Cardio & Renal Drugs

Question 1

Digoxin

Answer 1

• inhibits the Na/K-ATPase to indirectly inhibit the Na/Ca-exchanger and increase calcium concentration in cardiac myocytes as well as directly stimulating the vagus nerve
• used for the symptomatic treatment of heart failure and as rate control for supraventricular arrhythmias
• toxic effects include GI upset, xanthopsia, heart block, bradycardia, hyperkalemia, scooped ST segments, and a variety of arrhythmias
• toxicity may be exacerbated by hypokalemia or by drugs that inhibit it’s renal excretion, particularly other anti-arrhythmics
• it’s use is contraindicated with beta-blockers given that both prolong AV conduction and can cause heart block

Question 2

Mirlinone

Answer 2

• a phosphodiesterase inhibit that raising cAMP levels in cardiac myocytes to increase inotropy as well as to induce arterial vasodilation, reducing afterload
• used for the treatment of acute heart failure

Question 3

Nesiritide

Answer 3

• a synthetic BNP
• increases cGMP levels to cause arterial and venous dilation, which reduces afterload and preload, respectively
• also inhibits the renin-angiotensin system
• used for the treatment of acute heart failure

Question 4

ACE Inhibitors

Answer 4

• inhibit ACE to prevent activation of angiotensin II and the degradation of bradykinin
• inhibit ATII-driven remodeling to improve mortality in those with past MI or who are suffering from heart failure; also effective in treating hypertension and delay the progression of diabetic nephropathy
• expect a transient, first-dose rise in serum creatinine, which is most dramatic in those with the highest renin levels at initiation
• prolonged elevation of creatinine may indicate acute renal failure and is most likely in those with bilateral renal artery stenosis or who are taking NSAIDs, which both reduce renal blood flow
• orthostatic hypotension with syncope, dry cough, and hyperkalemia are all possible adverse effects
• contraindicated in pregnancy due to teratogenic effects and in those with a C1 esterase inhibitor deficiency (hereditary angioedema)

Question 5

ACE Inhibitors

Answer 5

• a group of drugs ending in the “-pril” suffix
• inhibit ACE to prevent activation of angiotensin II and the degradation of bradykinin
• improve mortality in those with past MI or heart failure by limiting ATII-driven remodeling
• also effective at treating hypertension and delaying the progression of diabetic nephropathy
• a bump in serum creatinine is expected with the first dose and will be most severe in those with the highest pre-treatment renin levels
• a sustained rise in creatinine is indicative of drug-induced acute renal failure and is most likely in those taking NSAIDs or who have bilateral renal artery stenosis
• other adverse effects include orthostatic hypotension and syncope, hyperkalemia, persistent cough, exacerbating of hereditary angioedema, and teratogenesis

Question 6

ARBs

Answer 6

• a group of drugs ending in the “-sartan” suffix
• antagonize the angiotensin II receptor without affecting bradykinin levels
• won’t cause a persistent cough or exacerbate hereditary angioedema but may still cause orthostatic hypotension, syncope, and hyperkalemia

Question 7

Aliskiren

Answer 7

• a direct renin inhibitor
• used in the treatment of hypertension, heart failure, past-MI, or diabetic nephropathy
• may cause hyperkalemia

Question 8

Acetazolamide

Answer 8

• a carbonic anhydrase inhibitor that works as a diuretic in the proximal convoluted tubule to prevent reabsorption of bicarbonate and thus sodium
• not a very potent diuretic; used instead for reducing CSF production and lowering ICP, preventing altitude sickness, and inhibiting aqueous humor production to treat glaucoma
• may cause a sulfa drug reaction, precipitate calcium oxalate stones, cause hypokalemia, or contribute to a type two renal tubular acidosis

Question 9

Mannitol

Answer 9

• an osmotic diuretic
• used in the treatment of glaucoma and to lower intracranial pressure
• initially there is a period of high volume state as fluid is drawn into the ECF; this may cause hyponatremia or fluid overload and exacerbated heart failure
• with extended treatment there may be a volume depleted state with hypernatremia

