Diuretics for HTN

classifications

-osmotic

-carbonic anhydrous inhibitors

-loop

-thiazides

-potassium-sparing 

natriuretic diuretics

-sodium loss

-carbonic anhydrous inhibitors

-loop

-thiazides

-potassium-sparing

loop diuretics

-furosemide, torsemide, bumetanide

thiazide diuretics

-hydrochlorothiazide, chlorothiazide, indapamide

potassium-sparing diuretics

-triamterene, amiloride

-spironolactone, eplerenone

common MOA 

-increased excretion of Na and Cl 

-decreased blood volume and venous return 

diuretic where blood volume returns to baseline but TPR decreases and maintains BP

-thiazide diuretics

clinical uses

-HTN

-heart failure

-edema

site of action - thick ascending loop of henle (TAL)

-actively reabsorbs Na, K and 2Cl

-loop diuretics 

sites of action - distal convoluted tubule (DCT)

-actively reabsorbs Na, Cl

sites of action - collecting ducts/tubules (CT)

-Na is exchanged for K

-regulated by aldosterone and ADH

MOA - loop diuretics 

-blocks Na/K/2Cl symport in TAL 

-rapid onset 

clinical uses - loop diuretics

-reserved for resistant HTN or edema following vasodilator therapy

-preferred in mod-severe heart failure

MOA - thiazides

-blocks Na/Cl symport in DCT

-Na, Cl, K excretion

diuretic effect - loop diuretics 

-high efficacy 

diuretic effect - thiazide

-mild-moderate efficacy

-combination with loop diuretics = synergistic effect

clinical uses - thiazides

-preferred first line therapy for HTN

-adjunct therapy for heart failure and edema

-beneficial in osteoporosis

common ADEs - loop and thiazides 

-fluid/electrolyte imbalance 

-Gi distress (nausea, vomiting, anorexia) 

-allergic reactions (rash, photosensitivity) 

fluid/electrolyte imbalances in loop and thiazides

-increased Na, K, Cl loss = hyponatremia, hypokalemia, hypochloremia

-decreased extracellular fluid volume = hypovolemia/dehydration, hypotension

-increased uric acid reabsorption = hyperuricemia

ADEs - loop diuretics

-increased Ca excretion (hypocalcemia)

-reversible ototoxicity

ADEs - thiazides 

-decreased Ca excretion = hypercalcemia 

-increased glucose = hyperglycemia

-dyslipidemia (high doses)

-ED (high doses) 

drug interactions - loop and thiazides

-digoxin = arrhythmias, nausea, visual disturbances

-NSAIDs = decreased diuretic and antihypertensive efficacy

potassium-sparing diuretics subclasses

-renal sodium channel blockers

-mineralocorticoid receptor antagonists

renal sodium channel blockers 

-amiloride 

-triamterene 

mineralocorticoid receptor antagonists

-spironolactone

-eplerenone

-finerenone

common MOA - potassium-sparing

-promote sodium excretion while causing K retention in collecting duct

diuretic effect - potassium-sparing 

-weak efficacy 

-combination with loop/thiazides = reduced K loss 

clinical uses - potassium-sparing

-not for HTN monotherapy

-MRAs = primary and secondary aldosteronism

primary and secondary aldosteronism

-heart failure, liver cirrhosis, nephrotic syndrome

MOA - renal sodium channel blockers 

-block Na channels in collecting duct 

-direct inhibition of Na reabsorption (prevents Na/K exchange = K loss) 

ADEs - renal sodium channel blockers (triamterene)

-kidney stones

ADEs - renal sodium channel blockers (amiloride)

-GI upset (nausea, vomiting, diarrhea)

MOA - MRA 

-blocks aldosterone receptors in collecting duct 

-indirect promotion of Na excretion and K retention 

ADEs - MRA (spironolactone)

-blocks androgen receptors (increases estrogen)

-males = gynecomastia, decreased libido, ED 

-females = menstrual irregularities, breast tenderness 

ADEs - MRA (eplerenone)

-lower affinity for androgen/progesterone receptors

-fewer hormonal s/e

drug interactions - potassium-sparing

-potassium supplements (hyperkalemia)

-RAAS inhibitors (ACE inhibitors, angiotensin receptor blockers, renin inhibitors0

-renal impairment

vasodilators classifications 

-venous 

-mixed 

-arterial 

venous vasodilators

-nitrates

mixed vasodilators

-a1 blockers

-ACE ihibitors

-Ang-II receptor blockers (ARBs)

-renin inhibitors

-calcium channel blockers (CCBs)

-nitroprusside

arterial vasodilators 

-minoxodil 

-hydralazine 

MOA - arterial vasodilators

-relaxation of arterioles, decreases afterload via decreased artiolar tone

MOA - hydralazine

-direct relaxation of arteriolar smooth muscle

-partially via NO release from endothelium

-partially via decreased Ca release

unique features - hydralazine 

-metabolized via acetylation (slow acetylators increases plasma levels 

MOA - minoxidil

-opens K channels in smooth muscle cells

-increased K efflux

-decreases arteriolar tone

unique features - minoxidil

-more potent than hydralazine

-reserved for severe/resistant HTN

-stimulates hair growth via increased blood flow to follicles

clinical uses - arterial vasodilators 

-mod-severe HTN 

-avoid in HTN with ischemic heart disease 

clinical uses - minoxidil

-alopecia

ADEs - hydralazine, minoxidil

-hypotension

-reflex tachycardia

-Na/fluid retention, edema

-headache

-flushing

clinical pearl - arterial vasodilators 

-always use with B blocker + diuretic 

-hydralazine = lupus-like symptoms 

-minoxidil = hypertrichosis