-methyltransferase) 336

concentration-dependentactivity 963

concentration–response curves14, 15, 158

conditioning 212–213, 216;see also memory

conductance, restingmembrane 258

conflicts of interest,pharmacoeconomics 174

Confusion Assessment Methodfor the ICU (CAM-ICU) 1049

congestive heart failure 1072

conjugation reactions 74

conscious memory 212, 216–219

consciousness, neural basis 177,188; see also sleep/consciousness

consolidation of memory/learning 217–218, 220

constipation 535

context-sensitive half-time 65intravenous infusion ofopioids 514, 515

open-loop TCI 109propofol 429, 431

continuous dose–responsecurves 14

contractile tissuemyocardial performance 324vascular smooth muscle 278,324–325

contrast-induced nephropathy(CIN) 794–795

control algorithm, closed-loopdrug administration115, 116

conversion to morphineequivalents, opioids1061–1062

convulsions 449, 533;see also antiepileptic drugs

cooperativity 202

COPD (chronic obstructivepulmonary disease) 452

coronary artery bypass graft(CABG) 1094

coronary artery disease (CAD)1097, 1099

coronary circulation 319, 326–327autoregulation of blood flow319, 320

blood pressure control/vascular tone 1084

metabolic control 319–320neurogenic control 320regulation of myocardialperfusion 319

coronary steal 410, 742

corticosteroidssee glucocorticoids

corticotropin-releasing hormone(CRH) 818–819

CORTICUS study 820

cortisol 815, 816, 819–820;see also glucocorticoids

costs/costing 168, 1029;see also pharmacoeconomics

costimulation 833–834

cotransmissions 194–195

coughing reflex 499, 534, 1027

covalent bonds 2

COX see cyclooxygenase

CP-122 864–865

craving, drugs/alcohol 1106

CRH (corticotropin-releasinghormone) 818–819

creatine 1140

critical care applicationsalpha-2 adrenoceptoragonists 487

delirium diagnosis 1049delirium prevention/management 1049–1052, 1053


nutritional pharmacology901–903

paradigms to improveoutcomes from sedation1046–1049

pharmacology of availabledrugs 1042–1044

sedation 484, 1041–1042,1044–1046

critical illness, effects onhypothalamic-pituitary-adrenal axis 820

CRP (C-reactive protein) 347

crystalloid fluids 800blood volume status 793comparison with colloids 809monitoring 1034solutions with electrolytes803–805

CSF (cerebrospinal fluid) 407

C-type inactivation 300

cumulation 66

cumulation ratio (CR) 66

curare 608, 633

Cushing reflex 649

Cushing’s syndrome 824

cyclic nucleotide gated (CNG)ion channels 40–41

cyclooxygenase (COX) 548expression in response totissue damage 550

expression/action 550inhibition by NSAIDs 550–552neuronal plasticity 550role in pain 548, 549

cyclooxygenase inhibitors 554,559, 955, 1063;see also aspirin; non-steroidalanti-inflammatory drugs

absorption 554cardiovascular effects 555–556CLASS 557clinical context 559distribution 554drug interactions 558gastrointestinal effects556–521

metabolism/excretion 554–555Oxford League Table of NNT555

pharmacodynamics 555–556pharmacokinetic parameters553–550

renal effects 557

cyclosporin A 93

cyclosporine 834–835, 1101, 1134

CYP see cytochrome

cys-loop drug-gated ion channel(LGICs) 3

cys-loop ion channel 35, 41,52

cystatin C 786

cystolic threonine kinases 51–52

cystolic tyrosine kinases 50–51

cytochrome (CYP) 74–78, 73,76, P450

alcohol 1107calcium channel blockers 745CYP1A2 78CYP2A6 78CYP2B 77CYP2C 78CYP2D 76–77, 77, 78, 1134CYP2E1 78, 1107CYP3A 75–76, 76, 81, 83, 84,519–520

pediatric pharmacology 1129ensure join all theseto cyp refs

pediatrics 81, 82pharmacogeriatrics 1140

cytokine receptors 50

cytokines 52, 352–353

cytoplasmic enzymes 50, 53

cytoskeleton, role in synaptictransmission 199

cytotoxic resistance 91–92, 93;see also efflux drugtransporters

Index

1170






dabigatran 915, 922–923

DAD (delayed afterdepolarization) 296, 297

damping, signal 13

danaparoid 915, 920–921clinical pharmacology 920dosage/administration 920–921mechanism of drug action 920new/emerging concepts 921

danger associated molecularpattern (DAMP) 349

dantrolene 625, 748, 988

darifenacin 673

DCCT (diabetes control andcomplications trial) 879

deadly nightshade 668–669

decision-making 166–167;see also pharmacoeconomics

declarative memory 212

decrement time, open-loopTCI 109

deep dorsal horn 235

definitions; see also terminologyaction potentials 248–249acute coronary syndromes1091–1092

addiction 1106aging 1139allergy 1117anaphylactic reactions1117–1118

anesthesia 361anti-emetics 855drug receptors 1drug targets 1drugs 1infants 1128memory/learning 212myocardial ischemia 1091neonates 1128open-loop TCI 105pain 227sedation/hypnosis 478xenobiotics 90

degradation, anesthetic 413

delayed after depolarization(DAD) 296, 297

delayed hypersensitivity(DTH) 354

delayed rectifier Kþ currentsdisease states 305, 306–307rapid 305slow 305–306ultra-rapid 306–307

delirium 221, 484diagnosis 1051–1049

prevention/management1049–1052, 1053

sedation 1041sedation complications 1042

delirium tremens 1108–1109

dendrites 226

dendritic spines 220

dense-cored vesicles 192

dependence, drug 1106, 1107;see also addiction

depolarizing blocking drugs 270

depressant drugs; see also moodeffects

alcohol 1107–1109benzodiazepines/barbiturates1111

cannabinoids 1110–1111opioids 1109–1110

depth of anesthesia monitors1032, 1033

descending modulatorypathways 230–231

desensitization see receptordesensitization

desflurane 397autonomic nervous systemeffects 411

glucocorticoids secretion 819inhaled anestheticspharmacology 397, 399

physicochemical properties 398sympathetic nervous system651

desmopressin 932–933clinical pharmacology 932–933dosage/administration 933mechanism of drug action 932new/emerging concepts 933

development, brain;see also pediatricpharmacology

anesthetic neurotoxicitysee neurotoxicity

pharmacodynamics 1133–1134pharmacogenetics 1134, 1135pharmacokinetics 1128, 1132

dexamethasone 860, 865

dexmedetomidine 185–187, 481,567, 656–657

analgesia, postoperative 1064for awake fiberoptic intubation1054

clinical pharmacology 567delirium prevention/management 1049, 1051

dosage/administration 567mechanisms of drug action567–568

preclinical pharmacology 567preemptive analgesia 1068sedation 1044, 1048–1049sleep/consciousness 218

dextrans 808

DHP see dihydropyridine

diabetes 53, 886–887;see also insulin

acute myocardial infarction 886autonomic nervous systemdysfunction 338–339

diet controlled 881emergency management 882hyperglycemic hyperosmolarstate 884–885

hypoglycemia 885–886immunosuppressants/anti-rejection drugs 836

ketoacidosis (DKA) 882–884metabolic control 881oral agents 880, 881–882perioperative management880–882, 992–993, 1000

perioperative risk factors 881postoperative nausea andvomiting 858


type 1 diabetes mellitus 879type 2 diabetes mellitus879–880

diabetes control andcomplications trial(DCCT) 879

diagnosis, delirium 1051–1049

diarrhea 906

diastolic ventricular function321–322

diazepamclinical pharmacology 469dosage/administration 473, 475drug actions on memory 215hypnotic activity 468immunosuppression 838myorelaxant activity 468pharmodynamics 472–473pharmokinetics 470–471, 470sedation/amnesia/anticonvulsant activity 467

diclofenac 548, 553–550, 555

dicyclomine hydrochloride 849

diet-controlled diabetes 881;see also nutritionalpharmacology

Digitalis glycosides 707–709, 719

digoxin 692, 694

dihydropyridine (DHP)733–734, 737, 741, 742, 743

dihydropyridine (DHP)-sensitivesubunit 743–744

diltiazem 692, 693–694, 700, 702

dipeptidyl peptidase-4 (DPP4)inhibitors 880

diphenoxylate hydrochloride851–852

dipravan see propofol

diprifusor 105

dipyridamole 928adverse drug reactions 928clinical pharmacology 928dosage/administration 928mechanism of drug action 928

direct costs 168–169

direct thrombin inhibitors(DTIs) 923–924

adverse drug reactions 924clinical pharmacology923–924

dosage/administration 924mechanism of drug action 923new/emerging concepts 924non ST elevation myocardialinfarction/unstable anginamanagement 1095

ST elevation myocardialinfarction management 1095

discounting costs 169

disease statesbiotransformation, drug 84–85cardiac rhythm 302–303

disopyramide 691–693, 695, 702

display systems, druginteractions 160–161

dissociation constants 4, 15

distribution

distribution phase of drugdelivery 59, 387–389;see also specific agents byname

mathematics of 389–390pediatric pharmacology1130–1131, 1132

disulfram 998, 1001, 1107

diureticscarbonic anhydraseinhibitors 790

cardiovascular patients990, 1000

dosage/administration 792loop diuretics 790–791osmotic diuretics 790pharmacotherapy 794potassium-sparing 791renal dopamine 786, 791thiazide diuretics 791

Index

1171






divergence, open-loop TCI 111

DKA (ketoacidosis) 882–884

DNA synthesis targeting drugs964, 976–978

dobutamine 659, 713, 719,1122–1123

dofetilide 692, 693, 699, 702

dolasetron 860, 864

dopamine 337, 659anaphylaxis therapy 1122–1123antipsychotic therapy 599–600dosage 719drug/alcohol users 1106postoperative nausea andvomiting 856

renal 786, 791, 794use in heart failure 712

dopaminergic receptor agonists658–659, 731, 735–736

dopexamine 712–713, 719

dorsal horn see spinal dorsal horn

dosage dependence, drugresponse analysis inindividuals 14

dose equivalence 66–68

dose–response relationships 57additive interactions 150linear/nonlinear 148target controlled infusion 103

double-reciprocal plot 5

downregulation 22

DPP4 (dipeptidyl peptidase-4)inhibitors 880

dreams 451

dronabinol 569

droperidol 860postoperative nausea andvomiting 861–862, 1030

safety considerations 861–862

drug abuse 531, 532, 540;see also addiction; drug/alcohol users

drug accumulation 66

drug addicts see addiction;drug/alcohol users

drug additives/preservatives,allergic reactions 1119

drug administration routes 123,124, 126, 129

drug dosage relativeto route 127

enteral routes 127, 898–899,903–904, 905–906

epidural 127–129, 523–524

extra vascular 436fentanyl 126, 1011induction of anesthesia 1011inhalation 125intrathecal 127–129, 523intramuscular administration123

methadone 127neuraxial routes 124, 127–129parenteral routes 904, 905rectal routes 127safety considerations 129subcutaneous administration124

sublingual administration 125transdermal administration124–125

transmucosal routes 125–127

drug/alcohol users 1106–1107,1113–1114

alcohol 1107–1109amphetamine 1112benzodiazepines/barbiturates1111

cannabinoids 1110–1111cocaine 1111drug abuse 531, 532, 540inhalants 1113opioids 1109–1110perioperative medication 998,1001

psychedelics/party drugs1112–1113

drug binding 4–6, 5, 6–13, 15

drug delivery modifications1046–1048

drug effects 6, 13–15

drug input, pharmacokinetics62–63

drug interactions 147, 151,161–162, 845

additive/synergistic/antagonistic interactions147–148, 153–154,1011–1012

aminoglycosides 972–973antiepileptic drugs 589–590antipsychotic drugs 601–604azoles 978, 979biotransformation, drug82–83, 84

calcium channel blockers746–747

carbepenems 969, 970cephalosporins 968–969dantrolene/calcium channelblockers 988

drug transporters 99echinocandins 978, 980fluoroquinolones 976–977gut motility/secretioninhibitors 851

histamine receptor antagonists844

induction of anesthesia1011–1012, 1013

interaction models 150–152isobologram 148–149ketamine 436lincosamides 974, 975–976lipopeptides 970, 971macrolides 973monobactams 969neuromuscular blockingdrugs 625

new/emerging concepts 158–160nitroimidazoles 978non-steroidal anti-inflammatory drugs 558

opioids/propofol 154–158,159, 519–520

oxazolidinones 974–975penicillins 966, 967pharmacogenetics 133polyenes 978, 980polymyxins 971–972propofol 432, 448proton pump inhibitors 845real-time visualization 160–161response surface methodology149–150, 151, 158–161

streptogramins 974, 975tetracyclines/glycylcyclines 974thiopental 424–425trimethoprim/sulfamethoxazole976, 977–978

vancomycin 970, 971volatile anesthetics/opioids152–154

drug metabolismsee biotransformation;clearance; enzymes

drug receptors see receptors

drug registration, role ofpharmacoeconomics 167–168

drug targets 1, 15; see also specificagents by name

pain transmission/transduction–generalanesthetics 232, 237–239

pain transmission/transduction–localanesthetics 239, 241

sleep/consciousness 185sleep/consciousness–class 1agents 185, 186, 187

sleep/consciousness–class 2agents 185

sleep/consciousness–class 3agents 185

drug tolerance see tolerance

drug transporters 90, 99–100;see also efflux drugtransporters

ABC gene family 92–95blood–brain barrier 93, 95, 96blood–cerebrospinal fluidbarrier 97

blood–retinal barrier 96–97cellular boundaries 91drug interactions 99experimental methods 98–99future study directions 99gastrointestinal tract 97,fig 7.6.

kidney 97–98lipid bilayers 90, 91liver 97localized pharmacokineticspaces 91

modulation for clinicalpurposes 93, 99

placenta 98SLC21 transporters 95–96small molecule partition90–91

specially protected anatomicspaces 96

xenobiotic transporters 92

drugs, definition 1

DTH (delayed hypersensitivity)354

DTIs see direct thrombininhibitors

d-tubocurarine 270

dual transmission,neurotransmitters 194–195

Duchenne muscular dystrophy303

EACA see epsilon-aminocaproicacid/tranexamic acid

eating behavior, andpostoperative nausea andvomiting 858;see also nutritionalpharmacology

