Cardiovascular Drugs Flashcards
Primary HTN Treatment
thiazide diuretics, ACE inhibitors, angiotensin II receptor blockers (ARBs), dihydropyridine Ca2+ channel blockers
HTN with heart failure Treatment
Diuretics, ACE inhibitors/ARBs, Beta blockers (compensated HF), aldosterone antagonists
Heart failure and beta blockers caution
beta blockers must be used cautiously in decompensated HF and are contraindicated in cardiogenic shock
HTN with Diabetes Mellitus Treatment
ACE inhibitors/ARBs, Ca2+ channel blockers, thiazide diuretics, beta blockers
ACEI/ARBs and DM
protective against diabetic nephropathy
HTN in pregnancy treatment
Hydralazine, labetalol, methyldopa, nifedipine
Name the dihydropyridine Ca2+ channel blockers
“-dipine) amlodipine, clevidipine, nicardipine, nifedipine, nimodipine
Site of action of dihydropyridines
act on vascular smooth muscle amlodipine = nifedipine > diltiazem > verapamil
Name the non-dihydropyridines
diltiazem, verapamil
Site of action of the non-dihydropyridines
act on the heart verapamil > diltiazem > amlodipine = nifedipine Verapamil = ventricle
Mechanism of Ca2+ channel blockers
block voltage-dependent L-type Ca2+ channels of cardiac and smooth muscle –> decreased contractility
Use of dihydropyridines (except nimodipine)
hypertension, angina (including Prinzmetal), Raynaud phenomenon
Use of nimodipine
subarachnoid hemorrhage (prevents cerebral vasospasm)
Use of clevidipine
Hypertensive urgency or emergency
Use of non-dihydropyridines
hypertension, angina, atrial fibrillation/flutter
Mechanism of hydralazine
increase cGMP –> smooth muscle relaxation vasodilates arterioles > veins reduces afterload
Use of hydralazine
severe HTN (particularly acute, HF (with organic nitrate) safe to use in pregnancy frequently co-administered with beta-blocker to prevent reflex tachycardia
Toxicity of hydralazine
compensatory tachycardia (contraindicated in angina/CAD), fluid retention, headache, angina Lupus like syndrome
Drugs to use in hypertensive emergency
Clevidipine (DHP Ca2+ channel blocker) Fenoldopam (D1 receptor agonist) Labetalol (beta blocker) Nicardipine (DHP Ca2+ channel blocker) Nitroprusside
Mechanism of nitroprusside
short acting to increase cGMP via direct release of NO
Toxicity of nitroprusside
can cause cyanide toxicity (release cyanide)
Mechanism of fenoldopam
Dopamine D1 receptor agonist - causes coronary, peripheral, renal and splanchnic vasodilation Decreases BP and causes a natriuresis
Name the nitrates
nitroglycerin, isosorbide dinitrate, isosorbide mononitrate
Mechanism of nitrates
vasodilate by increasing NO in vascular smooth muscle –> increase in cGMP and smooth muscle relaxation dilates veins >> arteries decreases preload
Use of nitrates
angina, acute coronary syndrome, pulmonary edema
Toxicity of nitrates
reflex tachycardia (treat with beta-blockers to prevent), hypotension, flushing, headache “Monday Disease” in industrial exposure
What is “Monday Disease”?
development of tolerance for the vasodilating action during the work week and loss of tolerance over the weekend –> tachycardia, dizziness, headache upon reexposure
Goal of antianginal therapy
reduce myocardial O2 consumption (MVO2) by decreasing 1 or more of these determinants: end-diastolic volume, BP, HR, or contractility
Nitrate effect on end-diastolic volume
decreases
Nitrate effect on blood pressure
decreases
Nitrate effect on contractility
NO EFFECT
Nitrate effect on heart rate
increase (reflex response) - give with beta blocker
Nitrate effect on ejection time
decreases
Nitrate effect on MVO2
decreases
Beta-blocker effect on end-diastolic volume
no effect or decrease slightly
Beta-blocker effect on blood pressure
decreases
Beta-blocker effect on contractility
decreases
Beta-blocker effect on heart rate
decreases
Beta-blocker effect on ejection time
increases
Beta-blocker effect on MVO2
decreases
Combined effect of nitrates and beta-blockers on end-diastolic volume
no effect or decrease
Combined effect of nitrates and beta-blockers on blood pressure
decreases
Combined effect of nitrates and beta-blockers on contracility
little/no effect
Combined effect of nitrates and beta-blockers on heart rate
no effect or decrease
Combined effect of nitrates and beta-blockers on ejection time
little/no effect
Combined effect of nitrates and beta-blockers on MVO2
decreases greatly
What is digoxin?
