Cardiac Pharmacology Pearls
Cardioselective beta-blockers act on beta-1 more than beta-2 and thus will not trigger or worsen asthma as much as non-cardioselective beta-blockers.
Carvedilol and labetalol are non-selective beta-blockers that also block alpha-1 receptors.
Propranolol and metoprolol are lipid soluble beta-blockers and can be used to treat anxiety, migraine headaches, tremor and stage fright.
The antidote for beta-blocker overdose is glucagon and inotropes (ie, dobutamine).
Alpha blockers can cause severe first-dose hypotension potentially resulting in syncope; thus, alpha blockers are frequently given at night before bedtime.
ACE inhibitors can cause angioedema, which may be life-threatening, though it is rare.
ACE inhibitors can cause hyperkalemia and renal failure. ACE inhibitors should be stopped if the creatinine increases to > 2.5 and/or the potassium to > 5.5.
ACE inhibitors can cause a dry cough thought to be related to the inhibition of bradykinin breakdown (resulting in bradykinin accumulation).
Angiotensin receptor blockers (ARBs) are the preferred drug in patients who are unable to tolerate ACE inhibitors due to a cough.
The dihydropyridine calcium channel blocker amlodipine has been shown to be safe in the setting of systolic heart failure.
Non-dihydropyridine calcium channel blockers must be used cautiously in patients with systolic heart failure due to their negative inotropic effects.
Amiodarone can cause liver failure (monitor liver function tests), either hyperthyroidism or hypothyroidism (monitor thyroid function tests) and pulmonary fibrosis (monitor pulmonary function tests).
Amiodarone can cause “blue man syndrome,” resulting in bluish discoloration of the skin.
Amiodarone intravenously can cause dramatic hypotension due to the solvents used in the drug preparation.
Amiodarone can cause ocular problems, including sudden blindness on rare occasions.
Amiodarone and dofetilide are the only two antiarrhythmic drugs safe to use in the setting of left ventricular systolic dysfunction.
Amiodarone is only FDA approved for the treatment of ventricular tachycardia and not atrial fibrillation, although it is commonly used for this indication.
Dronedarone is similar to amiodarone, but without the iodine component. This results in less toxicity, however, somewhat less efficacy.
Procainamide is used in the setting of Wolff-Parkinson-White syndrome and atrial fibrillation.
Procainamide and hydralazine can cause drug-induced lupus erythematosus, which can be diagnosed by measuring anti-histone antibodies.
Quinidine can cause cinchonism.
Disopyramide is used to treat vagally mediated atrial fibrillation and hypertrophic obstructive cardiomyopathy.
Disopyramide has strong anti-cholinergic properties.
Lidocaine toxicity can cause seizures and is used intravenously only for the treatment of ventricular arrhythmias.
Mexiletine is an orally available class 1B antiarrhythmic drug similar to lidocaine and can be used to treat ventricular tachycardia.
Sotalol has beta-blocker properties, can be used to treat atrial fibrillation and/or ventricular tachycardia, and can prolong the QT interval.
Sotalol must be initiated in the inpatient setting in individuals at high risk for QT prolongation to monitor the QT interval and for proarrhythmia.
Sotalol exhibits “reverse use-dependence,” meaning at faster heart rates (when potassium channels are being used more), the antiarrhythmic effect is less. The antiarrhythmic effect is greater when heart rates are slow.
Flecainide and propafenone (class IC antiarrhythmic drugs) must be used with an AV blocking drug (beta-blocker or non-dihydropyridine calcium channel blocker) in order to prevent 1:1 conduction of atrial flutter, which can be life-threatening.
Hydralazine can cause a reflex tachycardia; thus, an AV-blocking drug should be used simultaneously.
Minoxidil is a direct arterial vasodilator like hydralazine used in medicine to treat hypertension; however, it is also used over the counter to promote hair growth (Rogaine).
The combination of hydralazine and a long-acting nitrate (isosorbide mononitrate or isosorbide dinitrate) has similar hemodynamic effects compared to ACE inhibitors (reduced afterload by hydralazine and reduced preload by nitrates). This combination is used in the setting of systolic heart failure when ACE inhibitors and ARBs are not able to be tolerated.
Tachyphylaxis (tolerance) can occur with nitrates when used 24 hours/day; thus, they are recommended for intermittent use. For example, nitroglycerine patches are put on in the morning and taken off in the evening to allow a nitrate-free period.
Nitrates are contraindicated within 24 hours of sildenafil or 48 hours of vardenafil/tadalafil due to severe hypotension that can occur with the combination.
Eplerenone is an aldosterone antagonist (like spironolactone) that almost never causes gynecomastia, unlike other drugs in this drug class category.
Digoxin toxicity presents with nausea, vomiting, abdominal pain, visual disturbances and symptoms of arrhythmia.
Digoxin toxicity can cause any arrhythmia except rapidly conducted atrial arrhythmias (like atrial flutter with a fast ventricular response).
Three typical digoxin toxic rhythms are: atrial fibrillation with a slow ventricular response, atrial tachycardia with 2:1 block and bidirectional ventricular tachycardia.