ECC (excitation contractioncoupling) 323–324

ECG (electrocardiograms) 316

Echinaceae 999

echinocandins 977, 978, 980

eclampsia 953–954

ECM (extracellular matrix)277–278

Ecstasy 660, 1112–1113

ECV (extracellular fluid volume)800

ED50 15

edrophonium 1035

EEG see electroencephalography

Index

1172






effect compartment concept63–64

effect-site model 14, 64fentanyl/alfentanil 67–68open-loop TCI 106–107,107–109

propofol 429–432

efficacy, drug 6, 14, 15, 7

efflux drug transporters 91–92ABC gene family 92–95breast cancer resistanceprotein 92, 94–95

multi-drug resistant proteins92, 93–94

P-glycoprotein 92–93, 94

eicosanoids 734, 735–736, 737

electrical synapses 192;see also synaptictransmission

electrocardiograms (ECG) 316

electrochemical gradients 253

electroencephalography (EEG)central nervous systemmonitoring 1045–1046

class 1 agents 185, 186closed-loop drugadministration 114

depth of anesthesia 1032dose equivalence calculation67–68

inhaled anestheticspharmacology 405–406

memory/learning 210–211sleep/consciousness 179–180,181, 185, 187

elimination phase of drugdelivery 59

half-life 59–60inhaled anestheticspharmokinetics 389

local anesthetics 582neuromuscular blocking drugs616, 617, 618

organs/enzymes 73thiopental 422

ELISA diagnosis 918

Emax (maximal effect) models 6,15, 155

emergence from/maintenance ofanesthesia 1027, 1036


blood pressure control 1029cost of drugs 1029drug choice 1027–1029fluid pharmacokineticsmonitoring 1033–1035

ketamine 451malignant hyperthermia 1028

medicinal supplements toprimary anesthetic 1029–1031

monitors 1032–1034neuromuscular functionmonitoring 1032–1034

nitrous oxide 1031pain control 1031paralysis 1030–1031paralysis reversal 1035–1036patient stability 1027posterior scoliosis correction/wake-up test 1036

postoperative nausea andvomiting 1028, 1029–1030

postoperative pain 1028salivation 1028speed/quality of emergence/wakening 1027–1028

temperature 1031temperature monitors 1032ventilation 1035

en passant synapses 192

enantiomeric pairs 360, 361

encainide 692, 693

end-stage renal disease (ESRD)783; see also kidney function

endocrine effects, alpha-2adrenoceptor agonists481–482

endocytic drug receptors 4

endocytosis pathways 198, 206

endogenous opioid system230, 494

endoscopy sedation 1055

endothelin 282

endothelin agonists/antagonists774

clinical pharmacology 737dosage/administration735–736

vasodilators 732

endothelium, vascular 280,727–728, 729

endothelium-dependentrelaxation 280–281

endothelium-derivedhyperpolarizing factor281–282

endothelium-derived relaxingfactor see nitric oxide

endplate see neuromuscularjunction

endplate potential 196

end-stage organ failure743, 830; see alsoimmunosuppressants/anti-rejection drugs

energy expenditure 891–892,891–892

and ventricular function1080–1081, 1081–1082

enfluranemetabolism 392

enoximone 715

enteral routes of drugadministration 127, 898–899,903–904, 905–906

enteric nervous system 330, 333;see also autonomic nervoussystem

entropy monitors 180, 1032

environmental enrichment, andneurogenesis 1154

enzymes;see also biotransformation;clearance

cystolic tyrosine kinases 50–51cytochrome 73, 74–78, 76,77, 81

cytoplasmic 50, 53drug receptors 2, 4esterases 78–79glucuronosyltransferase 79–80glutathione-S-transferase 80intrinsic guanylate cyclaseactivity 50

intrinsic serine/threoninekinase activity 49–50

linked cell surface receptors 18receptor protein tyrosinephosphatases 48–49

tyrosine kinase-associatedreceptors 47–48, 49

ephedrine 651, 655, 660blood pressure control 1029dosage 719use in heart failure 714

epidural anestheticcomplications 1066obstetrics 951–952postoperative 1064–1065preemptive analgesia1068–1069

routes of drug administration127–129, 523–524

vasopressor treatment 957

epilepsy see antiepileptic drugs

epinephrine 330, 333, 651, 658–659

additives 580, 586anaphylaxis therapy 1121,1122–1123

dosage 719reversal syndrome 601use in heart failure 710–711

episodic memory 211, 212drug actions on 215, 216–219and procedural memory 216

serial parallel independenttaxonomy of memory215, 216

epsilon-aminocaproic acid/tranexamic acid 933–935

adverse drug reactions 935cardiac surgery 934clinical pharmacology 934dosage/administration 935mechanism of drug action933–934

new/emerging concepts 935orthopedic surgery 934

equianalgesic conversions1061–1062

equilibrium binding affinity 4

equilibrium dissociationconstants 4, 15

equipotency/potency ratios 67

equipotent infusion rates 68;see also pharmacokinetics

ergot alkaloids 661, 955–956

ERPs (event related potentials)210–211, 217–219

esmolol 79, 683, 699, 702

esomeprazole 846

ESRD (end-stage renal disease)783; see also kidney function

ester hydrolysis 617–618

esterases 78–79

estrogens 996

ethosuxamide 593, 594, 595, 596

etidocaine 578, 584–585

etomidate 436, 438, 452–453, 460allergic reactions 459anesthetic action mechanisms362–364, 366, 374, 378

cerebral ischemia andanesthetic neuroprotection1153

cortisol secretion 819critical care applications/adrenal insufficiency1017–1018

decrement time 431disposition parameters 445distribution/metabolism/excretion 436–437

dosage/administration 437hemorrhagic shock 1016induction of anesthesia 1008,1013

new formulations 457pharmacogeriatrics 1145physicochemical properties 436postoperative nausea andvomiting 859

Index

1173






etomidate (cont.)side effects 445structure–activityrelationships 362

structure/stereochemistry436, 445

sympathetic nervoussystem 651

trauma/hemodynamicallyunstable patients 1016

EuroQol (ED-5D) 170

event-related potentials (ERPs)210–211, 217–219

evolution, and pharmacogenetics134

excitation contraction coupling(ECC) 323–324

excitotoxicity 40, 1154

exercise, and neurogenesis1154

exocytosis 264, 335

experimental design

full factorial 150

pharmacoeconomics 172

experimental methods, drugtransporters 98–99

explicit memory 212

extracellular fluid volume(ECV) 800

extracellular matrix (ECM)277–278

extracellular signaling 18

extrapyramidal effects 600–601,603, 673

eye injury 1016–1017

eyelash reflex 1010

facilitated PCI 1093–1094

factor Xa inhibitors 1095;see also fondparinux

fainting 1078

false transmitters 660

families, receptor 2, 15

famotidine 845

fats see lipids

FDA (Food and DrugAdministration)

drug use in pregnancycategories 949

reporting mechanisms, allergicreactions 1121–1124

felbamate 591–592, 593, 598

femoral nerve blocks 1067

fentanyl

analogs, cardiovascular effects1013–1014; see alsoalfentanyl; buccal fentanyl;remifentanil; sufentanil

bioavailability 93bolus dosing of opioids510–513

dose equivalence calculation67–68

drug interactions 152–154,563

epidural 523–524hemorrhagic shock 1016induction of anesthesia 1008open-loop TCI 112oral transmucosaladministration 521

pharmacogeriatrics 1140–1141properties 538routes of drug administration126, 1011

sedation 1043subcutaneous administration521–522

transdermal administration124–125

fetal metabolism 950, 1109;see also obstetrics

fiberoptic intubation, sedationfor 1052–1054

fibrin clots 913; see also plateletfunction

fibrinogen therapy 1093

Fink effect 389

first-pass metabolism 73–74

fish oil 905, 907

5-aldosterone antagonists 1096

5-HT receptors see serotonin/5-HT receptors

5-lipoxygenase inhibitors758–760

flecainide 692, 693, 696, 702

fluconazole 519, 978, 979

fluid pharmacokinetics 802–803,802, 1033–1035

flumazenil 473

flunitrazepam 215

fluoride-induced nephrotoxicity401–402, 413

fluoroquinolones 964, 975,976–977

fluoxetine 519

focal ischemia 1151, 1154;see also cerebral ischemia

fondaparinux 915, 1094–1095clinical pharmacology 921dosage/administration 921mechanism of drug action 921

Food and Drug Administrationsee FDA

food, and postoperative nauseaand vomiting 858;see also nutritionalpharmacology

forgetting 217–218, 220;see also amnesia; memory

fornix 218

forward genetics 362

fosphenytoin 598–599

fospropofol 433, 455–456

Fourier theorem 179

Frank-Starling mechanism 1077

front-end kinetics 62, 423–424

full agonists 6, 11, 15

full factorial experimental design150

functionalization reactions 74

fungal infection agentssee antifungals

fuzzy logic 115

GABA (gamma-aminobutyricacid)


anesthetic neurotoxicity1155–1156

barbiturates, anesthetic 367benzodiazepines 466–467, 475chloral hydrate 487etomidate 362–364, 366neuroprotection/neurotoxicity1151

neurosteroids 368–369pediatric pharmacology 1133propofol 367receptors 12, 200–201, 467sleep/consciousness 186, 187,218

sleep/wakefulness switch377

structure–activity relationships362


gabapentin 564, 591–592, 593,594, 595, 598

analgesia, postoperative 1068clinical pharmacology565–566

dosage/administration 566mechanisms of drug action564, 565


preemptive analgesia 1068

ganglionic blockers 733,735–736, 737

gap junctions 297–298

garlic 992, 999

gastric acid secretion 345, 843;see also gut motility/secretioninhibitors

gastrointestinal effects 535alpha-adrenoceptor agonists486, 487

non-steroidal anti-inflammatory drugs556–521


opioids 499, 500proton pump inhibitors versushistamine receptorantagonists 847

gastrointestinal tract 97;see also gut; ulcers

gastroparesis 858

GCs see glucocorticoids

gelatin 809

gender differencesopioid effects 533postoperative nausea andvomiting 857

preconditioning effects 1154

general anesthesiaand Alzheimer’s disease 222awareness during 179–180drug actions on memory 215obstetrics 951, 952pain transmission/transduction 232, 237–239

and sleep 177, 188unconscious memory/learningduring 215–216

genetic engineering,thrombolytic agents 931

genetic pharmacodynamics135–136

genetic pharmacokinetics 134

genomic drug susceptibilityprofiling 142;see also pharmacogenetics

genotype–phenotypescorrelations 133

genotypes 133

Gepts model 428

geriatrics see pharmacogeriatrics

ginger 992, 999

Index

1174






Gingko biloba 992, 999

Ginseng 999

GLN (glutamine) 900, 904–905,907

global ischemia 1151

glomerular filtration rate (GFR)783, 787–788

glossary of terms, myocardialischemia 1091;see also definitions

GLP-1 (glycogen-like peptide )analogs 879–880

glucocorticoid receptors (GRs)814–815

glucocorticoids 814, 826anaphylaxis therapy 1123anti-emetics 860, 865asthma treatments 756–757cellular activity 814–815clinical pharmacology820–824, 821–823

mechanism of drug action 815metabolism/excretion 824organ specific/physiologicalresponses 816–818

perioperative management824–826, 997, 1000

preparation/potency 820–824,821–823

production/circulation/inactivation 815–816

side effects 817, 824

glucoseinfusion fluids 806–807intracellular fluid flux 803loading 807nutrition 892

glucose homeostasis 874, 875fasted state 874–876glucose intolerance/insulinresistance 876

metabolic responses tosurgery/trauma 876–877

metabolic syndrome 876postprandial state 874

glucuronosyltransferase (UGT)79–80

glutamate receptor family 36–40,41, 37, 232; see alsoN-methyl-D-aspartate(NMDA) receptors

AMPA receptors 37karinate receptors 37–39receptor localization 40synaptic transmission 200volatile anesthetics 371–373,373–374

glutamine (GLN) 900,904–905, 907

glutathione-S-transferase (GST)80, 402

glycine 200–201, 803receptors 39, 369–371

glycogen 874–876

glycogen-like peptide 1 (GLP-1)analogs 879–880

glycopeptides 964, 970–971

glycoprotein receptor inhibitors930–931

adverse drug reactions 930clinical pharmacology 930dosage/administration 931mechanism of drug action 930monitoring 930surgery/anesthesia 930–931

glycopyrrolate 672, 1036

glycylcyclines 964, 972, 973–974

goal-directed fluid therapy 805

goal-directed sedation 1046

gonadotropins 956–957

gout preparations 997

G-protein-coupled receptors(GPCRs) 2–3, 17, 18, 19,26, 286

autonomic nervous system 340heart contractility control 325local anesthetics 240–241, 576properties of signal transductionpathways 17–19, 20

receptor desensitization 22–24,23, 23

second messengers 24–26, 25signal damping 13signal transduction 17, 18, 18signaling pathway 19, 18slow synaptic transmission 201structure and function 19–22,20, 21

graded dose–response studies 15

graded drug effects 6

graded log drug concentrationresponse 14

granisetron 860, 864

growth factors 49

GST (glutathione-S-transferase)80, 402

GTP(guanine nucleotide) bindingproteins 19; see alsoG protein-coupled receptors

guanabenz 656, 657

guanfacine 656, 657

guanylate cyclase activity 50

guarded receptor hypothesis 576

guidelinesAmerican College of CriticalCare Medicine 627

ACCP 775Canadian Critical CareNutrition 903

delirium prevention/management 1052, 1053

Society of Critical CareMedicine 1041

gutbiotransformation, drug 80failure 901;see also gastrointestinaleffects; ulcers

integrity 903–904;see also glutamine

opioid metabolism 520

gut motility/secretion inhibitors842, 851, 852–853;see also proton pumpinhibitors

5-HT agonists 850adverse drug reactions 843–844,845, 848, 849, 850, 851

anti-muscarinic agents849–850

drug interactions 844, 845, 851gastric acid secretion 843histamine receptor antagonists843–845, 847–848

motility 842new/emerging concepts 852normal gut 842opioids 850–852practical approach to patients843

prebiotics/probiotics 852secretions/fluid turnover842–843

somatostatin and analogues848–849

hemorrhage, gastrointestinal 847

half-maximal effectconcentration 6, 15

half-time/half-life 59–60

hallucinations, and ketamine 451

halogenated anesthetics 362

haloperidol 599, 600, 601,604–605, 1051–1052

halothane 397, 399, 1155metabolism 392myocardial contractility/arrhythmias 409–410

physicochemical properties 398

Harlequin syndrome 1067

head trauma, infusion fluids 806

health policy 166;see also pharmacoeconomics

health-related quality of life 170

Health Utility Index (HUI2) 170

heart failure 325–326, 1072;see also myocardial ischemia;positive inotropic drugs

heart function 316, 317–319,326–327; see alsocardiovascular effects;coronary circulation

blood pressure control/vascular tone 1080, 1081

cardiac cycle 316–317cardiac pump function 317–319cell physiology 322–323contractile tissue 324contractility control 324–325diastolic ventricular function321–322

drug action targets 326and energetics 1080–1081,1081–1082

excitation contractioncoupling 323–324

heart failure 325–326

heart rate 671, 1084myocardial metabolism325–326

organ physiology 320–322pace-maker tissue 323–324

heat shock proteins (HSPs) 900

Helicobacter eradicationregimes 847

hematologic agents,perioperative medication992; see also platelet function

hemodynamics;see also hypertension;hypotension; vascular tone

alpha-adrenoceptor agonists480–481, 485

blood pressure control 114,1078–1079, 1080

calcium channel blockers 741impedance 1082–1083,1083–1084


inhaled anestheticspharmacology 409, 410


hemorrhagic shock, animalstudies 1016

hemostasis physiology 912–915fig 57.4.; see also plateletfunction

heparin 915, 915adverse drug reactions 917–918allergic reactions 1119

Index

1175






heparin (cont.)clinical pharmacology 917dosage/administration918–919

mechanism of drug action 915new/emerging concepts 919NSTEMI/unstable anginamanagement 1095

perioperative medication 992preclinical pharmacology915–917

STEMI management 1094

heparin-inducedthrombocytopenia (HIT) 918

hepatic function see liverfunction

hepatitisalcohol users 1108immune-mediated 398, 399,402–403

metabolism 392

herbal medicine 992, 998–999,1001

HERG blockade 305, 309–310

hernia, chronic pain 1069

heroin addiction 542;see also addiction; drug/alcohol users; opioidagonists/antagonists

herpes 980, 981

HES (hydroxyethyl starch) 793,808–809

high-dose opioid anesthesia 513

Hill analysis, multiple agonistsites 8

Hill coefficient 8

Hill equation 8

hippocampus 218anesthetic neurotoxicity 1155memory/learning 213–214, 219synaptic plasticity 203

hirudin related compoundssee direct thrombininhibitors

histamine receptor antagonists843–845


cimetidine 843–844drug interactions 844famotidine 845nizatidine 844–845neuromuscular blocking drugs613, 614

