Diuretics Flashcards
what are the carbonic anhydrase inhibitors (CAIs)
Acetazolamide,
Dorzolamide
MOA of Acetazolamide, Dorzolamide
inhibit C.A. IV on the
proximal convoluted tubule (PCT) brush border
inhibit cytoplasmic C.A. II
–> **Na+ reabsorption
–> *****↓ 85% PCT reabsorption of HCO3-
clinical indications of acetazolamide and dorzolamide
- glaucoma
- **acute mountain sickness
- to induce urinary alkalinization
- edema: combined with NKCC or NCC inhibitors
adverse effects of acetazolamide and dorzolamide
- Bicarbonaturia
- ***Hyperchloremic metabolic acidosis
- Hypokalemia
- Paresthesias
- Renal stones
- Sulfonamide hypersensitivity
contraindications of acetazolamide and dorzolamide
cirrhosis (increase plasma NH4+)
what is an osmotic diuretic drug
mannitol
MOA of mannitol
Osmotic Diuretics: freely filtered but poorly reabsorbed
increase tubular fluid osmotic pressure –>↓ tubular fluid reabsorption.
sites of action:
1. water-permeable
segments of the proximal tubule
2. **thin limbs of the loop of Henle (main site)
3. Increased distal flow stimulates K+ secretion
clinical applications of mannitol (osmotic diuretic)
To decrease intracerebral pressure in cerebral edema
Oliguric state: Prophylaxis of acute renal failure (*increase tubular fluid flow)
SE of mannitol
ECV expansion –> Risk of pulmonary edema in pts with heart failure
acute hypovolemia
Contraindications of minnitol
*** Active cranial bleeding (mannitol & urea)
- Anuria due to renal disease (kidney failure)
- Impaired liver function (urea)
what are the NKCC inhibitors (loop diuretics)
Rx: Furosemide, Ethacrynic acid
clinical indications for furosemide, ethacrynic acids (NKCC-I)
- Acute pulmonary edema
- Congestive heart failure
- Hypertension
- Refractory edema
- Acute renal failure
Adverse effects of furosemide, ethacrynic acid
Hypokalemia & alkalosis
what are the NCC inhibitors (thiazides and sulfonamides)
Chlorthalidone,
Hydrochlorothiazide,
MOA of chlorthalidone and hydrochlorothiazide
inhibit DCT Na+-Cl-
cotransporter (NCC) –> block coupled Na+ and Cl- reabsorption
- increase luminal Na+ & Cl- in DCT
- DIURESIS
MOA of fursoemide and ethacrynic acid
Inhibit Na+-K+-2Cl-
cotransporter (NKCC) –>
inhibit reabsorption of solute
from thick ascending limb segments
Venodilation:↓ right atrial pressure & pulmonary capillary wedge pressure within minutes (IV)
increase fractional Ca2+ excretion by 30% by decreasing the lumen-positive transepithelial potential that promotes paracellular Ca2+ reabsorption
increase fractional Mg2+ excretion > 60% by decreasing voltage-dependent paracellular transport
Clinical indications for furosemide, Ethacrynic acid?
Acute pulmonary edema
Congestive heart failure
Hypertension
Refractory edema
Acute renal failure
SE of furosemide and ethacrynic acid (NKCC inhibitors)
hypokalemia and alkalosis
NCC inhibitors (thiazides and sulfonamides) MOA - chlorthalidone, hydrochlorothiazide
* inhibit DCT Na+-Cl-
cotransporter (NCC)
block coupled Na+ and Cl- reabsorption
- increase luminal Na+ & Cl- in DCT
- DIURESIS
decrease Ca2+ excretion
vasorelaxation
(increase Ca2+-activated K+ channels)
clinical applications for NCC inhibitors (thiazides and sulfonamides) – chlorthalidone, hydrochlorothiazide
** Systemic Arterial Hypertension
- **most cost effective – mainstay of antihypertensive therapy
- less effective in patients with reduced renal function
- **Congestive heart failure – control of edema
hemodynamic and hormonal effects of NCC inhibitors (thiazides and sulfonamides) – chlorthalidone, hydrochlorothiazide
**Chronic antihypertensive effect: more related to decrease TPR than to dcrease BV
SE of NCC inhibitors (thiazides and sulfonamides) – chlorthalidone, hydrochlorothiazide
- hypokalemia
- hyperglycemia
- hyperlipidemia (except indapamide
Drug interactions and precautions with NCC inhibitors (thiazides and sulfonamides) – chlorthalidone, hydrochlorothiazide
avoid in pts with DM
MOA of amiloride?
inhibitor of renal epithelial Na+ channels
-Block epithelial Na+ channels on principal cells in the late DCT and initial connecting tubule and the cortical collecting ducts modest natriuresis & prevention of K+ loss
clinical indication for amiloride
used as K+-sparing agents in
hypokalemic alkalosis.
Used in combination with loop diuretics / thiazides to prevent
hypokalemia caused by these agents
MOA of spirnolactone and eplerenone
Antagonize aldosterone receptors in the renal collecting tubules
Decrease Na+ reabsorption –> natriuresis
Decrease loss of K+ in exchange for Na+
what drug does Prevention of LV remodeling and cardiac fibrosis
Spironolactone and eplerenone
clinical application of spironolactone
adjunct to K+-wasting diuretics: used in edema and hypertension (coadministered with thiazide or loop diuretics)
*added to standard therapy of heart failure
- *refractory edema associated with secondary aldosteronism**
- cardiac failure
- hepatic cirrhosis
- nephrotic syndrome
- severe ascites
SE of spionolactone
hyperkalemia
which drugs cause acidosis
Inhibition of carbonic anhydrase in PCT:
- acetazolamide
Block epithelial Na channels:
Amiloride
Triamterene
Block aldosterone receptor in collecting tubule:
Spironolactone
Eplerenone
which drugs cuase alkalosis
Inhibition of Na+/K+/2Cl- cotransporter in TAL:
Ethacrynic acid
Furosemide
Torsemide
Inhibition of Na+/Cl- cotransporter in DCT:
Chlorthalidone
Hydrochlorothiazide
Indapamide
Acetazolamide
effect on urinary electrolytes
incr. Na+
inc. K+
incr. HCO3-
Ethacrynic acid
Furosemide
Torsemide
effect on urinary electrolytes
Na+ K+ Ca2+ Mg2+ Cl-
increase all
Chlorthalidone
Hydrochlorothiazide
Indapamide
effect on urinary electrolytes
increase:
Na+
K+
Cl-
decrease:
Ca2+
Amiloride
Triamterene
Spironolactone
Eplerenone
effect on urinary electrolytes
incr. . Na+
decr. K+
