Diueretics, CCB, BB, ACEi, ARBs

diuretics are classified according to their

site of action

osmotic diuertic

mannitol

MOA of mannitol

Filtered at the glomerulus but poorly

reabsorbed; water is held in the lumen by

the osmotic effect producing diuresis

primary site of action of mannitol

proximal convoluted tubule

main therapeutic use of mannitol

-head trauma

-Rapid (emergent) treatment of increased intracranial pressure

carbonic anhydrase inhibitors

Acetazolamide

other carbonic anhydrase inhibitors used for glaucoma

•Dorzolamide (Trusopt ®)-topical eye drop

•Brinzolamide (Azopt ®)-topical eye drop

•Methazolamide (Neptazane®) –oral

Key to diuretic action in the PCT is inhibition of reabsorption of

•NaCl

•NaHCO3

MOA of CA inhibitors (acetazolamide)

inhibits carbonic anhydrase in the proximal convoluted tubule resulting in excretion of sodium bicarbonate

-decreases bicarb and sodium reabsorption

CA inhibitors makes the urine

alkalinized

acetazolamide is not a

good option for a diuretic

most potent diuretics

loop diuretics

key therapeutic uses of loop diuretics

-CHF

-edema

-kidney disease

site of action of loop diuretics

ascending limb of loop of henle (big site of reabsorption of many electrolytes)

MOA of loop diuertics

inhibits the sodium-potassium- chloride transporter and reducing Na reabsorption in the ascending loop of Henle

uIncreased loss of: Na, Cl, H2O, K, Mg, Ca

what do you lose when you use a loop diuretic

potassium

name the loop diuertics

uFurosemide (Lasix®)

uBumetanide (Bumex)

uTorsemide (Demedex)

uEthacrynic acid (Edecrin)

is about 40 times more potent than furosemide

bumetanide

may be used in patients allergic to other loop diuretics (not a sulfonamide)

Ethacrynic acid

Greater ototoxic potential than other loop diuretics

Ethacrynic acid

All loop diuretics are

ototoxic

-limit infusion rate of furosemide to 4mg/min

electrolyte imbalances of loop diuertics

Hypokalemia(arrythmias), hypochloremia, hypomagnesemia

alkalosis

moa of thiazide diuretics

Inhibit the reabsorption of sodium and chloride ions in the distal convoluted tubules by blocking the Na-Cl transporter

site of action of thiazide diuertics

distal convoluted tubule

name the thiazie diuretics

Chlorothiazide (Diuril©) - iv & po

Hydrochlorothiazide (HCTZ) - po

Metolazone (Zaroxolyn©) po

Chlorthalidone - po

Indapamide (Lozol ©) po

PTH is affiliated in the area of the

distal convoluted tubule and regulates calcium

which thiazide diuretic has a long half life (47 hours)

chlorthalidone

therapeutic use of thiazide diuertic

-HTN

-prevention hypercalcemic kidney stones

electrolyte imbalances of thiazide diuertics

Hypokalemia

Hypochloremia

Hypomagnesemia

decrease calcium excretion in the kidney and increase calcium in the blood.

thiazide diuertics can exacerbate

gout (hyperuricemia)

may be used together to optimize the diuretic efficacy by interfering with sodium reabsorption at the thick ascending loop and the distal convoluted tubule

Loop and thiazide

Treatment option for diuretic resistance

Loop and thiazide

which do you give first?

thiazide before loop

long term use of loop can cause

diuretic resistance: hypertrophy of distal nephron segments resulting in increased reabsorption of sodium at distal sites

loops decrease ____ and thiazides inc ____

calcium

potassium sparing diuretics site of action

last distal convoluted tubule and collecting duct

MOA of spirnolactone

synthetic hormone that competes with aldosterone in the collecting duct and late DCT for the mineralocorticoid site to reduce the synthesis of sodium channels resulting in loss of Na and retention of K (↓ Na, ↑ K)

SE of spirnolactone

gynecomastia

Spironolactone analog

More selective than spironolactone; less active on androgen site

Eplerenone

potassium sparing diuertics that block sodium channel activity in the collecting tubule