opioid clinical pharmacology535

ranitidine 844

succinylcholine 620versus proton pump inhibitors847–848

HIV (human immunodeficiencyvirus) 979, 980, 983

immunology 355–356opioids 501

HLA (human leucocyte antigens)349, 350, 356

Hofmann elimination 618

homeostasis 53, 1139

hormonal effectsopioid clinical pharmacology535

perioperative medication996–997, 1000

hormone response elements(HREs) 53

Horner’s syndrome 1067

HPA see hypothalamic-pituitary-adrenal axis

HPV (hypoxic pulmonaryvasoconstriction) 409,768–769

HSPs (heat shock proteins) 900

HU12 (Health Utility Index) 170

human leucocyte antigens (HLA)349, 350, 356

human plasma infusion fluidssee infusion fluids

humoral immunity 349

HX0507 456

hybrid physiologic models 61

hydralazine 771, 954

hydraulic model ofpharmacokinetics 58–59

hydrocodone 538

hydrogen bonds 2

hydrogen fluoride toxicity404–405

hydromorphone 516oral administration 521properties 538sedation 1043

hydrophobic interactions 2

hydroxyethyl starch (HES) 793,808–809

hyoscine butylbromide 673, 849

hyperalgesia 503, 1110

hyperglycemia 600–601,884–885, 906

hyper/hypocapnia 407

hyperkalemia 886

hyperlipidemia 836–837

hypersensitivity 353–354

hypertension 486;see also hemodynamics;pulmonary hypertension;vascular tone

alcohol users 1108

antihypertensive 954calcium channel blockers741–742

immunosuppressants/anti-rejection drugs 836


obstetrics 954

hypertonic electrolyte solutions805–806

hypnosis, definition 478

hypnotics; see also sedationallergic reactions 458–460benzodiazepines 468closed-loop drugadministration 115–116, 117

open-loop TCI 110pharmacogeriatrics1142–1145, 1144, 1146,

hypocretin 187–188

hypoglycemia 885–886, 906

hypotension;see also hemodynamics;vascular tone


vasopressor treatment 957

hypotensive anesthesia 486

hypothalamic-pituitary-adrenalaxis (HPA) 818

anesthetic action mechanisms376–377, 819–820

control of secretion818–819

critical illness effects 820feedback inhibition 819

hypothalamus 218

hypothermia 1031, 1032

hypovolemic shock 805

hypoxemia 770

hypoxia 389

hypoxic pulmonaryvasoconstriction (HPV) 409,768–769

hysteresis 424

ibuprofen 548, 553–550, 555

ibutilide 692, 693, 698–699, 702

ICDSC (Intensive Care DeliriumScreening Checklist)1051–1049

Ice 660

iceberg phenomenon 609, 610

ICF (intracellular fluid flux) 803

ICV (intracellular fluid volume)800, 803

ICP (intra-cerebral pressure) 407

idiopathic ventricular fibrillation(IVF) syndromes 296, 298,301, 302

IFV (interstitial fluid volume) 800

IL-18 786

ileal brake 842

ileus 535, 543, 890, 901

iloprost 773

IM (intramuscularadministration) 123, 522

imidazolines see alpha-adrenoceptor agonists

immobility 361anesthetic action mechanisms378

general anesthesia 232,237–239


immunoglobulin isotopes 346

immunology 345–346, 356–357acquired/adaptive immunity349–353

alpha-adrenoceptor agonists487

anatomical barriers to diseasepathogens 345, 346

B cells 352cancer 354–355cytokines 352–353

hepatitis 398, 399, 402–403HIV 355–356hypersensitivity 353–354inflammatory response 346,347–349

innate immunity 345–349physiological barriers todisease pathogens 345–347

T cells/cell mediated immunity350–352

transplantation 356

immunoreceptors 50–51, 340

immunosuppressants 830, 831,838–839; see also T-cells

adverse drug reactions 835anesthetic agents 838anesthetic implications 836–838

Index

1176






azathioprine 835conduct of anesthesia 838cyclosporine 834–835diazepam/thiobarbiturates 838drug interactions 834–835glucocorticoids 817–818mechanism of drug action830–833

mycophenolate mofetil 834,835–836

opioids 501, 838perioperative medication995–996, 1000


protocols 836, 837rapamycin 834, 835tacrolimus 835

impedance 317hemodynamics 1082–1083,1083–1084

matching to vasculature 1083

implicit memory 212–213

inactivationaction potentials 252ball- and-chain model 300cardiac rhythm 300–301slowly inactivating channels257–258

inamrinone 715–716, 719

incremental cost-effectivenessratio 168

indirect antagonists 10

indirect costs 169

indocyanine green dye 801

indoleamines 1112–1113

induction agents 1007

induction of anesthesia 1007,1020–1021

asthma patients 1017cardiovascular effects1012–1014

critical care applications/adrenal insufficiency1017–1018

drug choice 1007–1008drug interactions 1011–1012,1013

etomidate 1017–1018history 1007inhaled anesthetics 1010–1011intercranial pressure/compliance 1019

intubation withoutneuromuscular blockingagents 1011

laryngeal mask airwayinsertion 1018

myoclonus/rigidity 1014–1015

open eye injury 1016–1017opioids as sole agents 1010pain on injection 1014psychotomimetic effects 1015rapid sequence induction 1016remifentanil infusion 1020,1021

routes of drug administration1011

speed of onset 1007–1010spontaneous ventilationmaintenance 1018–1019

target-controlled infusion1019–1020

trauma/hemodynamicallyunstable patients 1015–1016

induction immunosuppression836, 837

infants; see also pediatricsdefinition 1128developmentalpharmacodynamics 1134

infection; see also antibacterials;antifungals; antimicrobials

acetylcholine receptors 624biotransformation, drug 85

control 838

postoperative 449

surgical site infections 982

infertility 53

inflammationacetylcholine receptors 624biotransformation, drug 85hypersensitivity 353–354

inflammatory response 347–349malignant 814;see also glucocorticoids

metabolic syndrome 876and neuronal death 1151–1152vascular endothelium 282–283

influenza 980–982, 981

information technology (IT) 160

infraclavicular blocks 1067

infusion fluids 800, 809, 810adverse drug reactions804–805, 806, 807, 808, 809

clinical use 804, 806, 807, 808,809

colloid fluids 807–809crystalloid fluids 803–805,809

fluid pharmacokinetics802–803, 802

glucose solutions 806–807hypertonic electrolytesolutions 805–806

intracellular fluid flux 803optimizing 805outcome studies 805

physiology of fluid distribution800, 801

plasma volume expansioncalculation 800–802

uncontrolled hemorrhage809–810

inhalants, drug/alcohol users 1113

inhaled anesthetics 369–374

administration 523anesthetic action mechanisms374, 378

asthma treatments 755–756cerebral ischemia andanesthetic neuroprotection1153

drug interactions 152–154hemodynamics 1079induction of anesthesia1010–1011

maintenance of/emergencefrom anesthesia 1027–1029

perioperative medication 997,1000

pharmacology see belowpharmacogeriatrics1146–1147, 1148

pharmokinetics see belowpostoperative nausea andvomiting 858–859

routes of drug administration125

inhaled anestheticspharmacology 397, 413

adverse autonomic nervoussystem effects 411

adverse circulatory effects409–411

adverse drug reactions 413adverse pulmonary effects407–409

background information onspecific drugs 398–400

beneficial effects 400–401cardio-protection 412cerebral injury 405–407, 413cerebral protection 412delivery systems 400, 401fluoride-inducednephrotoxicity 401–402, 413

hepatic injury 402–403, 413hepatic protection 412hydrogen fluoride toxicity404–405

malignant hyperthermia 401, 413minimum alveolarconcentration 397–398

minimizing injuriouseffects 405

organ protection 411–412physicochemical properties 398renal injury 403–404renal protection 412

inhaled anestheticspharmokinetics 385, 386, 394

age/pregnancy effects 393–394alveolar-arterial gradient 393breathing systems 392–393concentration/second gaseffects 385–388

diffusion into gas spaces 393distribution 387–389elimination 389lipid delivery 394mammillary model 390–391mathematics of distribution389–390

metabolism 391–392physiologically basedpharmacokinetic models 391

terminology 385–386, 387, 388uptake 386–387uptake measurement 390

inhaled nitric oxide (INO)771–773

inhibition, competitive/non-competitive 15, 16,15, 609

inhibitory postsynaptic potential(IPSP) 200–201

injectionpain on 449, 1014

speed, neuromuscular blockingdrugs 615

innate immunity 345–349

inositol triphosphate 24–26, 25

inotropes 1086–1087insulin 874, 886–887;see also diabetes

acute myocardial infarction 886acute severe illness 886administration 877–878analogs 878–879biosynthesis/release 877degradation 877delivery to tissues 877diabetic regimes 879, 881, 882glargine/detemir 879glucose homeostasis 874–877hyperkalemia 886isophane protamine 878perioperative medication 993pharmokinetics 878–879physiological effects 874resistance 876, 884, 892signal 877soluble/regular 878STEMI/UA/NSTEMIadjunctive therapies 1096

use as drug 877zinc/protamine suspensions 878

intangible costs 169

integration of drug effects 3, 13

Index

1177






integrins 51

Intensive Care DeliriumScreening Checklist (ICDSC)1051–1049

interaction models 147,150–152; see also druginteractions

intercranial compliance 1019

intercranial pressure 1019

interferons 346, 352–353

interleukin-2 receptor genetranscription 834

interleukin-2 receptor signaling832–833, 834

internalization 22

interscalene blocks 1067

interstitial fluid volume(IFV) 800

intestine see gutbiotransformation, drug 80opioid metabolism 520

intracathecal analgesia 1065

intracellular drug receptors 4,17, 18

intracellular fluid flux (ICF) 803

intracellular fluid volume (ICV)800, 803

intracerebral pressure (ICP) 407

intramuscular administration(IM) 123, 522

intrathecal routes of drugadministration 127–129, 523

intravenous anesthetics 444, 460allergic reactions 458–460new formulations 456–458opioid clinical practice/physiological principles513–517

pharmacokinetics 420, 437–438;see also barbiturates;etomidate; ketamine;midazolam; propofol

intrinsic efficacy 7, 15intrinsic guanylate cyclaseactivity 50


intubationnon-depolarizingneuromuscular blockingdrugs 620–621

without neuromuscularblocking agents 1011

inverse agonism 11, 15

ion channels 28, 41;see also calcium; ligand-gated; potassium; sodium;transient receptor potential;two-pore potassium

ion channels; voltage-gated ionchannels


antiarrhythmic agents 689,690–691, 690

cardiac rhythm 297, 299–301cerebral ischemiapathophysiology 1151–1152

drug action targets 308–310gating 251–253genetics 297membrane electrophysiology28

neuromuscular blocking drugs611

pain transmission/transduction 239–241

structure/function 299–301transmembrane currents 249transmembrane proteins 253

ion gradients 253

ion pumps 4, 253

ionic bonds 2

ionotropic receptors 34, 41, 35,200; see also positiveinotropic drugs for heartfailure

5-HT receptors 36, 35AMPA receptors 37cys-loop ion channel 35, 41five families of 34–35glutamate receptor family 37,41, 37

glycine receptors 36karinate receptors 37–39N-methyl-D-aspartatereceptors 39–40, 38

P2X receptor family 36, 41receptor localization 40

iontophoretic transdermalsystem (ITS) 1141

ipratropium 673

IPSP (inhibitory postsynapticpotential) 200–201

irreversibleantagonists 9–10, 15drug effects 6

ischemia 486; see also cerebralischemia

focal 1151, 1154inhaled anesthetics 401, 413

isobolograms 148–149

isoconcentration nomogram 514

isoflurane 397and Alzheimer’s disease 222drug interactions 152–154glucocorticoids secretion 820inhaled anestheticspharmacology 397, 398

metabolism 392neurogenesis 1155physicochemical properties 398

isophane protamine (NPH)insulin 878

isoproterenol 653, 657anaphylaxis therapy 1122–1123dosage 719use in heart failure 713–714

ISPOCD I trial 221

IT (information technology) 160

itraconazole 519

ITS (iontophoretic transdermalsystem) 1141

IVA-SIM 104

IVF (idiopathic ventricularfibrillation) syndromes 296,298, 301, 302

James, William 188

jimsonweed 668–669

JM1232 457–458

K channels see potassium ionchannels; two-porepotassium ion channels

kainate receptors (KAR) 37–39

Kalman filters 115

kava kava 999

ketamine 435, 438, 450–452,460, 563

administration routes, extravascular 436

allergic reactions 459and alpha-adrenoceptoragonists 486

analgesia, postoperative1063–1064

anesthetic action mechanisms374–375, 374

biotransformation, drug 434cerebral ischemia andanesthetic neuroprotection1153–1154

clinical pharmacology 563–564concentration/effectrelationship 435–436

disposition parameters 445distribution/metabolism/excretion 433–434, 435

dosage/administration 436, 564drug interactions 436indications 451

induction of anesthesia1008, 1019

mechanisms of drug action563, 564

nasal transmucosaladministration 126–127

patient-controlled analgesia1062

physicochemical properties 433preclinical pharmacology 563preemptive analgesia 1068psychotomimetic effects 1015side effects 445speed of onset 1007–1010structure/stereochemistry433, 445

transfer to effect site 435

ketoacidosis, diabetic (DKA)882–884

ketoacids 874–876kidney function 783, 795;see also acute kidney injury


analgesia, postoperative 1072antioxidants 794–795

aspirin 927atrial natriuretic peptide 795biotransformation, drug80–81, 85

calcium channel blockers 743,747

chronic disease 783, 784, 794clearance 802crystalloid fluids 805diuretics 790–791, 792, 794dopamine 794drug transporters 97–98

end-stage disease 783experimentalpharmacotherapy 795

fluoride-inducednephrotoxicity 401–402

glomerular filtration rate 783,787–788


inhaled anestheticspharmacology 403–404, 412

injury 783monitoring 785–786non-steroidal anti-inflammatory drugs 557

neuromuscular blockadereversal 637

neuromuscular blocking drugs616, 617, 622, 623

nutritional pharmacology 907opioid effects 533pediatric pharmacology1132, 1133

perfusion 793

Index

1178






perioperative morbidity784–785

pharmacogeriatrics 1140,1148

pharmacokinetics 430,524–525

pharmacotherapy 793–794propofol 430, 449protection during anesthesia412, 485, 791–793

salt/water homeostasis 786sugammadex 643urine formation 786–790volume status 791–793

