Review of Hemodynamics (Chapter 42)

Arterial Pressure RegulationOverview of control system:

• Arterial pressure = peripheral resistance × cardiac output• Arterial pressure is regulated by

– Autonomic nervous system (ANS)• Seconds to minutes

– Renin-angiotensin-aldosterone system• Hours to days• Renin- raises BP• Angiotensin- raises BP• Aldosterone- raises BP

– Kidneys• Weeks

– Family of natriuretic peptides• Where sodium goes water follows, lowers BP

ANS & Regulation of AP• Steady-state control via ANS

– Tone– Adjusts cardiac output (CO) and peripheral resistance (SVR)

• Rapid control by ANS: baroreceptor reflex– HR -Constricts nearly all arterioles, veins and Sympathetic branch of ANS– Resets to “new” norm if sustained for 1-2 days

RAAS Regulation of AP• Renin-angiotensin-aldosterone• Constriction of arterioles and veins (angiotensin II - vasoconstrictor)

– hours• Retention of water by the kidney (aldosterone)

– days

Kidneys & Regulation of AP• Retention of water

– Process: ¯BP¯®GFR®H20 retention• Postural hypotension

– Aka orthostatic hypotension• Natriuretic peptides

– Relieve preload fr. hypervolemia– Protect CV system fr. volume overload

• Atrial natriuretic peptide (ANP)• B- or brain natriuretic peptide (BNP)• C-natriuretic peptide (CNP)

Drugs Acting on the Renin-Angiotensin-Aldosterone System (Ch. 43)

• Physiology of the renin-angiotensin-aldosterone system (RAAS)• Angiotensin-converting enzyme inhibitors• Angiotensin II receptor blockers• Aldosterone antagonists

Physiology of the Renin-Angiotensin-Aldosterone System• Angiotensins I, II, & III• Actions of angiotensin II

– Vasoconstriction– Release aldosterone– Alter structure of heart and vessels

• Actions of aldosterone– Sodium and water– Fibrosis of vessels

Formation of Angiotensin II• Renin

– Released in response to BP, Na+, volume, and renal perfusion – Converts angiotensinogen to angiotensin I

• Angiotensin-converting enzyme (ACE)– Catalyzes conversion of angiotensin I (inactive) into angiotensin II (highly active)

Regulation of BP by RAAS• Effect modest in normal hemodynamics & Na+• Effect MAJOR in hemorrhage, dehydration, or sodium depletion• Acts in two ways

– Constricts renal blood vessels– Stimulates release of aldosterone fr. Adrenals thereby ….

• Tissue (local) angiotensin II production

Angiotensin-Converting Enzyme (ACE) Inhibitors = the “Prils”

Prototypes: captopril (Capoten), ramipril (Altace)

MOA / TE – Reduces angiotensin II & increases bradykinin to dilate vessels, excrete Na+ & H20, conserve K+ & help prevent vessel and heart tissue changes

Uses – HTN– heart failure– diabetic nephropathy– prevention of MI– stroke and death

Special benefits of ACE Inhibitors

– Do NOT interfere with heart reflexes – ok with exercise– Safe in asthma– Do NOT cause hypokalemia, hyperuricemia, or hyperglycemia– Do NOT induce lethargy, weakness or sexual dysfunction– DO reduce risk of cardiovascular mortality fr. HTN, MI, & stroke

(22%)– Reduce mortality following MI– Reduce chance of developing heart failure– Slow progression of renal disease

ADME – Nearly all are PO– Captopril and moexipril NOT with food– Renal excretion (monitor who?)

