Diuretics and Aquaretics Flashcards
What is the MOA of Acetazolamide?
- Potent competitive inhibitor of carbonic anhydrase.
- Act in proximal tubule (90%) distal tubule (10%).
- Inhibit C.A. resulting in bicarbonate loss into urine.
What is the net effect of acetazolamide?
alkaline urine, enhanced chloride reabsorption (hyperchloremic systemic acidosis)
What are the clinical uses of acetazolamide?
- Glaucoma to reduce intraocular pressure.
- Cystinuria to alkalinize tubular urine.
- Management of seizures.
- Treat/Prophylaxis of mountain sickness.
What is the example of an osmotic diuretic?
mannitol
What is the MOA of osmotic diuretics?
- Osmotically inhibit Na+/H2O reabsorption in proximal convoluted tubule.
- Expand extracellular volume & increase renal medullary blood flow.
- Decrease medullary tonicity to impair ability of thin segments of loop of Henle to extract water and absorb NaCl.
What is the net effect of osmotic diuretics?
- Increase urine flow with small increments of Na+, K+ & Cl-.
- Initially increase plasma volume & B.P.
What are the clinical uses of osmotic diuretics?
- Treatment of dialysis disequilibrium syndrome.
- Reduce intracranial pressure.
- Reduce intraocular pressure.
- Drug overdose
What are the adverse effects of osmotic diuretics?
pulmonary edema, dehydration
What are the contraindications of osmotic diuretics?
anuria, CHF
List examples of loop diuretics.
Furosemide, Bumetanide, Torsemide
What is the MOA of loop diuretics?
- Inhibit Na+-K+-2Cl— symporter in TALH.
- Increase renal blood flow
- Increase renal prostaglandins
- Stimulate renin release and maintain GFR.
What is the effect on increasing renal prostaglandins?
vasodilation of afferent arteriole
What is the net effect of loop diuretics?
- Copious diuresis with significant Na loss
- Increase K+, Ca2+ and Mg2+ excretion
- Increase excretion of H+ resulting in mild metabolic alkalosis
What are the indications for loop diuretics?
- Given orally for edema of cardiac, hepatic & renal origin
- Acute pulmonary edema. (Given I.V. for rapid mobilization of edema fluid)
- Hypercalcemia
- Hypertension(with low GFR)
- Prevention of renal failure
- Wash out toxins
How do loop diuretics decrease pulmonary edema?
- Decrase pulmonary wedge pressure
- Venodilation resulting in decrease left ventricular filling pressure
- Increasecompliance of pulmonary vasculature that facilitates mobilization of fluid
What are the toxicities of loop diuretics (furosemide)?
OH DANG! Ototoxicity Hypokalemia Dehydration Allergy (sulfa) Nephritis (interstitial) Gout (hyperuricemia) (also leads to increased BUN and hyperglycemia)
When would you take bumetanide?
In cases when patient is on Warfarin (CANNOT TAKE FUROSEMIDE with NSAIDs or WARFARIN)
What is the specific extra action of torsemide that the other loop diuretics do not have?
vasodilator (so more commonly used to treat HTN)
List examples of thiazide diuretics.
Hydrochlorothiazide, Chlorthalidone and Metolazone (potent), Quinothazone (potent)
What is the MOA of thiazides?
- Inhibit Na-CL symporter in early distal tubule
- Net effect: mild loss of sodium and water
- Increase K+ excretion…..Hypokalemia
What is the therapeutic utility of thiazides?
- Treatment of mild to moderate edema
- Essential hypertension
- Diabetes insipidus (nephrogenic)
- Hypercalciurea/osteoporosis
What are the side effects of thiazides?
"HyperGLUC" HyperGlycemia HyperLipidemia HyperUricemia HyperCalcemia (along with hyponatremia, hypomagnesemia, hypokalemia metabolic alkalosis)
List examples of aldosterone antagonists.
Spironolactone and Eplenorone
What is the MOA of aldosterone antagonists?
Competitive inhibitors to aldosterone in late D.T. and collecting ducts.
What is interesting about the pharmacokinetics of spironolactone?
- Spironolactone extensively metabolized
* active metabolite “Canrenone”
What is the net effect of aldosterone antagonists?
Increased Na+ excretion, reduces K+ secretion
Acts as mild diuretic with thiazides!
What are the adverse effects of spironolactone?
- Gynecomastia (in males)
* Hirsutism and uterine bleeding (in females
List the K+ sparing diuretics.
Triamterene and amiloride
What is the MOA of K+ sparing diuretics?
- Inhibits Na+ reabsorption and K+ secretion in late distal tubule and collecting ducts
- Combined with thiazides [Dyazide]
What adverse effect do aldosterone antagonists and K+ sparing diuretics have in common?
hyperkalemia that could lead to arrhythmias
What drugs is used to treat ADH-sensitive (central) diabetes insipidus?
Desmopressin
What is the MOA of desmopressin?
Agonist of V2R receptors that stimulates the Gs-cAMP-PKA pathway to increase rate of insert and phosphorylate aquaporin-2 containing vesicles into the apical membrane—which increases permeability of collecting duct to water.
What is the MOA of 8-arginine vasopressin?
Agonist of V1R that stimulates the Gq-PLC-IP3 pathway gets stimulated→ mobilizes Ca2+ to cause vasoconstriciton of vascular smooth muscle
What is the indication for 8-arginine vasopressin?
Post operative ileus
Decrase bleeding in esophageal varices and acute hemorrhagic gastritis
What is the treatment for Nephrogenic diabetes insipidus?
maintaining adequate water intake
thiazides
What drugs can cause SIADH?
- Psychotropics: SSRI, tricyclic anti-depressants
- Sulfonylureas: chloropropaide
- Vinca Alkaloids
What drugs can be used to treat SIADH?
Demeclocycline
Vaptans
What is the MOA of Demeclocycline?
antagonist of ADH at V2R
What is the other use for demeclocycline and sartans?
can also be used in patients with hyponatremia due to CHF, cirrhosis, and nephrotic syndrome.
List the vaptans.
Tolvaptan (very selective, oral)
Conivaptan (IV)
What is the MOA of vaptans?
Antagonist of V2R receptors that prevents the Gs-cAMP-PKA pathway to decrease rate of insert and phosphorylate aquaporin-2 containing vesicles into the apical membrane—which decreases permeability of collecting duct to water.
What are the adverse effects of tolvaptan?
CYP3 DDIs, hyperglycemia, GI problems, clotting problems
What are the adverse effects of conivaptan?
CYP3A4 metabolized, numerous AE, infusion site reaction