KIM-1 786

kinetic–dynamic model 158

Kir genes 307

kiss-and-run 198–199, 264

knockin animals 362, 467

knockout animals 362

labetalol 684, 954

lactated Ringer’s (LR) solution793, 803–804;see also crystalloid fluids

lactation 525–526

Lambert–Eaton myasthenicsyndrome 625

lamina, spinal dorsal horn 234–235

lamotrigine 591–592, 593, 594,595, 597

Langmuir isotherms 4

lansoprazole 846

laryngeal mask airway (LMA)insertion 1018

latex, allergic reactions 1120

layer-specific electrophysiology296

LD50 15

learning 220, 373;see also memory

leflunomide (LFM) 834

lethality (LD50) 15

leucocytes 349

leukotriene antagonists 758–760,997, 1000

levetiracetam 591–592, 593, 594,595–598

levobupivacaine 566clinical pharmacology 566–567dosage/administration 567mechanisms of drug action566


levosimendan 717–718, 719, 734

LGICs (cys-loop drug-gated ionchannels) 3

lidocaine 693antiarrhythmic agents 692,695, 702

cerebral ischemia/anestheticneuroprotection 1153

physico-chemical properties 578systemic effects 583toxicity 582–583

ligand-gated ion channels 18, 415-HT receptors 36, 35AMPA receptors 37autonomic nervous system 340cys-loop ion channel 35, 41five families of ionotropicreceptors 34–35, 35

glutamate receptor family36–40, 41

glycine receptors 36ionotropic glutamate receptors37, 37

ionotropic/metabotropicreceptors 34

kainate receptors 37–39N-methyl-D-aspartatereceptors 39–40, 38

P2X receptor family 36, 41receptor localization 40transient receptor potential ionchannels 40–41

ligands, opioid receptor 497

lincosamides 964, 974, 975–976

Lineweaver–Burke plot 5

lipid/s 893–899

bilayers 90, 91

drug delivery 394

emulsion 584–585

lowering drugs 1096nutritional pharmacology894–897

solubility 388, 577–578, 585

Lipinski’s rule of fives 97

lipopeptides 964, 970, 971

lipopolysaccharide (LPS) 348

lithium 603, 994, 1000

liver functionalcohol users 1108analgesia, postoperative 1072biotransformation, drug 84–85cirrhosis 428drug transporters 97immunosuppressants/anti-rejection drugs 837–838

inhaled anestheticspharmacology 402–403, 412

injury 402–403, 413neuromuscular blocking drugs618, 622, 623

non-steroidal anti-inflammatory drugs 558

nutritional pharmacology 905opioid effects 533organ failure 905, 1072pediatric pharmacology 1129,1132–1133

pharmacogeriatrics 1140,1148

propafol 427, 430, 449protection 412pharmacokinetics 427, 430, 524

LMA (laryngeal mask airway)insertion 1018

LMWH (low molecular weightheparin) 1095

local anesthetics 574, 586alkanization 580, 586allergic reactions 582cardiovascular effects 584central nervous system effects583–584

classification of peripheralnerves 575

distribution 581–582elimination 582epinephrine additives580, 586

functional anatomy of axons574–575

G protein-coupledreceptors 576

ion channels 239–241ionization 578–580lipid solubility 577–578, 585mechanisms of drug action575–576

methenoglobinemia 583molecular targets 239, 241new/emerging concepts584–585

obstetrics 951–952opioid additives 580, 586pharmacokinetic parameters582

pharmacokinetics 580physico-chemical properties577, 578

protein binding 578, 585systemic absorption 580–581systemic effects 583tissue toxicity 582–583

Loewe additivity druginteractions model 148

logistic equation 8

long QT syndrome (LQTS) 10,139–140, 296, 298, 301, 302

delayed rectifier Kþ currents305, 306

long-acting insulin analogs 879

long-term potentiation (LTP) 202maintenance 204–205memory/learning 210, 218, 220NMDA receptor dependent202–204

non NMDA-dependent 205and second messengers 204

long-term synaptic depression(LTD) 205–206

loop of Henle 786–790, 790–791

loop diuretics 790–791, 792

loperamide 93, 850–851

lorazepamclinical pharmacology 469dosage/administration 473,474–475

pharmodynamics 471–472pharmokinetics 469–470, 470sedation 1043, 1047

lower motor neuron lesions623–624

low-molecular-weight heparin(LMWH) 1095

LPS (lipopolysaccharide) 348LQTS see long QT syndrome

LSD (lysergic acid) 1112–1113

LTD (long-term synapticdepression) 205–206

LTP see long-termpotentiation

luciferase 360–361

lumbar paravertebralblocks 1067

lung function 81;see also pulmonaryhypertension; pulmonaryvasodilators

acetylcholinesteraseinhibition 637

acute lung injury 814, 1119adverse drug effects 407–409elimination 389, 427inhaled anestheticspharmacology 407–409

non-steroidal anti-inflammatorydrugs 557

pharmacogeriatrics 1140propofol 427, 449routes of drug administration125

lupus erythematosus 596

lymphocytes 349–350

lysergic acid (LSD) 1112–1113

M6G (morphine-6-glucuronide)1139; see also morphine

Index

1179






ma huang 651, 999

MAC see minimum alveolarconcentration

macrolides 964, 972, 973

magnesium 694, 733, 737

magnesium sulphatepre-eclampsia 953–954preterm labor 955STEMI/UA/NSTEMIadjunctive therapies 1096

magnetic resonance imaging(MRI) 1054–1055

maintenance of anesthesiasee emergence from/maintenance of anesthesia

maintenanceimmunosuppression 836, 837

major histocompatibilitycomplex (MHC) 349, 350,830–831

malignant hyperpyrexia 451, 453

malignant hyperthermia (MH)137–139, 138, 401, 413

dantrolene 748drug choice 1028xenon 399

malnutrition see nutritionalpharmacology

mammillary models 59etomidate 436–437inhaled anestheticspharmokinetics 390–391

methohexital 425propofol 427–429thiopental 422

mannitol 790, 792

MAOIs (monoamine oxidaseinhibitors) 340, 660, 993,1000

Mapleson’s water analogy 388,389

marijuana 1110–1111

marinol (dronabinol) 569

Mark II Health Utility Index(HU12) 170

Marsh model 111, 428, 429–432

mast cells 614

maternal pharmacokinetics949–951; see also obstetrics

mathematical modelsinhaled anestheticspharmokinetics 389–390

open-loop TCI 105–106pharmacodynamic model 57pharmacokinetic model 57

maximal effect (Emax) models 6,15, 155

maximizing efficiency of targetsedation and reducingneurological dysfunction(MENDS) study 484, 488

MBC (minimum bactericidalconcentration) 963

MDIs (metered dose inhalers) 523

MDMA (methylenedioxy/methamphetamine)1112–1113

MDR (multidrug resistancetransporter) genes 92

mean effect time (MET) 65–66, 429

mean residence time (MRT) 58

mechanotransduction ionchannels 236–237

medical decision-making 166–167;see also pharmacoeconomics

medullary vasomotor center 652,648–649

MedWatch program 1121–1124

meglinitides 879, 880

melatonin 458

membrane, cell 254, 800

active agents 964, 971–972, 978–980

capacitance 253, 254, 258

drug transporters 91

electrophysiology 28

potential 28

properties 253, 254

reaction time 254–255

transmembrane currents 249

transmembrane proteins 2, 253

transmembrane pumps 4

transmembrane receptors 51–53

memory 210–211, 222;see also amnesia

conscious 212, 216–219consolidation/forgetting217–218, 220

definitions 212–213delirium 221drug actions 215, 216–219drug targets 218–221during anesthesia 215–216neuro-mechanistic processes213–214

NMDA receptors 373perception/working memory212, 226

perioperative period 211–212

postoperative cognitivedysfunction 221–222

procedural memory/conditioning 212–213, 216

serial parallel independenttaxonomy 215, 216

unconscious 212–213, 215–216

MENDS (maximizing efficiencyof target sedation andreducing neurologicaldysfunction) study 484, 488

meperidine 538, 1141

mephentermine 653, 655–656

MEPP (miniature endplatepotential) 196

mesenchymal stem cells (MSC)356

mesolimbic dopamine system1106

MET (mean effect time)65–66, 429

metabolic responses to surgery/trauma 876–877; see alsosurgical stress response

metabolic syndrome 876

metabolism, drugsee biotransformation;clearance; enzymes

metabotropic glutamate receptor(mGlu5) agonists 242

metabotropic receptors 34, 41, 35

metamphetamine 660–661

metaraminol 653, 655–656

metered dose inhalers (MDIs) 523

metformin 879, 880, 993

methadone 126, 127, 516, 521, 538

methenoglobinemia 583

methohexital 425, 426, 438,446–447

adverse drug reactions 447allergic reactions 459decrement time 431disposition parameters 445dosage/administration 425–426pharmacokinetic modeling 425physicochemical properties 425side effects 445speed of onset 1007–1010structure/stereochemistry425, 445

methoxamine 653, 655

methoxyflurane 392

methylenedioxy-methamphetamine(MDMA) 1112–1113

methylphenidate 660–661

methylxanthines 753–754

metoprolol 683–684, 700, 702

mexiletine 692, 693, 695–696,702

Meyer–Overton correlation359, 360

mGlu5 (metabotropic glutamatereceptor) agonists 242

MH see malignant hyperthermia

MHC (major histocompatibilitycomplex) 349, 350, 830–831

MI (myocardial infarction) 886,1091–1092

MIC (minimum inhibitoryconcentration) 963–965

microemulsions 454

microtubules 199

midazolam 453, 460allergic reactions 459, 460clinical pharmacology 468CYP3A 84dosage/administration 473–474pharmacogeriatrics 1144–1145pharmodynamics 471pharmokinetics 469, 469sedation 1043structure/stereochemistry 445

midodrine 655

milrinone 715, 716, 719

minerals, nutritionalpharmacology 894–897,901–902, 904

miniature endplate potential(MEPP) 196

minimum alveolar concentration(MAC) 152–153, 397–398

obstetrics 951, 952pharmacogeriatrics 1147

minimum bactericidalconcentration (MBC) 963

minimum inhibitoryconcentration (MIC)963–965

mivacurium 623

MLCP (myosin light chainphosphatase) 726

MMF (mycophenolate mofetil)834, 835–836

MOC-etomidate 457

model predicted control 115

modeling, pharmacokinetic1135–1136

Index

1180






MODS (multiple organdysfunction syndrome) 814

modulated receptorhypothesis 576

modulation, pain 227, 230–231,236; see also paintransmission/transduction

molecular biology 1, 2

molecular targets see drug targets

moment analysis 58

monitoringmaintenance of/emergencefrom anesthesia 1032–1034

sedation 1044–1046

monoamine oxidase (MAOs)inhibitors 340, 660, 993,1000

monobactams 969

mood effects 340;see also depressant drugs

calcium channel blockers 742opioid agonist-antagonists539–540

propofol 448–449sedation complications 1042

moricizine 692, 693, 697, 702

morphine; see also opioidsbolus dosing 510–513drug interactions 563history 531intramuscular administration522

oral administration 520oral transmucosaladministration 521

Oxford League Tableof NNT 555

pharmacogeriatrics 1141properties 538sedation 1042subcutaneous administration521–522


mortality rates reduction,nutritional pharmacology890, 900, 907

motility, gut 842; see also gutmotility/secretion inhibitors

motion sickness 856, 858

motor functionsee neuromuscular function

motor neuron lesions 623–624

MRI (magnetic resonanceimaging) 1054–1055

MRPs (multi-drug resistantproteins) 92, 93–94

MRSA infection 982

MRT (mean residence time) 58

MSC (mesenchymal stem cells)356

mu partial agonists 537

mucociliary function, lung408–409

mucous membranes, barriers todisease pathogens 345

multicompartment models 390

multidrug resistance transporter(MDR) genes 92

multidrug resistant proteins(MRPs) 92, 93–94

multimodal analgesia,postoperative 1067–1068

multiple organ dysfunctionsyndrome (MODS) 814

MUMPS (multi-unit, multi-pathsystem) model 152

muscarine 668

muscarinic acetylcholinereceptors 666;see also parasympatholyticdrugs

acetylcholinesterase inhibition637


perioperative medication 995succinylcholine 618, 619

muscarinic antagonists 487–488,1036

muscle; see also neuromuscularfunction; vascular smoothmuscle

body composition in elderlypatients 1139–1140

contraction physiology 724–726distribution phase of drugdelivery 388

nicotinic acetylcholinereceptors 267–268, 269–270,270–271

muscle relaxants;see also vasodilators

benzodiazepines 468calcium channel blockers 747chemical structure 612closed-loop drugadministration 116, 117


perioperative medication 994

mutually exclusive binding 8

myasthenia gravis 624–625, 995

mycophenolate mofetil (MMF)834, 835–836

myelin sheath 574–575

myelination 256

myocardial contractility409–410

myocardial infarction 886,1091–1092; see alsonon-ST-elevation myocardialinfarction; ST-elevation

myocardial infarction

myocardial ischemia 1091,1101–1102

acute coronary syndromes1091

acute coronary syndromesdefinition/diagnosis1091–1092

acute coronary syndromespharmacologic/interventional management1092, 1093, 1094

antiplatelet therapy,perioperative 1099–1100

beta-blocker therapy,perioperative 1097–1099

cardioplegia 1100–1101glossary of terms 1091inhaled anestheticspharmacology 411

non-ST-elevation myocardialinfarction/unstable anginamanagement 1094, 1095

ST elevation myocardialinfarction management1092–1095

statin therapy, perioperative1098, 1099

STEMI/UA/NSTEMIadjunctive therapies1096–1097

thoracic sympathectomy 1100

myocardial performancesee cardiovascular effects;coronary circulation; heartfunction

myocardial perfusion 319

myoclonus 1014–1015

myofilament calcium sensitizersclinical pharmacology 717dosage 719levosimendan 717–718pimobendan 717preclinical pharmacology716–717

thyroid hormone 717–718

myogenic contraction 279–280

myogenic tone 726

myosin 278

myosin light chain phosphatase(MLCP) 726

Naþ channels see sodium ionchannels

N-acetylcysteine (NAC) 794–795

nalbuphine 537, 540

nalmefene 543

nalorphine 537

naloxone 542

naltrexone 542, 1107

NANC (nonadrenergicnoncholinergic) mechanisms284, 333

naproxen 548cardiovascular effects 556OxfordLeagueTable ofNNT 555pharmacokinetic parameters553–550

narcotics, terminology 531

Narcotrend 180

nasal transmucosal routes ofdrug administration 126–127

natural penicillins 966, 967

nausea see anti-emetics;postoperative nausea andvomiting

NDBs see non-depolarizingneuromuscular blocking drugs

nebivolol 681, 684

necrosis 1151–1152

nedocromil sodium 757–758

neonatesdefinition 1128metabolism 950

of drug addicts 1110

pediatric pharmacology 1128

neostigmine 633, 637, 1035;see also neuromuscularblockade reversal

Nernst equation 28, 249–250, 251

nerve growth factor (NGF)242, 571

nerve impulse 253, 254

nerve terminals 192

nervous system agonists 487

neural control of cardiacrhythm 293

neuraminidase inhibitors980–982, 981

neuraxial routes of drugadministration 124, 127–129

Index

1181






neuroanatomy 375

neurogenesis 1154–1155

neurogenic control 320

neurokinin type 1, 860 receptorantagonists 864–865

neuroleptic malignant syndrome(NMS) 994

neuroleptics 860, 861–862

neuromechanistic processes ofmemory/learning 213–214

neuromuscular blockade reversal633, 643–644, 1035–1036

according to anesthetic drugadministered 636

acetylcholinesterase drugs635–636

acetylcholinesterasesinhibitors 634

depth of blockade 635dosage/administration 636drug interactions 636–637monitoring 637–639neuromuscular junctionacetylcholinesterase 633–634

neuromuscular junctionplasticity 633

nonclassic drugs 639;see also sugammadex

pharmacokinetics 637residual effects 639side effects 637spontaneous clearance 636variation between patients 637,643

neuromuscular blocking agents(NMBAs) 608, 627–628;see also succinylcholine

acetylcholine receptors622–624, 624–625

acetylcholine receptor relaxanteffects 613

acetylcholinesterase enzyme611–612

administration 625–626adverse drug reactions 618allergic reactions 1119–1120bronchial smooth musclerelaxant effects 614

carotid body relaxant effects613–614

clinical pharmacology-non-depolarizing drugs 620–622

contraindications 619dosage/administration620–621

drug interactions 625duration of action 621elimination/metabolism 616,617–618

ester hydrolysis 617–618extended use 627

factors affectingpharmacokinetics 615–617

hepatic disease 622, 623histamine release 613, 614Hofmann elimination 618intrinsic activity 613intubation without 1011mechanisms of drug action609–611

neuromuscular function622, 624

neuromuscular transmission608–609

pharmacogeriatrics 1145–1146pharmacokinetics 615postsynaptic transmission 609preclinical pharmacology614–615

presynaptic transmission 608rapid sequence induction 626recovery index 621–622renal function 622, 623structure-activity relationships612, 613