Adverse effects – 1st Dose hypotension– Cough– Hyperkalemia– RF in renal artery stenosis– Angioedema– Neutropenia (rare)– Dysgeusia and rash– People with Lupus

Drug D Drug – Diuretics – withdraw 1 wk prior– Antihypertensive agents– Drugs that raise potassium levels– Lithium - raised– Nonsteroidal anti-inflammatory drugs

Angiotensin II Receptor Blockers (ARBs) – the “Sartans”

Prototypes: iosartan (Cozaar), valsartan (Diovan)

MOA / TE – Blocks action of angiotensin II – Protects fr. cardiovascular structural changes– Reduces excretion of K+ and ¯ aldosterone– Increases renal excretion of Na++ & H2O– Useful in migraine– Does not inhibit kinase II or increase bradykinin– MAIN difference between ACEs & ARBs – no cough or

hyperkalemia with ARBs

ADME – All PO– All ok with or without food

Adverse effects Same as ACEs 1st Dose hypotension– Cough– Hyperkalemia– RF in renal artery stenosis– Angioedema– Neutropenia (rare)– Dysgeusia and rash– People with Lupus

DrugDDrug – Antihypertensives

Aldosterone Antagonists

Prototype: eplerenone [Inspra]

MOA / TE – Selective blockade of aldosterone receptors for tx of HTN and heart failure

– Requires 4 weeks– Benefit in preventing mortality unknown

ADME – Absorption is not affected by food

Adverse effects – hyperkalemia

DrugDDrug – Inhibitors of CYP3A4• Can significantly raise levels of eplerenone

– Drugs that raise potassium levels– Caution when combined with lithium

Prototype: Spironolactone [Aldactone] – older drug

MOA – Blocks aldosterone receptors– Binds with receptors for other steroid hormones

Therapeutic uses – Hypertension and heart failure

Adverse Effects Hyperkalemia– Gynecomastia– Menstrual irregularities– Impotence– Hirsutism– Deepening of the voice

Calcium Channel Blockers (CCBs)• Normal physiology:

– Calcium in = contraction / force• Effects of Blocking

– Dilation of Vascular Smooth Muscles (VSM) = dilated peripheral arterioles / arteries & arteries of heart• Heart Ca++ Blocking Effects

– ¯ Inotropic effect– Slows conduction thru SA & AV nodes– Same effect as Beta1 blockers

Prototypes: Verapamil [Calan, Isoptin, Verelan] Diltiazem [Cardizem, Diltia XT] Amlodipine (Norvazac)

MOA / TE – Peripheral arterial dilation, ¯ arterial pressure, coronary perfusion, blockade at SA & AV nodes ¯ HR, ¯ force of contraction aiding in the relief of:

• Angina pectoris• Essential hypertension –1st line for chronic

• Cardiac dysrhythmias – A-flutter / fib / SVT• Migraine

Adverse Effects of verapamil / diltiazem

– Constipation – can be severe in elderly• Diltiazem not as constipating

– Dizziness, Facial flushing– Headache– Edema of ankles and feet– Gingival hyperplasia– Bradycardia– Heart block & ¯ stroke volume

• Contraindications?

DrugDDrug – Digoxin & Beta-adrenergic blocking agents – use caution! (Can slow HR too much!)

– Separate doses of Beta blockers and CCBs

Toxicity – Severe hypotension– Bradycardia and AV block– Ventricular tachydysrhythmias– Treat w Calcium Gluconate, nor-epi, atropine, pacer, cathartics, cardioversion

Prototype: Nifedipine [Adalat,Procardia]

MOA / TE – dilates arterioles ® lowers BP– no cardiac effect– can increase HR via baroreceptor effect– no decreasing contraction force or affect on automaticity of

conduction - used in:• Angina pectoris• Hypertension• Investigational basis to relieve migraine headache and to

suppress preterm labor

Adverse Effects of nifedipine

– Flushing - Dizziness– Headache– Peripheral edema– Gingival hyperplasia– Reflex tachycardia

DrugDDrug – Beta-adrenergic blockers• Used intentionally to prevent reflex tachycardia

Vasodilators (Ch. 45)

• MOA / TE– Selectively dilate arteries, veins, or both

• Principal indications– Essential hypertension & Hypertensive crisis– Angina pectoris & Myocardial infarction– Heart failure– Pheochromocytoma– Peripheral vascular disease– Pulmonary arterial hypertension

– Production of controlled hypotension during surgery- to decrease bleeding

Hydralazine [Apresoline]

MOA / TE – Selectively dilates VSM of arterioles lowering BP and reducing afterload for treatment of

• Essential hypertension • Hypertensive crisis (IV form)• Heart failure

ADME – Inactivated by acetylation (genetic trait)– Rapid vs slow acetylators

Adverse effects – Reflex tachycardia (baroreceptors)– Increased blood volume– SLE-like syndrome (drug induced Lupus)

• 6 mo to reverse• Pain, nephritis, fever, joint pain, ANA+

DrugDDrug – Other antihypertensive agents– Combine with Beta blocker to prevent ?

