Thiazide And Thiazide Like Diuretics

Question 1

What are some of the drugs in this class?

Answer 1

Thiazides (benzothiadizine derivatives): chlorothiazide, hydrochlorothiazide

Thiazide-like (sulfanamides)
1. Indapamide
2. Chlorthalidone
3. Metolazone
4. Xipamide
5. Clopamide

Question 2

What is their MOA?

Answer 2

• They work by inhibiting Sodium and chloride reabsorption in the early distal convoluted tubules which leads accumulation of sodium in the tubules thereby leads to water excretion (dependent on kidney function)
• increased sodium excretion leads to increased calcium resorption to compensate

Question 3

what are their pharmacokinetics?

Answer 3

They are well absorbed from the GIT, they begin their action within an hour and are excreted by the kidneys

Question 4

What are their therapeutic uses?

Answer 4

1. Mild or moderate essential hypertension: thiazide diuretics have long been the drug of choice for the treatment of hypertension (not anymore) due to their low cost, convenience of administration and well-tolerance, it takes 1-3 weeks to reach a steady drop in BP.
2. CHF: can be used in combination with loop diuretics (which are the drug of choice for this case) to increase efficacy
3. Hypercalciurea: they can be useful in the treatment of idiopathic hypercalciurea because they inhibit Ca excretion, this is particularly useful in patients with calcium renal stones.
4. Diabetes insipidus; thiazides have a unique ability to produce hyperosmolar urine (when sodium is excreted the body enters a hypovolemic state which induces the production of aldosterone, which increases water retention thereby decreasing the overall lost fluid from 11 l/day to just 3/day)

Question 5

What are their side effects?

Answer 5

1. Electrolyte imbalance:
   A. Hypokalemia (hypokalemic metabolic alkalosis)
   B. Hyponatremia (in short term use)
2. Hyperuricemia
3. Volume depletion (true of all diuretics)
4. Hyperglycemia: decreased insulin production and tissue uptake of glucose
5. Hyperlipidemia: up to 15% increase in serum cholesterol and LDL, lipid levels can level out in long term therapy
6. Hypersensitivity which can lead to bone marrow suppression, dermatitis, interstitial nephritis, necrotizing vasculitis (all are rare) esp. occurring in pts with sulfa- drugs sensitivity.