variation between patients 626

neuromuscular function 114,261, 265

acetylcholinesterase inhibition266–267

action potentials 262–263,265

calcium voltage-gated ionchannels 263–264

depolarizing blocking drugs 270monitoring 637–639,1032–1034

muscle nicotinic acetylcholinereceptors 267–268


neuromuscular junctionstructure/function 261, 262,263

neuromuscular transmission270–271

noncompetitive inhibitors269–270

nondepolarizing competitiveblocking drugs 270

presynaptic terminal,transmitter release 262–265

quantal transmitter release 264receptor activation 268–269receptor desensitization 269synaptic cleft 265–267vesicle cycling 264, 265vesicle fusion 263–264vesicle fusion proteins264–265, 266

neuromuscular junction (NMJ)acetylcholinesterases 633–634neuromuscular blockingdrugs 625

plasticity, synaptic 633structure/function 261, 262, 263succinylcholine 618, 619–620

neuromuscular transmission270–271, 608–609, 610

neuronal activity/signalling 29

neuronal death 1151–1152;see also neurotoxicity

neuronal plasticity 550

neuronal regulation 726, 727

neuropathic pain 231, 536

neuroprotection 1151,1158–1159; see also cerebralischemia; neurotoxicity

age effects 1157alpha-2 adrenoceptor agonists481

reconciliation of opposingeffects of anesthetics1157–1158

neuroradiology, sedation for1054–1055

neurosteroids 368–369, 374

neurotoxicity 1155–1156,1158–1159;see also neuroprotection

age effects 1157alcohol 1107mechanism of drug action1156, 1157


relevance of rodent models tohumans 1156–1157

neurotransmitters;see also synaptictransmission; specificneurotransmitters by name

agonist/antagonist drug actiontargets 206

biotransformation, drug actiontargets 206

calcium regulation 197chemical identity 193–194,194–195

classes of 194–195, 206drug transporters 90duration of action 199ganglionic blockers 733glutamate as 36mechanism of transmitterrelease 196

neurogenesis 1154

presynaptic release 262–265re-uptake drug actiontargets 206

stages of chemical transition193, 194

storage of neurotransmitters 196storage, drug action targets 206synthesis, drug actiontargets 206


neutrophil gelatinase-associatedlipocalin (NGAL) 785–786

newborn babies see neonates

NFAT (nuclear factor of activatedT cells) 831–832, 834

NFkB 52–53

NHLBI International ConcensusReport on Diagnosis andTreatment of Asthma 825

nicotine see smoking

nicotinic acetylcholinereceptors 2–4

acetylcholinesteraseinhibition 637

barbiturates, anesthetic 368drug receptor categorization 2ketamine 374

muscle 267–268, 269–270,270–271


neuromuscular function267–268, 269–270, 270–271

nifedipene 954–955

nitratescardiovascular patients,perioperative medication989, 999


nitric oxide 280, 281anesthetic action mechanisms374, 375

blood pressure control/vascular tone 1087

cardiovascular actions410–411

diffusion into gas spaces 393heart contractility control 325inhaled 771–773maintenance of/emergencefrom anesthesia 1031

metabolism 392nitrovasodilators 728–729pharmacology 399–400physicochemical properties 398postoperative nausea andvomiting 858

preterm labor 955signal transduction 17sympathetic nervous system 651toxicity 140, 141vascular reactivity 281

nitroimidazoles 964, 978

Index

1182






nitrovasodilators 728–729,737, 771

nizatidine 844–845

NMBAs see neuromuscularblocking agents

N-methyl-d-aspartate (NMDA)receptors 39–40, 38, 200


anesthetic neurotoxicity1155–1156

drug addicts 1110ketamine 374–375, 563, 564long-term potentiation202–204

neuroprotection/neurotoxicity1151

nitrous oxide 375psychedelics/party drugs1112–1113


volatile anesthetics 371–373xenon 375

N-methylnaltrexone 543

NMJ see neuromuscular junction

NMS (neuroleptic malignantsyndrome) 994

nocioception/nocioceptive pain227–228, 231, 1061–1063;see also pain transmission/transduction

nomenclature/categorization,drug receptors 2–4, 18

nonadrenergic noncholinergic(NANC)mechanisms 284, 333

noncompetitive block 15, 9, 10,10, 609

muscle nicotinic acetylcholinereceptors 269–270

neuromuscular blocking drugs609–611

nondepolarizing neuromuscularblocking drugs (NDBs) 270

clinical pharmacology620–622

recovery index 621–622

nonenzymatic decay 618

nonimmobilizers 359

nonionotropic/non-G-protein-coupled receptors 47, 54

acronyms 53caspases and NFkB 52–53cystolic serine/threoninekinases 51–52

cystolic tyrosine kinases 50–51cytokine receptors 50

cytoplasmic enzymes 53immunoreceptors 50–51integrins 51intrinsic guanylate cyclaseactivity 50


nuclear receptors 53–54plasma membrane receptorslinked to cytoplasmicenzymes 50

plasma membrane receptorswith intrinsic enzymeactivity 47

receptor tyrosine phosphatases48–49


non-operating-room anesthesia(NORA) 1054

non-rapid eye movement sleep(NREM) 182–183, 479

nonspecific binding 4

non-ST-elevation myocardialinfarction (NSTEMI) 1091,1101–1102

definition/diagnosis 1091–1092management strategies1094, 1095

pharmacologic/interventionalmanagement 1092, 1093,1094

nonsteroidal anti-inflammatorydrugs (NSAIDs) 548, 559;see also cyclooxygenase-2-specific inhibitors

absorption 551–552analgesia, postoperative 1063asthma 557bone healing 557–558cardiovascular effects 555–556chirality 551classification according tochemical structure 551

clinical context 559cyclooxygenase expression/action 550, 550

cyclooxygenase inhibition550–552

cyclooxygenase/prostaglandinsrole in pain 548, 549

distribution 552–553drug interactions 558gastrointestinal effects556–521, 847–848

hepatic effects 558metabolism/excretion 554neuronal plasticity 550Oxford League Tableof NNT 555


pharmacodynamics 555–556pharmacokinetics 551,553–550

platelet function 557preemptive analgesia 1068prostaglandins synthesis/action 548–550

renal effects 557

NORA (non-operating roomanesthesia) 1054

norepinephrine (NE) 284, 330,335–336, 659

anaphylaxis therapy 1122–1123dosage 719pharmacological modulation340–341

use in heart failure 711–712

norketamine 435

normal saline (NS) 793, 803, 804,805; see also crystalloid fluids

novel analgesics 563, 571–572alpha-adrenoceptor agonists567, 568

anticonvulsants 564–566calcium channel blockers568–569

cannabinoids 569ketamine 563–564peptide growth factor andreceptors 571

sodium channel blockers566–567

transient receptor potential ionchannels 570–571

NPH (isophane protamine)insulin 878

NREM (non-rapid eyemovement sleep)182–183, 479

NS (normal saline) 793, 803, 804,805; see also crystalloid fluids

NSAIDs see non-steroidalanti-inflammatory drugs

NSTEMI see non-ST-elevationmyocardial infarction

N-type inactivation 300

nuclear drug receptors 4

nuclear factor of activated T cells(NFAT) 831–832, 834

nuclear receptors, non-ionotropic/non-G protein-coupled53–54

nucleus tractus solitarius(NTS) 1078

nutritional pharmacology890–891, 907

administration routes 903–904arginine 900, 901

burn injury 901, 907carbohydrates 892, 894–897critical care applications901–903

designing nutritional supportregimes 894–897

energy expenditure 891–892,891–892

enteral routes 903–904, 905–906enteral routes formulary898–899

gastrointestinal complications905–906

glutamine 900glutamine (GLN) 904–905indications 901–903lipids 893–899, 894–897metabolic complications 906monitoring 904–905neurogenesis 1154

nutritional guidelines 903parenteral routes 904, 905proteins/amino acids 893–900,894–897

renal function 907supplements, alcohol users1107

surgical patients 901timing of feeding 904trace elements 901–902, 904

OATs (organic aniontransporters) 94, 95–96,97–98

OBD (opioid bowl dysfunction)535, 543

obesity; see also nutritionalpharmacology

neuromuscular blocking drugs615–616

postoperative nausea andvomiting 857

propofol pharmacokinetics428, 430

objective evaluation, andsubjective experience 177

obstetrics 81, 948, 949, 958–959see also neonates

absorption/uptake 949alcohol users 1109analgesia 952–953antiepileptic drugs 590antihypertensive therapy 954breast milk transfer 950–951distribution 949effects of pregnancy 393–394elimination 950ergot alkaloids 955–956fetal/neonatal metabolism 950general anesthesia 951, 952gonadotropins 956–957local anesthetics 951–952

Index

1183






obstetrics (cont.)maternal pharmacokinetics949–951

metabolism 949–950neuromuscular blockingdrugs 616

ocytocics 955oxytocin 955pharmacodynamics 951–953pharmacogenetics 948pharmacokinetics 525, 949

placental transfer/metabolism98, 950

pre-eclampsia 953–954progesterone antagonists 956propofol 957–958prostaglandins 956remifentanil 958tocolytics 954–955vasopressor treatment ofhypotension from spinalanesthesia 957

OCT (organic cationtransporters) 94, 97–98

octreotide 848–849

ocytocics 955

offset of drug effect 66

Ohm’s Law 248–249, 285

OHSS (ovarian hyperstimulationsyndrome) 956–957

olanzapine 599, 600, 601, 602

omalizumab 760–761omega–3 fatty acids 905, 907

omeprazole 845–846

ondansetron 860, 863–864

one-volume kinetic model 802

onset of drug effect 65, 615

open eye injury 1016–1017

open-loop TCI 103–104, 110,116–118; see also targetcontrolled infusion

comparison with manualinfusion 107–109

context-sensitive half-time/decrement time 109

control strategy 106, 107effect-site targeting 106–109history/definitions 104–105mathematical model 105–106model selection 111–112performance evaluation 109–111plasma targeting 106, 107–109variation between patients 112,113, 114

opioids 493, 494, 503–504,1061–1063; see also drugadministration routes;

fentanyl; morphine;meperidine; propofol;remifentanyl

acute/chronic effects 532addiction 1107additives 580, 586agonists/antagonistssee belowanalgesia, postoperative1061–1063

analgesic action mechanisms496–498

antitussive effects 499for awake fiberoptic intubation1054

cardiovascular effects 499classes of 497clinical pharmacologysee below

clinical practice/physiologicalprinciples see below

closed-loop drugadministration 114–115,116, 117

conversion to morphineequivalents 1061–1062

drug interactions 152–154,154–158, 519–520, 533

drug interactions, figures 153,155, 156, 157, 158, 159

drug/alcohol users/addicts1109–1110

effects not mediated by opioidreceptors 532

endogenous 494gastrointestinal effects 499, 500genetic responsivity 136genetics 136–137, 494, 496gut motility/secretioninhibitors 850–852

hyperalgesia 503immunosuppression 501, 838induction of anesthesia 1010intercranial pressure/compliance 1019

metabolism 518natural/semisynthetic/synthetic 493–494

obstetrics 959open-loop TCI 110,111–112, 114

perioperative medication997–998, 1000

pharmacogeriatrics1140–1142, 1143


protein binding 518pruritis 500–501receptor signaling 496receptor structure/ligandinteractions 495–496, 497

receptors 494–495, 496, 497, 498respiratory depression498–499

rotation, drug addicts 1110sedation 1042–1043, 1046–1047tolerance 23–24, 501–503,535–536, 563–564, 1070–1071opioid agonists/antagonistsalvimopan 543analgesia 537–539antagonist effects 540cardiovascular effects 540chronic administration 540–542general properties 537nalmefene 543naloxone 542naltrexone 542N-methylnaltrexone 543respiratory depression 540sedation/mood effects 539–540smooth muscle effects 540

opioid bowl dysfunction (OBD)535, 543

opioid clinical pharmacology496–498, 531, 532–533, 536,543–544

analgesia 532–533cardiovascular effects 534–535chronic effects 535–536chronic pain 536coughing reflex suppression534

histamine release 535hormonal effects 535nausea 534opioid agonists 531physical dependence 536pupil constriction 534respiratory depression533–534

sedation 533skeletal muscle rigidity 534smooth muscle spasm 535specific drugs 536–541, 538terminology 531

opioid clinical practice/physiological principles509, 526

apnea and rate of opioidadministration 518

bolus dosing of opioids510–513, 537

drug interactions 519–520epidural 523–524hepatic disease 524inhalational administration 523intramuscular administration522

intrathecal 523intravenous infusion 513–517,537

lactation 525–526opioid metabolism 518opioid protein binding 518oral administration 520, 520

oral transmucosaladministration 521

pharmacogenetics 518–519pharmacokinetic half-lives 516pharmacokinetic/pharmacodynamic data 511

plasma concentration profiles517, 540

pregnancy 525renal disease 524–525selection and use of opioids510, 511

subcutaneous administration521–522


opthalmic agents, perioperativemedication 998, 1000

opthalmic surgery 486

oral agents/administrationdiabetes 881–882hypoglycaemic agents 880opioids 520, 520platelet function 988

oral transmucosal administration(OTM) 521

oral transmucosal fentanyl citrate(OTFC) 125–126

orexin 187–188

organ protection

heart 743, 743

inhaled anesthetics 401, 411–412

kidney 412, 485, 791–793

liver 412

organic anion transporters(OAT) 94, 95–96, 97–98

organic cation transporters(OCT) 94, 97–98

orphan receptors 19

orthopedic surgery 934

orthosteric drug binding sites 4

OSCS (oversulfated chondroitinsulfate) 919

osmotic diuretics 790

OTFC (oral transmucosalfentanyl citrate) 125–126

OTM (oral transmucosaladministration) 521

outcome studies, sedation1046–1049

ovarian hyperstimulationsyndrome (OHSS) 956–957

oversulfated chondroitin sulfate(OSCS) 919

Index

1184






oxazolidinones 964, 974–975

oxcarbazepine 591–592, 593, 594,595, 597

Oxford League Table of NNT 555

oxybutinin 673

oxycodone 521, 538, 555

oxygen consumptionsurgical stress response 1041ventricular function1081–1082

oxytocin 955

oxytocin-receptor agonists 955

P2X receptor family 36, 41

PABA (para-amino benzoicacid) 582

pacemaker current 307–308

pacemaker tissue 323–324

pain; see also analgesia; regionalanalgesia

cyclooxygenase/prostaglandinsrole 548, 549

on injection 449, 1014

pain transmission/transduction227, 241; see also perception;pain

abnormal impulse activity257–258

ascending pathways 229–230biochemical/molecularmechanisms 236–237, 243

descending modulatorypathways 230–231

molecular targets–generalanesthetics 232, 237–239, 243

molecular targets–localanesthetics 239, 241, 243

neuron heterogeneity 232–234new/emerging concepts 242,243

nocioceptor types 232organ physiology 231, 243plasticity, synaptic 235–236primary afferent nocioceptors227–228, 231–232, 233, 243

spinal cord 228–229spinal dorsal horn neurondiversity 234–235

spinal dorsal horn synapse234, 243

systems physiology 227, 242–243voltage-gated ion channels237, 239–241

PAMPs (pathogen-associatedmolecular pattern molecules)346

pancreas 874–877, 1108;see also glucose homeostasis

pancuronium 608, 612, 1030–1031

pantoprazole 846–847

para-amino benzoic acid(PABA) 582

paracetamol 552, 553–550, 555,1063

paradoxical reactions 1145

paralysisbutyryl-cholinesterasedeficiency 134–135


reversal see neuromuscularblockade reversal

parametric drug responseanalysis in individuals 13

parasympathetic nervous system284, 330, 331–333;see also autonomic nervoussystem

parasympatholytic drugs668–669, 673–674


atropine 669–672clinical pharmacology 669glycopyrrolate 672mechanisms of drug action669

