Diuretics Flashcards
Na-K-2Cl symport inhibitor
Forosemide
Carbonic Anhydrase Inhibitor
Acetazolamide
NA-Cl Symport inhibitor
Chlorothiazide
Potassium sparring diuretic: Epithelial Na+ channel inhibitors
Amiloride, triamterene
Potassium sparing Diuretic: Aldosterone Antagonist
Spironolactone
Osmotic Diuretic
Mannitol
Vasopressin Receptor Antagonist
Demeclocycline
Na+/K+-ATPase- on the ______________ membrane of tubular epithelial cells maintains an intracellular ___ gradient that is the _________ __________ for tubular reabsorption of Na+
Basolateral,
Na+,
Driving force
Dodium transporters and channels- Exist on the ________ side of the tubular cells and are pathways for Na+ _______; they are the molecular targets for most diuretics (exception: aldosterone antagonists).
Apical (luminal),
entry
Compensation is when electrolyte (Na+) reabsorption at a particular site of nephron is blocked and then the nephron will attempt to “compensate” by reabsorbing downstream. What is a consequence of this?
Loss of K+: More Na+ in collecting duct=more K+ secreted
Site of action for Carbonic anhydrase Inhibitors (Acetazolamide)
Proximal tubule- compensation can occur to efficacy is moderate
MOA of Carbonic anhydrase inhibitors (Acetazolamide)
Competitive inhibitor of carbonic anhydrase (CA)
- CA is responsible for Na HCO3 reabsorption and acid secretion
- Inhibits both apical and membrane-bound (typeIV) and cytosolic (type II) CA
- Blocks formation of CO2 at the luminal surface and protons in the cytosol
What drug is this: Therapeutic uses rarely as diuretic. Major use for open-angle glaucoma, altitude sickness, and epilepsy.
Carbonic anhydrase inhibitors (Acetazolamide)
Adverse effects for Carbonic anhydrase inhibitors (Acetazolamide)
Big ones: Urinary alkalinization and METABOLIC ACIDOSIS producing secondary effects: RENAL STONE FORMATION, hepatic encephalopathy, reduced excretion of weak bases.
- Hypokalemia
- Toxicities associated with sulfonamides
Site of action for: Na+-K+-2Cl- Symport Inhibitors: Loop diuretics (Furosemide)
Thick ascending limb, loop of henle- high efficacy
MOA for Na+-K+-2Cl- Symport Inhibitors: Loop diuretics (Furosemide)
- Abolishes trans-epithelial potential difference that drives paracellular transport of Ca++ and Mg++
- Marked increase in excretion of Ca++ and Mg++
- Decreases Uric acid excretion (chronic effect)
- Reduces ability of kidney to 1) concentrate urine in hydropenia and 2) dilute urine during water diuresis
Therapeutic uses for Na+-K+-2Cl- Symport Inhibitors: Loop diuretics (Furosemide)
a) Acute pulmonary edema
b) CHF
3) Hypercalcemia
4) Hyponatremia
5) Edema for nephrotic syndrome
Adverse effects for Na+-K+-2Cl- Symport Inhibitors: Loop diuretics (Furosemide)
Mostly caused by fluid and electrolyte imbalance.
a) OTOTOXICITY
b) HYPERGLYCEMIA
c) hyponatremia and hypokalemia
d) Hypocalcemia
e) Hyperuricemia
f) NSAIDS reduce diuretic efficacy
Diuretic that acts at distal convoluted tubule
Na+-CL- Symport inhibitors- Thiazide and Thiazide-like diuretics (Chlorothiazide)
-Efficacy is moderate and dose response is shallow (compared to loops)
MOA for Na+-CL- Symport inhibitors- Thiazide and Thiazide-like diuretics (Chlorothiazide)
a) Weak inhibitor of Carbonic anhydrase in PT as well.
b) In contrast to loop diuretics, efficacy is substantially REDUCED when GFR is low. Ex: In CHF
c) Decreases excretion on Ca++
d) Attenuates ability of kidney to dilute urine during diuresis; concentrating ability is unchanged.
Therapeutic uses for Na+-CL- Symport inhibitors- Thiazide and Thiazide-like diuretics (Chlorothiazide)
a) HTN
b) Mild edema
c) Nephrogenic diabetes insipidus
d) Calcium nephrolithiasis and osteoporosis
Adverse Effects of Na+-CL- Symport inhibitors- Thiazide and Thiazide-like diuretics (Chlorothiazide)
A) Hyperlipidemia and hyperglycemia
B) ERECTILE DYSFUNCTION
C) Hypokalemia, hyponatremia
D) Drug interactions: NSAIDS (reduce efficacy) and Quinidine (Hypokalemia increase torsades de pointes)
What drugs site of action is at the late distal tubule and collecting duct?
Potassium Sparing Diuretics: Triamterene, Amiloride, Spirinolactone
Triamterene and Amiloride are what type of inhibitors?
Renal epithelial Na+ channel (ENaC) inhibitors
Spironlactone is what type of antagonist? MOA?
Aldosterone- block cytosolic mineralcorticoid receptors in principal cells
Therapeutic uses for Potassium Sparing Diuretics: Triamterene, Amiloride, Spirinolactone
-Not for their diuretic effect
A) Both used with other (K-Wasting) diuretics to prevent hypokalemia- because they both abolish transepithelial potential that drives tubular secretion of K+.
B) ENaC inhibitors: Liddle syndrome and cystic fibrosis
C) Aldosterone Antag.: Primary hyperaldosteronism, hepatic cirrhosis, CHF (reduces mortality)
Adverse effects of Potassium Sparing Diuretics: Triamterene, Amiloride, Spirinolactone
A) HYPERKALEMIA- Can be life threatening; use caution with NSAIDs and ACE Inhibitors.
B) Spironlactone- Affinity for steroid receptors can produce HYNECOMASTIA, IMPOTENCE, hirsutism, decreased libido
What drugs site of action is at loop of henle (primary) and renal tubules (secondary)?
Osmotic diuretics: Mannitol
MOA for Osmotic diuretics: Mannitol
- Increases osmolality of tubular fluid (and plasma).
- Reduces renal medullary tonicity, reducing passive reabsorption of NaCl in ascending loop of henle.
- Expands extracellular fluid volume and inhibits release of renin.
Effects on urinary excretion for Osmotic diuretics: Mannitol
Increases excretion of all electrolytes
Therapeutic uses for Osmotic diuretics: Mannitol
Dialysis disequilibrium syndrome; reduces pre- and postoperative CSF and intraocular pressure
Contraindications for Osmotic diuretics: Mannitol
Contraindicated in Heart failure (edema) and active cranial bleeding