• To prevent reflux tachycardia

Minoxidil [Loniten]

MOA / TE • Selective dilation of arterioles and decreases afterload for the treatment of severe hypertension.

• Used for hair growth

Adverse effects – Reflex tachycardia– Increased cardiac oxygen demand– Sodium and water retention– Hypertrichosis - hair– Pericardial effusion

Other Vasodilators• ACEs, ARBs, CCBs• Organic nitrates (NTG)• Sodium Nitroprusside (Nipride)

– Both venous and arterial• Sympatholytics• Nesiritide (Natrecor)

Drugs for Hypertension (Ch. 46)

Types of Hypertension• Primary (essential) hypertension• Secondary hypertension• Review JNC (Joint National Committee on Prevention, Detection and Treatment of Hypertension)• www.nhlbi.nih.gov/guidelines/hypertension/express.pdf

Consequences of Hypertension• Heart disease

– Myocardial infarction (MI)– Heart failure– Angina pectoris

• Kidney disease• Stroke

Pharmacological Treatment/ Therapy• Meds targeted to affect

• Heart rate• Myocardial contractility• Blood volume• Venous return / resistance

• Individualizing therapy• Initial Tx: Thiazides (cheap, reduces morbidity, well tolerated)• Beta Blocker, ACE (renal protective- good for use with ESRD), ARB

• Patients with comorbid conditions• Renal disease• Diabetes

• Minimizing adverse effects• Promoting adherence

• Why difficult to achieve?• Ways to promote adherence

• Educate patient• Teach self-monitoring• Minimize side effects – given med for HTN can cause hypoTN so they need to be careful going from laying down to

sitting and sitting to standing• Establish collaborative relationship• Simplify regimen• Other measures

Special populations• African Americans

– Diuretics / CCBs – Children and adolescents– avoid ACEs & ARBs in teenage girls

• The elderly– Helps prevent stroke / MI– Beta blockers and diuretics reduce mortality

Drugs for Hypertensive Emergencies• Sodium nitroprusside (Nipride)• Fenoldopam• Labetalol• Diazoxide

Alpha & Beta Adrenergic Antagonists (Ch. 18)

Therapeutic Effect of Alpha (a) Blockade• Essential hypertension

– Vasodilation• Reverses toxicity fr a1 agonists (EPI)

– Systemically & extravasation• Benign prostatic hyperplasia

– ¯ smooth muscle contraction in bladder neck• Pheochromocytoma

– Catecholamine secreting tumor• Severe!!

• Raynaud’s disease– Vasodilation

Selective a1 BlockerPrototype: Prazosin (Minipress)

MOA / TE – dilates arterioles & veins– relaxes smooth muscle in bladder neck and prostate capsule (off

label for BPH)

Adverse effects – Orthostatic hypotension (1 % - consciousness – 1st dose – start low – warnings – 1st dose at night)

– Reflex tachycardia - baroreceptor– Inhibition of ejaculation - reversible– Nasal congestion - vasodilation

Non-selective a1 & a2 BlockadePrototype: phentolamine (Regitine)

MOA / TE – dilates arterioles & veins– relaxes smooth muscle in bladder neck and prostate capsule (off

label for BPH)– used for tx of pheochromocytoma and prevent tissue necrosis in

extravasation of norepinephrine

Adverse effects – Same – has more reflex tachy effect

Therapeutic Effects of Beta Blockade - the “olols and lols”• Major effects:

– ¯ heart rate & ¯force of contraction– ¯ velocity of impulses through AV node

• Therapeutic management of – *Angina pectoris & Myocardial infarction– *Hypertension – *cardiac dysrhythmias– Heart failure– Hyperthyroidism, migraine, stage fright– Pheochromocytoma– Glaucoma

