anesthesia pharmacology
TRANSCRIPT
Clinical Pharmacology of Anesthetic drugs
Dr. Waddah H. Awad
PSHM – Anesthesiologist
General Anesthesia
• Definition – Induced, Reversible, controlled, loss of sensation
• Components:
1. Analgesia
2. Muscle relaxation
3. Amnesia
4. Suppression of excessive autonomic
responses
Practical Conduct :
• Pre Anesthetic check up• Just preoperative monitoring • Induction • Maintenance• Recovery• Post operative Care
Anesthesiologist Tools
Drugs : Hypnotics, Analgesics, Muscle
relaxants & others
Gases : Oxygen, Nitrous Oxide
Vapors: Halothane, Isoflurane, Sevoflurane
Equipments : Anesthetic Machine - Breathing
Circuits, Monitors…….
Others: iv access, Infusion fluid, Airway
equipments……..,…..
Premedication
Reasons for administration of pre-medications
1. Reduction of fear and anxiety
2. Reduction of saliva secretion
3. Prevention of vagal reflexes (caused by surgical stimulation like squint op., stretching of anal sphincter, or associated with medication e.g. β-blockers
4. As part of anesthetic technique e.g. use of narcotics
5. To produce amnesia
- Hyoscine ( Scopolamine)
- Benzodiazepines - anterograde amnesia
- Diazepam -hyoscine – in 75% pts complete amnesia
6. For specific therapeutic effects
- Transdermal glyceryl nitrate patches for angina pts,
- Steroids
- βblockers
Premedication
Drugs :
1. Anxiolysis\ Amnesia: BNZ, Hyosc., Antihist. (H1 Blochers) 2. Analgesia: Opiates
3. Adjuvant to GA : BNZ & Ketamine
4. Anti-emetic : Metoclopramide, Antihist.
5. Antacids : H2 blockers, Antihist., Na Citrate
6. Antihist. : Promethazine,Diphinhydramine
7. Antivagal / Antisialagogues: Atrop, Hyos.,AntiH
8. Antitromb. / Anticoag.: Heparin, Stockings
9. Antibiotics: Infective Endocarditis Prophylaxis
10: Attention to pre-existing medications:
Continue: unless otherwise
Stop : MAOI, Contraceptive pills
Change : Insulin, oral hypogly., Steroids
Drugs :
Common Premadications
Drug Dose Route TimingDiazepam 5-15 mg oral 1-2 hrLorazepam 1-3 mg oral preop.
Morphine 5-15 mg IM Hyoscine 0.2-0.4 mg IM 1hr pre
Pathedine 50-100mg IM preopPromethazine 12.5-25mg IM Midazolam 2.5-5 mg IM
Children
Drug Dose Route Timing
Diazepam Syrup 0.2mg\kg oral 1 hr Medazolam 70-100 mcg\kg IM preop
Promethazine2-5yr 10-20mg oral 1hr preop5-10 yr 20-25 mg 1\2dose for IM Morphine 0.1-0.2mg\kg IMHyoscine 5mcg\kg IM
Side effect of premadications :
Delayed recovery and interaction of Specific drugs
Opioids
Act on opioid receptors located through out CNS
• Identified as mu - mu1 & mu2
keppa (k)
delta (d)
sigma • Most effective as producing analgesia• They provide some degree of sedation
IV opiates
Drugs Dose Onset Duration
Morphine 0.1-0.2mg\kg slowest long
Pathedine 1-2 mg\kg slow long
Fentanyl 1-2mcg\kg rapid short
Alfentanil 10-20mcg\kg v. rapid v. short
Sufentanil 0.2-0.4mcg\kg rapid short
Induction
Check: pt \ machine\ Monitors
Monitoring:
Basic Monitoring:
Anesthetics, clinical, Airway, EKG,NIBP,SpO2, Capenography
Add.: PNS\Temp.\ CVP
Agent for induction : IV vs. Inhalational
Analgesia: Opiates
IV Induction Agents
• The ideal intrav. Agent reliably and pleasantly induces full anesthesia within one arm-brain circulation time
- is free of side effects
- completely wears off in a few minutes
- it must be capable of infusion to maintain
anesthesia without problems.
I.V. anesthetic agents may be used for
1. Induction of anesthesia
2. As a sole agent for operation (TIVA)
3. To supplement volatile anesthesia or regional anesthesia
4. For sedation
IV Induction Agents
Propofol – - Mechanism of action – facilitation of inhibitory
neurotransmission mediate by GABA - Not water soluble- 1% solution aqueous solution is available for IV
use as an oil-in-water emulsion containing - soybean oil - egg lecithin - glycerol
• Only for IV administration
• Rapid on set ( one arm brain circulation time)- 1\2 life 2-8 min. ( recovery rapid, no hangover)- high clearance rate( 10 time that of thiopentone)
• Conjugation in liver results in inactive metabolites
• Excretion – in urine
• Can be used in Chr. Renal F, hepatic ds.
Thiopent. Propofol Ketamine barbiturate phenol phencyclidine
Pain - - + - -
Phleb. Less more less
Rapid onset ++ +++ +
BP decrease decrease increase
Analgesia -- -- +
Bronch ppt Asthma -- +
Mech. of act. GABA GABA Desociat.