other anticholinergic agents672–673

scopolamine 672

parasympathomimetic drugs 666clinical pharmacology667–668

mechanisms of drug action666–667

preclinical pharmacology 667synthetic choline esters667–668

parecoxib 553–550;see also cyclooxygenase-2-specific inhibitors

parenteral nutrition 904, 905

Parkinson’s disease 603, 604

perioperative medication 994,1000

paroxetine 519

partial agonists 6, 9, 11, 15, 537

partial pressure 385–388

party drugs 1112–1113

PASMCs (pulmonary arterysmooth muscle cells) 768–769

pathogen-associated molecularpattern molecules(PAMPs) 346

patient compliance, dosingregimes 520

patient state index (PSI) 1032

patient-controlled analgesia(PCA) 515–517,1061–1063

patient-controlled epiduralanalgesia (PCEA) 1065

patient-controlled transdermalfentanyl (PCT-fentanyl)125, 522

pattern recognition receptors(PPRs) 346, 347

PBPKs (physiologically basedpharmacokinetic models)61–62, 391, 422–424, 432

PCI see percutaneous coronaryintervention

PCP (phencyclidine) 1112–1113

PDE inhibitorssee phosphodiesteraseinhibitors

peak effect, morphine 1141

pediatric pharmacology 1128,1136

absorption 1129–1130, 1132analgesia, postoperative1071–1072

biotransformation, drug 81, 82blood–brain barrier 1131definitions 1128developmentalpharmacodynamics1133–1134

developmentalpharmacogenetics 1134, 1135

developmentalpharmacokinetics 1128,1132

distribution 1130–1131, 1132drug metabolism 1131–1132extrahepatic elimination1133

hepatic elimination 1129,1132–1133


neonates 1128pharmacokinetic modeling1135–1136

protein binding 1131renal elimination 1133

PEEP (positive end-expiratorypressure) 1035

penicillins 964, 966, 967allergic reactions 1118

pentazocine 537

pentoxifylline 992

peptide growth factor/receptors571

perceptionmemory/learning 212

pain 140, 227; see also paintransmission/transduction

perceptual memory 215, 216

percutaneous coronaryintervention (PCI)

facilitated 1093–1094primary 1093reperfusion therapy 1093rescue 1093

perfusion, neuromuscularblocking drugs 615

perioperative cardioprotection743, 743

perioperative ischemiaevaluation study (POISE)1097–1099, 1101

perioperative medication 987,988, 999; see alsocardiovascular patients;perioperative medication

analgesics/anti-inflammatories997–998, 1000

anticoagulant medications992, 1000

anti-diabetic agents 992–993,1000

antiinfective agents 995, 1000anti-neoplastics 988, 995, 996,1000

antiplatelet agents 990–992, 996central/peripheral nervoussystem agents 993, 1000

glucocorticoids 824–826herbal preparations998–999, 1001

hormones/metabolics996–997, 1000

immunosuppressants995–996, 1000

opthalmic agents 998, 1000pentoxifylline 992respiratory agents 997, 1000tobacco/alcohol cessationagents 998, 1001

peripheral nervous system648–649, 993, 1000

persistent vegetative states178, 179

personalized medicine 83

PF0713 457

P-glycoprotein (P-gp) 92–93, 94,99; see also ABC drugtransporters

phagocytosis 345–346

Index

1185






phantom limb pain 1069–1070

pharmacodynamics 1, 15drug receptors 1–4drug-receptor interactions4–6, 6–13, 147

effects on organisms 13–15genetic 135–136models 57non-steroidal anti-inflammatory drugs 555–556

pharmacoeconomics 166, 174–175computer modeling 172, 173conflict of interest 174cost-benefit analysis 172cost-effectiveness/utilityanalysis 170, 171–172

cost-identification analysis 171costs 168direct costs 168–169discounting 169

drug costs 1029health policy 166health-related quality of life170

incremental cost-effectivenessratio 168

indirect costs 169intangible costs 169medical decision-making166–167

quality of life 169quality of postoperativerecovery 170

quality-adjusted life years 171,170–171, 171–172

results interpretation 173–174,174

role in drug registration 167–168skewness in cost data 169, 169willingness to pay 172

pharmacogenetics 83–84, 132, 142analytical validity 133–134anesthetic action mechanisms362–363

autonomic nervous system340–341

basic concepts 132–133biotransformation, drug 83–84butyryl-cholinesterasedeficiency 134–135

calcium channel blockers 747cardiac rhythm 297, 310clinical utility 134clinical valididy 134drug susceptibility profiling 142genetic pharmacodynamics135–136

genetic pharmacokinetics 134genotype-phenotypescorrelations 133

genotypes 133longQT syndrome 10, 139–140

malignant hyperthermia 136,137–139

new/emerging concepts 141,140–141

obstetrics 948opioids 136–137, 494, 496,518–519, 533

pediatric pharmacology 1134,1135

phenotypes 133voltage-gated ion channels 41

Pharmacogenetics KnowledgeBase 141

Pharmacogenetics ResearchNetwork 140

pharmacogeriatrics 1139, 1147absorption 1139anticholinesterases 1146autonomic nervous systemdysfunction 338

biotransformation, drug 82body composition 1139–1140,1147

cardiopulmonary function1140

clinical pharmacology-general1140

hepatic function 1140, 1148inhaled anestheticspharmokinetics 393–394

minimum alveolarconcentration 398

neurogenesis 1154neuromuscular blocking drugs616, 1145–1146

neuroprotection/neurotoxicity1157

opioids 533, 1140–1142,1143

postoperative nausea andvomiting 856–857

propofol pharmacokinetics428, 430

renal function 1140, 1148sedative hypnotics 1142–1145,1144, 1146

volatile anesthetics 1146–1147,1148

pharmacokinetics 69, 57;see also specific agents byname

basic parameters 57–58compartment models 58–61dose equivalence 66–68drug accumulation 66drug input 62–63drug interactions 147effect compartment concept63–64

genetic 134local anesthetics 580–582modeling 57

pediatric pharmacology1135–1136

physiologically based models61–62

predictors of offset 65–66predictors of onset 64–65special compartment models 57variation between patients68–69

pharmacologic potencysee potency

pharmaconutritionsee nutritional pharmacology

pharmokinetic closed-loop drugadministration 113–114

pharmokinetic-dynamic closed-loop drug administration103, 114–115

phase II block, neuromuscularblocking drugs 611

phase III metabolism 91;see also ion channels; lipidbilayers

phencyclidine (PCP) 1112–1113

phenobarbital 593, 594, 595, 596

phenobenzamine 656, 661

phenothiazine-thioxanthenes599, 600–601, 601–603

phenotypes 133

phentolamine 662

phenylalkylamines 742, 743

phenylephrine 654–655, 1029

phenylpropanolamine 661

phenytoin 592–595, 692, 693

phosphodiesterase (PDE)inhibitors 732

anaphylaxis therapy 1123blood pressure control/vascular tone 1087

clinical pharmacology 714–715dosage/administration 719,735–736

enoximone 715inamrinone 715–716milrinone 715, 716preclinical pharmacology 714pulmonary vasodilators 774

physical dependence 536

physicochemical interactions 147

physiologically basedpharmacokinetic models(PBPK) 61–62, 391,422–424, 432

PID (proportional-integral-differential) controller 115

pilocarpine 668

pimobendan 717

pipenzepine 673

piperazinyl quinazoles 662

pituitary-adrenal failure 825

PKC (protein kinase C) 26, 279,286–287

placental transfer/metabolism 98,950; see also obstetrics

plasma cholinesterases 79, 617–618plasma infusion fluidssee infusion fluids

plasma membrane receptorslinked to cytoplasmicenzymes 50

cystolic tyrosine kinases 50–51cytokine receptors 50immunoreceptors 50–51integrins 51

plasma membrane receptors withintrinsic enzyme activity 47

intrinsic guanylate cyclaseactivity 50


receptor protein tyrosinephosphatases 48–49


plasmamembrane transporters 90

plasma protein binding 615

plasma targeting, open-loop TCI106, 107–109

plasma volume (PV) 800–802

plasticity, synaptic 24, 202, 203,220, 550

neuromuscular junction 633N-methyl-D-aspartatereceptors 373

spinal dorsal horn synapse235–236

platelet function agents 919,936–937; see alsoanticoagulants; heparin

aprotonin 935–936argatroban 921–922aspirin 926–928calcium channel blockers 746dabigatran 922–923danaparoid 920–921desmopressin 932–933dipyridamole 928epsilon-aminocaproic acid/tranexamic acid 933–935

fondaparinux 921glycoprotein receptorinhibitors 930–931

hemostasis physiology 912–915

Index

1186






hirudin related compounds923–924

non-steroidal anti-inflammatory drugs 557

non ST elevation myocardialinfarction/unstable anginamanagement 1095

oral agents 988perioperative medication990–992, 996, 1099–1100

prostacyclin 928protamine 919–920rivaroxiban 921ST elevation myocardialinfarction management1095

thienopyridines 928–930thrombolytic agents931–932

warfarin 924–926

pleiotropy 19

PMNs (polymorphonuclearleukocytes) 576

POCD (post-operative cognitivedysfunction) 140, 212,221–222, 1157

POI (postoperative ileus) 535,543, 890, 901

POISE (perioperative ischemiaevaluation study) 1097–1099,1101

political decision-making, healthpolicy 166; see alsopharmacoeconomics

polydrug abuse 1106;see also drug/alcohol users

polyenes 977, 978, 979–980

polymorphism, pediatricpharmacology 1134, 1135;see also pharmacogenetics

polymorphonuclear leukocytes(PMNs) 576

polymyxins 964, 971–972

polypeptides, allergicreactions 1120

PONV see postoperative nauseaand vomiting

popliteal nerve block 1067

population-based drug responses14–15, 14

population efficacy 15

population pharmacokinetics68–69

porphyria 447

positive end-expiratory pressure(PEEP) 1035

positive inotropic drugs for heartfailure 706–707, 719–720;see also catecholamines

administration 718–719Digitalis glycosides 707–709,719

dosage 719mechanisms of drug action707, 708

myofilament calciumsensitizers 716–718, 719

phosphodiesterase inhibitors714–715, 716, 719

posterior scoliosis correction1036

postganglionic sympatheticnerves 649

postherpetic neuralgia (PHN)564, 565–566

postoperative analgesia 1061,1072–1073

ambulatory analgesia 1070caregiver controlled analgesia1062–1063

chronic pain 1069–1070clonidine 1064, 1068dexmedetomidine 1064, 1068drug choice 1028epidural 1064–1065, 1066,1068–1069

heart failure 1072immunosuppressants/anti-rejection drugs 838

inpatients/special populations1070–1072

intracathecal analgesia 1065ketamine 1063–1064, 1068liver failure 1072multimodal 1067–1068non-steroidal anti-inflammatory drugs 1063,1068

opioids 1061–1062,1061–1063, 1070–1071

patient-controlled analgesia1061–1063

pediatrics 1071–1072preemptive analgesia 1068–1069renal insufficiency 1072systemic 1061–1064

postoperative cognitivedysfunction (POCD) 140,212, 221–222, 1157

postoperative ileus (POI) 535,543, 890, 901

postoperative nausea andvomiting (PONV) 855,868–869; see also antiemetics

anesthesia 865–866anesthesia-related risk factors858–859

drug choice 1028incidence 855maintenance of/emergencefrom anesthesia 1029–1030

patient risk factors 856–858physiology 855–856, 857risk-adapted prophylaxis867–868

scoring system 866–867definition 855ketamine 451opioids 499, 500, 516, 534post-operative 452–453

postsynaptic dorsal columnpathway 230

postsynaptic membrane 193

postsynaptic potential 200–201

postsynaptic response, nicotinicacetylcholine receptors267–268

postsynaptic transmission,neuromuscular blockingdrugs 609

post-traumatic stress disorder484, 1041, 1042

potassium ion channels 32–34,49; see also two-porepotassium ion channels

local anesthetics 239neuroprotection/neurotoxicity1151

volatile anesthetics 371, 372

potassium ion channelactivators 537

clinical pharmacology 737dosage/administration 735–736vasodilators 732–733

potassium ion channel blockersadverse drug reactions 699antiarrhythmic agents 693

potassium-sparing diuretics 791

potency 15drug effects 6equipotency ratios 67neuromuscular blockingdrugs 615

potential energy 1081

POVOC scoring, postoperativenausea and vomiting 867

PPRs (pattern recognitionreceptors) 346, 347

prazozin 662

prebiotics 852

preconditioning effects, andgender 1154

prediction errors, open-loopTCI 109

pre-eclampsia 953–954

preemptive analgesia 1068–1069

pregabalin 594, 598

pregabalin 564clinical pharmacology 565–566dosage/administration 566mechanisms of drug action564, 565


preemptive analgesia 1068pregnancy

pregnancy see obstetrics

prehospital resuscitation 806

premedicationanti-emetics 865immunosuppressants/anti-rejection drugs 838

pressure–volume analysis

energetics 1080–1081impedence matching tovasculature 1083

ventricular function 1080–1081

pressure–volume loops 318

presynaptic inhibition 201

presynaptic transmission262–265, 608

presystemic metabolism 73–74

preterm labor 954–955

primary afferent nocioceptors227–228, 231–232, 233

primary PCI 1093

primidone 594, 595, 596

priming 212–213, 620, 621

proarrhythmia 745–746

probiotics 852

procainamide 691–693, 694, 702

procedural memory 212–213, 216

progesterone antagonists 956

propafenone 692, 693, 696–697,702

propantheline 673, 849–850

propofol 426–427, 438, 447–448,460

administration 108, 432–433adverse drug reactions 449–450allergic reactions 459–460analogs 433, 454–456anesthetic action mechanisms374, 367, 378

for awake fiberopticintubation 1054

Bayesian optimization115, 116

Index

1187






propofol (cont.)cerebral ischemia andanesthetic neuroprotection1153

closed-loop drugadministration 115–116

compartmental analysis427–429, 430

context-sensitive half-time429, 431

decrement time 431disposition parameters 445distribution/metabolism/excretion 427

drug dosage parameters 113drug interactions 154–158,159, 432, 448

formulations 432–433glucocorticoids secretion 819hemorrhagic shock 1016induction of anesthesia 1008infusion syndrome 140, 450laryngeal mask airwayinsertion 1018


model selection 111new formulations 453–454nonhypnotic effects 448–449obstetrics 957–958open-loop TCI 114pharmacogeriatrics1142–1144, 1144

physicochemical properties 427physiologically basedpharmacokinetic models 432

postoperative nausea andvomiting 859, 1028

sedation 448–449, 1043–1044,1048–1049, 1054

side effects 445speed of onset 1007–1010structure-activity relationships362

structure/stereochemistry 427,445

sympathetic nervous system651

transfer to effect site 429–432

proportional-integral-differential(PID) controller 115

propranolol 682, 692, 700, 702

prostacyclin 773–774, 928

prostaglandinsobstetrics 956

role in pain 548, 549

synthesis/action 548–550

prostanoids 281

protamine 919–920allergic reactions 1120clinical pharmacology 919–920

dosage/administration 920mechanism of drug action 919new/emerging concepts 920

suspensions 878

protein binding; see also receptorbinding

local anesthetics 578, 585neuromuscular blocking drugs615

obstetrics 949opioids 518pediatric pharmacology 1131thiopental 421

protein kinase C (PKC) 26, 279,286–287

proteins 893–900

as drug targets 360–361, 378nutritional pharmacology894–897

structure, drug receptors 1–2vesicle fusion 264–265, 266

proton pump inhibitorsadverse drug reactions 845drug interactions 845esomeprazole 846versus histamine receptorantagonists 847–848