Non-Selective Beta (b) BlockersPrototype: propranolol (Inderal)

MOA / TE • Major effects: – ¯ heart rate & ¯force of contraction– ¯ velocity of impulses through AV node

• Therapeutic management of – *Angina pectoris & Myocardial infarction– *Hypertension – *cardiac dysrhythmias– Heart failure– Hyperthyroidism, migraine, stage fright– Pheochromocytoma– Glaucoma

Adverse effects – Bradycardia– AV heart block– *Precipitation of heart failure– Reduced cardiac output– Rebound cardiac excitation w abrupt cessation (ST and VT)– Bronchoconstriction (Beta2)– Blockade of glycogenolysis (Beta2)

Precautions / contraindications

– Severe allergic conditions• If occurs beta blockade interferes w EPI

Diabetes • Compensatory glycogenolyis is impaired• Can mask sxms of hypoglycemia (ST)• Heart failure• AV block• Bradycardia • Asthma • Bronchospasm and depression (crosses easily into CNS)

Drug interactions – Calcium channel blockers – esp. verapamil– Insulin – sxms of hypoglycemia

Nsg Implications Taper off gradually– Masking of hypoglycemia reactions– Heart rates: Brady or Rebound tachy

Cardioselective Beta1 BlockersPrototype: metoprolol (Lopressor, Toprol)

MOA / TE – Beta1 AT THERAPEUTIC DOSES– Global at higher doses – Don’t cause bronchoconstriction – otherwise same as propranolol

Adverse effects – same EXCEPT bronchoconstriction and glycgogenolysis– safer in asthmatics and diabetics

Indirect-Acting Antiadrenergic Agents (Ch. 19)

Centrally Acting Alpha2 AgonistsPrototype: clonidine (Catapres)

MOA / TE decreases release of norEpi, limiting vasoconstriction, therefore lowering blood pressure and heart rate. Also used in severe pain of cancer

ADME – Effects start in 30’ and can last for 24 hrs

Adverse Effects – Rebound HTN fr. sudden withdrawal– Drowsiness– Xerostomia (DRY MOUTH)– Embryotoxic– Constipation– Impotence– gynecomastia

Administration PO and patches

Anticoagulant, Antiplatelet, and Thrombolytic Drugs (Ch. 51)

Review: Physiology & Pathophysiology of Coagulation• Hemostasis

– Stage 1 - Platelet plug via aggregation– Stage 2 - Intrinsic & Extrinsic pathways– Keeping hemostasis under control– Physiologic removal of clots

• Thrombosis– Arterial thrombosis– Venous thrombosis

Parenteral Anticoagulants I: Heparin and Related DrugsPrototype: Heparin (unfractionated)

MOA / TE / Uses – rapid-acting anticoagulant interfering w Thrombin & Factor to treat;– Pulmonary embolism (PE)– Evolving stroke– Massive deep venous thrombosis (DVT)– Is DANGEROUS

ADME IV only – no po

Adverse effects – Hemorrhage– Heparin-induced thrombocytopenia (HIT) – immune response– Hypersensitivity reactions– Long term – osteoporosis

Warnings – Hemophilia– PUD– Aneurysm – HTN– Threatened AB

Contraindications – Bleeding– Thrombocytopenia – Surgeries of eye, brain, or spine

Given in units- 2 nurses must check!

– Intermittent via INT– Continuous – loading dose common– Deep subcut – well away from umbilicus– Low-dose pre-op prophylactically

Protamine Sulfate – For ODMonitoring – Activated partial thromboplastin time (aPTT) –

– Increase from norm (40 sec) 1.5 to 2 times– Above 80 seconds too long

Low-Molecular-Weight HeparinsPrototype: enoxaparin (Lovenox)

MOA / TE / Uses Heparin preparations w shorter molecules than unfractionated that selectively inactivates Factor Xa & used in

– Prevention of DVT following surgeries– Treatment of established DVT– Prevention of ischemic complications

