Diuretics Flashcards
acetazolamide
Dichlorphenamide 30X, methazolamide 5X , dorzolamide-topical
MOA: reversible inhibition of carbonic anhydrase
-inhibits reabsorption of HCO3- in the proximal tubule
Adverse:
Metabolic acidosis
Hypokalemia-increased HCO3 in tubule leads to increased lumen negative potential–>lumen negative potential enhances efflux of K from the principal cells
Calcium phosphate stones
Hypersensitivity rxns, drowsiness, paresthesias
Contraindication
-cirrhosis (increased urine pH reduces NH3 secretion and thereby increases serum NH3)
Clinical indications:
- Diuretic agent: weak, but ok as backup
- Glaucoma: reduction of intraocular pressure
- Urinary alkalinization: drug overdose/some stones(weak acid trapped)
- Acute motion sickness: buys some time only
mannitol
MOA: osmotic diuretic
-major osmotic effects in proximal tubule and descending limb of the loop of Henle; collecting ducts too, if ADH is present
- IV administration causes expansion of intravascular volume
- not orally absorbed
- t1/2=1.2 hr
- adverse effects predominate if filtration is impaired
Adverse effects:
- increased plasma osmolality-with reduced glomerular filtration rate (CHF or renal failure)-water moves out into ECF worsening heart failure, Na moves out leading to hyponatremia
- acute pulmonary edema
- dehydration
- headache, nausea, vomiting
Contraindications:
- congestive heart failure
- renal heart failure
- pulmonary edema
Indications:
- Maintain or increase urine volume
- may be useful to treat or prevent ACUTE renal failure
- may promote renal excretion of toxic substances (contrast dye or myoglobinemia) - Reduce intracranial pressure
- Reduce intraocular pressure
Loop Diuretics
Furosemide
Bumetanide (40x, short hl) Torsemide (longer hl-3) Ethacrynic acid (last resort for hypersensitivity-nephro and oto tox)
MOA: Block Na/K/2Cl cotransporter in thick ascending limb of Henle’s loop
- increases urinary water Na, K, Ca and Mg excretion
- MOST efficacious diuretic class; can cause excretion of 20% of filtered Na
- dilation of venous system and renal vasodilation–effects may be mediated by prostaglandins
(inhibit Na/K/Cl and Vasodilation)
- loss of positive liminal charge–>less ca and mg reabsorption
- renal vasodilation improves renal blood flow
Kinetics: -oral absorption **short half-life 1-1.5 hours, duration efflux of K from principle cells) *metabolic alkalosis (increased Na and Cl leads to increased lumen negative potential-->efflux of H+ from the intercalated cells ) *ototoxicity -dehydration -hypersensitivity rxns -mild hyperglycemia
Indications:
- acute pulmonary edema
- edema associated with congestive heart failure
- acute hypercalcemia
- acute hyperkalemia
- hypertension (not usually becuase have to take so many times a day)
Thiazides
Hydrochlorothiazide
Chlorothiazide (1/10 pot, 1.5 hl)
**Metolazone (10X pot,4-5hl, only one used in renal insufficiency, different structure)
Indapamide (20x, 10-22hl, metabolized by liver)
Chlorthalidone (44hl)
MOA: inhibition of Na/Cl cotransporter in distal tubule
Dynamics:
- mild diuresis
- *increased Ca reabsorption
- when Na/Cl blocked it decreases Na, so now Na/Ca is more active(need Na) and more Ca is pumped out to blood and reabsorbed
Kinetics:
- good oral absorption and renal elimination
- half life 2.5 (short for this class which has long half lives)
Adverse Effects
***Hyperglycemia and hyperlipidemia (unique to thiazides)
*Hyponatremia and hypokalemia
(hypokalemia because of increased Na and Cl leads to increased lumen negative potential–>efflux of K+ from principle cells)
*Metabolic alkalosis
(increased Na and Cl leads to increased lumen negative potential–>efflux of H+ from the intercalated cells )
-dehydration
-hyperuricemia
-weakness, fatigue, paresthesias, and hypersensitivity
Indications:
- Hypertension
- Congestive heart failure
- reduce Ca excretion to prevent kidney stones
What are the potassium sparing drugs? What should they never be given in? What drugs and disorders can cause this?
Spironolactone, Eplerenone, Amiloride, Triamterene
SEAT
-never be given in the setting of hyperkalemia
disease: diabetes mellitus, multiple myeloma, tubulointerstitial renal disease, and renal insufficiency
drugs: potassium supplements and ACE inhibitors
Spironolactone
MOA: Competitive inhibition of the aldosterone receptor
-anti-androgenic effects
Dynamics:
- Mild diuresis due to decreased Na reabsorption secondary to aldosterone inhibition
- Sparing of K and H+ also secondary to aldosterone inhibition
Kinetics:
- slow onset of action; days to take effect
- liver metabolism to several active metabolites
Adverse Effects:
- Hyperkalemia
- Metabolic acidosis
- Gynecomastia, amenorrhea, impotence, decreased libido
- GI upset, including association with peptic ulcers
- CNS effects: headache, fatigue, confusion
Clinical indications:
- liver cirrhosis**
- primary hyperaldosteronism
- secondary hyperaldosteronism
- hypertension
- decreased lumen negative potential
- reduced driving force of H+
- decreased expression of H+ pumps
Eplerenone
competitive binding of aldosterone receptor
-it doesn’t not inhibit testosterone binding and therefore does not induce gynecomastia or other related anti-androgenic side effects
Amiloride
MOA: blocks Na channels in principal cells
Dynamics: blocking Na influx decreases the driving force for K+ efflux so K+ is spared
Kinetics:
Half life 21 hr
secreted into the tubule via the organic base transporter
excreted unchanged by the kidney
Adverse Effects:
- Hyperkalemia (NSAIDs can exacerbate this)
- GI upset: nausea, vomiting, diarrhea
- Muscle cramps
- CNS effects: headache, dizziness
Clinical indications:
- Edema
- Hypertension
- Usually used in combination with other diuretics to reduce K+ loss***
Triamterene
MOA: blocks Na channels in the principal cells
Dynamics: blocking Na influx decreases the driving force for K+ efflux so K+ is spared
-active form can precipitate in the tubules and obstruct flow
Kinetics:
Half life-4hr
-10X less potent than amiloride
-liver metabolizes the drug to its active
-active metabolite secreted using the organic base trnasporter
What are the old ADH antagonist ?
Demeclocycline-a tetracycline antibiotic-nephrotoxic
Lithium- a psych drug used for treatment of mania-nephrotoxic
What are the V2 receptor ADH antagonist?
tolvaptan, mozavaptan, and lixivaptan
What is the V1a and V2 receptor antagonist ?
Conivaptan
What does Tolvaptan do?
induces increased, dose-dependent urine production of dilute urine
- does not alter serum electrolyte balance
- hl 6-8 hr
Adverse Side Effects:
- hypernatremia????????????????
- thirst
- dry mouth
- hypotension
- dizziness
Indications:
- SIADH
- euvolemic or hypervolemic hyponatremia
- congestive heart failure
intravenous formulation of conivaptan is available for the treatment of euvolemic hyponatremia
