ICU Primary Snippet – Furosemide Vs Acetazolamide

Dr Swapnil Pawar April 11, 2024 93 1

ICU Primary Snippet – Furosemide Vs Acetazolamide
Dr Swapnil Pawar

Compare and contrast the pharmacology of Furosemide and Acetazolamide

Written by Dr Madhuri Anupindi

	Furosemide	Acetazolamide
Pharmaceutics
Class	Loop diuretic	Carbonic anhydrase inhibitor
Formulations	Tablets: 20mg, 40mg Oral solution: 10mg/ml Injection: 10mg/ml available in 20mg, 50mg or 250mg vials.	Tablets: 250mg Injection: 500mg
Pharmacokinetics
Administration	PO or IV, can be given IM IV doses should be given no faster than 4mg/min to avoid ototoxicity	PO or IV IV requires reconstitution with water before use
Absorption	60-69% bioavailability in healthy patients Reduces to 43-46% in patients with end stage renal failure. Onset of action 30 – 60 minutes after PO and 5 minutes after IV administration.	Bioavailability of 90% Onset of action 1-2 hours after PO and 2 minutes after IV administration
Distribution	Highly protein bound 91-99%, mainly to albumin Crosses the placenta	Highly protein bound: approximately 90-98% Tightly bound to carbonic anhydrase and accumulates in tissues containing this enzyme especially red blood cells and renal cortex
Metabolism	Minimal hepatic and renal metabolism – main metabolite is furosemide glucuronide.	Nil metabolism
Elimination	Half-life of about 2 hours in patients with normal renal function (prolonged in patients with renal or hepatic failure) 80% of an IV or IM dose is excreted in the urine within 24 hours by both glomerular filtration and proximal tubular secretion. Remainder excreted in faeces.	Half life 4- 9 hours Excreted unchanged by tubular secretion in the urine – this is enhanced in alkaline urine
Pharmacodynamics
Target in kidney	Thick ascending limb loop of Henle	Proximal tubule
Mechanism of action	Blocks the Na-K-2Cl transporter à reduces reabsorption of these ions à increases amount of solute delivered to distal nephron which increases water excretion and also disrupts the counter-current multiplier system by decreasing the reabsorption of these ions into the medullary interstitium due to decreased osmotic gradient between the duct and inner medulla	Inhibits carbonic anhydrase à blocks conversion of carbonic acid into co2 and h20 in the tubular lumen and its conversion back into carbonic acid in the proximal tubule cellsà normally the c02 + h20 diffuses into the proximal tubule cells and is converted back into carbonic acid by carbonic anhydrase. The hydrogen ions can then be exchanged with sodium from the tubular lumen. Acetazolamide therefore decreases sodium and bicarbonate resorption.
Indications	Oedema: CCF, liver cirrhosis, renal disease Hypertension	Metabolic alkalosis Oedema: adjunctive with other diuretics Prevention of acute mountain sickness High altitude cerebral oedema Elevated intra-ocular pressure associated with acute angle closure glaucoma Chronic open angle glaucoma Idiopathic intracranial hypertension
Contraindications/precautions	Allergy to furosemide or sulfonamides Prostatic obstruction (can precipitate urinary retention) Anuria Severe hypovolemia Treatment with other ototoxic medication	Hyperchloraemic acidosis Hyponatremia Hypokalemia Renal failure GFR < 10ml/min Hypersensitivity to acetazolamide, sulphonamide or sulphonamide derivatives Severe hepatic impairment or Hepatic failure (decreases ammonia clearance à can precipitate hepatic encephalopathy) Long term administration in patients with chronic non-congestive angle-closure glaucoma
Use in pregnancy and breastfeeding	Category C: can cause electrolyte disturbances in neonate and thrombocytopenia Passes into breastmilk and inhibits lactation	Category B3: shown to be teratogenic in animals at very high doses. No well controlled human studies – avoid use especially in first trimester. Passes into breastmilk: use caution
Adverse effects	Ototoxicity Hypovolemia Hypotension Electrolyte imbalances (see below) Anorexia, nausea Pancreatitis, transaminitis (rare) Increased triglycerides and cholesterol Aplastic anaemia, thrombocytopenia, haemolytic anaemia, leukopenia TENs, SJS, erythema multiforme, drug rash, pruritis, urticaria Gout	Paraesthesia Fatigue and drowsiness Hypersensitivity reactions Nausea, vomiting, diarrhoea Electrolyte imbalances (see below) Aplastic anaemia, thrombocytopenia, agranulocytosis, neutropenia SJS
Electrolyte effects	Metabolic alkalosis Hypernatremia Hypokalaemia Hypomagnesemia Hypophosphatemia Hypocalcemia Hyperuricaemia	Metabolic acidosis Hyponatremia Hypokalemia Hyperchloremia
Significant drug interactions	Aminoglycosides, cephalorodine: cisplatin: increases risk of ototoxicity Chloral hydrate: flushing, hypertension, tachycardia Lithium: decreases excretion of lithium ACEI: may cause hypotension or deterioration in renal function Theophylline: IV furosemide increases theophylline levels	Salicylates: decreases protein binding and renal clearance of acetazolamide à can result in severe metabolic acidosis Lithium: increases lithium excretion Phenytoin: increases phenytoin levels, accelerates osteomalacia Cyclosporine: increases cyclosporine levels Amphetamines: reduces urinary excretion of amphetamine

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