cardiology pharmacology

Question 1

Primary (essential) hypertension

Answer 1

1. Thiazide diuretics,
2. ACE inhibitors,
3. angiotensin II receptor blockers (ARBs),
4. dihydropyridine Ca2+ channel blockers

Question 2

Hypertension with heart failure

Answer 2

1. Diuretics,
2. ACE inhibitors/ARBs,
3. β-blockers (compensated HF),
4. aldosterone antagonists.

β-blockers must be used cautiously in decompensated HF and are contraindicated in cardiogenic shock.

In HF, ARBs may be combined with the neprilysin inhibitor sacubitril.

Question 3

Hypertension with diabetes mellitus

Answer 3

1. ACE inhibitors/ARBs,
2. Ca2+ channel blockers,
3. thiazide diuretics,
4. β-blockers.

ACE inhibitors/ARBs are protective against diabetic nephropathy.

Beta-blockers can mask hypoglycemia so use with caution

Question 4

Hypertension in asthma

Answer 4

1. ARBs,
2. Ca2+ channel blockers,
3. thiazide diuretics,
4. cardioselective β-blockers.

Avoid nonselective β-blockers to prevent β2-receptor–induced bronchoconstriction.

Avoid ACE inhibitors to prevent confusion between drug or asthma-related cough

Question 5

Hypertension in pregnancy

Answer 5

1. Hydralazine
2. labetalol
3. methyldopa
4. nifedipine

Question 6

Calcium channel blockers

Amlodipine,

clevidipine,

nicardipine,

nifedipine,

nimodipine (dihydropyridines, act on vascular smooth muscle);

diltiazem,

verapamil (non-dihydropyridines, act on heart).

Answer 6

MECHANISM Block voltage-dependent L-type calcium channels** of cardiac and smooth muscle –> **decrease muscle contractility.

Vascular smooth muscle—amlodipine = nifedipine > diltiazem > verapamil.

Heart—verapamil > diltiazem > amlodipine = nifedipine (verapamil = ventricle).

CLINICAL USE Dihydropyridines (except nimodipine): hypertension, angina (including Prinzmetal), Raynaud phenomenon.

Nimodipine: subarachnoid hemorrhage (prevents cerebral vasospasm).

Nicardipine, clevidipine: hypertensive urgency or emergency.

Non-dihydropyridines: hypertension, angina, atrial fibrillation/flutter.

ADVERSE EFFECTS Non-dihydropyridine: cardiac depression, AV block, hyperprolactinemia, constipation, gingival hyperplasia.

Dihydropyridine: peripheral edema, flushing, dizziness.

Question 7

Hydralazine

Answer 7

MECHANISM increased cGMP –> smooth muscle relaxation.

Vasodilates arterioles > veins; afterload reduction.

CLINICAL USE Severe hypertension (particularly acute), HF (with organic nitrate). Safe to use during pregnancy. Frequently coadministered with a β-blocker to prevent reflex tachycardia.

ADVERSE EFFECTS Compensatory tachycardia (contraindicated in angina/CAD), fluid retention, headache, angina. SLE-like syndrome.

Question 8

Hypertensive emergency

Treat with clevidipine, fenoldopam, labetalol, nicardipine, or nitroprusside

Nitroprusside Short acting; increase cGMP via direct release of NO. Can cause cyanide toxicity (releases cyanide).

Fenoldopam: Dopamine D1 receptor agonist—coronary, peripheral, renal, and splanchnic vasodilation. decrease BP, increase natriuresis.

Also used postoperatively as an antihypertensive. Can cause hypotension and tachycardia.

Question 9

Nitrates

Nitroglycerin,

isosorbide dinitrate,

isosorbide mononitrate

MECHANISM Vasodilate by increased NO in vascular smooth muscle –> increased in cGMP and smooth muscle relaxation. Dilate veins >> arteries. decreased preload.

CLINICAL USE Angina, acute coronary syndrome, pulmonary edema.

ADVERSE EFFECTS Reflex tachycardia (treat with β-blockers), hypotension, flushing, headache, “Monday disease” in industrial exposure: development of tolerance for the vasodilating action during the work week and loss of tolerance over the weekend –> tachycardia, dizziness, headache upon re-exposure.

Contraindicated in right ventricular infarction.