Question 10

Loop Diuretics

Answer 10

• includes furosemide and the non-sulfa ethacrynic acid
• function by blocking absorption through the NKCC transporter in the ascending limb of the loop of Henle
• also induce expression of COX-2, which produces prostaglandins that promote afferent arteriole dilation and additional salt excretion
• the preferred diuretic for ascites, pulmonary edema, and edema secondary to heart failure; less commonly used for the treatment of hypertension
• may cause hypokalemia as well as hypomagnesemia and hypocalcemia from the lack of potassium ion backflow
• other side effects include contraction alkalosis, ototoxicity, acute interstitial nephritis, hyperuricemia, and sulfa drug reaction

Question 11

Thiazide Diuretics

Answer 11

• function in the DCT by blocking the Na/Cl cotransporter and indirectly activating the basolateral Na/Ca exchanger
• a first-line agent for hypertension and also useful in the treatment of calcium oxalate stones, osteoporosis, heart failure, nephrogenic diabetes insipidous
• may cause hypercalcemia, hypokalemia, hyponatremia, or hyperuricemia
• may also contribute to hyperglycemia, hyperlipidemia, and enhanced lithium toxicity

Question 12

Amiloride

Answer 12

• a potassium-sparing diuretic that functions in the collecting duct by inhibiting ENaC
• useful in the treatment of primary or secondary hyperaldosteronism, lithium-induced diabetes insipidous, Liddle’s syndrome, and heart failure
• adverse effects include hyperkalemia or a type 4 renal tubular acidosis

Question 13

Triamterene

Answer 13

• a potassium-sparing diuretic that functions in the collecting duct by inhibiting ENaC
• useful in the treatment of primary or secondary hyperaldosteronism, Liddle’s syndrome, and heart failure
• adverse effects include hyperkalemia or a type 4 renal tubular acidosis

Question 14

Spironolactone

Answer 14

• a potassium-sparing diuretic that functions in the collecting duct by antagonizing the aldosterone receptor
• useful in the treatment of primary or secondary hyperaldosteronism and as a means to prevent cardiac remodeling and improve mortality in heart failure
• unique in that it blocks 17a-hydroxylase as well as the androgen receptor, thus it can be used to treat PCOD but may be accompanied by impotence or gynecomastia in men
• adverse effects include hyperkalemia or a type 4 renal tubular acidosis

Question 15

Eplerenone

Answer 15

• a potassium-sparing diuretic that functions in the collecting duct by antagonizing the aldosterone receptor
• useful in the treatment of primary or secondary hyperaldosteronism and as a means to prevent cardiac remodeling and improve mortality in heart failure
• adverse effects include hyperkalemia or a type 4 renal tubular acidosis

Question 16

Amiloride

Answer 16

• a potassium-sparing diuretic that works in the collecting tubule by blocking ENaC
• useful in the treatment of primary or secondary hyperaldosteronism, lithium-induced diabetes insipidous, and Liddle’s syndrome
• may cause hyperkalemia or a type 4 tubular acidosis

Question 17

Triamterene

Answer 17

• a potassium-sparing diuretic that works in the collecting tubules by blocking ENaC
• useful in the treatment of primary or secondary hyperaldosteronism, lithium-induced diabetes insipidous, and Liddle’s syndrome
• may cause hyperkalemia or a type 4 tubular acidosis

Question 18

Spironolactone

Answer 18

• a potassium-sparing diuretic that functions in the collecting duct by antagonizing the aldosterone receptor
• improves mortality in those with heart failure by preventing aldosterone-induced remodeling and is useful in the treatment of hyperaldosteronism
• unique in that it blocks 17a-hydroxylase and androgen receptors, thus causing anti-androgenic effects in men such as gynecomastia and impotence
• other side effects include hyperkalemia and type 4 tubular acidosis

Question 19

Eplerenone

Answer 19

• a potassium-sparing diuretic that functions in the collecting duct by antagonizing the aldosterone receptor
• improves mortality in those with heart failure by preventing aldosterone-induced remodeling and is useful in the treatment of hyperaldosteronism
• may cause hyperkalemia or a type 4 tubular acidosis
• more selective than spironolactone and thus less likely to have anti-androgenic effects

Question 20

Class I Anti-Arrhythmics

Answer 20

• bind to and inhibit open or inactive sodium channels on cardiac myocytes, slowing conduction
• cause a widening of the QRS complex
• demonstrate use-dependence and have a stronger effect on more rapidly depolarizing tissues