Hypokalemia and hypercalcemia potentiate digoxin toxicity.
Since digoxin acts by blockage of the sodium/potassium ATPase pump, digoxin toxicity can result in hyperkalemia.
Calcium should not be given intravenously when the potassium is high related to digoxin toxicity, as this theoretically could cause serious arrhythmia, since hypercalcemia potentiates the actions of digoxin (end-point of digoxin mechanism is opening Ca channels allowing increased Ca influx, this IV calcium markedly would increase Ca influx). There is little evidence to support this theory.
Digoxin toxicity can cause “xanthopsia” or yellowing of the vision, which the artist Vincent Van Gogh was thought to suffer from toward the end of his life. He was using foxglove to treat a seizure disorder.
The only three beta-blockers FDA approved to treat systolic heart failure are metoprolol succinate (not metoprolol tartrate), carvedilol and bisoprolol.
Ticlopidine was shown to cause thrombotic thrombocytopenic purpura (TTP) and thus is not used to a large extent any further.
Prasugrel (Brilinta, AstraZeneca) is contraindicated in patients with a prior transient ischemic attack (TIA) or stroke.
Apixaban (Eliquis, Bristol Myers Squibb/Pfizer) , a Factor Xa inhibitor, showed superiority in a head-to-head trial against warfarin in patients with atrial fibrillation in regard to stroke prevention and mortality. Apixaban is indicated to reduce risk for stroke and systemic embolism in patients with nonvalvular atrial fibrillation, to prevent deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients undergoing hip or knee replacement surgery, to treat DVT and PE and to reduce risk for recurrent DVT and PE.
Dabigatran is an orally available direct thrombin inhibitor indicatted to reduce risk for stroke and systemic embolism in nonvalvular atrial fibrillation and can cause significant GI upset. It is also indicated to treat deep vein thrombosis and pulmonary embolism in patients treated with a parenteral anticoagulant for 5 to 10 days, to reduce risk for recurrent DVT and PE in previously treated patients and to prevent DVT and PE in patients having hip replacement surgery.
Rivaroxaban (Pradaxa, Boehringer Ingelheim) is a Factor Xa inhibitor indicated to reduce risk for stroke and systemic embolism in patients with nonvalvular atrial fibrillation, to treat deep vein thrombosis (DVT) and pulmonary embolism (PE), to prevent recurrent DVT and PE, to prevent DVT in patients undergoing knee or hip replacement surgery and to prevent new DVT or PE in acutely mentally ill patients. It is also indicated to reduce risk for cardiovascular events in patients with coronary artery disease and peripheral artery disease.
Exodaban (Savaysa, Daiichi Sankyo) is a Factor Xa inhibitor indicated to reduce risk for stroke and systemic embolism in patients with nonvalvular atrial fibrillation provided they do not have creatinine clearance > 95 mL/min. It is also indicated for treatment of deep vein thrombosis and pulmonary embolism after 5 to 10 days of therapy with a parenteral anticoagulant.
Thiazide diuretics can cause hyponatremia, hypokalemia and sun sensitivity.
Nesiritide is a b-type natriuretic peptide (BNP) analog which is used intravenously in acute decompensated heart failure.
Ivabradine is a hyperpolarization-activated cyclic nucleotide-gated channel blocker used to treat patients with heart failure and ejection fraction 35% or less when their heart rate is at least 70 beats per minute (clinical benefit shown in this subgroup).
Sacubitril/valsartan (Entresto, Novartis) is an angiotensin receptor/neprilysin inhibitor indicated to reduce risk for cardiovascular death and heart failure hospitalization in patients with chronic heart failure, with benefits shown most strongly in patients with ejection fraction lower than normal.
Rosuvastatin has the greatest LDL reduction and HDL raising of the HMG-CoA reductase inhibitors.
There is evidence that pravastatin may be the safest HMG-CoA reductase inhibitor in the setting of liver disease.
The rate of liver failure in patients taking HMG-CoA reductase inhibitors is the same as the rate of liver failure in patients not taking HMG-CoA reductase inhibitors.
HMG-CoA reductase inhibitors have been loosely associated with increased risk for diabetes, proteinuria and memory loss.
Lovastatin interacts with cyclosporine (raises levels) and for this reason was historically used in transplant patients in order to reduce the dose of cyclosporine needed (due to the high cost of cyclosporine).
HMG-CoA reductase inhibitors (statins) frequently cause myalgias (muscle aches), but rarely cause rhabdomyolysis (about 1.5 in 100,000). There is evidence that some myalgias are caused by the “nocebo effect” as opposed to statins themselves.
The first HMG-CoA reductase inhibitor discovered was mevastatin in the fungus Penicillium citrinum; however, it caused liver cancer in lab animals. Lovastatin was then isolated from Aspergillus terrus. The in vivo actions of these drugs are thought to be antibacterial (like penicillin), creating interest in research into possible infectious etiologies to the atherosclerotic properties.
Using coenzyme Q10 and replacing vitamin D in those deficient has been thought to potentially help reduce statin-induced myalgias.