Amiloride

Triameterene

frequently combined with HCTZ to prevent hypokalemia

Triameterene

SE of potassium sparing diuertics

hyperkalemia especially when used alone

action of the calcium channel

Increased concentration of cytosolic Ca+2 causes contraction in vascular smooth muscle and cardiac cells

MOA of calcium channel blockers

Blocks the flow of calcium into vascular smooth muscle and cardiac muscle resulting in decreased intracellular calcium

dihydropyridine CCB

Amlodipine

Nifedipine

Clevidipine

Felodipine

Nondihydropyridines CCB

Diliriazem

Verapamil

most negative ionotropic CCB

verapamil

decreasing contraction and conduction

verapamil

dilitazem

vasodilates the most (CCB)

amlodipine

all CCB cause

vasodilitation

_____ CCB best for HTN

dihydropyridine

____ CCB best for arrythmias

nondihydropyridine

ADE of verapamil

constipation

ALL CCBs ADE

Peripheral edema

Headache

Gingival hyperplasia

SE specific to DHP CCBs

Reflex tachycardia

Flushing

SE specific to nDHP CCBs

Bradycardia

Heart block

be cautious using a nDHP with a

beta blocker

action of BB in the heart

Block action of norepinephrine and epinephrine at β1 receptors on cardiac muscles

-Reduce HR and contractility → decreased cardiac output

BB action on the kidneys

Decrease renin release from juxtaglomerular cells → decreased total peripheral resistance (TPR)

uMixed α- and β- Blockers

Block action of norepinephrine at α-1 receptors -> vasodilation with no reflex tachycardia

Chronic use of BB results in upregulation of Beta receptors resulting in super-sensitivity to

β agonists (always taper a beta blocker)

cardioselective BB

B1 > B2

name the cardioselective BB

•Metoprolol succinate (Toprol XL)

•Metoprolol tartrate (Lopressor)

•Atenolol (Tenormin)

•Esmolol (Brevibloc)

•Acebutolol (Sectral)**

•Betaxolol (Kerlone)

•Bisoprolol (Zebeta)

•Nebivolol (Bystolic)

dont use ____ BB with asthmatic pts

non selective (because they also block B2)

name the mixed a and b

carvedilol

labetalol

name the nonselective BB

•Nadolol (Corgard)

•Propranolol (Inderal)

•Sotalol* (Betapace)

•Pindolol (Visken)**

•Timolol (Blocadren)

always used as an antiarythmic

Sotalol

have intrinsic sympathomimetic activity

Pindolol

Acebutolol

partial agonist activity providing beta stimulation at rest but acts as a typical beta-blocker when sympathetic activity is high.

Pindolol

Acebutolol

is a racemic mixture

sotalol

ADE of BB

-mask the signs of hypoglycemia

-bradycardia

-heart block

-erectile dysfunction

-depression

SE of nonselective BB

bronchoconstriction

is a naturally occurring peptide hormone of the renin-angiotensin-aldosterone system (RAAS) that causes increased vasoconstriction and increase in blood pressure

angiotensin II

MOA of ACEi

Inhibit ACE to block conversion of angiotensin I to angiotensin II

how do ACEi affect bradykinin

Inhibition of bradykinin metabolism increased PG = vasodilation & decreased BP

ADE of ACEi

Dry cough

angioedema

hyperkalemia

ACEi contraindicted in

pregnancy

do not use ACEi in patients with

bilateral renal artery stenosis

name some ACE inhibitors

Captopril

Enalapril

Lisinopril

Ramipril

MOA of arbs

selective, competitive angiotensin II receptor blockade

Blocks the vasoconstriction and aldosterone - secreting effects of angiotensin II

SE of ARBs

Less incidence of cough and angioedema than with ACE inhibitors

Hyperkalemia (monitor K)

Contraindicated for use in pregnancy

Acute kidney injury (Monitor Scr)

Do not use in bilateral renal artery stenosis

name some ARBs

Candesartan

Losartan

Olmesartan

Valsartan

ARBS act on the

AT1 receptor (not AT2 receptor)