Wake PA Unit 3: (PHARM) Anti-Hypertensives

What are the classes of anti-hypertensives?

ACE inhibitors/AR blockers/renin inhibitors

Beta blockers

Calcium channel blockers

Diuretics

Miscellaneous agents

What are the classes of diuretics?

loop, thiazide, potassium sparing

(carbonic anhydrase inhibitors & osmotic diuretics not used as anti-HTN)

where do thiazide diuretics work?

at the distal convoluted tubule

where do loop diuretics work?

at the ascending loop of Henle

mechanism of action: loop diuretics

block sodium and chloride exchange at ascending loop of Henle (nephron)

which is more potent: diuretic, thiazide or loop diuretic?

loop diuretics (25%) are more potent than the thiazides (5%)

where do aldosterone antagonists work?

collecting duct

What does aldosterone do?

sodium reabsorption, water follows passively

What class of medications does hydrochlorothiazide belong to?

thiazide diuretics

What class of medications does chlorthalidone belong to?

thiazide diuretics

What class of medications does metolazone belong to?

thiazide diuretics

What class of medications does chlorothiazide belong to?

thiazide diuretics

side effects of thiazide diuretics

"AHH DANG"

allergy (rash)

hypokalemia

hypomagnesemia

dehydration

alkalosis

nephritis

gout

how are thiazide diuretics cleared

primarily renal

MOA thiazide diuretics. What do they waste?

inhibit Na+ absorption at distal convoluted tubule.

waste potassium and magnesium

What are the common indications for thiazide diuretics?

hypertension, heart failure

what class of medications does furosemide belong to?

loop diuretics

what class of medications does bumetanide belong to?

loop diuretics

what class of medications does torsemide belong to?

loop diuretics

How are loop diuretics metabolized?

primarily renal

What are the side effects of loop diuretics?

OHH DAANG:

ototoxicity

hypokalemia

hypomagnesemia

dehydration

allergy (rash)

alkalosis

nephritis

gout

What are the common indications for loop diuretics?

heart failure, hypertension, acute/chronic hyperkalemia

What are the classes of potassium-sparing diuretics?

aldosterone antagonists &

sodium/potassium exchange inhibitors

What is the mechanism for aldosterone antagonists?

block effects of aldosterone in distal tubules (sodium retained, water follows)

What is the mechanism for sodium/potassium exchange inhibitors?

inhibit the exchange of sodium and potassium in the collecting duct

(secreted into the lumen by proximal tubule cells)

what class of medications does spironolactone belong to?

aldosterone antagonists

what class of medications does eplerenone belong to?

aldosterone antagonists

What are the side effects of spironolactone?

hyperkalemia, gynecomastia, breast tenderness, hirsutism

What are the side effects of eplerenone?

hyperkalemia

Where are aldosterone antagonists metabolized?

hepatic

What are the side effects of Na/K exchange inhibitors?

hyperkalemia, rash

What are the common indications for aldosterone antagonists?

heart failure

hypertension

hyperaldosteronism

cirrhosis

What are the common indications for Na/K exchange inhibitors?

hypertension

volume overload

chronic hypokalemia

What is the mechanism of action for calcium channel blockers?

(in the smooth muscle vs in the heart)

block influx of calcium into:

- smooth muscle: decreased actin-myosin cross-bridging = vasoconstriction

- heart: increased contractility, increased heart rate

What are the sub-classes of calcium channel blockers?

non-dihydropyridines (NDHP)

dihydropyridines (DHP)

What is the mechanism of action for NDHPs?

work primarily in the heart:

decrease heart rate

decrease contractility

slow SA node conduction

slow propagation of depol

negative inotropes, negative chronotropes

What is the mechanism of action for DHPs?

arteriole vasodilation

what class of medications does nifedipine belong to?

DHP

what class of medications does amlodipine belong to?

DHP

what class of medications does diltiazem belong to?

NDHP

what class of medications does verapamil belong to?

NDHP

What are the side effects of NDHPs?

brady-arrhythmias, hypotension, constipation, gingival hyperplasia, rash

Where are NDHPs metabolized?

hepatic (many drug-drug interactions)

what class of medications does felodipine belong to?

DHP

what class of medications does nicardipine belong to?

