Pharmacology of Diuretics and Digoxin

Adverse Effects of Loop and Thiazide Diuretics

• Hyponatremia, hypochloremia, dehydration, hypotension, hypokalemia, and ototoxicity
• Hyperglycemia, hyperuricemia, reduced HDL, and increased LDL

Adverse Effects of Spironolactone

• Hyperkalemia, deep voice, impotence, menstrual irregularities, and hirsutism

Identifying Adverse Effects

• Monitor patients for signs of ototoxicity, dehydration, hypo- or hyperkalemia, and hypotension

Digoxin

• MOA: treats CHF and dysrhythmias, increases myocardial contraction force, and alters eclectic activity of the heart
• AE/CI: digoxin-induced dysrhythmias, narrow therapeutic window, hypokalemia, and many interactions

Amiodarone

• MOA: delays repolarization and prolongs action potential
• Use: life-threatening dysrhythmias (a fib, v tach, v fib)
• CI: 2nd and 3rd degree HB, sick sinus syndrome
• AE: lung damage, visual impairment, thyroid toxicity, optic neuropathy, photosensitivity, bradycardia, and hypotension

Beta-Blockers

• CI: hypotension, sick sinus syndrome, 2nd or 3rd degree HB, and grapefruit juice
• Note: grapefruit juice can intensify effects of beta blockers

Calcium Channel Blockers

• Verapamil can be used in infants
• Diltiazem (Cardizem)
• Nifedipine (Procardia) 10-20 mg IR and 30-60 mg ER
• Reflex effects occur primarily with the immediate-release (IR) formulation, not with the slow-release (SR) formulation

Renin-Angiotensin-Aldosterone System (RAAS)

• Decreased perfusion pressure in the afferent arteriole stimulates the secretion of renin by juxtaglomerular cells.
• Renin reacts with angiotensin in the liver to make Angiotensin I, which converts to Angiotensin II in the lungs.
• Angiotensin II causes vasoconstriction in blood vessels and becomes Angiotensin III in the adrenal cortex, stimulating aldosterone release.
• Aldosterone increases Na and water reabsorption by kidney tubules, leading to increased blood volume and blood pressure (BP).

Calcium Channel Blockers (CCBs)

• Prevent calcium ions from entering cells, affecting the heart, blood vessels, and vascular smooth muscle (VSM).
• Prevent contraction and lead to vasodilation.
• Similar effect on the heart as Beta blockers, reducing heart contractile force, heart rate (HR), and suppressing conduction through the AV node.

Specific CCBs

• Verapamil: can be used in infants.
• Diltiazem (Cardizem): no specific notes.
• Nifedipine (Procardia): 10-20 mg IR and 30-60 mg ER formulations available.
• Reflex effects occur primarily with the immediate-release (IR) formulation, not with the slow-release (SR) formulation.

Contraindications and Interactions

• Hypotension, sick sinus syndrome, 2nd or 3rd degree HB, and grapefruit juice can intensify the effects of Beta blockers.

Diuretics and Renal Impairment

• Furosemide (loop diuretic) is the preferred diuretic in patients with low GFR (renal impairment).
• Low potassium levels can increase the risk of heart arrhythmia when taking diuretics.

Patient Education for Furosemide

• Monitor blood pressure and watch for signs and symptoms of postural hypotension (stand slowly to avoid).
• Eat potassium-rich foods (dried fruit, nuts, spinach, potatoes).

Contraindications and Interactions with Furosemide

• Avoid prescribing digoxin, NSAIDS, antihypertensive drugs, and lithium with furosemide.

Loop Diuretics vs. Thiazide Diuretics

• Loop diuretics (e.g., furosemide) work by inhibiting sodium and chloride reabsorption in the loop of Henle, leading to a significant increase in urine production.
• Thiazide diuretics act on the distal convoluted tubule, inhibiting sodium reabsorption to a lesser extent, resulting in a moderate increase in urine output.

Hydrochlorothiazide (Microzide)

• Not suitable for patients with inadequate renal functioning (GFR below 30).
• Diuresis starts in 2 hours and peaks 4-6 hours.
• Monitor blood pressure, heart rate, weight, and signs and symptoms of hypokalemia and gout before prescribing.

Spironolactone (Aldactone)

• Potassium-sparing diuretic.
• Produces a modest increase in urine and a substantial decrease in potassium excretion.
• Often used alongside other diuretics to counteract potassium loss.
• Main reason for prescription: to counteract potassium loss caused by thiazide and loop diuretics.
• Adverse effects: hyperkalemia, gynecomastia, menstrual irregularities, impotence, hirsutism, and deep voice.
• Can cause tumors in rats; avoid unnecessary use.

Triamterene (Dyrenium)

• Potassium-sparing diuretic.
• Works by disrupting the sodium and potassium exchange, resulting in decreased sodium absorption and reduced potassium secretion.
• Not suitable for patients with elevated potassium levels.
• Starts working in a few hours.

ACE Inhibitors and ARBs

• ACE inhibitors (e.g., Lisinopril) are preferred over ARBs due to their proven ability to decrease cardiovascular morbidity and mortality.
• Adverse effects: angioedema, renal failure, and fetal harm.
• Losartan (Cozaar) is an example of an ARB.

Aliskiren (Tekturna)

• Direct renin inhibitor (DRI).
• MOA: inhibits the conversion of angiotensinogen into angiotensin I, suppressing the entire RAAS.
• Adverse effects: cough, hyperkalemia, diarrhea, and fetal injury and death.
• Important education: high-fat meals and grapefruit juice decrease absorption and lower effect.

Eplerenone (Inspra)

• Potassium-sparing aldosterone antagonist.
• MOA: selective blockade of aldosterone receptors, promoting retention of K and increased secretion of Na and water, reducing blood volume and BP.
• Current recommendation guidelines: add to standard HF therapy only in patients with persistent symptoms despite adequate treatment with an ACEI and a β blocker.
• Contraindications: K supplements, K-sparing diuretics, elevated K levels, and impaired renal function.