Diuretics and Antiarrhythmics Flashcards
Which of the following correctly describes the mechanism by which thiazide diuretics cause a metabolic alkalosis?
A. Inhibition of intracellular receptor→Decreased ENaC sodium uptake→Reduced negative luminal potential
B. Inhibition of luminal enzyme→Decreased carbonic acid formation→Decreased H+ recycling
C. Inhibition of sodium cotransporter→Decreased potassium backleak→Decreased luminal electropositivity
D. Inhibition of sodium cotransporter→Volume depletion→RAAS activation
D. RAAS. Thiazide diuretics inhibit the NaCl cotransporter, leading to natriuresis and volume depletion. This in turn upregulates the renin-angiotensin-aldosterone system, which increases both Na+/H+ exchange in the proximal tubule and increased distal tubule H+ excretion by H+ ATPase. Ultimately this results in a hypochloremic (contraction) alkalosis.
A physician is discussing starting a patient with Type 2 diabetes on a thiazide for essential hypertension. Which of the following possible side effects would be important to discuss with the patient?
A. Diabetes insipidus
B. Gynecomastia
C. Increased insulin requirement
D. Kidney stones
C. Increase insulin. Thiazide diuretics can cause hyperglycemia, both in patients with diabetes as well as those with insulin resistance, and so an increased dose of insulin may be required. Thiazides also increase total cholesterol and LDL, although this effect is not believed to be durable. While thiazides are effective at improving blood pressure, the other metabolic effects of these medications should be considered before starting a patient on a thiazide.
Thiazides may be prescribed for patients with heart failure and benefit these patients via a number of mechanisms. Which component of the pathology of heart failure is likely to worsen with thiazide use?
A. Afterload
B. Contractility
C. Preload
D. Renin-angiotensin-aldosterone signaling
D. RAAS. By decreasing total plasma volume, thiazides cause activation of the renin-angiotensin-aldosterone system (RAAS). This can lead to hypochloremic (contraction) alkalosis with overuse. Aldosterone receptor blockers such as spironolactone block the downstream signaling of the RAAS pathway.
Chlorthalidone is a thiazide diuretic with a number of metabolic effects which extend beyond its diuretic action. Which of the following is likely to decrease with thiazide use?
A. Lithium clearance
B. Postprandial glucose
C. Serum LDL
D. Serum uric acid
A. Thiazides decrease renal clearance of lithium leading to elevated lithium levels. As a result, thiazides are generally considered a second line treatment for lithium induced diabetes insipidus. Amiloride, a potassium sparing diuretic, is first line for this indication as it blocks lithium reabsorption in the collecting duct and increases lithium clearance.
After taking the nephrology team out for milkshakes, a hospital pharmacist begins to extol the many advantages of thiazide diuretics. The effects of thiazide diuretics on calcium handling may be beneficial in all of the following conditions EXCEPT:
A. Hypoparathyroidism
B. Nephrolithiasis
C. Osteoporosis
D. Sarcoidosis
D. Hypercalcemia in sarcoidosis is due to uncontrolled synthesis of 1,25-dihydroxyvitamin D3 by macrophages, which leads elevated calcium levels. Thiazide diuretics can worsen hypercalcemia by enhancing calcium reabsorption and decreasing calcium excretion.
Which side effect is associated with the prolonged use of loop diuretics?
A. Hypomagnesemia
B. Hyperkalemia
C. Increase in blood pressure
D. Increase in sodium reabsorption
A. Hypomagnesemia is associated with prolonged use of loop diuretics. This generally occurs in patients with insufficient dietary magnesium intake.
What is the mechanism of action of loop diuretics?
A. Inhibition of the Na-Cl cotransporter
B. Inhibition of the Na-K-Cl cotransporter
C. Inhibition of the Na-K ATPase
D. Activation of the Na-K ATPase
B. Loop diuretics (e.g. furosemide) inhibit the Na-K-Cl cotransporter, reducing reabsorption of those ions. This results in greater intraluminal osmotic pressure, leading to diuresis.
