cardiovascular drugs chris g. wherrett, md, frcpc department of anesthesiology ottawa hospital...
TRANSCRIPT
Cardiovascular Drugs
Chris G. Wherrett, MD, FRCPC
Department of Anesthesiology
Ottawa Hospital General Campus
October 11, 2012
2
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
3
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
6
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
7
Metoprolol overdose should be treated with:
1) Atropine
2) Dopamine
3) Isoproterenol
4) Dobutamine
5) Glucagon
6) Ca++
8
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
9
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
10
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
11
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
12
Contra-Indicated in hypertrophic
cardiomyopathy: 1) Nifedipine 2) Propranolol 3) NTG 4) Ephedrine 5) Dobutamine
13
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
14
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
15
Nifedipine:
1) Is contraindicated in hypertensive emergencies
2) Is useful for treatment of hypertension in the PACU
3) Indications
16
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
17
Which Beta Blocker has longest duration of action?
Labetalol Propranolol Nadolol Metoprolol Atenolol Acebutolol Bisoprolol
18
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
19
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
20
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
21
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
22
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
23
Amiodarone:
1) What are indications? 2) What is unique about PK 3) What is IV dosing:
24
Side effects of amiodarone:
1) Thyroid hyperfunction 2) Thyroid hypofunction 3) Bradycardia 4) Pulmonary fibrosis 5) Facial discolouration
25
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
26
Useful drugs in aortic dissection:
1) Beta blockers 2) Nitroprusside 3) Both of above 4) Hydralazine 5) CEBs
27
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
28
Withdrawal syndromes may occur with (1):
1) Diltiazem 2) Beta blockers 3) Clonidine 4) Methyldopa 5) Reserpine 6) ACEIs 7) CEBs
29
Withdrawal syndromes may occur with: (2)
1) Diltiazem 2) Beta blockers 3) Clonidine 4) Methyldopa 5) Reserpine 6) ACEIs 7) CEBs
30
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
31
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?
32
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
33
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
34
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
36
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
37
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
38
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”
39
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
40
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
41
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
42
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
43
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
44
NTG, list clinical indications
1) Approved
2) Off Label
3) Other
45
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
46
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
47
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
48
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
49
Diastolic perfusion time is increased by:
1) Dobutamine 2) Isoproterenol 3) Propranolol
50
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
51
The initial hemodynamic effects of Dopamine, Phenylephrine,
and Epinephrine include:
1) Increased afterload 2) Increased contractility 3) Increased HR 4) Increased preload
52
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