Benefits of Lovenox over Heparin

– Can be fixed dose, can be used at home, less thrombocytopenia

Adverse effects and interactions

– Bleeding– Immune-mediated thrombocytopenia– Cost

Nursing considerations – Hypersensitivity to pork

Oral AnticoagulantsPrototype: warfarin (Coumadin)

MOA / TE / Uses • Antagonist of vitamin K, blocks biosynthesis of factors VII, IX, X, and prothrombin used in

– Long-term prophylaxis of thrombosis– Prevention of VTE and associated PE– Prevention of thromboembolism (in patients with prosthetic heart

valves)– Prevention of thrombosis during AF

ADME – Longer onset sec. to circulating clotting factors – may be days on & off

– Implications for surgery, ok for DDS

Adverse effects – Hemorrhage– Teratogenesis (Cat X)– Red-orange urine (not blood)– Alopecia

DDD & DDF (Table 51-4) Drugs that ¯or anticoagulant effects– Drugs that promote bleeding: NSAIDs – including acetominphen, Heparin– Foods: broccoli, spinach, dark greens

Nursing considerations Monitoring INR, PT (Table 51-3)– Vit K for OD (po, diluted IV - NO subcut)

Anti-platelet DrugsClass is used to prevent arterial thrombosisProtoype: acetylsalicylic acid (Aspirin) ASA – she said to review notes on this!!

MOA / TE / Uses – Non-selective COX Inh (inhibits cox 1 & 2)– Analgesic, antipyretic, anti-inflammatory– Suppression of platelet aggregation

• Irreversible for 8 d – life of platelet• Treat / prevent Ischemic stroke (lack of oxygen), TIA,

MIs (acute & old), anginas, adjunct to angioplasty & revascularization

• Helps blood to flow smoothly through vessels (manages angina)

– Dysmenorrhea - cramps– Cancer prevention– Prevention of Alzheimer’s disease – but not treatment– An initial DOC for RA and juvenile arthritis– Dose related to use!

ADME – Rapidly absorbed orally, slower rectally– Half-life (2 h to 20 h)– Distributes to all body tissues – pregnant? – don’t use if pregnant -

contraindicated– Excretion pH dependent (increase pH increase excretion 4x)

Side effects – Gastric distress, heartburn, nausea

Adverse effects (hidden) – Gastrointestinal – (occult- occult blood in stool) and overt)– Bleeding– Renal impairment – Signs?

• acute/reversible – Na+/H2O• Pre-existing condition dependent

– Salicylism – acid/base – tinnitis (ringing of the ears –sometimes irreversible)

– Reye’s syndrome – liver failure or impact on the liver in children (don’t give aspirin to children)

– Hypersensitivity – asthma – rhinorrhea to shock

Contraindications – PUD & Bleeding disorders– Hypersensitivity– Extreme caution in pregnancy

DDD – Anticoagulants & other NSAIDs– Glucocorticoids (gastric ulcertion)– Ibuprofen – impairs cardio protective properties

Acute Poisoning – LD adult = 20-25 g - LD children = 4 g– Sxms

• Resp excitation ® depression ® hyperventilation • Hyperthermia, stupor, coma, death

– Treatment• Supportive, charcoal, alkalinization of urine (give them a

base)• Dialysis• Hyperthermia – ice packs to arm pits, groin

Ticlopidine [Ticlid] & Clopidogrel [Plavix]

– Irreversible blockade of ADP-mediated aggregation

Adverse effects • Neutropenia / agranulocytosis / thrombotic thrombocytopenic purpura

Thrombolytic DrugsPrototype: Streptokinase [Streptase]

MOA / TE • Binds plasminogen to make plasmin to break up clot & is used in– Acute coronary thrombosis (acute MI)– Deep venous thrombosis (DVT)– Massive pulmonary emboli

Adverse effects Bleeding, hypotension– Antibody production, fever

Drugs for Deficiency Anemias (Ch. 54)• Anemia—decrease in erythrocytes (RBC)

