Question 16

Compare and contrast the pharmacology of furosemide (frusemide) and acetazolamide.

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College Answer

The use of a table assisted with both clarity and the ability to compare the two drugs. Writing separate essays about each makes it difficult to score well. It was expected that candidates would follow a standard pharmacology format and discuss pharmaceutics, pharmacokinetics, pharmacodynamics and adverse drug reactions. Both of these drugs are ‘Level A’ in the syllabus and a suitable level of detail was expected. It was expected candidates would discuss in detail the mechanism of action, electrolyte and acid-base effects. Pharmacokinetic values were poorly answered. Qualitative terms such as ‘moderate, good and some’ are vague and should be avoided. Only correct numerical values (or ranges) attracted full marks


Name Furosemide Acetazolamide
Class Loop diuretic Carbonic anhydrase inhibitor
Chemistry Anthranilic acid derivative Sulfonamide derivative
Routes of administration IV, IM, oral, sublingual, and as a neb IV, oral
Absorption Variable oral bioavailability, between 10 and 100% (interindividual variability).
Mainly absorbed in the stomach
Oral bioavailability of about 60%
Solubility Acidic drug; pKa 3.6. Highly ionised (therefore poorly lipid soluble) in the relatively alkaline small intestine, as well as in the blood pKa 7.2; slightly soluble in water
Distribution VOD = 0.1-0.2L/kg, i.e. mainly confined to the circulating volume. 95% protein bound. Decreased albumin levels increase the volume of distribution and decrease the delivery of the drug to its useful site of action (tubular lumen) VOD = 0.3L/kg, 90-90% protein bound
Target receptor Binds competitively to the chloride binding site of the NKCC2 sodium-potassium-0chloride transport protein in the thick ascending limb of the loop of Henle Acetazolamide binds to and blocks the activity of carbonic anhydrase in the proximal tubule, thereby preventing thr reabsorption of filtered bicarbonate
Metabolism 50% of the dose is metabolised in the kidney into an active glucouronide (which has only 25% of the parent drug agctivity) No metabolism occurs
Elimination Cleared renally - 50% of the administered dose is eliminated in this way, mainly by active secretion via the OAT organic anion transport proteins in the proximal convoluted tubule. Half life is about 30-120 minutes All of the administered dose is cleared renally; half-life is about 6-10 hours
Time course of action Effect lasts for six hours Duration of effect is ~ 8-12 hrs
Mechanism of action Blockade of the NKCC2 transporter decreases the reabsorption of sodium potassium and chloride in the thick ascending limb
This increases the delivery of sodium potassium and chloride to the distal nephron. The increased solutes in the collecting duct lumen decrease the osmotic gradient between the duct and inner medulla, preventing water reabsorption in the collecting duct, resulting in diuresis.
Because of the main site of sodium reabsorption being the proximal tubule, theoretically only up to 20% of filtered sodium can be excreted by the blockade of all NKCC2 channels, which means loop diuretic therapy has a ceiling effect.
Produces diuresis by increasing the concentration of osmotically active bicarbonate in the proximal tubule. Also decreases the secretion of aqueous
humour and results in a drop in intraocular pressure. By preventing the reabsorption of bicarbonate, alkalinises the urine and acidifies the body fluids (by decreasing the amount of available buffer)
Clinical effects Hypovolemia (diuretic effect)
- Hypotension (esp.orthostatic)
- Hypokalemia
- Metabolic alkalosis (hypochloraemia)
- Hypernatremia (as sodium is retained by ENaC)
- Hypomagnesemia
- Hypophosphatemia
- Acidification of the urine
- Ototoxicity
Hypotension (extension of the diuretic effect)
- Metabolic acidosis
- Hypokalemia
- Hyponatremia
- Hyperchloremia
- May inhibit folate metabolism
Drug interactions:
- Inhibits the clearance of amphetamines, salicylates, phenytoin, quinidine
Single best reference for further information FDA PI data sheet INCHEM article


Ponto, Laura L. Boles, and Ronald D. Schoenwald. "Furosemide (frusemide) a pharmacokinetic/pharmacodynamic review (part I)." Clinical pharmacokinetics 18.5 (1990): 381-408.

Ponto, Laura L. Boles, and Ronald D. Schoenwald. "Furosemide (frusemide) a pharmacokinetic/pharmacodynamic review (part II)." Clinical pharmacokinetics 18.6 (1990): 460-71

Huang, Xiaohua, et al. "Everything we always wanted to know about furosemide but were afraid to ask." American Journal of Physiology-Renal Physiology 310.10 (2016): F958-F971.

Maxwell, Robert A., and Shohreh B. Eckhardt. "Furosemide." Drug Discovery. Humana Press, Totowa, NJ, 1990. 67-77.

Wile, David. "Diuretics: a review." Annals of clinical biochemistry 49.5 (2012): 419-431.

Lang, H-J., and M. Hropot. "Discovery and development of diuretic agents." Diuretics. Springer, Berlin, Heidelberg, 1995. 141-172.