Cardiovascular Drugs

Chris G. Wherrett, MD, FRCPC

Department of Anesthesiology

Ottawa Hospital General Campus

October 11, 2012

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Objectives

To highlight clinically relevant features of basic clinical pharmacology of cardiovascular drugs used in anesthesia and critical care

To highlight clinically irrelevant features of these drugs that find their way into exams

To stimulate some interest in a topic that can be overwhelming

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References

1) Stoelting, 4th Edition (2006)– Chapters 12-16

2) TOH Parenteral Drug ManualInfonet > Pharmacy Dept.

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Q & A Format

Not real exam questions

Anything goes

Previous sessions “format confusing”– I’ve simplified some questions

– Please ask for clarification

– Intended to challenge in a different way

I’ve addressed all comments in feedback that I could understand

Some of you may not agree with this format

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Re: Propranolol

1) Greatest incidence of CNS effects of beta

blockers 2) Half life after IV

administration 3-4 hr 3) Depression of myocardial

contractility and reduction in heart rate occur at similar serum levels

4) Maximum IV dose 0.2 mg/kg

5) Has ISA and MSA 6) Increases SVR

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Re: Propranolol (2)

1) Greatest incidence of CNS effects of beta

blockers 2) Half life after IV

administration 3-4 hr 3) Depression of myocardial

contractility and reduction in heart rate occur at similar serum levels

4) Maximum IV dose 0.2 mg/kg

5) Has ISA and MSA 6) Increases SVR

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Metoprolol overdose should be treated with:

1) Atropine

2) Dopamine

3) Isoproterenol

4) Dobutamine

5) Glucagon

6) Ca++

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Beta blockers, actions:

1) Decrease myocardial ischemia through effects on myocardial oxygen consumption, diastolic perfusion period and collateral

flow 2) Decrease infarct size in AMI 3) Decrease morbidity and

mortality in AMI 4) CXD in hypertrophic

cardiomyopathies 5) Improve EF in patients with

CHF 6) Reduce mortality in

noncardiac surgery

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Sotalol:

1) Nonselective Beta antagonist

2) Indicated for supraventricular dysrhythmias and life-threatening ventricular tachydysrhythmias

3) Effect due to blockade of cardiac beta receptors to SNS

4) Safety profile similar to other Beta blockers

5) Less effect on contractility than other Beta blockers

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Timolol:

1) Useful to treat glaucoma because it decreases production of aqueous humour

2) Deleted

3) When administered topically, systemic effects are rare

4) Has less Beta-2 effect than Betaxolol

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Which antihypertensive drugs cause cerebral

vasodilation? 1) SNP 2) NTG 3) Hydralazine 4) Enalaprilat 5) Trimethaphan 6) Labetalol, Esmolol 7) Diltiazem, Nifedipine,

Nimodipine 8) Phenoxybenzamine

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Contra-Indicated in hypertrophic

cardiomyopathy: 1) Nifedipine 2) Propranolol 3) NTG 4) Ephedrine 5) Dobutamine

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CEBs, hemodynamic effects:

1) Negative inotropes 2) Negative chronotropes 3) Diltiazem has least

negative inotropy 4) Verapamil can

significantly decrease myocardial function

5) Diltiazem is the most potent coronary vasodilator

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CEBs, hemodynamic effects: (2)

1) Negative inotropes (all) 2) Nifedipine increases CO,

HR, contractility 3) Diltiazem has least

negative inotropy 4) Verapamil can

significantly decrease myocardial function

5) Diltiazem is the most potent coronary vasodilator

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Nifedipine:

1) Is contraindicated in hypertensive emergencies

2) Is useful for treatment of hypertension in the PACU

3) Indications

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Esmolol:

1) Half-life 9 min 2) Prolonged duration with

atypical plasma

cholinesterase 3) Beta-1 selective 4) Causes more hypotension

than propranolol 5) Safe in bronchospastic

disease 6) Prolongs duration of

succinylcholine 7) Useful to convert acute

Atrial Flutter to sinus

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Which Beta Blocker has longest duration of action?