– Number, Size, Color– Look in patho unit 4 lectures

• Causes– Blood loss– Hemolysis– Bone marrow dysfunction– Deficiencies

Iron Deficiency: Oral TreatmentPrototype: Ferrous sulfate (Feosol)

MOA / TE – DOC -restores iron for production of hemoglobin to prevent or relieve symptoms of microcytic hypochromic anemia

ADME – Absorbed fr Fe rich foods, uptake in GI tract, stored by liver – Lose 1 g / d - requirements r/t rate of RBC production - pregnancy /

menses

Adverse effects – GI: N, heartburn, bloating, constipation, & diarrhea– Aggravation of: PUD, regional enteritis, ulcerative & colitis –

shouldn’t take p.o.– Dark green / black stools– Liquid form – stains teeth – drink thru straw and avoid teeth all

together

Toxicity – Leading cause of poison death in kids– Tx: Lavage if tabs in gut / deferoxamine

DDD Antacids – reduce (2 hrs before, 4 hrs after)– Tetracycline - reduce– Ascorbic acid – increases & potentiates adverse effects

DDF – Absorbs best w/o food– Foods protect against bad effects– Milk, cereals, dietary fiber, tea, coffee, and eggs, may decrease

absorption

Iron Deficiency: Parenteral TxPrototype: Iron dextran (INFeD)

MOA / Use • Indicated when orals don’t work – can’t be absorbed – blood loss is excessive – and GI problems

Adverse effects – Anaphylaxis fr. Dextran– Hypotension– Pain / tumors at IM sites – intervention?

Nursing Implications – Monitor serum Fe for rise of 2 g /dL – goal is 15 g / dL– If unresponsive – monitor for adherence– Therapy possibly for months

IV – test dose– 25 mg– Monitor 15 min

Avoid IM site if possible Tumors– Greatest risk of anaphylaxis– Prolonged pain / discoloration at site

Vitamin B12 Deficiency TreatmentPrototype: Vitamin B12 (Cyanocobalamin)

MOA / Uses provide B12 for synthesis of DNA to alleviate macrocytic anemia, neuro damage, and GI disturbances from deficiency

ADME – A: requires intrinsic factor (IF)– E: very slow – stored ______________– Routes: PO, IM, deep SubQ, Intranasal

• No IV

Adverse effects – Secondary hypokalemia

Dietary sources Microorganisms– Animal products (liver, dairy products)– Fortified foods

Treatment regimen – Lifelong if Ø IF

Folic Acid Anemia: TreatmentPrototype: Folic acid aka folate

MOA / Uses • replace vitamin essential for DNA synthesis, replication, cell division to prevent neural tube defects, colorectal cancers, and treat megaloblastic anemia

ADME – A: early segment small intestine– E: Significant amounts daily– Daily requirements– Dietary sources—all foods

Treatment Oral supplementationMonitor Labs

Basic Principles of Neuropharmacology (Ch. 12)

Basic Mechanisms of NeuroPharm Actions• Synapse

– Predominant• Axonal

– Local anesthetics– non-selective

• Receptors– All effects from drugs - direct / indirect (except anesthetics)

Physiology of the Peripheral Nervous System (Ch. 13)

Primary Parasympathetic NS Functions r/t Drugs1. Slows heart rate2. Increases gastric secretion3. Empties the bladder4. Empties the bowel5. Focuses eye for near vision6. Constricts the pupil7. Contracts bronchial smooth muscle

Primary Sympathetic NS Functions r/t to Drugs1. Regulates cardiovascular system

– Blood flow to brain, body during exercise & compensation in blood loss2. Regulates body temperature

– Temp via blood flow to skin, secretion of sweat, “goose pimples” aka piloerection3. Implements “fight” / “flight”

– HR, shunts blood to muscles, dilates bronchi & pupils, mobilizes energy stores

ParaSympathetic & Sympathetic Relationship• Innervation by both in opposition• Innervation by both in compliment• Innervation by only one• Major mechanisms

– Feedback systems– Baroreceptor reflex – most important– Autonomic tone – ParaS for most organs

• Exception - vasculature

Neurotransmitters of the Peripheral Nervous System• Acetylcholine (Ach)