Question 10

antianginal therapy

Goal is reduction of myocardial O2 consumption (MVO2) by decreased 1 or more of the determinants of MVO2: end-diastolic volume, BP, HR, contractility.

end-diastolic volume-

1. nitrates decreases,

2. beta-blockers have no effect or increased,

3. nitrates + beta-blockers: no effects or decrease

blood pressure: decreased nitrates, beta-blockers, nitrate + beta-blockers

contractility:

1. nitrates: no effect,

2. beta-blockers: decreased,

3. nitrates + beta-blockers: little/no effect

HR:

1. nitrates: increased (reflex response),

2. decreased beta-blockers

3. no effect or decrease if given nitrates + beta-blocker

Ejection time:

nitrates decreased,

beta-blockers increase,

nitrates + beta-blockers (little/no effect)

MVO2: decreased nitrates, beta-blockers, nitrates + beta-blockers

verapamil is similar to beta-blockers in effect

pindolol and acebutolol are partial beta-agonists that should be used with caution in angina

Question 11

MECHANISM Inhibits the late phase of sodium current thereby reducing diastolic wall tension and oxygen consumption. Does not affect heart rate or contractility.

CLINICAL USE: Angina refractory to other medical therapies.

ADVERSE EFFECTS Constipation, dizziness, headache, nausea, QT prolongation.

Question 12

Milrinone

MECHANISM: Selective PDE-3 inhibitor.

In cardiomyocytes: increased cAMP accumulation –> increased Ca2+ influx–> increased inotropy and chronotropy.

In vascular smooth muscle: increase cAMP accumulation –> inhibition of MLCK activity –> general vasodilation.

CLINICAL USE Short-term use in acute decompensated HF.

ADVERSE EFFECTS Arrhythmias, hypotension.

Question 13

MOA: prevents degradation of natriuretic peptide, angiotension 2, and substance P by neprilysin

Clinical use: used in combination with ARB (alsartan) for treatment of HFrEF

Adverse effects: Hypotension, hyperkalemia, cough, dizziness; contraindicated with ACE inhibitors due to angioedema

Question 14

HMG-CoA reductase inhibitors (eg, lovastatin, pravastatin)-decrease LDL and triglycerides, increased HDL.

MOA: inhibit conversion of HMG-CoA to mevalonate, a cholesterol precursor; decreased mortality in CAD patients

adverse effect/problems: hepatotoxicity (increase LFTs), myopathy (when used with fibrates or niacin)

Question 15

Bile acid resins: Cholestyramine, colestipol, colesevelam

LDL decreased, HDL, triglyceride increased. MOA: Prevent intestinal reabsorption of bile acids; liver must use cholesterol to make more

GI upset, decreased absorption of other drugs and fat-soluble vitamins

Question 16

Ezetimibe

LDL decreased, HDL increase, triglyceride decrease

MOA: Prevent cholesterol absorption at small intestine brush border

adverse effect: Rare increased LFTs (liver function test), diarrhea

Question 17

Fibrates: Gemfibrozil, bezafibrate, fenofibrate

LDL decreased, HDL increase, TAG decrease

MOA: Upregulate LPL –> increased TG clearance Activates PPAR-α to induce HDL synthesis

adverse effect: Myopathy (increased risk with statins), cholesterol gallstones (via inhibition of cholesterol 7α-hydroxylase

Question 18

Niacin (vitamin B3)

LDL decrease, HDL increased, TG decreased

MOA: Inhibits lipolysis (hormonesensitive lipase) in adipose tissue; reduces hepatic VLDL synthesis

adverse effects: Red, flushed face, which is decreased by NSAIDs or long-term use Hyperglycemia,

Hyperuricemia

Question 19

PCSK9 inhibitors: Alirocumab, evolocumab

LDL decrease, HDL increased, TG decreased

MOA: Inactivation of LDL-receptor degradation, increasing amount of LDL removed from bloodstream

Adverse effect: Myalgias, delirium, dementia, other neurocognitive effects

Question 20

LDL and HDL slight increased

TG decrease at high doses

MOA: decrease FFA delivery to liver and decrease activity of TG-synthesizing enzymes

Adverse effects: nausea, fish-like taste

Question 21

cardiac glycosides (Digoxin)

MECHANISM Direct inhibition of Na+/K+ ATPase –> indirect inhibition of Na+/Ca2+ exchanger. increase [Ca2+] i –> positive inotropy. Stimulates vagus nerve –> decrease HR.

CLINICAL USE HF (increased contractility); atrial fibrillation (decrease conduction at AV node and depression of SA node).

ADVERSE EFFECTS Cholinergic—nausea, vomiting, diarrhea, blurry yellow vision (think van Gogh), arrhythmias, AV block.

Can lead to hyperkalemia, which indicates poor prognosis.

Factors predisposing to toxicity: renal failure (decreased excretion), hypokalemia (permissive for digoxin binding at K+-binding site on Na+/K+ ATPase), drugs that displace digoxin from tissue-binding sites, and decrease clearance (eg, verapamil, amiodarone, quinidine).

ANTIDOTE Slowly normalize K+, cardiac pacer, anti-digoxin Fab fragments, Mg2+.

Question 22

Slow or block (decreased) conduction (especially in depolarized cells). decreased slope of phase 0 depolarization. Are state dependent (selectively depress tissue that is frequently depolarized [eg, tachycardia]).