lansoprazole 846omeprazole 845–846pantoprazole 846–847rabeprazole 847

pruritis 448–449, 500–501, 535

pseudoephedrine 661

pseudo-irreversible drugeffects 6

PSI (patient state index) 1032

psychedelics/party drugs1112–1113

psychiatric disorders 1106

psychotomimetic effects 1015

pulmonary artery smooth musclecells (PASMCs) 768–769

pulmonary function see lungfunction

pulmonary hypertension 409,767–768, 776

approaches 775classification 768evaluation 769hypoxic pulmonaryvasoconstriction 768–769

new/emerging therapies775–776

therapy 769–770

pulmonary vasodilators 770, 776;see also vasodilators

adverse drug reactions 770


cardiovascular patients,perioperative medication989, 999

combination therapies 774–775endothelin antagonists 774nitric oxide inhalation 771–773nitrovasodilators 771phosphodiesterase inhibitors774

prostacyclin 773–774

pumps, ionic 4, 253

pupil constriction, opioids 534

purinergic agonists 735–736

PV (plasma volume) 800–802

qualia 177

quality of life 169, 170

quality of postoperativerecovery 170

quality-adjusted life years(QALYs) 170–171, 171–172,171

quantal responses/quantaldose–response curves 14

quantal transmitter release 264

quetiapine 600, 601, 602, 605

quinidine 519, 691–693,694–695, 702

RA (rheumatoid arthritis) 998

rabeprazole 847

radioactive tracers 801

radiology, sedation for 1054–1055

RAGE (receptor for advancedglycation end products) 349

Ramsay Sedation Scale (RS)1044, 1045

ranitidine 844

rapamycin 834, 835

rapid acting insulin analogs878–879

rapid delayed rectifier current 305

rapid eye movement sleep (REM)178, 183–184

rapid sequence induction620–621, 626, 1016

RAS see renin angiotensin systemantagonists

RASS (Richmond Agitation-Sedation Scale) 1045, 1049,1050

rate of rise of alveolarconcentration 385

ray experimental design 150

Raynaud’s disease 282

real-time visualization160–161

rebound effects, statin therapywithdrawal 1099

rebound hypoglycemia 807

receptor/s 1–4, 15, 10

activation, neuromuscularfunction 268–269

for advanced glycation endproducts 349

binding 4–13, 15definition 1desensitization 2, 22–24, 23,269, 337

downregulation 22families 2, 15guanylyl cyclases 18internalization 22neuromuscular blocking drugs611

nomenclature/categorization2–4, 18

opioids 494–495physico-chemical forces 2

protein structure 1–2

protein tyrosine phosphatases 18,48–49, 286

selectivity 6

serine/threonine kinases 18signaling 496, 831–832,832–833

structure/ligand interactions495–496

superfamilies 2, 15, 18, 10TNF 52–53

tyrosine kinases 18, 47–48, 49,50–51, 242

recirculatory models 61, 424

recovery curves 65

recovery index, neuromuscularblocking drugs 615, 621–622

rectal routes of drugadministration 127

rectification 690

red man syndrome 971, 982

REE (resting energy expenditure)891–892, 891–892

reentrant arrhythmias 294–295

refractory periods 252

regional analgesiaambulatory 1070clinical outcomes 1065–1066complications 1066–1067

Index

1188






postoperative 1064–1067,1071–1072

techniques 1064–1065

registration, drug 167–168

regression of left ventricularhypertrophy 742

rejection, transplants 830, 831;see also immunosuppressants

relative decrement times 65

REM (rapid eye movement sleep)178, 183–184

remifentanil 63for awake fiberoptic intubation1054

bolus dosing 510–513drug interactions 158, 159enzymes of drugmetabolism 79induction of anesthesia 1020,1021


obstetrics 958open-loop TCI 112pharmacogeriatrics 1141–1142,1143

pharmacokinetics 69properties 538sedation 1043, 1046–1047speed of onset 1007–1010

renal function see kidneyfunction

renal threshold 807

renin angiotensin system (RAS)antagonists 732, 999

dosage/administration735–736

pharmacology 731–733, 737,988–989

reperfusion therapy 1093

rescue PCI 1093

resistance, cytotoxic 91–92, 93;see also efflux drugtransporters

respiratory agents, perioperativemedication 997, 1000

respiratory depression;see also breathing systems

alpha-adrenoceptor agonists486

analgesia, postoperative 1069benzodiazepines 473drug interactions 1012, 1013maintenance of/emergencefrom anesthesia 1035

opioid agonist-antagonists 540opioids 498–499, 509, 512,518, 533–534

pharmacogeriatrics 1140

and rate of opioidadministration 518

threshold 407

response surface methodology(RSM) 149–150, 151

agonists 151navigating the responsesurface 159

new/emerging concepts158–160

opioids 153, 155propofol 155, 156, 157real-time visualization 160–161remifentanyl 156, 157volatile anesthetics 153

resting energy expenditure (REE)891–892, 891–892

resting potential 249–250, 251

retching, definition 855;see also anti-emetics;postoperative nausea andvomiting

reteplase 932;see also thrombolytic agents

reticular activating system 377

retrograde messengers 205

revatropate 673

reverse genetics 362–363

reverse use-dependent block 690

reversible drug effects 6, 1155

rheumatoid arthritis (RA) 998

Rho-activated protein kinases279, 286–287

ribosomal protein synthesisinhibitors 964, 972–976

Richmond Agitation-SedationScale (RASS) 1045, 1049, 1050

RIFLE criteria, acute kidneyinjury (AKI) 784

rigidity 534, 1014–1015

Riker Sedation-Agitation Scale(SAS) 1044, 1045

Ringer’s (LR) solution 793,803–804; see also crystalloidfluids

risk factors, postoperative nauseaand vomiting 856–858,858–859

risperidone 599, 600, 601, 602

ritodrine 658

rivaroxiban 915, 921

RKTs (receptor tyrosinekinases) 18, 47–48, 49,50–51, 242

rofecoxib see cyclooxygenaseinhibitors

ropivacaine 566clinical pharmacology 566–567dosage/administration 567mechanisms of drug action 566preclinical pharmacology 566

routes of drug administrationsee drug administration routes

R-PTP (receptor protein tyrosinephosphatases) 48–49, 286

RS (Ramsay Sedation Scale)1044, 1045

RSM see response surfacemethodology

ryanodine receptor (RYR1)137–139

SAAM II software system 510

safety considerationsalternate routes of drugadministration 129


droperidol 861–862, 1030neuromuscular transmission609, 610

opioids 526sugammadex 643

saline, normal (NS) 793, 803,804, 805; see also crystalloidfluids

salivation 1028

salt/water homeostasis 786

SAS (Riker Sedation-AgitationScale) 1044, 1045

saturated disc model 270–271

scales, sedation 1044–1045

SCCM (Society of Critical CareMedicine) guidelines 1041,1052, 1053

Schild analysis 8

Schnider population PK model428, 429–432

Schüttler model 428

sciatic nerve block 1067

scopolamine 487–488, 672;see also parasympatholyticdrugs


anti-emetics 860mechanisms of drug action 669psychedelics/party drugs1112–1113

second gas effects 387, 388

second messengers 19, 24–26,651; see also cAMP

autonomic nervous system 338calcium ions/inositoltriphosphate 24–26

and long-term potentiation 204slow synaptic transmission 201

secretions, gut 842–843;see also gut motility/secretioninhibitors

sedation 361, 1041, 1056;see also delirium; hypnotics;and see specific agents by name

amnistics 478, 487–488;see also alpha-adrenoceptoragonists


for awake fiberoptic intubation1052–1054

benzodiazepines 467, 1043,1047, 1053

cardiology 1055central nervous systemmonitoring 1045–1046

complications 1041–1042definition 478dexmedetomidine 1044,1048–1049, 1051, 1054

drug choice 1046–1049endoscopy 1055goal-directed/protocolized1046

modifying delivery pattern1046–1048

monitoring 1044–1046opioid agonist-antagonists539–540

opioids 533, 1042–1043,1046–1047, 1054

outside operating room1054–1055

paradigms to improveoutcomes 1046–1049

pharmacogeriatrics1142–1145, 1146

pharmacology of availabledrugs 1042–1044

propofol 448–449, 1043–1044,1048–1049, 1054

radiology procedures1054–1055

scales 1044–1045

SEDline 180

seizures 449, 533, 583;see also antiepileptic drugs

selective serotonin reuptakeinhibitors (SSRIs) 519, 993,1000

selectivity 6, 15

selenium 901–902

Index

1189






self-medication 1106;see also drug/alcohol users

semantic memory 212, 215,216

senescencesee pharmacogeriatrics

serial parallel independent (SPI)taxonomy of memory 215,216

serine 49–50

serotonin/5-HT receptors 36, 52

agonists 850, 1112–1113

antagonists 860, 862–864and postoperative nausea andvomiting 856

set-point, closed-loop drugadministration 115

seven-transmembrane receptorssee G-protein-coupledreceptors

severe illness, insulin therapy 886

sevoflurane 397glucocorticoids secretion 820induction of anesthesia1010–1011

inhaled anestheticspharmacology 397, 398–399

metabolism 392neurogenesis 1155physicochemical properties398

sex differences see genderdifferences

SF-36 (36-Item Short Form) 170

shivering 485

short bowel syndrome 848

short-term memory 226

Sicilian Gambit 691, 692

signaling

amplification 12–13, 17

cell signaling 17, 18, 18

damping 13G protein-coupled receptors19, 18

interleukin-2 receptor 832–833properties 17–19transduction 17, 18, 18

T cell receptor 831–832, 832–833

silent synapses 205

single nucleotide polymorphisms(SNPs) 340–341;see also pharmacogenetics

SIRS (systemic inflammatoryresponse syndrome) 814

skeletal muscle rigidity 534,1014–1015

skin, barriers to diseasepathogens 345

SLC (solute carrier) proteins 90

SLC (solute carrier) transporters95–96

sleep/consciousness 177, 177, 188alpha-adrenoceptor agonists482–483, 484, 488

anesthetic action mechanisms376–377

awareness in clinical context179–180

awareness in cognitive context177–179

brain/cell physiology 177class 1 agents 185, 186, 187class 2 agents 185class 3 agents 185and general anesthesia 177, 188memory/learning 218molecular targets 185new/emerging anesthetics185–188

non-rapid eye movement sleep182–183

rapid eye movement sleep183–184

switching between sleep/wakestates 184–185, 376–377

wakefulness 180–182

slow delayed rectifier current305–306

slow synaptic transmission 201

small hydrophyllic drugs 6

small molecule partition 90–91

smoking 330coughing reflex 1027postoperative nausea andvomiting 857

tobacco cessation agents 998,1001

smooth muscle effects;see also vascular smoothmuscle; vasodilators

opioid agonist-antagonists 540neuromuscular blocking drugs614

spasm 535

SMX (sulfamethoxazole) 975,976, 977–978

SNAP II 180

SNARE complex 196–197, 265

SNPs (single nucleotidepolymorphisms) 340–341;see also pharmacogenetics

Society of Critical Care Medicine(SCCM) guidelines 1041,1052, 1053

sodium bicarbonate 1123

sodium ions 803

sodium ion channels 31, 237,243, 309

cardiac rhythm 301–303dysfunction/disease states302–303

factors affecting conductionvelocity 258

local anesthetics 239, 575–576,585

regulation 302structure and function 301–302sodium ion channel blockers;see also bupivacaine;levobupivacaine; ropivacaine

with intermediate bindingkinetics 691–693, 694, 695

with rapid binding kinetics 693,695, 696

with slow binding kinetics 693,696, 697

sodium cromoglycate 757–758

solifenacin 673

solubility coeffcient, blood-gas386, 387, 388

solute carrier proteins 90

solute carrier transporters 95–96

somatic nociception 231

somatostatin 848–849

sotalol 682, 692, 693, 698, 702

spare receptors 12, 15, 13

specificity 6, 15, 17, 202

speed of injection,neuromuscular blockingdrugs 615

SPI (serial parallel independent)taxonomy ofmemory 215, 216

spinal anesthesia 957;see also epidural

anesthetic action mechanisms374, 375–376

pain transmission/transduction 228–229

spinal dorsal horn 234neuron diversity 234–235plasticity 235–236synapse 234

spinobulbar projections 230

spinohypothalamic tract 230

spinothalamic tract 229, 230

SSIs (surgical site infections) 982;see also antibacterials;antifungals; antimicrobials;infection

SSRIs (selective serotoninreuptake inhibitors) 519,993, 1000

ST elevation myocardial infarction(STEMI) 1091, 1101–1102;see alsomyocardial ischemia

definition/diagnosis 1091–1092management strategies1092–1095


St John’s Wort 999

Stanpump 104

starch 808–809

Starling equation 800

statinsperioperative medication 990,999, 1098, 1099

vasodilators 736

steal, coronary 410

Stellenbosch 104

Stelpump 104

stem cell therapy 736, 795

stereoselectivity 6

steroid anesthetics 362, 456–457;see also glucocorticoids

steroid receptor superfamily 18

Stevens-Johnson syndrome595, 596

stimulantsamphetamine 1112cocaine 1111inhalants 1113psychedelics/party drugs1112–1113

stoichiometry 5–6

streptogramins 964, 974, 975

streptokinase 932;see also thrombolytic agents

stressautonomic nervous system 330corticotropin-releasinghormone 819

glucocorticoids 816induction of anesthesia1015–1016

metabolic responses to 876–877opioids 499

surgical stress response 339–340,825, 826, 990, 1041

Index

1190






ulcers, proton pump inhibitorsversus histamine receptorantagonists 848

stroke see cerebral ischemia

structure-activity relationshipsanesthetic action mechanisms362


subcutaneous administration124, 521–522

subjective experience, andobjective evaluation 177

subliminal memory 212–213, 226

sublingual administration 125

subthreshold responses255–256, 257

succinylcholine 608adverse drug reactions 618chemical structure 612clinical pharmacology618–620

contraindications 619elimination/metabolism 616non-competitive block 609–611pharmacogeriatrics 1146phase II block 611rapid sequence induction 626

sufentanil 538

sugammadex 643–644chemistry 640paralysis reversal 1036pharmacodynamics 641–643pharmacokinetics/metabolism640–641


safety considerations 643variation between patients 643

suicide 601

sulfamethoxazole (SMX) 975,976, 977–978

sulfiting agents, allergicreactions 1119

superactivation 502superfamilies 2, 15, 18, 10

supraclavicular blocks 1067

supra molecular activationclusters 830

surgeryaspirin 927glycoprotein receptorinhibitors 930–931

metabolic/stress responses to339–340, 825, 826, 876–877,990, 1041

nutritional pharmacology 901

type, and postoperative nauseaand vomiting 858

thienopyridines 929

surgical site infections (SSIs) 982;see also antibacterials;antifungals; antimicrobials;infection

surmountability 8, 15

sympathetic hyperactivity 339–340

sympathetic microneurography651

sympathetic nervous system283–284, 330, 648, 662;see also autonomic nervoussystem

amplification response 330anesthetics 651baroreflex 649–651, 650basal autonomic tone 648medullary vasomotor center648–649

postganglionic sympatheticnerves 649

systems physiology 330–331,332

sympatholytic drugs 661, 663clinical pharmacology 661–662mechanisms of drug action 661

sympathomimetic drugs 651,662–663

alpha-adrenoceptor agonists654–657

background/history 651beta-adrenoceptor agonists657–658

clinical pharmacology 654indirect-acting 659–661mechanisms of drug action651–652, 653, 654