Which of the following is NOT a function of loop diuretics?
A. Increasing synthesis of prostaglandins
B. Blocking the NKCC cotransporter
C. Promoting absorption of chloride
D. Inhibiting Mg2+ reabsorption
C. Chloride.
Loop diuretics, such as furosemide, are primarily known for their action in the loop of Henle in the kidneys, where they block the NKCC2 cotransporter (Na+-K+-2Cl− cotransporter) in the thick ascending limb. This blockade leads to decreased reabsorption of Na+, K+, and Cl- ions, which in turn increases the excretion of these ions and water, leading to diuresis. Loop diuretics can also lead to increased excretion of Mg2+, thereby inhibiting Mg2+ reabsorption. Additionally, they can lead to an increase in the synthesis of prostaglandins, which can cause vasodilation and contribute to their diuretic effect.
NSAIDs may reduce the effect of loop diuretics through inhibition of which of the following?
A. Sulfonamide receptor
B. COX-2
C. NKCC cotransporter
D. Sodium-potassium ATPase pump
B. COX-2.
NSAIDS inhibit COX-2, which stops the synthesis of prostaglandins synthesized through the action of loop diuretics. Prostaglandins increase renal blood flow and salt excretion.
Which part of the kidney do loop diuretics act on?
A. Proximal convoluted tubule
B. Descending limb of the loop of Henle
C. Ascending limb of the loop of Henle
D. Distal convoluted tubule
C. Ascending LOH.
Loop diuretics specifically act on the thick ascending limb of the loop of Henle. This region is where sodium chloride is actively reabsorbed, which loop diuretics impede, effectively promoting volume excretion.
What serious side effect can be caused by high doses of loop diuretics?
Ototoxicity.
A patient with newly diagnosed heart failure is started on a number of medications, including an ACE inhibitor, beta blocker, loop diuretic, and eplerenone. The mechanism of action of spironolactone is best described as:
A. Inhibition of a luminal enzyme
B. Inhibition of an apical cotransport protein
C. Inhibition of an apical ion channel
D. Inhibition of an intracellular receptor
D. Spironolactone is a potassium sparing diuretic that antagonizes the mineralocorticoid receptors located in the intracellular space of the principal cells and alpha-intercalated cells of the collecting duct.
A man presents with a headache, fatigue, and hypertension. Lab values demonstrate hypokalemia and metabolic alkalosis, and he is found to have a left adrenal mass on CT. Why might spironolactone be selected to control his symptoms prior to surgery?
A. Aldosterone blocking effect
B. Prevention of pathologic myocyte remodeling
C. Prevention of urinary stones
D. Superior blood pressure control
A. This vignette describes a patient with hypertension, hypokalemia, and an adrenal mass—suspicious for an aldosterone secreting adrenal tumor. These tumors are relatively rare, but tend to be diagnosed late in their course. Spironolactone is a useful medication for patients with this type of malignancy as it blocks the effects of aldosterone.
Class 1A antiarrhythmic drugs can be used in the treatment of which of the following syndromes?
A. Marfan syndrome
B. Long QT syndrome
C. Takotsubo cardiomyopathy
D. Wolff-Parkinson-White syndrome
D. WPW syndrome. Class 1A antiarrhythmic medications, such as quinidine, procainamide, and disopyramide, are particularly useful in treating Wolff-Parkinson-White syndrome. This supraventricular tachycardia involves extra signals traveling through an accessory pathway outside the AV node, and type 1A antiarrhythmics can block conduction through the accessory pathway.
Which class of antiarrhythmic drugs is effective in treating ischemia-induced ventricular arrhythmias?
