Wake PA Unit 3: (PHARM) Anti-Hypertensives

What are the classes of anti-hypertensives?

Diuretics

Angiotensin converting enzyme inhibitors (ACEI)

Angiotensin II receptor blockers (ARB)

ARNI (Angiotensin receptor - neprilysin inhibitor)

Calcium channel blockers (CCB)

Beta blockers (BB)

Alpha-1 Receptor Blockers

Alpha-2 Receptor Blockers

Aldosterone synthase inhibitors

What are the classes of diuretics?

Thiazides, loops, carbonic anhydrase inhibitors, potassium sparing (Na+/K+ exchange inhibitors, aldosterone antagonists)

(FYI - osmotic diuretics for intracranial pressures)

Which is more potent diuretic: thiazide, loop, or carbonic anhydrase inhibitors?

1. Loop diuretics

2. Carbonic anhydrase inhibitors

3. Thiazide diuretics

What is the MOA thiazide diuretics? What do they waste?

inhibit Na+ absorption at distal convoluted tubule.

waste potassium and magnesium

List the thiazide diuretics

Hydrochlorothiazide (HCTZ), chlorthalone, metolazone, chlorothiazide

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

Which thiazide is available as intermittent IV?

Chlorothiazide

How often are thiazides taken?

daily

How are thiazide diuretics metabolized?

Primarily renal

What are the side effects of thiazide diuretics?

"AHH DANG"

allergy (rash)

hypokalemia

hypomagnesemia

dehydration

alkalosis

nephritis

gout

**KEY: potassium and magnesium wasting, rash (sulfa induced)

What are the common indications for thiazide diuretics?

Hypertension, excess volume removal (diuresis)

Which thiazide diuretic is most potent?

metolazone

What is the MOA for loop diuretics?

Inhibit Na+/2 Cl- absorption at ascending loop of Henle

List the loop diuretics

furosemide (Lasix), bumetanide (Bumex), torsemide

What class of medications does furosemide (Lasix) belong to?

loop diuretics

what class of medications does bumetanide (Bumex) belong to?

loop diuretics

what class of medications does torsemide belong to?

loop diuretics

What is the route and dosing for loop diuretics?

PO, intermittent IV, IV infusion (furosemide, bumetanide)

PO (torsemide)

daily - bid/tid

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

KEY: sodium and magnesium wasting, rash (sulfa induced)

What are the common indications for loop diuretics?

Excess volume removal (diuresis), hyperkalemia, BP reduction

What is the MOA for carbonic anhydrase inhibitors?

inhibits resorption of HCO3- by tubular cells (↑ –HCO3 in tubular lumen => loss of –HCO3, loss of ↑ Na+)

Work at the proximal convoluting tubule

What class of medications does acetazolamide belong to?

Carbonic anhydrase inhibitors

What is the route and dosing for carbonic anhydrase inhibitors?

PO or intermittent IV daily

Where are carbonic anhydrase inhibitors (acetazolamide) metabolized?

Renal

What are the side effects for carbonic anhydrase inhibitors?

hyponatremia

hypokalemia

hyperuricemia

metabolic acidosis

KEY: electrolyte wasting, metabolic acidosis (not alkalosis like loops and thiazides)

What are the indications for carbonic anhydrase inhibitors?

Excess volume removal (diuresis), glaucoma, altitude sickness

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/collecting duct (sodium not retained, so water follows and is excreted)

Also known as mineralocorticoid antagonists (MRAs)

What is the mechanism for sodium/potassium exchange inhibitors?

inhibit the exchange of sodium and potassium in the collecting duct, distal tubule

(secreted into the lumen by proximal tubule cells)

List the aldosterone antagonists

spironolactone (Aldactone), eplerenone, finerenone

List the Na+/K+ exchange inhibitors

triamterene, amiloride

what class of medications does spironolactone belong to?

aldosterone antagonists

what class of medications does eplerenone belong to?

aldosterone antagonists

what class of medications does finerenone belong to?

aldosterone antagonists

What are the side effects of spironolactone?

hyperkalemia

gynecomastia

breast tenderness

Can be used to treat hirsutism

What are the side effects of eplerenone and finerenone?

hyperkalemia

Where are aldosterone antagonists metabolized?

hepatic

What is the route and dosing of potassium sparing diuretics?

PO daily

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

hyperkalemia, rash (sulfur)

which ACE inhibitor is shortest acting? Longest acting?

captopril: short (three times daily)

enalapril: intermediate (daily-BID)

lisinopril/ramipril: long (daily)

what class of medications does captopril belong to?

ACE inhibitors

what class of medications does enalapril (Vasotec) belong to?

ACE inhibitors

what class of medications does lisinopril (Prinivil) belong to?

