Cardiac Pharm from FA (and UWorld questions) Flashcards
Digoxin: what does it directly inhibit?
what does this cause?
cardiac myocyte Na/K ATPase.
causes increased intracellular Na, which causes increased intracellular Ca due to loss of Na/Ca co-transporter activity.
generally, what are the 2 effects of Digoxin?
- increases intracellular Ca -> increases inotropy
- stimulates vagus nerve -> decreases HR
2 clinical uses for digoxin?
- CHF (because it will increase contractility)
- afib (because it will decrease conduction at the AV node and depress the SA node) -> incr diastolic filling time.
digoxin - toxicity?
Cholinergic toxocity ie nausea, vomiting, diarrhea, blurry yellow vision/yellow-green halos (think Van Gogh)
digoxin: changes to ECG?
increase PR, decrease QT, ST scooping, T wave inversion, arrythmia, AV block
Digoxin: what factors predispose patients to toxicity?
- renal failure
- hypokalemia (K and Dig compete for the same binding site)
- verapamil (Ca channel blocker)
- amiodarone (K channel blocker)
- quinidine (decreased digoxin clearance; displaces digoxin from tissue-binding sites)
Digoxin: antidote?
what not to do?
- slowly normalize K levels
- cardiac pacer
- anti-digoxin Fab fragments
- Mg2+
- DO NOT give calcium gluconate to patients with hyperK in setting of digoxin toxicity
Digoxin: class?
cardiac glycoside
aka digitalis
found in Foxglove plant in so many suburban gardens.
Big picture: what are the types of anti-arrhythmic drugs? (4 classes + misc)
- Class I: Na channel blockers (IA, IB, IC)
- Class II: Beta-blockers
- Class III: K channel blockers
- Class IV: Ca channel blockers
Other: Adenosine (kicks K out of cells) and Mg2+ (for Torsades and Digoxin toxicity)
Which classes of anti-arrhythmics cause QT prolongation?
IA (Na blockers)
III (K blockers)
Of the 4 Class III (K+ channel blocking) antiarrhythmics, which one also has beta-blocking ability?
Name the 4 K blocker anti-arrhythmics
- Sotalol (causes bradycardia)
- Class III (K+ channel blockers) = Amidarone, Ibutilide, Dofetilide, Sotalol
“AIDS” (can give you Kaposi’s Sarcoma — K association to remember the AIDS anti-arrhy drugs?!?)
what do beta blockers do?
slow the heart rate, lower contractility by blocking AV nodal activity.
slow Phase 4 depolarization.
Of the 2 Class IV antiarrhythmics, which is more cardioselective?
Verapamil is more cardioselective than Diltiazem.
(these are Ca blockers)
both will cause slight decr in BP due to some action on peripheral vasculature
what is the mech of action for Aspirin?
If a pt is allergic to aspirin, what is a possible alternative for a patient with angina?
Irreversibly inhibits COX1 and COX2 (by acetylation). (–>prevents synth of thromboxane A2 and prostaglandins)
Platelets can’t synth new cyclo-oxygenase enzyme so effect lasts until new platelets come on the scene.
One alternative = Clopidogrel - Irreversibly blocks ADP receptors on platelets -> inhibits platelet aggregation.
Aspirin and Clopidogrel are equally effective in prevention of thrombo-embolic disease.
Aspirin and Clopidogrel: synergistic effect? why/not?
Yes
because they have different mechanisms.
if you need to restore blood flow emergently post-MI or cerebrovascular incident, what is a possible drug to use?
Streptokinase
Thrombolytic agent
3 types of hypertension that are treated with different drug classes?
- Primary/essential HTN
- HTN with CHF
- HTN with diabetes
what classes of drugs are used to treat primary/essential HTN?
diuretics, ACE inhibitors/ARBs, Ca channel blockers
what classes of drugs are used to treat HTN with CHF?
Diuretics, ACE inhibitors, ARBs, beta-blockers, aldosterone antagonists
what classes of drugs are used to treat HTN with diabetes?
ACE inhibitors/ARBs, Ca channel blockers, diuretics, beta blockers, alpha blockers
for HTN with CHF, what drug do we use with caution in decompensated CHF? when is this drug contraindicated?
for decompensated CHF use beta blockers cautiously
they are contraindicated with cardiogenic shock
what drugs are protective against diabetic nephropathy?
