Diuretic Pharmacology Flashcards
1
Q
Loop diuretics (Furosemide): Site/MOA @ nephron
A
- Inhibit NaCl transport (Na+-K+2Cl- transporter) in the ascending limb of the loop of henle – more Na+, K+, and Cl- are retained in the urine
- Associated with increased Mg2+ and Ca2+ excretion
- Increase renal blood flow (via effect on renin-angiotensin system)
2
Q
Loop diuretics (Furosemide/Ethacrynic acid): Pharmacokinetics
A
- Furosemide
- Rapid oral absorption; extremely rapid IV response
- Excreted by renal secretion and filtration
- Ethacrynic acid:
- IV
- renal secretion
- rapid onset
3
Q
Loop diuretics (Furosemide): uses
A
- edema due to CV, renal, hepatic disease
- Used in HF patients with volume overload in conjunction with salt restriction
- Acute pulmonary edema
- hypercalcemia
4
Q
Loop diuretics (Furosemide): Adverse effects
A
- metabolic alkalosis
- Hypokalemia
- Hyponatremia
- Ototoxicity
- Hyperuricemia
- Hypomagnesemia/Hypocalcemia
- Overdose –> rapid blood volume depletion
5
Q
Thiazides: Examples & Site/MOA @ nephron
A
- hydrocholorothiazide, chlorthalidone, metolazone
- Inhibit the Na+/Cl- cotransporter and increase urinary excretion of NaCl (a modest diuretic effect since only 5-10% of filtered Na+ is reabsorbed here)
- less effective than loop diuretics
- metolazone: potent thazide; combo w/furosemide
- Increase reabsorption of Ca2+ (lowering of intracellular Na+ drives Ca2++ exchanger)
6
Q
Thiazides (Hyrdrochlorothiazide): Pharmacokinetics
A
- Oral absorption, best tolerated early in the day
- Hydrochlorothyozide – twice daily dosing
- Secreted by organic acid secretory system @ PT; competition with uric acid secretion may precipitate gout attacks
7
Q
Thiazides (Hyrdrochlorothiazide): Uses
A
- First line for mild hypertension
- Tx for Hypercalcuria – increased reabsorption of Ca2+ –>reduced urinary excretion –> decreases incidence of kidney stones
- edema (primarily metolazone): synergistic diuretic effect with loop diuretics
8
Q
Thiazides (Hyrdrochlorothiazide): Adverse effects
A
- Hypokalemia, hypomagnesaemia
- Hyperuricemia – avoid in patients with gout
- hyponatremia/chloremia
- Impaired carbohydrate tolerance (hyperglycemia, glucosuria) and hyperlipidemia
- hypercalcemia
9
Q
Potassium-sparing diuretics: Site/MOA @ nephron
A
- Diuretics that block the Na+ channel or antagonize the aldosterone receptor will decrease Na+ reabsorption and _decrease K+ excretion _
- Spironolactone = antagonsits of aldosterone; bind receptors @ ald-dependent Na-K exchange site @ DCT
- Eplerenone = binds mineralcorticoid receptor => blocks binding of aldosterone
10
Q
Aldosterone Antagonists (Sprionolactone): Site/MOA
A
- competitive antagonist at aldosterone receptor
- prevents enhancement of protein synthesis; blockade of aldosterone effect at collecting tubule
- –> less Na+ is reabsorbed, lumen potential becomes more positive, and less K+ ions move into the urine
- Promotes only moderate increase in Na+ excretion; mild diuresis when used alone
11
Q
Aldosterone Antagonists (Sprionolactone): Pharmacokinetics
A
- oral
- renal, biliary excretion
- dosed 1-2x/day with slow onset of action
12
Q
Aldosterone Antagonists (Sprionolactone): Clinical uses
A
- Congestive heart failure
- Raises serum potassium to counter risk of hypokalemia-induced arrhythmias resulting from K+ wasting diuretics
- Hyperaldosteronism
- HTN
13
Q
Aldosterone Antagonists (Sprionolactone): Adverse Rxns
A
- Hyperkalemia –> arrhythmias
- Endocrine abnormalities: gynecomastia with spironolactone, amenorrhea
14
Q
Osmotic diuretics: examples/MOA
A
- mannitol = sugar that’s not metabolized + not reabsorbed @ PT
- induced diuresis via elevation of osmolarity of glomerular filtrate = decreased tubular reabsorption of water
- increased Na & Cl excretion
15
Q
Osmotic diuretics: pharmacokinetics
A
- IV administration
- ECF distribution
- Renal excretion