– Employed at most junctions of the peripheral nervous system • Norepinephrine (NE)

– From postganglionic neurons to sympathetic• Epinephrine (EPI)

– From the adrenal medulla

– Increased HR and increased pressure

Receptors of the Peripheral Nervous System• Cholinergic receptors – regulated by Ach

– NicotinicN & release of epi at adrenals– NicotinicM – Muscarinic (glandular)

• Adrenergic receptors – regulated by Epi / Norepi– Alpha1 and alpha2, beta1 and beta2– Dopamine– Comes from adrenelin

Receptor Subtypes• Alpha1 (eyes, vessels, male sex organ, prostatic capsule & bladder)

– Vasoconstriction– Ejaculation– Contraction of bladder neck and prostate

• Alpha2 (nerve terminals) – not clinically sign.– Located in presynaptic junction– Minimal clinical significance

• Beta1-Adrenergic Receptor Subtypes– Kidney

• Renin release– Heart

• Increase rate• Increase force of contraction• Increase velocity of conduction of AV nodes

• Beta2-Adrenergic – Various effects

• Bronchial dilation• Relaxation of uterine muscle• Vasodilation• Glycogenolysis

– Dopamine • Dilates renal blood vessels

• Receptor Subtypes

Specificity of Adrenergic Neurotransmitters• Epinephrine

– Activates all alpha & beta receptors– Does NOT activate dopamine receptors

• Norepinephrine– Activates alpha1 & 2 and beta1 – Does NOT activate beta2 or dopamine receptors

• Dopamine – Only transmitter that can activate dopamine receptors– Activates alpha1, beta1, and dopamine receptors.

Muscarinic Agonists and Antagonists (Ch. 14)

Muscarinic AgonistsPrototype: Bethanechol (Urecholine)

MOA / Uses – binds reversibly to muscarinic cholinergic receptors to activate and selectively produce effects on the

• Heart (¯HR)• Exocrine glands (sweating, salivation, bronchial

secretions, gastric acid)• Smooth muscles (constriction of bronchi & tone &

motility of GI tract)• Contraction of detrusor – relaxation of trigone/sphincter • Eye (miosis and accommodation)

Principle indication Urinary retention

Adverse effects – Hypotension and bradycardia– Bloating, cramps, hypersecretions of acid, involuntary defecation– Bladder rupture in persons with urinary tract obstruction or weak

bladder wall– Bronchoconstriction– Dysrhythmias in hyperthyroid

Muscarinic Antagonist: AtropinePrototype: atropine (Sal-Tropine)

MOA / TE • Competitive blocking of Ach at muscarinic receptors to treat the following:– Pre-anesthetic medication– Disorders of the eye (surgery)– Bradycardia– Intestinal hypertonicity and hypermotility– Muscarinic agonist poisoning (WMDs)– Peptic ulcer disease (Not DOC)– Asthmas (Not DOC)– Biliary colic– Increase HR– Decrease secretions from glands– Relaxation of bronchi, decrease bladder tone, decrease GI motility– Dilation of pupil and focus for far vision– High doses can cause CNS excitation and ultimately death

Adverse Effects – Xerostomia (dry mouth)– Blurred vision, photophobia– intraocular pressure (glaucoma)– Urinary retention– Constipation– Anhidrosis (no sweating)– Tachycardia– Thick bronchial secretions

DDD Antihistamines– Phenothiazine antipsychotics– Tricyclic antidepressants

Too high = Death

Anticholinergics for OABPrototype: oxybutynin (Ditropan)

MOA / TE • Partially selective for M3 receptor blocking to target bladder detrusor and alleviate sxms associated with urge incontinence & urinary frequency

Adverse effects • like those of Atropine– DRY mouth, constipation, impaired vision

Antidote Physostigmine – Charcoal

Other AnticholinergicsScopalamine Like atropine – except: sedative, antiemetic

Ipratropium Bromide (Atrovent) Inhaled – so fewer SE (dryness, etc)

Drugs for Epilepsy (Ch. 24)