A. Class 1A
B. Class 1B
C. Class 1C
D. Class 3
B. Class 1B antiarrhythmic drugs, such as lidocaine, phenytoin, and mexiletine, are effective in treating ischemia-induced ventricular arrhythmias. These drugs are more selective for tissues with sodium channels in the open or inactive state and are highly selective for ventricles and the His-Purkinje system.
Which class of antiarrhythmic drugs is contraindicated in patients with a history of structural or ischemic heart disease, particularly post myocardial infarction (MI)?
A. Class 1A
B. Class 1B
C. Class 1C
D. Class 2
C. Class 1C antiarrhythmic drugs, such as flecainide and propafenone, are contraindicated in patients with a history of structural or ischemic heart disease, especially post MI. The prominent use-dependence effects of these drugs can cause a delay in conduction speed that can promote arrhythmias in these patients.
Which class of antiarrhythmic drugs has the strongest binding to sodium channels, exhibiting the highest use dependence and most significant effect on the Phase 0 upstroke?
A. Class 1A
B. Class 1B
C. Class 1C
D. Class 2
C. Class 1C antiarrhythmic drugs bind most strongly to sodium channels, which results in the highest use dependence and the most significant effect on the Phase 0 upstroke of the cardiac action potential. This leads to a drastic slowing of the action potential upstroke and a more dramatic effect on the QRS duration.
Which of the following is a treatment for digoxin toxicity?
A. Idarucizumab antibody fragments
B. Dimercaprol
C. Digoxin-specific antibody fragments
D. Fomepizole
C. Digoxin-specific antibody fragments, also known as Digoxin immune fab, is a treatment for digoxin toxicity.
Which of the following side effects are associated with chronic use of digoxin?
A. Hyperkalemia
B. Arrhythmias
C. Xanthopsia
D. All of the above
D. Chronic use of digoxin is associated with several side effects including hyperkalemia, a variety of arrhythmias, and visual disturbances such as xanthopsia (objects appearing yellow).
Digoxin, a cardiac glycoside, is notable for its action on what cellular structure?
A. Sodium-potassium ATPase
B. Aquaporins
C. ATP-driven calcium pump
D. Proton pump
A. Cardiac glycosides, including digoxin, primarily work through inhibition of the sodium-potassium ATPase at the cell membrane.
Which of the following changes could be seen on an EKG from a chronic digoxin user?
A. T-wave changes
B. QT interval shortening
C. ST depression
D. All of the above
D. All of the above.
Chronic use of digoxin can lead to a variety of EKG changes including T-wave changes, QT interval shortening, and ST depression.
Which of the following exacerbates digoxin toxicity when found in low concentration in the body?
A. Sodium
B. Potassium
C. Calcium
D. Magnesium
B. Potassium.
Hypokalemia, or low potassium levels, can increase the toxicity of digoxin.
Dismayed by her array of daily medications, a 59-year-old woman asks why one pill can’t just do everything. One of her medications is sotalol which exerts its antiarrhythmic effects by two distinct mechanisms. Apart from Class III potassium channel blockade, at what other channel or receptor does sotalol bind?
A. Adenosine receptor
B. Beta-adrenergic receptor
C. Calcium channel
D. Sodium channel
B. Sotalol is a nonselective beta blocker in addition to functioning as a Class III antiarrhythmic. The drug was first approved for ventricular arrhythmias, but like other Class III agents it is also effective in treating supraventricular arrhythmias, such as atrial fibrillation.
A 64-year-old man is discussing starting amiodarone with his doctor for recurrent ventricular tachycardia. What test is important to check before starting this medication?
A. Antinuclear antibodies
B. C-reactive protein and erythrocyte sedimentation rate
C. Thyroid stimulating hormone
D. Uric acid level
C. TSH.
Amiodarone has a very poor side effect profile and affects many organ systems, including the thyroid. Because the drug is approximately 40% iodine by weight, it can cause either hyper- or hypothyroidism. Due to the prominent hepatic and pulmonary toxicity associated with administration, liver function and pulmonary function tests are often checked as well.
