VPT 311: General and Systemic Veterinary Pharmacology (2+1)

LOOP DIURETICS

• Loop diuretics ( High ceiling diuretics) are the most effective diuretics
• A fairly high proportion of Na+ is also reabsorbed in the loop of Henle (22%).
• They are inhibitors of Na⁺, K⁺ Cl^- symport
  
• Main effect of this group of diuretics is inhibition of chloride pumping throughout the whole length of the thick ascending limb of Henle, thus paralysing the kidney’s ability to concentrate and to dilute the urine.
• Their effect is from the luminal surface of the loop cells.
• These drugs are extensively bound to plasma proteins and relatively little is filtered in the glomerulus.
• They are actively secreted by the organic anion transporters at the site of action. Substances, like probenecid which block this mechanism , can reduce their efficacy.
• Examples of Loop diuretics: Frusemide, Bumetanide and Ethacrynic acid.
• Frusemide and bumetamide are sulphonamide derivatives while ethacrynic acid is not a sulphonamide derivative.
• Ethacrynic acid may produce clinical dehydration and acute circulatory collapse as it produces severe diuresis after administration.
• Frusemide produces rapid diuresis and hence is useful in emergency cases.
• It is easier to control the degree of diuresis with this drug by varying the dose rate.
• There is an increase in the excretion of calcium and magnesium and a decreased excretion of uric acid.
• The effect on calcium is made use of in the treatment of hypercalcaemia.
• The loop diuretics are readily absorbed from the gastrointestinal tract and can also be administered parenterally.

Administration

• Orally or intravenously at 1-5 mg/kg in dogs.
• This can be doubled with successive doses until an effect is obtained.
• Duration of action is 4-6 hours.
• In horses the drug is given at the rate of 0.5 mg/kg to reduce incidence of epistaxis.
• In cattle given orally at 0.5-1 mg/kg, 12-24 hourly. Loop diuretics are useful in patients with salt and water overload due to acute pulmonary oedema, chronic heart failure, hepatic cirrhosis complicated by ascites, nephrotic syndrome etc.
• Hypertension especially if accompanied by renal impairment.
• Acute treatment of hypercalcaemia.
• Untoward effects include potassium loss, metabolic alkalosis, depletion of calcium and magnesium, hypovolaemia and hypotension.
• Local irritation of the gastronintestinal tract and competition with other drugs like digitalis are noticed.
• As with other potent diuretics, hyponatraemia can occur, but deafness is an adverse effect peculiar to loop diuretics.
• Hence concurrent dosing with aminoglycosides is contraindicated.