Ch 28: Hypertension

pathophysiology of hypertension

activation of SNS and RASS = increase neurohormone levels = increase BP

what drugs can increase sympathomimetic activity to increase blood pressure

• ADHD drugs (ie amphetamine, methylphenidate)

• Decongestants (ie pseudoephedrine, phenylephrine)

• recreational substances

• antidepressants (TCAs, SNRIs, MAOIs)

what drugs can increase blood viscosity to increase blood pressure

erythropoiesis-stimulating agents (ie epoetin alfa)

what drugs can increase sodium and water retention and increase blood pressure

• NSAIDs

• immunosuppressants (ie cyclosporine)

• systemic steroids

what drugs can increase blood pressure thru other mechanisms

• oral contraceptives (with higher estrogen content)

• VEGF inhibitors (ie bevacizumab, sunitinib)

what is a HTN diagnosis based on

an average of at least 2 readings taken on at least 2 separate occasions

normal BP

SBP <120 and DBP <80

elevated BP

SBP 120-129 and DBP <80

stage 1 hypertension

SBP 130-139

OR

DBP 80-89

stage 2 hypertension

SBP >140
OR

DBP >90

recommended sodium intake in diet

<1500 - 2300mg daily

what are common natural medicines patients may use to lower blood pressure but may increase their bleeding risk

garlic and fish oil

when to start treatment for HTN

• stage 1 HTN and any of the following: (clinical CVD/diabetes/CKD, 10 ASCVD risk score >7.5%, does not meet goal after 3-6 months of lifestyle change)

• stage 2 HTN

initial drug selection for HTN treatment

• thiazide diuretic

• DHP CCB

• ACE or ARB

initial drug selection for patient with CKD

ACE or ARB

initial drug selection for patient with history of stroke or TIA

thiazide diuretic + ACE/ARB

patients that have stage 2 HTN should be initiated on __ drugs from the preferred classes

2

how often is BP monitored to assess response

monthly → titrate if not at goal

Zestoretic combination

lisinopril + HCTZ

Hyzaar combination

losartan + HCTZ

Benicar HCT combination

olmesartan + HCTZ

Diovan HCT combination

valsartan + HCTZ

Lotrel combination

benazepril + amlodipine

Exforge combination

valsartan + amlodipine

Tenoretic combination

atenolol + chlorthalidone

Ziac combination

bisoprolol + HCTZ

Maxzide combination

triamterene + HCTZ

MOA of thiazide diuretics

inhibit sodium reabsorption at distal convoluted tubule to increase sodium and water excretion (as well as K+, Mg, and Cl)

drugs that can cause sodium and water retention (ie NSAIDs) can do what to thiazide diuretics

decrease effectiveness

thiazide diuretics effect on lithium

decrease renal clearance

increase risk for toxicity

MOA of DHP CCBs

more selective for vascular smooth muscle; peripheral arterial vasodilation to decrease SVR and BP and causes coronary artery vasodilation

MOA of non-DHP CCBs

more selective for myocardium; decreases force of ventricular contraction (negative inotrope) and decrease HR (negative chronotrope)

what drugs should be avoided with non-DHP CCBs

• BB

• digoxin

• clonidine

• amiodarone

• dexmedetomidine

which CCBs are major substrates of 3A4

all CCBs except clevidipine

diltiazem and verapamil are substrates/inhibitors of what transporters/CYPs

substrates and inhibitors of Pgp

moderate inhibitors of 3A4

MOA of RAAS inhibitors (ACE and ARB)

inhibit effects of ANG II (blocks effects at efferent arteriole in nephron)

all RAAS inhibitors increase the risk of

hyperkalemia

why should NSAIDs not be used in combination of ACE/ARBs

increased risk of renal impairment and reduced antihypertensive efficacy

ACE/ARB effects on lithium

decrease renal clearance

increased risk of toxicity

important consideration when swapping from ACE to sacubitril/valsartan

36-hour washout period

MOA of K sparing diuretics

directly block sodium channels in distal convoluted tubule and collecting duct = water and sodium excretion and conserves potassium

MOA of spironolactone/eplerenone

indirectly blocks sodium channels by blocking aldosterone receptor site

eplerenone is a major substrate of

3A4

MOA of BB

competitively block beta 1 and/or beta 2 receptors

beta 1 = decrease HR and myocardial contractility

beta 2 = bronchoconstriction

which BB also block alpha 1 receptors (also decreases peripheral vasoconstriction to lower BP)

carvedilol and labetalol

which BB are preferred if a patient also has HFrEF

carvedilol, metoprolol succ, or bisoprolol

MOA of BB with intrinsic sympathomimetic activity (ISA)

partially stimulate beta receptors at rest while blocking effects of catecholamines (ie NE)

list BB with ISA

acebutolol and pindolol

which BB are a major substrate of 2D6

carvedilol

propranolol

metoprolol

nebivolol

which BB are inhibitors of Pgp

carvedilol and propranolol

MOA of alpha 2 agonists

stimulate presynaptic alpha 2 receptors in the brain = decrease sympathetic outflow of NE = reduce SVR and HR

at what point do patients fall under HTN emergency

markedly elevated BP (>180/120)

define hypertensive emergency

evidence of acute target organ damage (ie encephalopathy, stroke, acute kidney injury, acute coronary syndrome, aortic dissection, acute pulmonary edema)

what IV medications can be used for HTN emergency

• clevedipine

• enalaprilat

• esmolol

• hydralazine

• labetalol

• nicardipine

• nitroglycerin

• nitroprusside

how to treat hypertensive emergency

• treat with IV meds

• decrease BP by no more than 25% in the first hour

• next 2-6 hours decrease to <160/100

• next 24-48 hours to normal

define severe hypertension

markedly elevated BP but no evidence of acute target organ damage

how to treat severe hypertension

• outpatient setting; initiate, restart, or intensify oral antihypertensive meds

intermittent use of additional IV or oral meds to acutely reduce BO is ___ recommended for severe hypertension

NOT

what are the recommended agents for chronic hypertension in pregnant patients

• labetalol

• nifedipine extended release

• methyldopa

what is the BP goal for pregnant patients

<140/90

what medication is recommended for patients at high risk for preeclampsia

daily low dose ASA after the first trimester