Labetalol Propranolol Nadolol Metoprolol Atenolol Acebutolol Bisoprolol

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Enalaprilat:

1) Is a pro-drug of enalapril, given intravenously

2) Is contraindicated in renovascular

hypertension 3) IV dose is 0.625 - 1.25 mg

q6h 4) Postinduction hypotension

is more common if ACEIs taken on the morning of surgery

5) Hypotension can be treated with crystalloid, phenylephrine, and vasopressin

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Angiotensin Receptor Blockers:

1) Act independently of ACE

2) Antagonize Angiotensin I at AT1 receptors

3) Losartan is the prototype

4) Side effects profile is similar to ACEI’s

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Ephedrine:

1) Is a sympathomimetic, a synthetic, and a catecholamine

2) Has both direct and indirect actions at adrenergic nerve endings

3) May produce arrhythmias 4) Hemodynamic profile is

the same as Epinephrine 5) Is limited by

tachyphylaxis 6) Comes from a Chinese

plant "Ma Huang" 7) Can be given IV, IM, PO

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Ephedrine: (2)

1) Is a sympathomimetic, a synthetic, and a catecholamine

2) Has both direct and indirect actions at adrenergic

nerve endings 3) May produce arrhythmias 4) Hemodynamic profile is the

same as Epinephrine 5) Is limited by tachyphylaxis 6) Comes from a Chinese

plant "Ma Huang" 7) Can be given IV, IM, PO 8) Associated with lower

umbilical Artery pH than Phenylephrine

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Phenoxybenzamine:

1) Is a nonselective alpha antagonist

2) Requires up to 2 weeks to control BP in pheochromocytoma

3) Causes orthostatic hypotension, miosis, nasal stuffiness, tachycardia, impotence

4) Uses include:– Preop control with pheo– Excessive vasoconstriction e.g.

Raynaud’s– Acute hypertensive emergencies

5) Should be given prior to beta blockade

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Amiodarone:

1) What are indications? 2) What is unique about PK 3) What is IV dosing:

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Side effects of amiodarone:

1) Thyroid hyperfunction 2) Thyroid hypofunction 3) Bradycardia 4) Pulmonary fibrosis 5) Facial discolouration

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NaHCO3 in cardiac arrest:

1) Indicated with pre-existing metabolic acidosis, hyperkalemia, TCA overdose

2) Prolongs survival in animal models

3) May precipitate with catecholamines

4) Improves ability to defibrillate

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Useful drugs in aortic dissection:

1) Beta blockers 2) Nitroprusside 3) Both of above 4) Hydralazine 5) CEBs

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Calcium:

1) Theoretical detrimental effects in cardiac arrest

2) Can precipitate dig toxicity

3) Serum ionised Ca++ does not decrease when citrated blood given < 100mL / 70kg / min

4) CaCl2 contains 3x as much Ca++ as gluconate but is irritating to veins

5) List 4 indications

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Withdrawal syndromes may occur with (1):

1) Diltiazem 2) Beta blockers 3) Clonidine 4) Methyldopa 5) Reserpine 6) ACEIs 7) CEBs

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Withdrawal syndromes may occur with: (2)

1) Diltiazem 2) Beta blockers 3) Clonidine 4) Methyldopa 5) Reserpine 6) ACEIs 7) CEBs

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Verapamil

1) More effective than digoxin in controlling HR in AF

2) Ineffective in converting AF to NSR

3) CXD in VT 4) CXD in SVT with

Aberrancy due to WPW 5) CXD in narrow complex

SVT 6) CXD in AF with WPW

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A 50 kg patient is having a CAPD catheter removed

The patient is on Nifedipine for HTN

She is being treated with Vancomycin for CAPD catheter-related peritonitis

Why is “40 of Roc” asking for trouble?

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Amrinone:

1) A nonspecific phosphodiesterase inhibitor

2) Increases cAMP which increases intracellular Ca++

3) Increases HR

4) Increases MVO2

5) Has T/2 3.5 hr 6) Effective in presence of

Beta- blockade

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Milrinone

1) A second generation PDE-5 inhibitor

2) More potent than Amrinone

3) Side effects include thrombocytopenia

4) Improves diastolic relaxation

5) Decreases pulmonary vascular resistance

6) Causes hypotension

7) Rapid onset inotropic effect

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Phenylephrine:

1) Has effects similar to Norepinephrine

2) Decreases coronary perfusion

3) Causes miosis

4) Can decrease CO

5) Overdose should be treated withBeta-blockers

Extravasation of vasopressors

1) List some drugs causing skin necrosis

2) Tx

3) Other effects of extravasation

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Effects of Dopamine

1) Diminished response in CHF

2) Skin necrosis with extravasation

3) Renal vasoconstriction

4) Increased MVO2

5) Shifts blood flow away from skeletal muscle

6) Causes hypoglycemia 7) May impair functional

myocardial recovery following ischemic

injury

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Effects of Dopamine (2)

1) Diminished response in CHF

2) Skin necrosis with extravasation

3) Renal vasoconstriction 4) Increased MVO2 5) Shifts blood flow away

from skeletal muscle 6) Causes hypoglycemia 7) May impair functional

myocardial recovery following ischemic injury

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Renal Dose Dopamine

1) Decreases incidence of ARF in surgical patients at risk

2) Improve creatinine clearance after a renal insult

3) Is antagonized by Droperidol and Metoclopramide

4) Improves Na+ and H2O excretion

5) Can cause intrapulmonary shunting and mesenteric ischemia

6) “bad medicine”

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Dobutamine receptor effects:

1) Is a pure Beta-1 agonist 2) Produces vasoconstrictive

effects through stimulation of alpha receptors

3) Produces vasodilatory effects through stimulation of Beta-2 receptors

4) Produces inotropic effects through

myocardial alpha-1 receptors

5) May produce vasoconstriction in beta-blocked patients

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Dobutamine receptor effects (2):

1) Is a pure Beta-1 agonist 2) Produces vasoconstrictive

effects through stimulation of alpha receptors

3) Produces vasodilatory effects through stimulation of Beta-2 receptors

4) Produces inotropic effects through

myocardial alpha-1 receptors

5) May produce vasoconstriction in beta-blocked patients

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Dobutamine, hemodynamic effects:

1) Increased SV 2) Decreased SVR, PVR 3) No effect on RBF 4) Improves coronary

supply:demand ratio 5) BP increases, decreases,

or remains same 6) Has minimal effect on HR

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Isoproterenol, indications:

1) 3rd Degree heart block 2) Post cardiac transplant 3) Countereffect profound

Beta blockade 4) Post CABG surgery low

output syndrome 6) Asthma 7) Torsade de Pointes

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NTG, most important mechanism in myocardial

ischemia 1) Coronary vasodilation 2) Decreased LVEDP 3) Decreased afterload 4) Redistribution of flow to

ischemic areas 5) Vasodilation of pulmonary

arteries and veins

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NTG, list clinical indications

1) Approved

2) Off Label

3) Other

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Glucagon:

1) Acts independently of Beta receptors and

Phosphodiesterase 2) Increases myocardial

contractility and HR 3) Stimulates release of

catecholamines 4) Metabolic effects include

hypokalemia, hypoglycemia

5) Used to diagnose pheochromocytoma

6) Inhibits gastric motility

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What are mechanisms for the decrease in HR with digoxin

therapy in CHF? 1) Prolongation of AV node

conduction 2) Enhanced

parasympathetic nervous system activity

3) Dose-related increase in myocardial

contractility 4) Reduced sympathetic

tone

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Digoxin, List Some Precautions/Contraindication

s: 1) Hypokalemia,

hypomagnesemia, hypercalcemia

2) Hypertrophic cardiomyopathies

3) WPW 4) Pt requiring cardioversion 5) Impaired renal function 6) SA node dysfunction

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List common cardiac manifestations of digoxin

toxicity Answers:

Atrial tachycardia with block– Commonest

Junctional tachycardias, escape rhythms

Bigeminy, PVCs, VT VF

– Commonest cause of death

Worsening CHF

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Diastolic perfusion time is increased by:

1) Dobutamine 2) Isoproterenol 3) Propranolol

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Epinephrine

1) Decreases RBF 2) Alpha effect in skeletal

muscle 3) Beta effect in skin,

mucosa 4) Drug of choice for ____

shock 5) May decrease cardiac

output 6) Overdose best treated

with Propranolol

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The initial hemodynamic effects of Dopamine, Phenylephrine,

and Epinephrine include:

1) Increased afterload 2) Increased contractility 3) Increased HR 4) Increased preload

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Adenosine

1) Indicated in atrial flutter 2) A1 receptors mediate SA

node slowing and AV Node conduction

delay 3) Side effects include

flushing, headache, bronchospasm, chest pain, hypotension, and

tachycardia 4) Should be given by slow

IV push