BP/HTN Pharmacology and PKPD

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major categories of antihypertensives

• diuretics

• block RAAS

• direct vasodilators

• sympatholytic agents

diuretics

lower BP by depleting the body of sodium and reducing blood volume

block RAAS

• reduces total; vascular resistance

• may reduce blood volume

direct vasodilators

relaxing vascular smooth muscle → arterial vasodilation

sympatholytic agents

decrease BP by decreasing sympathetic input and/or increase parasympathetic input

classes of diuretics

• thiazide diuretics

• loop diuretics

• mineralocorticoid (aldosterone) receptor antagonists

• potassium sparing diuretics

classes that block RAAS

• ACEi

• ARB

• direct renin inhibitors

classes of direct vasodilators

• calcium channel blockers

• hydralazine

• minoxidil

classes of sympatholytic agents

• beta-blockers

• clonidine

diuretics

• can lower BP up to 10-15 mmHg in most patients

• can be used as monotherapy for mild hypertension, but often used in combination with other agents

thiazide diuretics MOA

increases sodium (and therefore water) and chloride excretion by blocking reabsorption in the distal convoluted tubule of the nephron by blocking the Na+/Cl- transporter (NCC)

chlorthalidone class

thiazide diuretic

chlorthalidone brand name

hygroton, thalitone

hydrochlorothiazide class

thiazide diuertic

indapamide class

thiazide diureticin

indapamide brand name

Lozol

metolazone class

thiazide diuretic

metolazone brand name

Zaroxolyn

thiazide diuretic pearls

not as effective if CrCl < 30 mL/min

loop diuretic MOA

actively secreted via the nonspecific organic acid transport system into the lumen of the thick ascending limb of Henle’s loop, where is decreases sodium reabsorption by competing for the chloride site on the Na+K+2Cl- cotransporter

furosemide class

loop diuretic

furosemide brand

Lasix

loop diuretic pearls

• most efficacious diuretic (causes most fluid removal)

• BBW: potent diuretic, at high doses can lead to profound fluid and electrolyte loss

torsemide brand

demadex

torsemide class

loop diuretics

bumetanide class

loop diuretic

bumetanide brand

Bumex

ethacrynic acid class

loop diuretic

mineralocorticoid receptor antagonist (MRA) MOA

competes with aldosterone for receptor sites in the distal renal tubules, increasing sodium chloride and water excretion while conserving potassium and hydrogen ions; may block the effect of aldosterone on arteriolar smooth muscle as well

spironolactone class

mineralocorticoid receptor antagonist (MRA)

spironolactone brand

Aldactone, CaroSpir

eplerenone class

mineralocorticoid receptor antagonist (MRA)

eplerenone brand

Inspra

mineralocorticoid receptor antagonist (MRA) pearls

minimally efficacious blood pressure control when used as monotherapy

loop diuretic DDI

increased risk of ototoxicity if used with aminoglycosides

mineralocorticoid receptor antagonist (MRA) DDI

eplerenone: strong CYP3A4 inhibitors will increase concentrations

potassium sparing diuretic MOA

competitive inhibition of epithelial sodium channel (ENaC) in the collecting duct of the nephron → decrease sodium reabsorption and increase potassium reabsorption

triamterene class

potassium-sparing diuretics

amiloride class

potassium-sparing diuretic

potassium sparing diuretic pearls

almost always in a combination tablet to decrease rates of hypokalemia with thiazide diuretics