ACE inhibitors/ARBs
what class of drugs prevents remodeling of the heart that may result from chronic HTN?
ACE inhibitors
MOA of Ca channel blockers? effect?
blocks voltage-dependent L type Ca channels on cardiac and smooth muscle.
effect = reduce muscle contractility
name the 5 Ca channel blockers
which are dihydropyridines and which are not?
Amlodipine
Nimodipine
Nifedipine
Diltiazem
Verapamil
ANN = dihydropyridines
D/V = non-dihydropyridines
of the Ca channel blockers, which are most effective on vascular smooth muscle?
Amlodipine and Nifedepine
of the Ca channel blockers, which are most effective on heart?
Verapamil, then Diltiazem (the non-dihydropyridines)
“Verapamil -> Ventricle”
Amlodipine and Nifedipine: Clinical use?
Ca channel blockers
Use = HTN, angina (including Prinzmetal), Raynaud’s
Nimodipine: clinical use?
Ca channel blocker
Use = subarachnoid hemorrhage. Prevents cerebral vasospasm.
Diltiazem, Verapamil: clinical use?
Ca channel blockers
HTN, angina, afib/atrial flutter
Calcium channel blockers: tox?
Cardiac depression, AV block, peripheral edema, flushing, dizziness, hyperprolactinemia, constipation
Hydralazine: class?
anti-hypertensive
Hydralazine: clinical use?
severe HTN, CHF.
First line for HTN with pregnancy (along with methyldopa).
Coadministered with a beta blocker to prevent reflex tachycardia.
Hydralazine: tox?
compensatory tachycardia, fluid retention, nausea, HA, angina, lupus-like syndrome
Hydralazine: contraindication?
in angina/CAD
due to compensatory tachycardia.
commonly used drugs in a hypertensive emergency? (5)
- nitroprusside
- nicardipine
- clevidipine
- labetolol
- fenoldopam
Nitroprusside: use?
mech? tox?
Used in hypertensive emergency
Mech: increases cGMP via direct release of NO. Short-acting.
Tox = releases cyanide (CN-, binds cytochrome C oxidase and stops cellular respiration)
Fenoldopam: use?
mech? tox?
used in hypertensive emergency.
Mech: Dopamine D1 receptor agonist. Vasodilates coronary, peripheral, renal, splanchnics.
Decr BP and incr naturiuresis.
Nitroglycerin, Isosorbide dinitrate
Mech?
Vasodilation
incr NO in vascular smooth muscle -> incr cGMP -> smooth muscle relaxation.
Dilates veins >>> arteries.
Decr preload.
Nitroglycerin, Isosorbide dinitrate
Use?
Angina, coronary artery syndrome, pulm edema
what is Monday Disease?
Secondary to industrial exposure: develop tolerance for Nitroglycerin/isosorbide dinitrate during the workweek (tolerance to vasodilating action). Then lose tolerance over weekend.
Monday re-exposure results in tachycardia, dizziness, headache.
Nitroglycerin/isosorbide dinitrate: tox?
Monday disease
Reflex tachy, hypotension, flushing, headache
Revlex tachycardia due to Nitroglycerin/isosorbide dinitrate: treatment?
beta blockers
what is the goal of antianginal therapy?
Reduce myocardial O2 consumption by decreasing 1 or more of these:
- end-diastolic volume
- blood pressure
- HR
- contractility
Nitrates affect Preload or Afterload?
effect on:
EDV?
BP?
contractility?
HR?
Ejection time?
MVO2?
Nitrates affect Preload
EDV? DECR
BP? DECR
contractility? INCR (reflex)
HR? INCR (reflex)
Ejection time? DECR
MVO2? DECR
Beta blockers affect Preload or Afterload?
EDV?
BP?
contractility?
HR?
Ejection time?
MVO2?
Beta blockers affect Afterload
EDV? INCR
BP? DECR
contractility? DECR
HR? DECR
Ejection time? INCR
MVO2? DECR
Nitrates + beta blockers together - effect on:
EDV?
BP?
contractility?
HR?
Ejection time?
MVO2?
EDV? no effect
BP? DECR
contractility? no effect
HR? DECR
Ejection time? no effect
MVO2? DECR A LOT
(ie everything is either decreased or no effect)
what are 2 partial beta agonists that are contraindicated in angina?
