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Drugs affecting the kidney and renal functioning (Thiazide and Thiazide…
Drugs affecting the kidney and renal functioning
Thiazide and Thiazide-like Diuretic
mechenism of action
It causes active pumping out of chloride from the cells lining the ascending limb of Loop of Henle and distal tubule by blocking the chloride pump. Since sodium passively moves with chloride to maintain electrical neutrality, both sodium and chloride are excreted in the urine.
indications
Considered to be a milder form of diuretics compared to loop diuretics.
First-line drugs for management of essential hypertension
side effects
GU: hypokalemia (can precipitate hyperglycemia), hypercalcemia, hyperuremia, slightly-alkalinized urine (can lead to bladder infections)
GI: GI upset
CNS: weakness
CV: hypotension, arrhythmias
contraindication
Bipolar disorder. Can be exacerbated by calcium changes brought about by the use of this drug.
Liver disease. Could interfere with drug metabolism and lead to drug toxicity.
Fluid and electrolyte imbalances. Can be potentiated by the changes in fluid and electrolyte levels caused by diuretics.
Pregnancy, lactation. Can cause potential adverse effects to the fetus and baby. Routine use of this drug in pregnancy is not appropriate and should be used only when there is underlying pathological conditions. For lactating women, an alternative method of feeding should be instituted.
Allergy to loop diuretics. Prevent severe hypersensitivity reactions.
storage conditions, and route of administration
Ethacrynic acid is used in oral form in some situations but not in infants.
route
Route Onset Peak Duration
Oral 60 min 60-120 min 6-8 h
IV, IM 5 min 30 min 2 h
T1/2: 120 min
Metabolism: liver
Excretion: urine
Loop Diuretics
mechanism of action
Blocks the action of chloride pump in the ascending limb of the loop of Henle, where 30% of sodium is normally reabsorbed. This causes decreased reabsorption of chloride and sodium.
Exerts the same effect on the descending limb of loop of Henle and distal tubule causing sodium-rich urine.
indications
Indicated for treatment of acute HF, acute pulmonary edema, and edema associated with HF or with renal or liver disease, and hypertension.
Drug of choice when rapid and extensive diuresis is needed. It can produce a fluid loss up to 20 pounds per day.
Proven to be effective even with the presence of acid-base disturbances, renal failure, electrolyte imbalances, and nitrogen retention.
Also used in the treatment of pulmonary edema but its effect only influences the blood that reaches the nephrons.
Ethacrynic acid is used less frequently in the clinical setting because newer drugs are more potent and reliable.
sides effects
CNS: dizziness
CV: hypotension
GI: GI upset
GU: hypokalemia (can precipitate hyperglycemia), increased bicarbonate excretion (can lead to alkalosis), hypocalcemia and tetany
EENT: ototoxicity, reversible loss of hearing
contraindication
Allergy to thiazides and sulfonamides. Prevent severe hypersensitivity reactions.
Electrolyte depletion. Can be potentiated by the changes in fluid and electrolyte levels caused by diuretics.
Severe renal failure, anuria. Exacerbated by the effects of the drug.
Systemic lupus erythematosus (SLE). Can precipitate renal failure because the disease already causes changes in glomerular filtration.
Glucose tolerance abnormalities and diabetes mellitus. Worsened by glucose-elevating effect of some diuretics
Gout. Already reflects abnormality in tubular reabsorption and secretion.
Hepatic coma. Exacerbated by fluid shifts associated with drug use.
Potassium-Sparing Diuretics
mechanism of action
This type of diuretics causes a loss of sodium while promoting the retention of potassium.
Spironolactone acts as aldosterone antagonist which blocks the action of aldosterone in the distal tubule. On the other hand, amiloride and triamterene block potassium secretion through the tubule.
indications
This is often used as adjuncts with thiazide or loop diuretics or in patients who are especially at risk if hypokalemia develops.
Spironolactone is the drug of choice for treating hyperaldosteronism typically seen in patients with liver cirrhosis and nephrotic syndrome.
sides effects
CNS: lethargy, confusion, ataxia
CV: arrhythmias
Musculoskeletal: muscle cramps
GU: hyperkalemia, increased loss of bicarbonate (can lead to metabolic acidosis)
Associated with various androgen effects such as hirsutism, gynecomastia, deepening of the voice, and irregular menses.
contraindication
Allergy to potassium-sparing diuretics. Prevent severe hypersensitivity reactions.
Hyperkalemia, renal disease, anuria. Exacerbated by the effects of the drug.
Pregnancy, lactation. Can cause potential adverse effects to the fetus and baby. Routine use of this drug in pregnancy is not appropriate and should be used only when there is underlying pathological conditions. For lactating women, an alternative method of feeding should be instituted.
route of administration and storage conditions
Pharmacokinetics
Route Onset Peak Duration
Oral 24-48 h 48-72 h 48-72 h
T1/2: 20 h
Metabolism: liver
Excretion: urine (unchanged)