Question 21

Quinidine

Answer 21

• a class IA anti-arrhythmic
• inhibits inactive and open sodium channels as well as potassium channels, slowing conduction and prolonging repolarization
• demonstrates moderate use-dependence
• useful rate control for supraventricular and ventricular arrhythmias, particularly Wolfe-Parkinson Wright syndrome
• may cause a cinchonism (tinnitus, headache, dizziness), thrombocytopenia, or prolonged QT and torsades de pointe

Question 22

Procainamide

Answer 22

• a class IA anti-arrhythmic
• inhibits inactive and open sodium channels as well as potassium channels, slowing conduction and prolonging repolarization
• demonstrates moderate use-dependence
• useful rate control for supraventricular and ventricular arrhythmias, particularly Wolfe-Parkinson Wright syndrome
• may cause a lupus-like syndrome or prolonged QT and torsades de pointe

Question 23

Disopyramide

Answer 23

• a class IA anti-arrhythmic
• inhibits inactive and open sodium channels as well as potassium channels, slowing conduction and prolonging repolarization
• demonstrates moderate use-dependence
• useful rate control for supraventricular and ventricular arrhythmias, particularly Wolfe-Parkinson Wright syndrome
• has negative inotropic effects and may exacerbate heart failure or induce torsades de pointe

Question 24

Lidocaine

Answer 24

• a class IB anti-arrhythmic
• inhibits inactive and open sodium channels to slow conduction and shortens the time for repolarization
• has low affinity for sodium channels and limited use-dependence
• useful as rhythm control for ischemia-induced ventricular arrhythmias
• may cause neurologic side effects including tremor or paresthesia

Question 25

Phenytoin

Answer 25

• a class IB anti-arrhythmic
• inhibits inactive and open sodium channels to slow conduction and shortens the time for repolarization
• has low affinity for sodium channels and limited use-dependence
• useful as rhythm control for ischemia-induced ventricular arrhythmias
• may cause neurologic side effects including tremor or paresthesia

Question 26

Mexiletine

Answer 26

• a class IB anti-arrhythmic
• inhibits inactive and open sodium channels to slow conduction and shortens the time for repolarization
• has low affinity for sodium channels and limited use-dependence
• useful as rhythm control for ischemia-induced ventricular arrhythmias
• may cause neurologic side effects including paresthesia or tremor

Question 27

Flecainide

Answer 27

• a class IC anti-arrhythmic
• binds to and inhibits open and inactive sodium channels, slowing depolarization, without any affect on potassium channels or rate of repolarization
• has high affinity for sodium channels and strong use-dependence
• excellent rhythm control for atrial flutter and fibrillation but suitable for both ventricular and supraventricular arrhythmias
• should not be used in those with pre-existing structural or ischemic heart disease as it may induce arrhythmias

Question 28

Propafenone

Answer 28

• a class IC anti-arrythmic
• binds to and inhibits open and inactive sodium channels, slowing the rate of conduction, without affecting potassium channels or the rate of repolarization
• has strong affinity for sodium channels and demonstrates strong use-dependence
• excellent rhythm control for atrial flutter and fibrillation but suitable for supraventricular and ventricular arrhythmias
• should not be used in those with pre-existing ischemic or structural heart disease as it may cause arrhythmias

Question 29

Sotalol

Answer 29

• a beta blocker and type III anti-arrhythmic
• functions to inhibit potassium channels and prolong repolarization as well as the refractory period
• useful as rhythm control for both supraventricular and ventricular arrhythmias
• may cause QT prolongation and torsade de pointes

Question 30

Dofetilide

Answer 30

• a class III anti-arrhythmic like others with the suffix “tilide”
• functions by inhibiting potassium channels to prolong repolarization and the refractory period
• useful as rhythm control for both supraventricular and ventricular arrhythmias
• may cause QT prolongation and torsades de pointe

Question 31

Amiodarone

Answer 31

• a class III anti-arrhythmic with class I, II, and IV properties
• primary action is to inhibit potassium current and prolong both repolarization and the refractory period
• useful as rhythm control for supraventricular and ventricular arrhythmias
• may cause neurologic side effects, grey retinal microdeposits, pulmonary fibrosis, hypo- or hyperthyroidism, heart block, heart failure, a blue-gray discoloration of sun-exposed skin, hypersensitivity hepatitis, or CYP inhibition