- Pindolol
- Acebutolol
Nifedipine
effect is more similar to nitrates or beta blockers?
Nitrates
Verapamil
effect is more similar to nitrates or beta blockers?
Beta blockers
5 categories of lipid-lowering agents?
- HMG-CoA reductase inhibitors
- Niacin
- Bile acid resins
- Cholesterol absorption blockers
- Fibrates
what are the 5 HMG-CoA reductase inhibitors listed?
(unless there are differences between them, probably just need to know -STATINS)
Lovastatin
Pravastatin
Simpastatin
Atorvastatin
Rosuvastatin
HMG-CoA reductase inhibitors: Mechanism of action?
Inhibit conversion of HMG-CoA to mevalonate (which is a cholesterol precursor)
(remember that HMG-CoA is kind of in the middle between Acetyl-CoA/TCA, cholesterol synth, and ketone synthesis)
Statins: effect on LDL? HDL? TAGs?
LDL: decrease dramatically
HDL: increase
TAGs: decrease
Niacin: effect on LDL? HDL? TAGs?
LDL: decr
HDL: incr (niacin = best for this)
TAGs: decr
Bile Acid resins: effect on LDL? HDL? TAGs?
LDL: decr
HDL: incr (slight)
TAGs: incr (slight)
Cholesterol absorption blockers: effect on LDL? HDL? TAGs?
LDL: decr
HDL: no effect
TAGs: no effect
Fibrates: effect on LDL? HDL? TAGs?
LDL: decr
HDL: incr
TAGs: decrease A LOT (best for this)
Statins: SEs?
- Hepatotoxicity (increases LFTs)
- Rhabdomyolysis (esp when used with fibrates and niacin)
Niacin: Mech?
Inhibits lipolysis in adipose tissue
Reduces hepatic VLDL synthesis
Niacin: SEs?
- Red flushed face (will decrease with aspirin or long term use)
- Hyperglycemia (acanthosis nigricans)
- Hyperuricemia (exacerbates gout)
Bile acid resins: Mech?
Prevent intestinal re-absorption of bile acids
->liver must use more cholesterol to make more
Bile acid resins: SEs?
Patients hate these: they taste bad and they cause GI discomfort
also decr absorption of fat-sol vitamins
Ezetimibe: Mech?
Directly prevents chol absorption at the small intestine brush border
Ezetimibe: SEs?
- increased LFTs (rarely)
- diarrhea
Fibrates: mech?
- Upregulate LPL to increase clearance of TAGs from bloodstream
- Activates PPAR-alpha to induce HDL synthesis
Fibrates: SEs?
- Myositis (increased risk with concurrent statins)
- Hepatotoxicity (increases LFTs)
- Cholesterol gallstones (esp with concurrent bile acid resins)
Anti-arrhythmics Class IA, IB, IC (Na channel blockers)
Mech?
- Slow/block conduction, esp of depolarized cells.
- Decrease slope of Phase 0 depolarization, increase threshold for firing in abmornal pacemaker cells.
- State-dependent: they selectively depress tissue that is more frequently depolarized (eg in tachycardia)
Anti-arrhythmics Class IA, IB, IC (Na channel blockers)
what causes increased toxicity for all Class I drugs?
hyperkalemia
Class IA drugs: name them (3)?
Quinidine
Procainamide
Disopyramide
“The Queen Proclaims Diso’s pyramid”
Class IA drugs (Quinidine, Procainamide, Disopyramide)
Mech (specific to IA)?
General Class I mech: slows/blocks conduction, decr slope of Phase 0 depol, incr threshold for firing in abnl pacemaker cells.
Class IA:
- Incr AP duration
- Incr effective refractory period (ERP)
- Incr QT interval
Class IA (Quinidine, Procainamide, Disopyramide): clinical use?
Atrial arrhythmia
Ventricular arrhythmia
Esp re-entrant and ectopic SVT and VT
Class IA (Quinidine, Procainamide, Disopyramide): Tox?
Cinchonism (HA, tinnitus with quinidine), thrombocytopenia, torsades de pointes due to incr QT interval
Procainamide: Reversible SLE-like syndrome
Disopyramide: heart failure
Class IB drugs: name them (2)
- Lidocaine
- Mexiletine
- Phenytoin can also fall into this category
Class IB drugs (Lidocaine, Mexiletine): Mech?
