| Class | Thiazide |
|---|---|
| Chemistry |
Benzothiadiazine |
| Routes of administration |
Oral only |
| Absorption |
Oral bioavailability 65-75% |
| Solubility |
pKa 9.09; practically insoluble in water |
| Distribution |
VOD= 1.5-4.2L/kg; 40-68% protein bound |
| Metabolism |
Does not undergo any hepatic metabolism |
| Elimination |
Virtually all of the dose is eliminated renally; half life is 6-9 hours |
| Time course of action |
With oral dosing, peak effect is seen within 1-2 hours; mortality-reducing antihypertensive effects develop over months and years |
| Target receptor |
NCC sodium/chloride cotransporter in the distal convouted tubule |
| Mechanism of action |
By decreasing the reabsoprtion of sodium and chloride in the distal convoluted tubule, thiazides block the reabsorption of up to 5% of the total filtered sodium. This increases the delivery of sodium 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. |
| Clinical effects |
Hypokalemia, hyponatremia, unexplained vasodilatory antihypertensive effects in the long term |
| Literature reference |
FDA PI data sheet |
| CICM details of understanding | Not specifically listed in the CICM syllabus |
| Mentioned around Deranged Physiology | |
| Related SAQs |
Question 17 from the second paper of 2022 |