ACE inhibitors

what class of medications does ramipril (Altace) belong to?

ACE inhibitors

What are the side effects of ACE inhibitors? When should you avoid use?

Hyperkalemia

Angioedema

Acute Kidney Injury

Cough (bradykinin excess)

Hypotension

Avoid use in pregnancy and bilateral renal artery stenosis!

How are ACE inhibitors metabolized?

renally

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 are the indications of ACE inhibitors?

hypertension

HFrEF
diabetic nephropathy

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

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

List the ARBs

candesartan

losartan

valsartan

what class of medications does candesartan belong to?

ARBs

what class of medications does losartan (Cozaar) belong to?

ARBs

what class of medications does valsartan (Diovan) belong to?

ARBs

How are ARBs metabolized?

Primarily renal

What is the route and dosing of ARBs?

PO daily

What are the side effects of ARBs?

Hyperkalemia,

Angioedema (rare),

Acute Kidney Injury,

Hypotension,

Avoid use in pregnancy and bilateral renal artery stenosis!

What are the indications for ARBs?

Hypertension

HFrEF

Diabetic nephropathy

What is the MOA for ARNIs (A-II receptor blocker + neprilysin inhibitor)?

ARB: block A-II receptor

Neprilysin inhibitor: Neprilysin is an enzyme that breaks down vasodilator enzymes into inactive peptides. Sacubitril blocks that enzyme so we have an accumulation of these vasodilators —> lower BP

Name the ARNI

vasartan/sacubitril (Entresto)

What is the route and dosing for ARNIs?

PO BID

What is the metabolism for ARNIs?

Renal

What are the side effects of ARNIs?

Hyperkalemia,

Angioedema (rare),

Acute Kidney Injury

Hypotension

Cough (bradykinin breakdown inhibited)

Avoid use in pregnancy and bilateral renal artery stenosis!

Explain precautions when switching between ACE/ARNI/ARB

If switching from an ACE to an ARNI, wait 36 hours to start the ARNI to decrease the risk of angioedema (wash out period)

Don’t need wash out period going from ARB to ARNI because ARB is a component of ARNI

What is the mechanism of action for renin inhibitors? SE? Uses?

Binds to renin enzyme blocking formation of A-I

Same SE as ACE inhibitors/ARBs/ARNIs

Use for hypertension

What class does alskiren belong to?

Renin inhibitors

What are the classes of calcium channel blockers?

Non-dihydropyridines (NDHP)

Dihydropyridines (DHP)

What is the net result of preventing calcium efflux into the arteries?

vasodilation

What is the MOA of NDHP CCBs?

Block calcium channels in the heart —> decreased AV conduction velocity, decreased SA node pace maker rate, decreased myocardial contractility

Negative inotropic effect (verapamil > diltiazem)

Negative chronotropic effect (verapamil > diltiazem)

What is the MOA of DHP CCBs?

Block calcium channels on smooth muscle cells —> vasodilation of mainly arteriolar smooth muscle (increased O2 supply, lower BP)

List the NDHP CCBs

verapamil (Calan), diltiazem (Cardizem)

What class of medications does verapamil (Calan) belong to?

NDHP CCBs

What class of medications does diltiazem (Cardizem) belong to?

NDHP CCBs

What is the route and dosing for NDHP CCBs?

PO, intermittent IV injection, continuous IV infusion

daily - QID (long acting formulations available)

Where are NDHP CCBs metabolized?

Hepatic

What are the side effects of NDHP CCBs?

bradycardia

AV nodal blockade

HoTN

constipation

gingival hyperplasia

rash

What are the indications for NDHP CCBs?

Hypertension

Angina

Ventricular rate control

Migraine HA prophylaxis

*cornerstone to HTN therapy

What are the drug interactions for NDHP CCBs?

NDHPs inhibit clearance of other drugs through CYP3A4 pathway —> Drug interactions!! Must have functioning liver. Ask pharmacist to screen for drug interactions when prescribing

List the DHP CCBs

nifedipine (Procardia)

nicardipine

amlodipine (Norvasc)

What class of medications does nifedipine (Procardia) belong to?

DHP CCB

What class of medications does nicardipine belong to?

DHP CCB

What class of medications does amlodipine (Norvasc) belong to?

DHP CCB

What is the route and dosing for DHP CCBs?

PO, daily

Nicarpidine: PO/IV, BID for PO

How are DHP CCBs metabolized?

Hepatic

What are the side effects for DHP CCBs?

Pedal edema (not diuretic responsive)

Reflex tachycardia

Hypotension

**risk of drug interactions is lower than with NDHPs

What are the indications of DHP CCBs?

Hypertension

Hypertension in pregnancy (nifedipine)

Angina

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