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

THIAZIDE DIURETIC

• Thiazide diuretics group includes chlorthiazide, hydrochlorthiazide, bendrofluazide, cyclopenthiazide.
• These drugs are more potent than carbonic anhydrase (CA) inhibitors. Most thiazides are weak inhibitors of CA, but this is not the basis of their action.
• Site of action of thiazide diuretic is at the distal tubule (hence they are medium acting diuretics) where there is only a small amount of reabsorption of sodium since most of the Na⁺ is already absorbed in the earlier parts of the nephron.
• In the distal tubule, Na⁺ is reabsorbed via a Na⁺ Cl^- co-transport.
• Thiazides inhibit this co-transport mechanism, thus preventing Na⁺ from being reabsorbed.
• Thiazides may also inhibit the Na⁺ K⁺ ATPase indirectly.
• Due to Na⁺ K⁺ counter exchange at the collecting tubule, potassium loss may be induced by these drugs leading to serious hypokalemia.
• The thiazides are active by mouth as well as by parenteral administration.
• Their effects are fairly slow in onset.
• Thiazides are used in the treatment of oedema in cardiac failure. In hepatic cirrhosis, much K⁺ loss is not appreciable.
• Hence thiazides are given in conjunction with K⁺ tablets or with a K⁺ sparing diuretic.
• Thiazides are secreted in the kidney via the organic acid secretary system.

Side effects

• Hypokalemia
• Increase in blood sugar (hyperglycemia), especially in diabetics,
• Reduced insulin also causes increased glycogenolysis and reduced glycogenesis.
• Thiazides may cause a reduced excretion of uric acid, leading to gout. The thiazides are sulphonamides, and so share cross reactivity with other drugs of this group.
• Therefore, if a patient is allergic to a sulphonamide, chances are that the patient will also be allergic to thiazides.
• Photosensitivity and haemolytic anaemia may occur.