a cardiac glycoside
Mechanism of digoxin
direct inhibition of Na/K ATPase –> indirect inhibition of Na/Ca exchange increased Ca –> positive inotropy stimulates the vagus nerve –> decreased HR
Use of digoxin
HF (to increase contractility); atrial fibrillation (to decrease conduction at AV node and depression of SA node)
Toxicity of digoxin
Cholinergic - nausea, vomiting, diarrhea, blurry yellow vision, arrhythmias, AV block can lead to hyperkalemia –> poor prognosis
Factors predisposing to digoxin toxicity
renal failure (decreased excretion) hypokalemia (permissive for digoxin binding at K+ binding site on Na/K ATPase) Verapamil, amiodarone Quinidine (decrease digoxin clearance; displaces digoxin from tissue binding sites)
Antidote to digoxin
Anti-digoxin Fab fragments, slowly normalize K+, cardiac pacer, Mg2+
Pharmacokinetic properties of class I antiarrhythmics
slow or block conduction (especially in depolarized cells) decrease slope of phase 0 depolarization are state dependent (selectively depress tissue that is frequently depolarized - e.g. tachycardial)
Name the class IA antiarrhythmics
Block sodium channels Quinidine, Procainamide, Disopyramide
Mechanism of class IA antiarrhythmics
increase AP duration increase effective refractory period (ERP) in ventricular action potential increase QT interval
Use of class IA antiarrhythmics
both atrial and ventricular arrhythmias especially reentrant and ectopic SVT and VT
Toxicity of class IA antiarrhythmics
Cinchonism (headache, tinnitus with quinidine) Reversible SLE-like syndrome (procainamide) Heart failure (disopyramide) Thrombocytopenia, torsades de pointes due to increased QT interval
Mechanism of class IB antiarrhythmics
decrease AP duration preferentially affect ischemic or depolarized Purkinje and ventricular tissue phenytoin can also fall into the IB category
Name the class IB antiarrhythmics
Lidocaine, Mexiletine
Use of class IB antiarrhythmics
acute ventricular arrhythmias (especially post-MI), digitalis induced arrhythmias IB is Best post-MI
Toxicity of class IB antiarrhythmics
CNS stimulation/depression, cardiovascular depression
Name the class IC antiarrhythmics
Flecainide, Propafenone
Mechanism of class IC antiarrhythmics
significantly prolongs ERP in AV node and accessory bypass tracts no effect on ERP in Purkinje and ventricular tissue minimal effect on AP duration
Use of class IC antiarrhythmics
SVTs, including atrial fibrillation only as a last resort in refractory VT
Toxicity of class IC antiarrhythmics
PROARRHYTHMIC, especially post-MI (contraindicated) IC is CONTRAINDICATED in structural and ischemic heart disease
What is site of action of class I antiarrhythmics?
Block Na channels
What is site of action of class II antiarrhythmics?
Beta-blockers
Name the class II antiarrhythmics
metoprolol, propranolol, esmolol (very short acting), atenolol, timolol, carvedilol
Mechanism of class II antiarrhythmics
decrease SA and AV nodal activity by decreasing cAMP, decreasing Ca2+ currents suppress abnormal pacemakers by decreasing slope of phase 4 AV node particularly sensitive –> increased PR interval
Use of class II antiarrhythmics
SVT, ventricular rate control for atrial fibrillation and atrial flutter
Toxicity of class II antiarrhythmics
Impotence Exacerbation of COPD and asthma Cardiovascular side effects (bradycardia, AV block, HF) CNS effects (sedation, sleep alteration) - may mask signs of hypoglycemia
Specific toxicity of metoprolol
causes dyslipidemia
Specific toxicity of propranolol
can exacerbate vasospasm in Prinzmetal angina
Careful with beta-blockers given alone
Beta-blockers cause unopposed alpha-agonism esp if given alone for pheochromocytoma or cocaine toxicity
Treatment for beta-blocker overdose
saline, atropine and glucagon
What is the site of action of class III antiarrhythmics?
block K+ channels
Name the class III antiarrhythmics
amiodarone, ibutilide, dofetilide, sotolol
Mechanism of class III antiarrhythmics
increase AP duration, increase ERP, increase QT interval
Use of class III antiarrhythmics
atrial fibrillation, atrial flutter; ventricular tachycardia (amiodarone and sotolol)
Toxicity of sotolol
torsades de pointes, excessive beta blockade
Toxicity of ibutilide
torsades de pointes
Toxicity of amiodarone
pulmonary fibrosis hepatotoxicity hypothyroidism/hyperthyroidism (40% iodine by weight) acts as hapten (corneal deposits, blue/gray skin deposits resulting in photodermatitis) neurologic effects constipation cardiovascular effects (bradycardia, heart block, HF)
Special note about amiodarone
lipophilic and has class I, II, III and IV effects
Labs needed when using amiodarone
monitor PFTs, LFTs and TFTs when using this drug
What is site of action of class IV antiarrhythmics?
block Ca2+ channels
Name the class IV antiarrhythmics
diltiazem and verapamil (Non-DHP)
Mechanism of class IV antiarrhythmics
decrease conduction velocity, increase ERP, increase PR interval
Use of class IV antiarrhythmics
prevention of nodal arrhythmia (e.g. SVT), rate control in atrial fibrillation
Toxicity of class IV antiarrhythmics
constipation, flushing, edema, cardiovascular effects (HF, AV block, sinus node depression)
Mechanism of adenosine
increase K+ out of cells –> hyperpolarizing the cell and decreasing Ica
Use of adenosine
drug of choice in diagnosing/abolishing supraventricular tachycardia
Pharmacokinetics of adenosince
very short acting (~15 seconds) effects blunted by theophylline and caffeine (both are adenosine receptor antagonists)
Side effects of adenosine
flushing, hypotension, chest pain, sense of impending doom, bronchospasm
Use of Mg2+
effective in torsades des pointes and digoxin toxicity