Decr AP duraction
Preferentially affect ischemic or depol Purkinje and ventricular tissue.
Class IB drugs (Lidocaine, Mexiletine): Clinical Use?
- Acute ventricular arrhythmia, esp post-MI. (B is BEST post-MI)
- Digitalis-induced arrhythmias
Class IB drugs (Lidocaine, Mexiletine): Tox?
CNS stimulation/depression
CV depression
Class IC drugs: name them (2)
Flecainide
Propafenone
“Can I have Fries Please”
Class IC (Flecainide, Propafenone): Mech?
- Significantly prolongs refractory period in AV node
- Minimal effect on AP duration
Class IC (Flecainide, Propafenone): Clinical Use?
- SVTs, including afib.
- Last resort in refractory VT
Class IC (Flecainide, Propafenone): Tox?
Contraindications?
- Pro-arrhythmic
- Contraindicated Post-MI
“IC is Contraindicated in structural and ischemic heart disease”
Class II (beta blockers) name them (6)
- Metoprolol
- Propranolol
- Esmolol
- Atenolol
- Timolol
- Carvedilol
- Note labetalol is NOT a beta blocker (used for hypertensive emergency)
Beta blockers: Mech?
- Decrease SA and AV nodal activity by decr cAMP, decr Ca currents
- Suppress abnormal pacemaker cells by decr slope of Phase 4 depolarization
- AV node is particularly sensitive -> increased PR interval
Which beta blocker is very short acting?
Esmolol
Beta blockers: Clinical Use?
- SVT
- Slowing ventricular rate during afib and atrial flutter
Beta blockers: Tox?
Impotence
Exacerbation of COPD and asthma
CV effects (bradycardia, AV block, CHF)
CNS effects (sleep, sedation)
May mask signs of hypoglycemia
Beta blockers: Contraindication?
Trmt for OD?
CI in cocaine users
because of risk of unopposed alpha-adrenergic receptor agonist activity.
OD: give glucagon.
Toxicity specific to Metoprolol?
Dyslipidemia
Toxicity specific to Propranolol?
Exacerbation of vasospasm in Prinzmetal angina
Class III (K channel blockers) name 4
- Amiodarone
- Ibutilide
- Dofetilide
- Sotalol
“AIDS”
Class III K channel blockers (Amiodarone, Ibutilide, Dofetilide, Sotalol): mech?
Incr AP duration
Incr ERP
Incr QT interval
Used when other anti-arrhythmics fail!
Class III K channel blockers (Amiodarone, Ibutilide, Dofetilide, Sotalol): Use?
Afib
Atrial flutter
Amiodarone and Sotalol: ventricular tachycardia
Sotalol: toxicity?
torsades de pointes
excessive beta blockade
Ibutilide: tox?
torsades de points
Amiodarone: tox?
what labs should we check when using amidarone?
- pulmonary fibrosis
- hepatotoxicity
- hypothyroidism/hyperthyroidism (amiodarone is 40% iodine)
- corneal deposits
- skin deposits (blue/gray) –> photodermatitis
- neuro effects
- constipation
- CV effects (bradycardia, heart block, CHF)
- LABS: check PFTs, LFTs, TFTs
- Amiodarone has Class I, II, III, IV effects and alters the lipid membrane
Class IV antiarrhythmics (Ca channel blockers) name them (2)
Verapamil
Diltiazem
Ca channel blockers (Verapamil, Diltiazem): mech?
- Decr conduction velocity
- Incr ERP
- Incr PR interval
Ca channel blockers (Verapamil, Diltiazem): Clinical Use?
- Prevention of nodal arrhythmias (ie SVT)
- rate control in afib
Ca channel blockers (Verapamil, Diltiazem): tox?
- constipation
- flushing
- edema
- CV effects (CHF, AV block, sinus node depression)
Adenosine: class? Mech?
Misc antiarrhythmic
Increases K+ outflow -> cell hyperpolarizes -> intracellular Ca decreases
Adenosine: Use?
Tox?
what blocks its effects?
Use: drug of choice in diagnosing/aboloshing superventricular tachycardia. Very short acting (15 sec)
Tox: flusing, hypotension, chest pain
Blocked by theophylline (bronchodilator) and caffeine
Mg2+: class? Use?
- Misc anti-arrhythmic
- Used in torsades de pointes, digoxin toxocity