mixed receptor agonists658–659

synapse specificity 202

synaptic boutons 192

synaptic cleft 192, 265–267

synaptic plasticity see plasticity;synaptic

synaptic transmission 39–40,192, 206–207;see also neurotransmitters;vesicles; synaptic

chemical identity ofneurotransmitters 193–194,194–195

chemical synapses structurefunction 192–193

control of vesicle secretion196–197

cytoskeleton role 199drug action targets 206

dual transmission 194–195electrical synapses structure/function 192

endocytosis pathways 198fast transmission in CNS 200GABAA receptors 200–201glutamate receptors 200kiss-and-run 198–199long-term depression 205–206long-term potentiation 204–205mechanism of transmitterrelease 196

neurotransmitter duration ofaction 199

NMDA receptor dependentlong-term potentiation202–204

non-NMDA-dependentlong-term potentiation 205

presynaptic inhibition 201retrograde messengers 205second messengers 201, 204silent synapses 205slow synaptic transmission 201stages of chemical transition193, 194

storage of neurotransmitters 196

synergistic drug interactions147–148, 153–154,1011–1012

synthetic choline esters 667–668

systemic absorption 580–581

systemic inflammatory responsesyndrome (SIRS) 814

T cells 349, 350–352, 830;see also immunosuppressants

antigen presentation/cellsurface events 830–831

calcium/calmodulin/calcineurin-induced nuclearfactor 832

clonal proliferation 834immunosuppressants/anti-rejection drugs 833

interleukin-2 receptor signaling/cell cycle regulation832–833, 834

receptor signalling 831–832,832–833

tachyplasis 13, 15

tacrolimus 835

tardive dyskinesia 600, 603

TARGET (therapeutic arthritisresearch and gastrointestinalevent trial) 557

target controlled infusion (TCI)103–104, 116–118;see also closed-loop drugadministration; open-loop TCI

dose–response relationship 103induction of anesthesia1019–1020

targets see drug targets

T-cell antigen receptor complex(TCR) 830, 833

TCI see open-loop TCI; targetcontrolled infusion

TCR (T-cell antigen receptorcomplex) 830, 833

TD4756 458

TD50 15

TEA (thoracic epiduralanesthesia) 1100

telenzepine 673

temiverine 673

temperature, bodysee thermoregulation

tenecteplase 932;see also thrombolytic agents

terbutaline 658

terminal plexus 649

terminology; see also definitions

drug receptors 2–4, 18inhaled anestheticspharmokinetics 385–386,387, 388

myocardial ischemia 1091opioids 531

test doses, allergic reactions 1121

tetracyclines 964, 972, 973–974,973–974

tetrodotoxin (TTX) 566–567

TFPI (tissue factor pathwayinhibitor) 282

TGAs (thermally generatedaerosols) 523

thalamus, anesthetic actionmechanisms 377

theophylline 753–754, 997, 1000

therapeutic arthritis research andgastrointestinal event trial(TARGET) 557

therapeutic end points 15

therapeutic index 15

thermally generated aerosols(TGAs) 523

thermoregulationmaintenance of/emergencefrom anesthesia 1031

temperature monitors 1032neuromuscular blocking drugs616–617

Index

1191






thermoTRP ion channels 236

thiamylal 445, 446, 459

thiazide diuretics 791, 792

thiazolinediones (TZD) 879, 880,993

thienopyridinesadverse drug reactions 929clinical pharmacology 929dosage/administration 929mechanism of drug action 929new/emerging concepts929–930

platelet function 928–930surgery/anesthesia 929

thiopental 68, 420, 438, 444–446,460

allergic reactions 459compartment models 422decrement time 431disposition parameters 445distribution 421–422dosage/administration 425, 426drug interactions 424–425early mixing 422elimination 422history 1007induction of anesthesia1008

pharmacogeriatrics 1144physicochemical properties420–421

physiologically basedpharmacokinetic models61–62, 391, 422–424, 432

protein binding 421side effects 445speed of onset 1007–1010structure/stereochemistry 420,421, 445

sympathetic nervous system651

transfer to effect site 424, 424

36-Item Short Form (SF-36) 170

thoracic epidural anesthesia(TEA) 1100

thoracic paravertebral blocks1067

thoracic sympathectomy 1100

threonine kinases 49–50, 51–52

thresholds, action potentials256–257

thrombolysis in myocardialinfarction (TIMI) 1094

thrombolytic agents 931–932adverse drug reactions 932clinical pharmacology931–932

dosage/administration 932evaluation 931

genetic engineering 931mechanism of drug action 931

thrombomodulin (TM) 282

thrombophlebitis 452

thrombosis, role of vascularendothelium 282–283

thrombus formation 912–915;see also platelet function

THRX-918661 458

thyroid hormone 717–718,996–997, 1000

TIAC (titration of intravenousagents by computer) 104

tiagabine 591–592, 593, 594, 595,597

tidal volumes 1035

tight glucose control 906

time to peak effect 432

time-dependent activity 963

TIMI (thrombolysis inmyocardial infarction) 1094

tiotropium 673

tissue binding, pediatricpharmacology 1131

tissue factor pathway inhibitor(TFPI) 282

tissue plasminogen activator(tPA) 931–932

titration of intravenous agents bycomputer (TIAC) 104

TIVATrainer 104

TLRs (toll-like receptor ligands)347, 348

TM (thrombomodulin) 282

TMN (tuberomammillarynucleus) 376–377

TMP (trimethoprim) 975, 976,977–978

TNF see tumor necrosis factor

TNS (transient neurologicalsyndrome) 583

tobacco cessation agents 998,1001; see also smoking

tocainide 692, 693, 696, 702

tocolytics 954–955

tolazoline 662

tolerance 13, 15addicts, to opioids 1109–1110alpha-adrenoceptor agonists480

ketamine reversal of opioid 563

opioids 23–24, 501–503,535–536, 563–564, 1070–1071

toll-like receptor ligands (TLRs)347, 348

tolterodine 673

top-down costing 168–169

top-down pathways, sleep/consciousness 177, 188

topiramate 591–592, 593, 594,595, 597

total body water 800

total duration of action,neuromuscular blockingdrugs 615

toxicity 15; see also adverse drugreactions; allergic reactions;neurotoxicity

tPA (tissue plasminogenactivator) 931–932

trace elements 894–897, 901–902,904

tramadol 538, 555, 1063

tranexamic acid see epsilon-aminocaproic acid/tranexamic acid

transactivation 53

transdermal administration124–125, 522–523

transdermal therapeutic systemof fentanyl (TTS-fentanyl)522

transduction, pain see paintransmission/transduction

transfer to effect siteketamine 435propofol 429–432thiopental 424, 424

transfusion-associated acute lunginjury (TRALI) 1119

transgenic animals 362–363

transient neurological syndrome(TNS) 583

transient outward current 304

transient receptor potential(TRP) ion channels 4, 40–41,570

thermoTRP 236TRPA1 571TRPV1 570, 571TRPV4 570–571

transitional compounds 359

transmembrane currents 249

transmembrane proteins 2, 253

transmembrane pumps 4

transmembrane receptors51–52, 52–53

transmission, pain see paintransmission/transduction

transmitter-gated ion channels 4

transmucosal routes of drugadministration 125–127,126–127

transplantation 356, 830, 831;see also immuno-suppressants

transrepression 53

TREK-1 see two-pore potassiumion channels

TRP ion channels see transientreceptor potential ionchannels

trauma see stress

treprostinil 773–774

tricyclic antidepressants 335, 340,993, 1000

triggered automaticity 296–297,298, 299

triggering receptor expressed onmyeoloid cells (TREM-1) 348

trimethoprim (TMP) 975, 976,977–978

tropisetron 860, 864

tropomyosin 1092

troponin 1092

TRPA1 571

TRPV1 channels 241

TRPV1 receptor agonists/antagonists 570, 571

TRPV4 channels 570–571

truncal rigidity 534

TTS-fentanyl 522

tuberculosis 501

tuberomammillary nucleus(TMN) 376–377

tumor necrosis factor (TNF) 890

inhibitors 998, 1000

receptors 52–53

two-pore potassium ion channels(TREK-1)


nitrous oxide 375volatile anesthetics 371xenon 375

tyrosine 335, 651

Index

1192






tyrosine hydroxylase 335

tyrosine kinase-associatedreceptors 18, 47–48, 49,50–51, 242

TZD (thiazolinediones) 879, 880,993

UA see unstable angina

UGT (glucuronosyltransferase)79–80

ulcers, gastric 486non-steroidal anti-inflammatorydrugs 556–521, 847–848

proton pump inhibitors versushistamine receptorantagonists 848

ultra-rapid delayed rectifier306–307

unconscious memory 212–213,215–216; see also sleep/consciousness

unfractioned heparin (UFH) 1095

unitary theory of anesthesia 359,360, 361, 378

United States Renal Data System(USRDS) 784

unstable angina (UA) 1091,1092, 1101–1102;see also myocardial ischemia

definition/diagnosis1091–1092

management strategies 1094,1095


upper motor neuron lesions623–624

uptake measurement, inhaledanesthetics 390

uptake rate, terminology 385

urethane 177

urine formation 786–790

urine output calculation 801

urine retention 535

use-dependent block 690

uterine contraction 955

valdecoxib 553–550;see also cyclooxygenase-2-specific inhibitors

validity, analytical 133–134

valproate 593, 594, 595, 596

vamicamide 673

Van der Waals interactions 2

vancomycin 970–971, 982

vanillylmandeic acid (VMA) 336

vaporizers 400

variable conductances , 251–253

variation between patients;see also gender differences

biotransformation, drug 85clearance 82, 83disease states 84–85drug biotransformation 82–85drug interactions 82–83, 84

drug response analysis inindividuals 13–14, 14

drug response analysis inpopulations 14–15, 14

neuromuscular blocking drugs626

obstetrics 949open-loop TCI 112, 113, 114opioid effects 532–533pain perception 140pharmacogenetics 83–84pharmacokinetics 68–69

vascular reactivity 277, 288angiogenesis 280, 283angiotensin II 284–285arginine vasopressin 285coagulation/inflammation282–283

control of 285–286drug action targets 286–287endothelin 282endothelium-dependentrelaxation 280–281

endothelium-derivedhyperpolarizing factor281–282

endothelium-derived relaxingfactor 280, 281

extracellular matrix 277–278nitric oxide 281nonadrenergic noncholinergicmechanisms 284

parasympathetic nervoussystem 284

prostanoids 281sympathetic nervous system283–284

vascular endothelium 280,727–728, 729

vascular smooth muscle (VSM)278, 288, 726;see also vasodilators

calcium voltage-gated ionchannels 278, 278, 279

contractile proteins 278contraction mechanisms 278,278

control of contractile site 726endothelium role 727–728, 729

molecular mediators/pharmomechanical coupling725, 726–727, 728

myogenic contraction 279–280neuronal regulation of vasculartone and electromechanicalcoupling 726, 727

physiology of musclecontraction 724–726

vascular surgery, infusionfluids 806

vascular system 317, 1079–1080;see also cardiovasculareffects; heart function

vascular tone 1077–1078,1088;see also hemodynamics;hypertension; hypotension

autonomic nervous system1077–1078, 1079, 1080

coronary perfusion 1084energetics 1080–1081,1081–1082

heart rate 1084hemodynamic problems andimpedence 1083–1084

hemodynamics 1078–1079,1080

impedence/optimalhemodynamics 1082–1083

inotropes 1086inotropes-risks 1086–1087nitric oxide 1087oxygen consumption1081–1082

pharmacology of availabledrugs 1083, 1084–1085

pressure-volume analysis 1083

vasoactive agents 991;see also vasodilators

ventricular function1080–1081, 1081–1082

vasodilators 348, 724, 736–737,1085–1086;see also pulmonaryvasodilators

alpha-adrenergic agonists/antagonists 730–731,735–736

angiotensin convertingenzyme inhibitors 731,735–736

angiotensin receptor blockers732, 735–736

beta-adrenergic agonists 731,735–736, 737

blood pressure control/vascular tone 1085–1086

calcium channel blockers733–734, 735–736, 737

calcium sensitizer 734,735–736

catecholamine receptorpharmacology 729–730, 737

clinical pharmacology 737control of contractile site 726dopamine agonists 731,735–736

dosage/administration735–736

eicosanoids 734, 735–736, 737endothelin receptor agonists732, 735–736, 737

endothelium role 727–728, 729ganglionic blockers 733,735–736, 737

hemodynamics 1078magnesium 733, 737mechanism of drug action724, 725

molecular mediators/pharmomechanical coupling725, 726–727, 728

myogenic tone 726neuronal regulation of vasculartone/electromechanicalcoupling 726, 727

new/emerging concepts734–736

nitrovasodilators 728–729, 737phosphodiesterase inhibitors732, 735–736

physiology of musclecontraction 724–726

potassium channel activators732–733, 735–736, 737

renin inhibitors 732, 735–736renin-angiotensin pathwaypharmacology 731–733, 737

vasopressin see argininevasopressin

Vaughan Williams drugclassification 691

vecuronium 612

ventilation mode 410–411

ventilatory depressionsee respiratory depression

ventricular functionsee cardiovascular effects;coronary circulation; heartfunction

ventrolateral preoptic nucleus(VLPO) 376–377

verapamil 692, 693–694, 700, 702

vesicles, synaptic 192;see also synaptic transmission

control of vesicle secretion196–197

cycling 197–198, 206, 264, 265drug action targets 206fusion 263–264, 264–265, 266heterogeneity 199

Index

1193






vesicles, synaptic (cont.)neuromuscular function263–264, 265

storage of neurotransmitters 196

vessel-poor group 388

vessel-rich group 388

vigabatrin 591–592

VIGOR (vaux gastrointestinaloutcomes research) 557

viral infection, and cancer 354;see also antivirals

visceral nociception 231, 232

vitamins 904alcohol users 1108nutritional pharmacology894–897, 901–902

VLPO (ventrolateral preopticnucleus) 376–377

VMA (vanillylmandeic acid) 336

volatile anesthetics see inhaledanesthetics

voltage-gated ion channels 4, 41,301; see also calcium ionchannels; potassium ionchannels; sodium ionchannels

effect on neuronal activity/signalling 29

local anesthetics 239–241pain transmission/transduction 237

structure and function 29–31types of 29

voltage-sensitive gating299, 301

volume kinetics 802–803, 802

volume of distribution 57, 615

volume status, kidney function791–793

vomiting; see also anti-emetics;postoperative nausea andvomiting

definition 855physiology 855–856, 857

voriconazole 978, 979

VSM see vascular smooth muscle

wakefulness 177, 179, 180–182;see also sleep/consciousness

wakening see emergence fromanesthesia

wake-up test 1036

warfarin 915, 924–926adverse drug reactions925–926

clinical pharmacology 925dosage/administration 926mechanism of drug action924–925

new/emerging concepts 926pediatric pharmacology 1134

waterbody composition in elderlypatients 1139–1140


total body water 800

water tank analogy 388, 389

websitesdelirium 1049nutritional pharmacology 907

willingness to pay 172

withdrawal from drugs/alcohol1106, 1108–1109

wobble, open-loop TCI 111

Wolff–Parkinson–White (WPW)syndrome 703, 746

working memory 212, 226

xenobiotic transporters 92

xenobiotics 90, 97, 833

xenon 1156anesthetic action mechanisms374, 375

cerebral ischemia and anestheticneuroprotection 1154

diffusion into gas spaces 393inhaled anestheticspharmacology 399

metabolism 392

zero-phase coherence 219

ziconotide 568clinical pharmacology568–569

dosage/administration 569drug interactions 746–747mechanisms of drug action568–569


zinc fingers 53

zinc suspensions 878

ziprasidone 599, 600, 602

Zollinger–Ellison syndrome 847

zonisamide 591–592, 593, 594,595, 597

Index

1194






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