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Diuretics (Exam 5)
Diuretics
17
Pharmacology
Graduate
12/01/2010

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Term
Acetazolamide
Definition
proximal tubule (urine alkalinizing)
MOA: reversible inhibition of carbonic anhydrase
PD: inhibits reabsorption of HCO3- in proximal tubule
PK: well absorbed orally; effect beings within 30 min and is maximal within 2 hrs; duration=12 hrs; renal secretion via organic acid transporter
AE: metabolic acidosis, hypokalemia, calcium phosphate stones, drowsiness, parethesias and hypersensitivity rxns
ConIn: cirrhosis (impairs NH4+ excretion)
CI: diuretic agent (weak), glaucoma, urinary alkalinization (drug overdose/stones), acute mountain sickness
Term
Furosemide
Definition
loop diuretic
MOA: inhibits Na+/K+/Cl- cotransporter, vasodilation
PD: reduce reabsorption of Na+, K+, Cl-, also Ca2+ and Mg2+; renal vasodilation improves renal blood flow
PK: oral absorption rapid but variable, ½ life short=1.5-2hrs, duration=2-3hrs, renal secretion, oral acid transporter
AE: hyponatremia, hypokalemia, hypomagnesia, dehydration, metabolic alkalosis, hyperuricemia, ototoxicity, hypersensitivity rxns
CI: acute pulmonary edema, edema associated w/ CHF, acute hypercalcemia, acute hyperkalemia, acute renal failure?
Term
Bumetanide
Definition
loop diuretic
40x more potent than furosemide
shorter ½ life than furosemide (~1hr)
50% metabolized by liver
Term
Torsemide
Definition
loop diuretic
longer ½ life than furosemide (~3hrs)
longer duration of action (~5-6hrs)
better oral absorption than furosemide
80% metabolized by liver
Term
Ethacrynic Acid
Definition
loop diuretic
last resort-used only when others exhibit sulfur hypersensitivity
nephrotoxic and ototoxic
Term
Spironolactone
Definition
potassium-sparing
MOA: competitive inhibitor of aldosterone; anti-andronergic effects (decrease testosterone synthesis, competitive inhibition of DHT receptor)
PD: mild diuresis due to decreased Na+ reabsorption secondary to aldosterone inhibition, sparing of K+ and H+ also secondary to aldosterone inhibition
PK: slow onset of action-days to take effect, liver metabolism to several active metabolites
AE: hyperkalemia, metabolic acidosis, gynecomastia, impotence, decreased libido, GI upset (peptic ulcers), CNS effects-headache, fatigue, confusion
CI: liver cirrhosis, primary and secondary hyperaldosteronism, hypertension
Term
Eplerenone
Definition
potassium-sparing
brand new (expensive) alternative to spironolactone but without the SEs
same action as spironolactone
Term
Amiloride
Definition
potassium-sparing
MOA: blocks Na+ channels in principal cells
PD: blocking Na+ influx decrases driving force for K+ efflux so K+ is “spared”
PK: 1/2 life=21 hrs, secreted into tubule via organic base transporter, excreted unchanged by kidney
AE: hyperkalemia (NSAIDs can exacerbate), GI upset (nausea, vomiting, diarrhea), muscle cramps, CNS effects (headache, dizziness)
CI: edema, hypertension, combo with other diuretics to reduce K+ loss, adjunct for lithium Tx (mania) to decrease diabetes insipidus
Term
Triamterene
Definition
potassium-sparing
MOA: blocks Na+ channels in the principal cells
PD: blocking Na+ influx decrases driving force for K+ efflux so K+ is “spared”; active form can precipitate in the tubules and obstruct flow
PK: ½ life=4hrs, 10x less potent than amiloride, liver metabolizes drug to active form -> secreted using the organic base transporter
Term
Hydrochlorothiazide
Definition
thiazide
MOA: inhibition of Na+/Cl- cotransporter in distal tubule
PD: relatively mild diuresis, increased Ca2+ reabsorption
PK: good oral absorption and renal elimination; ½ life=2.5hrs
AE: hyponatremia and hypokalemia, dehydration, metabolic alkalosis, hyperuricemia, hyperglycemia, hyperlipidemia (increased LDL), weakness, fatigue, paresthesias and hypersensitivity rxns
CI: hypertension, CHF, idiopathic hypercalciuria, nephrogenic diabetes insipidus
Term
Metolazone
Definition
thiazide
10x more potent than hydrochlorothiazide
½ life=4-5hrs
Term
Indapamide
Definition
thiazide
20x more potent than hydrochlorothiazide
½ life=10-22hrs, metabolized extensively by liver
Term
Chlorothalidone
Definition
thiazide
same potency as hydrochlorothiazide
½ life=44hrs
Term
Mannitol
Definition
osmotic agent
MOA: major osmotic effects in proximal tubule and loop of Henle
PD: IV admin causes expansion of intravascular volume, powerful diuretic effect once it reaches kidney
PK: not orally absorbed-must be injected IV to reach kidney, bolus excreted within 30-60min
AE: acute pulmonary edema, dehydration, hypernatremia, headache, nausea, and vomiting
ConIn: CHF, pulmonary edem
CI: increased intracranial pressure, renal excretion of toxic substances (contrast dye, myoglobinemia)
Term
Tolvaptan
Definition
vasopressin (ADH) antagonist
selective V2 receptor antagonist-renal ADH receptors
Term
Conivaptan
Definition
vasopressin (ADH) antagonist
V1A and V2 receptor antagonist-vasodilator and ADH antagonist
Term
Aliskiren
Definition
renin inhibitor
lower elevated blood pressure, combo w/ ACE inhibitors, ARBs, aldosterone antagonists -> synergistic effects
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