Diuretics Flashcards
What is an ADH Antagonist? MOA? PK?
Conivaptan
MOA: antagonist of V1 and V2 receptors, dilute urine produced
PK: Conivaptan must be administered intravenously. It is metabolized by and is a potent inhibitor of CYP 3A4.
Uses of Conivaptan?
Treatment of euvolemic and hypervolemic hyponatremia in hospitalized patients.
Treatment of SIADH (Syndrome of Inappropriate ADH Secretion).
Conivaptan is only used in the management of heart failure when the benefits outweigh the risks as the safety of the agent has not been established.
AE of conivaptan?
Contraindications?
Adverse Effects
Nephrogenic Diabetes Insipidus: If serum Na+ is not monitored closely. Conivaptan can cause severe hypernatremia and nephrogenic diabetes insipidus.
Infusion site reactions
Atrial fibrillation, GI & electrolyte disturbances
Thirst
Contraindications
Hypovolemic hyponatremia
Renal failure
Uses of Mannitol?
Reduction of increased intracranial pressure associated with cerebral edema;
reduction of increased intraocular pressure;
the promotion of urinary excretion of toxic substances genitourinary irrigant in transurethral prostatic
resection or other transurethral surgical procedures
Increases urine flow in patients with acute renal failure
MOA off Mannitol?
• Raises osmotic pressure of the plasma thus draws
H20 out of body tissues & produces osmotic diuresis
increase the osmolality of plasma and tubular fluid
Expand Extracellular fluid volume, decrease blood viscosity, and inhibits renin release.
• Does not effect Na+ excretion directly, increases urinary secretion of nearly all electrolytes Na+, K+, Ca2+, Mg2+, Cl- , HCO3 - and phosphate.
• Only drug that truly increases urine volume
• Loop Diuretics?
Site of Action?
• Furosemide
Site of Action: Thick ascending Loop of Henle
Thiazides?
Site of Action?
Hydrochlorothiazide, chlorthalidone, metolazone
Site of Action: Distal Convoluted Tubule
Potassium-Sparing Diuretics?
Site of Action?
Spironolactone, eplerenone, triamterene, amiloride
Site of Action: Collecting Duct
Carbonic anhydrase inhibitors
Site of Action?
Acetazolamide
Site of action: Proximal Convoluted Tubule
Furosemide Clinical Applications and overview
- aka ‘High-Ceiling’ diuretics
- Highest efficacy in removing Na+ & Cl- from body
- Act on ascending limb of Loop of Henle
Clinical applications:
• Diuretics of choice for managing edema associated
with heart failure, hepatic or renal disease
• Hypertension (moderate-severe)
Loop diuretic MOA? Actions?
- Act in the ascending limb of the loop of Henle
- Block NKCC2 Na+/Cl- /K+ cotransporter
- [Na+] & [Cl-] & [K+] in tubular fluid à H20 excretion
Actions: • Increased Ca2+ excretion • Increased Mg2+ excretion • Decreased renal vascular resistance • Increased renal blood flow • Increased prostaglandin synthesis
Loop Diuretic PK and AE?
PK: • Oral & parenteral
• t1/2 = 2-4 h
AE: • Ototoxicity • Hyperuricemia • Acute hypovolemia • K+ depletion • Hypomagnesemia • Allergic reactions
Overview and Clinical Applications of Thiazides?
Act on distal tubule – all have equal maximum effects
Clinical applications:
• Hypertension (either alone or in combination with
other antihypertensives)
• Heart failure (mild-moderate)
• Hypercalciuria (inhibit Ca2+ excretion, particularly
useful for kidney stones)
• Diabetes insipidus (produce hyperosmolar urine)
• Premenstrual edema
Loop diuretic increase urinary secretion and decreased urinary secretion?
Increased Urinary Excretion Na+ K+ Mg2+ Ca2+ Urine volume
Thiazide MOA?
- Act predominantly in distal convoluted tubule
- Block NCCT Na+/Cl- cotransporter
- [Na+] & [Cl-] in tubular fluid à H20 excretion
• Increased Na+ & Cl- excretion
• Increased K+ excretion
• Increased Mg2+ excretion
• Decreased urinary Ca2+ excretion
• Decreased peripheral vascular resistance
• Initially due to decrease in blood volume. With
continued therapy, volume recovery occurs
although hypotensive effects remain