Class IA

Quinidine, Procainamide, Disopyramide. “The Queen Proclaims Diso’s pyramid.”

MECHANISM increased AP duration, increase effective refractory period (ERP) in ventricular action potential, increase QT interval, some potassium channel blocking effects.

CLINICAL USE Both atrial and ventricular arrhythmias, especially re-entrant and ectopic SVT and VT.

ADVERSE EFFECTS Cinchonism (headache, tinnitus with quinidine), reversible SLE-like syndrome (procainamide), HF (disopyramide),

thrombocytopenia, torsades de pointes due to increase QT interval.

Question 23

Class IB

Lidocaine, Mexiletine. “I’d Buy Liddy’s Mexican Tacos.”

MECHANISM decrease AP duration. Preferentially affect ischemic or depolarized Purkinje and ventricular tissue. Phenytoin can also fall into the IB category.

CLINICAL USE Acute ventricular arrhythmias (especially postMI), digitalis-induced arrhythmias. IB is Best post-MI

ADVERSE EFFECTS CNS stimulation/depression, cardiovascular depression

Question 24

Class IC

Flecainide, Propafenone. “Can I have Fries, Please.”

MECHANISM Significantly prolongs ERP in AV node and accessory bypass tracts. No effect on ERP in Purkinje and ventricular tissue. Minimal effect on AP duration

CLINICAL USE SVTs, including atrial fibrillation. Only as a last resort in refractory VT

ADVERSE EFFECTS Proarrhythmic, especially post-MI (contraindicated). IC is Contraindicated in structural and ischemic heart disease.

Question 25

Antiarrhythmics— β-blockers (class II)

Metoprolol, propranolol, esmolol, atenolol, timolol, carvedilol.

MECHANISM Decrease SA and AV nodal activity by decrease cAMP, decrease Ca2+ currents. Suppress abnormal pacemakers by decrease slope of phase 4. AV node particularly sensitive—increased PR interval. Esmolol very short acting.

CLINICAL USE SVT, ventricular rate control for atrial fibrillation and atrial flutter.

ADVERSE EFFECTS Impotence, exacerbation of COPD and asthma,

cardiovascular effects (bradycardia, AV block, HF)

CNS effects (sedation, sleep alterations). May mask the signs of hypoglycemia.

Metoprolol can cause dyslipidemia.

Propranolol can exacerbate vasospasm in Prinzmetal angina.

β-blockers (except the nonselective α- and β-antagonists carvedilol and labetalol) cause unopposed α1-agonism if given alone for pheochromocytoma or cocaine toxicity.

Treat β-blocker overdose with saline, atropine, glucagon.

Question 26

Antiarrhythmics— potassium channel blockers (class III)

Amiodarone, Ibutilide, Dofetilide, Sotalol

MECHANISM increased AP duration, increased ERP, increased QT interval.

CLINICAL USE Atrial fibrillation, atrial flutter; ventricular tachycardia (amiodarone, sotalol).

ADVERSE EFFECTS

Sotalol—torsades de pointes, excessive β blockade.

Ibutilide—torsades de pointes.

Amiodarone—pulmonary fibrosis, hepatotoxicity, hypothyroidism or hyperthyroidism (amiodarone is 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)

Remember to check PFTs, LFTs, and TFTs when using amiodarone. Amiodarone is lipophilic and has class I, II, III, and IV effects.

Question 27

Antiarrhythmics— calcium channel blockers (class IV)

Verapamil, diltiazem

MECHANISM decrease conduction velocity, increase ERP, increase PR interval.

CLINICAL USE Prevention of nodal arrhythmias (eg, SVT), rate control in atrial fibrillation.

ADVERSE EFFECTS Constipation, flushing, edema, cardiovascular effects (HF, AV block, sinus node depression).

Question 28

Adenosine

increased K+ out of cells –> hyperpolarizing the cell and decreased I_Ca, decreasing AV node conduction.

Drug of choice in diagnosing/terminating certain forms of SVT.

Very short acting (~ 15 sec). Effects blunted by theophylline and caffeine (both are adenosine receptor antagonists).

Adverse effects include flushing, hypotension, chest pain, sense of impending doom, bronchospasm.

Question 29

Mg2+

Effective in torsades de pointes and digoxin toxicity

Question 30

Ivabradine

MECHANISM Selective inhibition of funny sodium channels (If ), prolonging slow depolarization phase (phase 4). decrease SA node firing; negative chronotropic effect without inotropy. Reduces cardiac O2 requirement.

CLINICAL USE Chronic stable angina in patients who cannot take β-blockers. Chronic HF with reduced ejection fraction.

ADVERSE EFFECTS Luminous phenomena-phosphene-a ring or spot of light produced by pressure on the eyeball or direct stimulation of the visual system other than by light./visual brightness, hypertension, bradycardia.