Recovery Hang over clean headed Emerg. Delir.
PONV + - Antiemetic + antipruritic
Duration 10 min 10 min < 10min
Route iv i.v i.v \ i.m
Life Support During Induction
A. Airway : Support: manual \ Atrif. Airway
B. O2 FM + circuit +- An. Agent
Chest expansion\ bag \ monitor
C. Circulatory Support
D. Definitive Airway : Guedel`s Airway
Laryngeal Mask Airway
ETT MR + Circuit + IPPV
MAINTENANCE
Anesthesia ( Tetrad) :
Unconsciousness : Inhal. Vs TIVA
Analgesia : N2O + Opioids / LA
Relaxation : M.R.
Autonomic : Pares. : Anticholin.
: Symp. : GA
Opioids
CVS drugs
Inhalational Anesthetics
• The greater the uptake of anesthetic agent, the greater the difference b\w the inspired and alveolar conc. And slower the rate of induction.
• Three factors affect anesthetic uptake
1. Solubility in the blood
2. Alveolar blood flow
3. partial pressure difference b\w alveolar gas
and venous blood.
• The relative solubility's of an anesthetic in air, blood, and tissues are expressed as Partition Coefficients
Partition Coefficients• N2O 0.47 ( insoluble in blood)
• Halothane 2.4• Isoflurane 1.4• Desflurane 0.42• Sevoflurane 0.65 (Factors that speed induction also speed recovery)
• MAC – the alveolar conc. of an inhalational anesthetic
that prevents movement in 50% in response to
surgical stimulus.
- a measure of potency
Agent MAC%
Nitrous oxide 105
Halothane 0.75
Isoflurane 1.2 Sevoflurane 2.0
Desflurane 6.0
Inhalation Agents
• ISOFURANE – dilates coronary arteries ( but less potent than nitroglycerine or adenosine).
- Can cause (coronary steal syndrome) regional myocardial ischemia)
• DESFLURANE – Low solubility of desflurane in blood and tissues causes a very rapid wash in and wash out of anesthetic.
• SEVOFLURANE – Excellent choice for rapid and smooth inhalational induction.
( b\c of non pungency and rapid increases in alveolar anesthetic conc.)
VOLATILE ANESTHETICS
Halothane Isoflurane Sevoflurane
Pleasant Smell + + - - + -
MAC 0.75% 1.2% 2%
HR ↓ arrhythmia ↑ or no change minimal
SVR + - - - - -
Contractility - minimal - minimal
BP - - - - -
CO ↓ + or minimal + or minimal
Catachol. sensitisation + + + - -
Bronchi Dilatation less less
Uterus Relaxation less less
Hepatic Tox. + - - - -
Renal Tox. - - - +
• Neuromuscular Blocking Agents( Ms relaxants) ( no anesthesia, amnesia or analgesia)
• Depolarizing Nondepolarizing Acetyl-choline competitive antagonist receptor agonistNondepolarizing Muscle relaxants are not significantly
metabolized ( except mivacurium metabolized by pseudocholinestrase & atracurium – metabolized by hofmann elimination and ester hydrolysis )
Need reversal agents ( Cholinesterase inhibitors) that inhibit acetylecholinesterase enzyme activity.
• Characteristics of cholinergic receptors
Nicotinic Muscarinic• Location Autonomic Ganglia Glands ( Lacrimal
Sympathetic & salivary, gastric)
parasympathetic Smooth muscle
ganglia (Bronchial, GIT,
Skeletal muscle bladder, bld vessels)
Heart(SA node,AV node)• Agonists Acetylcholine Acetylcholine
Nicotine Muscarine• Antagonist N D P M relaxants Antimuscarinics
( Atropine, Scopolamine,
Glycopyrrolate)[email protected]
• RECOVERY :
Titrate : Reversal : (Muscle relaxant)
Atropine + Neostegmine
opiate : Nalaxone
Benzodiazepine : flumazinil
Extubation \ Airway
oxygenation
Consciousness
Pharmacological character of anticholinerg. Dg
Atropine Scopolamine Glycopyrrolate
Tachycardia +++ + ++
Bronchodilat. ++ + ++
Sedation + +++ 0
Antisialagogue ++ +++ +++
effect
Post- Operative Care :
R. Room : A. Airway, recovery position
B. O2
C. CVS : Consciousness
Analgesia
MONITORING
COMPLECATION IN THE RECOVERY ROOM HYPOTENTION-HYPERTENSION-ARRHYTHMIA
RESPIRATORY : Airway Obstruction, Hypoxia, Hypoventilation
Delayed recovery
Pain
PONV
Complication in recovery room
CVS : Hypotension – hypertension – arrhythmia
Respiratory : Airway obstruction, Hypoxia,
Hypoventilation
Delayed Recovery
Pain
PONV
RECOVERY :
Stop Anaesthesia
# Titrate : Reversal : MR : Prostig. + Atropine. Opioids : naloxone
A. Extubation \ Airway B. O2 C. Consciousness
