Diuretic Drugs Flashcards
Acetazolamide:
Carbonic Anhydrase Inhibitor
MOA of Acetazolamide?
Potent competitive inhibitor of carbonic anhydrase.
- Inhibit C.A. resulting in bicarbonate loss into urine.
- Net effect: alkaline urine, enhanced chloride reabsorption
Clinical use of Acetazolamide?
- Glaucoma to reduce intraocular pressure.
- Cystinuria to alkalinize tubular urine.
- Management of mountain sickness.
- Prophylaxis of mountain sickness.
Mannitol
Osmotic diuretic
MOA of Mannitol?
- Osmotically inhibit Na+/H2O reabsorption in proximal convoluted tubule.
- Expand extracellular volume and inc renal medullary blood flow.
- inc medullary tonicity to impair ability of thin segments of loop of Henle to extract water and absorb NaCl.
Effect of Mannitol?
Increased urine flow with small increments of Na, K+ & Cl-.
•Initially increased plasma volume & B.P.
Clinical uses of Mannitol?
Reduce intracranial pressure
Name the loop diuretics? (3)
- Furosemide
- Bumetanide
- Torsemide
MOA of Loop diuretics?
•Inhibit Na+-K+-2Cl symporter in Thick AL of LOH
- by competing for Cl- binding site
- also prevents Mg and Ca bc K+ doesn’t come back out into the lumen to restore voltage grad.
• *Increase renal prostaglandins (vasodilate) by inhibiting the MD
- Increase renal blood flow
- Stimulate renin release (maintain GFR)
- GFR also maintained by inc % filtration
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
Uses and administration of Loop diuretics?
- Edema of cardiac, hepatic & renal origin (oral)
- Acute pulmonary edema.
- Given I.V. for rapid mobilization of edema fluid
- By decreasing preload
T or F: Loop diuretics are filtered through the glomerulus?
FALSE
- They are secreted through and organic acid transporter in the proximal tubule
Side effects of Furosemide?
- Fluid and electrolyte imbalance
- Ototoxicity,
- Increase BUN, hyperglycemia, hyperuricemia
Drug interactions with Furosemide?
- Lithium
- indomethacin
- Procenecid
- Warfarin
What drug can be safely used with warfarin?
Bumetanide
Uses of Bumetanide?
May be substituted for furosemide in select group of patients receiving warfarin, but significantly more $$$.
Unique PK of Torsemide?
- Has longer half-life than other loop diuretics
Name the Thiazide Diuretics (3)
- Hydrochlorothiazide (Class I)
- Chlorthalidone (Class I)
- Metolazone (Class II)
MOA of Thiazide Diuretics:
•Inhibit Na-CL symporter in early distal tubule (i.e. DCT and CD)
- Net effect: mild loss of sodium and water
Clinical use of Thiazide Diuretics:
- Treatment of mild to moderate edema
- Essential hypertension (augment others)
- Diabetes insipidus (nephrogenic)
- Hypercalciuria
Side effects of Thiazide Diuretics:
- Hypokalemia
- Hypomagnesemia
- Hyperuricemia,
- Hypercalcemia,
5 Hyperglycemia - Lipid disorders
How is metolazone different from the other two thiazide diuretics?
More potent
When are the class I thiazide diuretics preferred?
GFR > 50
What occurs when thiazide diuretic doses exceed 25 mg?
- no increase in pharm effects (max out)
- but, more side effects
Increasing dosage of Loop diuretics compared to Thiazides
The effect of loop diuretics increases with increasing dosage until levels off at 25% NaCl excreted
- Thiazide maxes out at 5%
- Loop Diuretics much more efficient
Aldosterone Antagonist (2)
- Spirolactone
2. Eplenerone
MOA of Aldosterone Antagonist?
Competitive inhibitors to aldosterone receptors in DCT and collecting ducts
- prevent the translocation of Aldosterone to the nucleus
- Reduce the aldosterone-induced ENAC channels (involved in Na reabsorption)
Pharmalogical effect of Aldosterone Antagonists?
- Increase Na+ excretion
2. Reduces K+ secretion (“K+ sparing”)
Side effects of Spirolactone?
- Hyperkalemia
- Gynecomastia (male)
- Hirsutism (female)
- Uterine bleeding (female)
Advantage Eplenerone?
Less side effects
- due to lower affinity for androgen receptor compared to spirolactone
Clinical uses of Aldosterone Antagonists?
- Diuretic (used in combo w/ HCTZ due to hyperkalemia)
- CHF
- Cirrhosis**
Potassium Sparing diuretics (2)
- Triametrene
2. Amiloride
MOA of K+ sparing diuretics
Inhibits Na+ reabsorption and K+ secretion in DCT and CD
- by blocking ENaC channels
Pharmalogical effects of K+ sparing diuretics
- Increase Urinary excretion of Na+ (weak)
2. Inhibit secretion of K+ and H+
Clinical use of K+ sparing diuretics?
Combined with HCTZ to increase their effectiveness and decrease K+ secretion
Side effects of K+ sparing diuretics?
- Hyperkalemia
- Megaloblastic anemia (in PTs w/ Cirrhosis)
- Triamtrene can rarely form Kidney stones