Antiepileptic Drugs• Effects

– Suppress discharge of neurons at focus – Suppress propagation of seizure activity from focus to other areas of brain

• Mechanisms of action– Suppress sodium influx – reversible binding– Suppress calcium influx– Antagonize glutamate – excitatory transmitter– Potentiate GABA – an inhibitory transmitter

Epilepsy: Therapeutic Considerations• Diagnosis and drug selection• Drug evaluation – seizure freq. chart• Non-drug therapy

– Neurosurgery (best success rate)– Vagal nerve stimulation– Ketogenic diet

• Monitoring plasma drug levels– Traditional AEDs

• Promoting patient adherence• Withdrawing antiepileptic drugs

Classification of Antiepileptic Drugs• Traditional antiepileptic drugs (AEDs)

– Phenytoin (Dilantin)– Carbamazepine (Tegretol)– Valproic acid (Depakote)– Phenobarbital

• Newer AEDs– Oxcarbazepine, gabapentin, zonisamide, and others

AED: Phenytoin [Dilantin]

MOA / Uses – Selective inhibition of sodium channels to suppress cerebral irritability to treat partial and tonic-clonic seizures & selected cardiac dysrhythmias

ADME – Varied oral absorption– Half-life 8 to 60 hours– Metabolism variance– Blood levels (10 mcg/mL)

Adverse effects – Nystagmus, diplopia– Sedation– Ataxia - gait– Cognitive impairment– Gingival hyperplasia – floss / gum massage– Skin rash – stop therapy (Stevens-Johnson)– Effects in pregnancy - teratogen– Cardiovascular effects – IV use in SE, heart blocks

DDD – Phenytoin decreases effects of• oral contraceptives, warfarin (Coumadin), and

glucocorticoids– Drugs that increases phenytoin levels:\

• diazepam (Valium), isoniazid, cimetidine (Tagamet), alcohol (acute), valproic acid (Depakote)

– Drugs that decrease phenytoin levels• Carbamazepine, phenobarbital, chronic ETOH

ADME – Administration: po with food– IV – slowly! – compatibility issues

Additional Nsg considerations

Driving– Hazardous work

AED: Carbamazepine [Tegretol]

MOA / Uses – Much like phenytoin & used to treat epilepsy (not absence), Bipolar disorder, trigeminal and glossopharyngeal neuralgias – minimal effects on cognitive function

Adverse effects – Nystagmus, ataxia, HA, blurred vision, vertigo– Leukopenia, anemia, thrombocytopenia– Hypo-osmolarity – water excretion– Rash, photosensitivity reactions & teratogenic

DDD – Decreases effect of warfarin and contraceptives– Is decreased by phenobarbital– Is increased by grapefruit

Nsg Considerations Minimal cognitive impairment effects– Tolerance to other SE develops

AED: Valproic Acid [Depakote]

MOA / Uses – Seizure disorders (all) – including absence seizures, Bipolar disorder, & migraine

Adverse effects – GI effects– Hepatotoxicity: liver failure– Pancreatitis– Teratogenic effects

AED: Phenobarbital

MOA / Uses • known since 1912 – potentiates GABA– Epilepsy (partial and generalized tonic-clonic seizures)

Adverse effects – Promotes sleep and sedation– Physical dependence– Rickets, osteomalacia

Newer Antiepileptic DrugsPrototype: oxcarbazepine (Trileptal)

MOA / Uses Blocks sodium channels and is indicated for monotherapy & adjunctive therapy of partial seizures in children & adults

Adverse effects • better tolerated than Tegretol– Dizziness, drowsiness, nystagmus, HA– Hyponatremia– Skin reactions – Stevens-Johnson

Gabapentin (Neurontin)

MOA / Uses May increase production of GABA. Approved for partial seizures & post-herpetic neuralgia.

80% of use is off-label (Neuropathic pain & Migraine prophylaxis). Well tolerated.

Adverse effects Somnolence, dizziness, ataxia, fatigue, nystagmus & peripheral edema

Management of SE• Medical emergency

– ETOH story• IV meds

– Benzodiazepine (Ativan or Valium)• Oral management once controlled