Question 32

Class IV Anti-Arrhythmics

Answer 32

• non-dihydropyridine CCBs like verapamil and diltiazem
• function to decrease calcium currents at the SA and AV nodes, prolonging phase 4 and effectively slowing pacemaker activity as well as conduction speed
• useful as rate control for supraventricular arrhythmias
• use caution when combining with other potential heart-blocking agents

Question 33

Class II Anti-Arrhythmics

Answer 33

• beta blockers function to inhibit calcium channel currents at the SA and AV nodes, prolonging phase 4 and effectively slowing pacemaker activity and conduction
• useful as rate control for supraventricular arrhythmias
• use caution when combining with other potentially heart-blocking agents

Question 34

Digoxin as an Anti-Arryhtmic

Answer 34

directly stimulates the vagus nerve to provide rate control for atrial fibrillation

Question 35

Magnesium as an Anti-Arrhythmic

Answer 35

useful in the treatment of torsades de pointe

Question 36

Adenosine as an Anti-Arrhythmic

Answer 36

• a purine that activates inhibitory A1 receptors on myocardium and at the SA and AV nodes
• increases the outward potassium current while reducing the inward calcium current
• the first line agent for rate control of supraventricular arrhythmias
• may cause cutaneous flushing, chest pain, shortness of breath, sense of doom, hypotension, and headache
• reverse or inhibit with theophylline

Question 37

Dihydropyridine CCBs

Answer 37

• a group of drugs ending in “-dipine”
• block L-type calcium channels in smooth muscle, reducing afterload and improving coronary perfusion
• useful in the treatment hypertension and hypertensive emergency, Raynaud’s phenomenon, and stable and unstable angina
• nimodipine, in particular, can be used to prevent or treat vasospasm in the days/weeks following subarachnoid hemorrhage
• nifedipine is useful for treating hypertension in pregnancy but may cause a profound hypotension and reflex tachycardia, worsening myocardial ischemia in those with pre-existing MI or unstable angina
• all dihydropyridine CCBs carry a risk for edema, reflex tachycardia, lightheadedness, and headache

Question 38

Non-Dihydropyridine CCBs

Answer 38

• verapamil has more cardio selectivity than diltiazem
• both act on cardiac myocytes and in the SA and AV nodes to reduce heart rate, inotropy, and oxygen demand
• useful in the treatment of hypertension and angina, as rate control for supraventricular arrhythmias, and for migraine prophylaxis
• may cause constipation or heart block and can worsen heart failure

Question 39

Treatment of Benign Hypertension

Answer 39

• CCBs and thiazide diuretics are preferred for primary hypertension in the elderly and in African Americans
• ACE inhibitors are preferred in those with diabetes, prior MI, or heart failure
• two agents should be used for initial therapy in those with BP > 150/90

Question 40

Treating Hypertensive Emergency

Answer 40

• hypertensive urgency is a BP > 180/120 and hypertensive emergency is that with signs of organ damage or failure
• IV beta blockers such as esmolol and metoprolol are suitable therapy, as is labetolol
• IV dihydropyridine CCBs like clevidipine and nicardipine cause vasodilation and reduce afterload
• hydralazine is a direct vasodilator used to treat hypertensive emergency in pregnant women but may cause reflex tachycardia and worsen angina, so it is often co-administered with a beta-blocker
• hydralazine can also be combined with nitrates, which provides a survival benefit in those with heart failure
• nitroprusside is a nitrate that increases cGMP to cause arterial and venous dilation, but may cause cyanide toxicity
• fenoldopam is a D1 agonist that induces a cAMP cascade to cause arteriolar vasodilation while improving coronary and renal perfusion

Question 41

Hydralazine

Answer 41

• a direct arteriolar vasodilator
• useful in the treatment of both hypertensive emergency and in women who are pregnant
• may cause a reflex tachycardia, so it is often co-administered with a beta-blocker
• can also be co-administered with a nitrate, providing a mortality benefit to those with heart failure
• may cause a lupus-like syndrome