BP/HTN Pharmacology and PKPD

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major categories of antihypertensives

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1

major categories of antihypertensives

  • diuretics

  • block RAAS

  • direct vasodilators

  • sympatholytic agents

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diuretics

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

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3

block RAAS

  • reduces total; vascular resistance

  • may reduce blood volume

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4

direct vasodilators

relaxing vascular smooth muscle → arterial vasodilation

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sympatholytic agents

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

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6

classes of diuretics

  • thiazide diuretics

  • loop diuretics

  • mineralocorticoid (aldosterone) receptor antagonists

  • potassium sparing diuretics

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7

classes that block RAAS

  • ACEi

  • ARB

  • direct renin inhibitors

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8

classes of direct vasodilators

  • calcium channel blockers

  • hydralazine

  • minoxidil

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9

classes of sympatholytic agents

  • beta-blockers

  • clonidine

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10

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

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11

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)

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12

chlorthalidone class

thiazide diuretic

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chlorthalidone brand name

hygroton, thalitone

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14

hydrochlorothiazide class

thiazide diuertic

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15

indapamide class

thiazide diureticin

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16

indapamide brand name

Lozol

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17

metolazone class

thiazide diuretic

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metolazone brand name

Zaroxolyn

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19

thiazide diuretic pearls

not as effective if CrCl < 30 mL/min

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20

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

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furosemide class

loop diuretic

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22

furosemide brand

Lasix

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23

loop diuretic pearls

  • most efficacious diuretic (causes most fluid removal)

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

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torsemide brand

demadex

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25

torsemide class

loop diuretics

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26

bumetanide class

loop diuretic

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27

bumetanide brand

Bumex

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28

ethacrynic acid class

loop diuretic

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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

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spironolactone class

mineralocorticoid receptor antagonist (MRA)

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spironolactone brand

Aldactone, CaroSpir

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eplerenone class

mineralocorticoid receptor antagonist (MRA)

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eplerenone brand

Inspra

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34

mineralocorticoid receptor antagonist (MRA) pearls

minimally efficacious blood pressure control when used as monotherapy

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35

loop diuretic DDI

increased risk of ototoxicity if used with aminoglycosides

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36

mineralocorticoid receptor antagonist (MRA) DDI

eplerenone: strong CYP3A4 inhibitors will increase concentrations

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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

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38

triamterene class

potassium-sparing diuretics

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39

amiloride class

potassium-sparing diuretic

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40

potassium sparing diuretic pearls

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

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41
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