Diuretics Flashcards
What is a diuretic?
: diuretic are agents that increase renal excretion of water and salts (mostly sodium).
What are the therapeutic use of diuretics?
: reduces the fluid volume in the body
edema, congestive heart failure, hypertension.
What are the classes of diuretics?
Thiazides K+ sparing Carbonic anhydrase osmotic diuretics loop diuretic
What is the site of action for thizade/
DCT
What are the name of all the thiazides?
Hydrochlorothiazide, Chlorothiazide, Chlorthalidone, Bendroflumethiazide, Indapamide, Metolazone
What are thiazides derivatives of?
Sulfanamide
What is the mechanism of action of Thiazides?
Inhibits sodium-chloride cotransporterm - NCC
What is the result of thiazide MOA?
Increase renal excretion of:
Sodium and chloride
Potassium
Hydrogen (causing metabolic alkalosis)
Decrease renal excretion of:
calcium
What are the therapeutic uses of Thiazides?
Hypertension.
Edema associated with congestive heart failure, hepatic cirrhosis and renal diseases.
Nephrolithiasis (calcium stones).
Nephrogenic diabetes insipidus.
What are the SE of thiazides?
- Water and electrolyte imbalance: hypokalemic metabolic alkalosis, and hyperuricemia.
Hypercalcemia.
Hyponatremia.
Hyperglycemia associated to hypokalemia.
Allergic reaction (sulfonamide).
Weakness, paresthesia, impotence.
What are advers reactions of sulfas?
Skin reactions, from benign rash to potentially lethal toxidermias, are adverse drug reactions to sulfonamides
What is the site of action of Loop diuretics?
TALH
What are the classes of Loop diuretics?
Sulfonamide derivative:
- Furosemide, Bumetanide, Torsemide
Non-sulfonamide loop diuretic:
- Ethacrynic acid
What is the MOA of loop diuretics?
inhibit Na/K/2Cl co-transporter on TALH
inhibit the reabsorption of Ca2+ and Mg2+, Na, K, Cl, H+(causing metabolic alkalosis)
direct effect on vasculature (prostaglandins)
increase renal blood flow
increase systemic venous capacitance
What are the therapeutic uses of loop diuretics?
acute pulmonary edema and other edema chronic congestive heart failure hypertension acute hypercalcemia hyperkalemia (in combination with NaCl) intoxication with anion: bromide, fluoride, iodide
What are the side effects and toxicity of loop diuretics?
hypokalemic metabolic alkalosis ototoxicity hyperuricemia (gout) hypomagnesemia allergic reactions to sulfonamides
What is the site of action of carbonic anhydrase inhibitors?
PCT
What are the cabonic anhydrase inhibitors?
Acetazolamide, Methazolamide – sulfonamide derivatives
What is the MOA of Carbonic anhydrase inhibitors?
Inhibits carbonic anhydrase at PCT
acidifies the urine
alkalizes the blood.
What is the result of the MOA of carbonic anhydrase inhibitors?
Inhibits carbonic anhydrase
Increase renal excretion of:
Sodium (mild)
Potassium
Bicarbonate (alkalinization of urine)
Decrease renal excretion of:
Hydrogen (acidosis)
What are the therapeutic uses of carbonic anhydrase inhibitors?
glaucoma (open angle).
cystinuria by enhancing the excretion of uric acid and organic acid.
metabolic alkalosis.
acute mountain sickness.
What is the side effects and toxcity of carbonic anhydraes inhibitors?
hyperchloremic metabolic acidosis. stones: phosphate and calcium. drowsiness and paresthesias. potassium wasting. allergic reactions to sulfonamides.
What is the mechanism of K+ loss?
Enhanced Na+ delivery results in K+ loss in the collecting duct
What is the site of action of Osmotic diuretics?
PCT
Descending limb
What are the osmotic diuertics?
Mannitol
administrated systemically (orally -> osmotic diarrhea)
What are the MOA of Osmotic diuretics?
induce osmotic diuresis by preventing water reabsorption.
extract water from intracellular compartment
expands extracellular fluid volume (initially)
What are the therapeutic uses of osmotic diuretics?
increase urine volume in preference to Na+ excretion.
reduction of intracranial pressure.
reduction of intraocular pressure: acute glaucoma.
What are the side effects of osmotic diuretics?
excessive loss of more water relative to sodium:
-> dehydration and hypernatremia (hyperkalemia)
initial expansion of extracellular fluid volume may result in hyponatremia:
-> pulmonary edema and heart failure
What is the site of action forPotassium sparing:
Aldosterone antagonist?
CCT
What are the Potassium sparing: Aldosterone antagonist?
Spironolactone, Eplerenone
What is the MOAPotassium sparing: Aldosterone antagonist?
inhibit the mineralocorticoid receptor in the principal cells of the collecting tubule and collecting duct. :
repress the expression of EnaC and Na+/K+ ATPase.
increase sodium, calcium secretion
inhibit potassium, hydrogen secretion
What is the therapeutic use of Potassium sparing: Aldosterone antagonist?
edema and hypertension.
enhance Na+ excretion and reduce K+ wasting.
primary hyperaldosteronism.
edema associated with secondary hyperaldosteronism.
off label use of spironolactone to treat androgen-dependent hirsutism.
drug-resistant hypertension
What are the side effects of Potassium sparing: Aldosterone antagonist?
metabolic acidosis in cirrhotic patients
ataxia, confusion, drowsiness, headache, lethargy
Spironolactone may cause gynecomastia, impotence,
irregular menses, postmenopausal bleeding (less with Eplerenone).
What is the site of action forPotassium sparing: Na+ channel inhibitor?
CCT
What are the Potassium sparing: Na+ channel inhibitor?
Amiloride, Triamterene
What is the MOA for Potassium sparing: Na+ channel inhibitor?
Inhibits Na+ channel (ENaC)
Increase renal excretion of:
Sodium
Calcium (moderate)
Decrease renal excretion of:
Potassium
Hydrogen (acidosis)
What is the therapeutic use of Potassium sparing: Na+ channel inhibitor?
counteract the loss of potassium induced by loop diuretics or thiazides.
pseudo-hyperaldosteronism (Liddle’s syndrome).
lithium-induced nephrogenic diabetes insipidus (can induce Li+ toxicity)
improve mucociliary clearance in patients with cystic fibrosis.
What are side effects and toxicity of Potassium sparing: Na+ channel inhibitor?
hyperkalemia.
hyperchloremic metabolic acidosis.
nausea, vomiting, headache.
What are the side effects of Potassium sparing: Na+ channel inhibitor: Triamterene?
reduce glucose tolerance
interstitial nephritis and renal stone (drug precipitate)
What does Triamterene do to uurine?
turns urine blue
What is the MOA for sodium polylstyrene sulfonate?
Cation-exchange resin used to reduce hyperkalemia
Administered orally or as enema:
-> not absorbed and chelate K+ ion in the large intestine
What is the the therapeutic use of Sodium polystyrene sulfonate?
severe) hyperkalemia
Correction may be long and emergency situation may require alternative approaches
What are the side effects of Sodium polystyrene sulfonate?
Hypokalemia, hypocalcemia, hypomagnesemia - hypernatremia - anorexia, constipation, diarrhea, fecal impaction (bezoar)