DHP

what are the side effects of DHPs?

pedal edema, reflex tachycardia

Where are DHPs metabolized?

hepatic (not CYP3A4 system)

What are the indications for NDHPs?

hypertension

stable angina

ventricular rate control

vascular vasospasm

migraine prophylaxis

What are the indications for DHPs?

hypertension

stable angina

vascular vasospasm

Which DHP medication has a longer onset and duration? how long does it take for full effects?

amlodipine (takes about 3 days to reach full efficacy)

where are beta one receptors primarily located?

on the heart and in kidneys

What does activation of beta 1 receptor cause?

in heart: increased heart rate, contractility & BP

in kidneys: increased renin release, increased BP

where are beta 2 receptors primarily located?

lungs and blood vessels

What does activation of beta 2 receptors cause?

vasodilation

bronchodilation

What does blockage of beta 1 receptor cause?

in heart: decreased HR, contractility & BP

in kidneys: decreased renin release, decreased BP

What does blockage of beta 2 receptor cause?

bronchoconstriction

bronchospasm

Where are alpha receptors located (alpha 1 & 2)

alpha 1 in vasculature

alpha 2 in vasculature & brain

What does blockage of alpha 1 receptor cause?

vasodilation

What does activation of alpha 1 receptor cause?

vasoconstriction

What does blockage of alpha 2 receptor cause?

enhanced sympathetic nervous system effects

What does activation of alpha 2 receptor cause?

vasodilation, sedation

what class of medications does atenolol belong to?

beta blockers (B1)

what class of medications does bisoprolol belong to?

beta blockers (B1)

what class of medications does metoprolol belong to?

beta blockers (B1)

what class of medications does esmolol belong to?

beta blockers (B1)

What receptors does labetalol block?

alpha 1

beta 1

beta 2

List four beta 1-specific blockers (only act on beta 1 receptor)

atenolol

bisoprolol

metoprolol

esmolol

What are the side effects of beta 1 specific blockers?

drowsiness

lethargy

confusion

broncho reactive events

AV nodal blockade

which beta 1 blockers are metabolized by the kidneys? and how are the other beta 1 blockers metabolized?

atenolol

bisoprolol

others metabolized in liver (except esmolol)

how is esmolol cleared?

RBC esterases

which receptors do labetalol and carvedilol block?

alpha 1, beta 1, beta 2

which receptors does propranolol block?

beta 1, beta 2

what class of medications does labetalol belong to?

non-specific beta blocker

what class of medications does carvedilol belong to?

non-specific beta blocker

what class of medications does propranolol belong to?

non-specific beta blocker

What are the indications for prescribing beta blockers?

stable angina

heart failure

hypertension

ventricular rate control

migraine prophylaxis

stage fright

hypertensive emergency

What are the effects of angiotensin II?

vasoconstriction

aldosterone release

vasopressin release

SNS activation

increased BP and increased Na/H2O retention

what is the mechanism of action of angiotensin receptor blockers (ARBs)?

Blocks the binding of angiotensin II to the angiotensin II receptor sites.

What is the mechanism of action of ACE inhibitors?

blocks conversion of angiotensin I to angiotensin II by blocking angiotensin-converting enzyme (ACE), causing decrease in blood pressure.

what class of medications does captopril belong to?

ACE inhibitors

which ACE inhibitor is shortest acting?

captopril (three times daily)

what class of medications does enalapril belong to?

ACE inhibitors

what class of medications does lisinopril belong to?

ACE inhibitors

What are the side effects of ACE inhibitors?

Hyperkalemia,

Angioedema,

Acute Kidney Injury,

Cough,

Hypotension,

Avoid use in pregnancy!

How are ACE inhibitors metabolized?

renally

what class of medications does ramipril belong to?

ACE inhibitors

Why do ACE inhibitors cause cough?

poisons ACE enzyme (kininase II), preventing bradykinins from breaking down to inactive peptides. bradykinins accumulate in the lungs, causing cough.

what class of medications does candesartan belong to?

ARBs

what class of medications does losartan belong to?

ARBs

what class of medications does valsartan belong to?

ARBs

How are ARBs metabolized?

renal

What are the side effects of ARBs?

Hyperkalemia,

Angioedema,

Acute Kidney Injury,

Hypotension,

Avoid use in pregnancy!

What is the mechanism of action for renin inhibitors?

binds to renin enzyme to block conversion of angiotensinogen to angiotensin I

What are the side effects of renin inhibitors?

Hyperkalemia,

Angioedema,

Acute Kidney Injury,

Hypotension

Avoid use in pregnancy!

what class of medications does doxazosin belong to?

peripheral alpha-1 receptor blockers (all the -zosins)

what are the side effects of alpha-1 receptor blockers?

first dose syncope,

dizziness,

lethargy

what class of medications does hydralazine belong to?

direct-acting vasodilators

what are the side effects of hydralazine?

reflex tachycardia,

drug-induced lupus

what class of medications does minoxidil belong to?

direct-acting vasodilators

what are the side effects of minoxidil?

hair growth,

sodium/water retention