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🏥 Renal Pharmacology — Diuretics (MUHS Exam Notes)

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What are Diuretics?

Types (Easy Table):

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1. Carbonic Anhydrase Inhibitors (e.g., Acetazolamide)

Site of Action: PCT (Proximal Convoluted Tubule)

How it works (Simple):

• Normally, kidneys reabsorb sodium + bicarbonate (HCO₃) using an enzyme called carbonic anhydrase.
• Acetazolamide blocks this enzyme → so bicarbonate + sodium stay in the urine and are excreted.
• This causes mild diuresis (not used as primary diuretic — too weak).

Uses:

1. Glaucoma — Reduces fluid (aqueous humour) in the eye → lowers intraocular pressure (IOP)
   • Acetazolamide: oral/IV for acute glaucoma
   • Dorzolamide, Brinzolamide: eye drops for chronic glaucoma
2. Alkalinize urine — To treat poisoning with acidic drugs (e.g., aspirin)
3. Acute Mountain Sickness — Acetazolamide reduces CSF formation, helps in prevention + treatment

Side Effects (Adverse Effects):

• Hypersensitivity (skin rash, fever, nephritis)
• Drowsiness, tingling (paraesthesia)
• Hypokalaemia (low potassium)
• Metabolic acidosis
• Headache
• Renal stones

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2. Osmotic Diuretics (e.g., Mannitol, Glycerol)

How it works (Simple):

• Mannitol is given IV — it's not absorbed or metabolized in the body.
• Freely filtered at the glomerulus → stays in the tubule → pulls water along with it (osmotic effect).
• Site of action: Loop of Henle + proximal tubule

Uses:

Side Effects:

• Too much IV Mannitol → pulmonary oedema (fluid overload in lungs)
• Headache, nausea, vomiting
• Glycerol can cause hyperglycaemia

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3. Loop Diuretics (High-Ceiling) — Most Important!

Drugs: Furosemide, Bumetanide, Torsemide

Site of Action: Thick Ascending Limb of Loop of Henle

How it works (Simple):

• Loop diuretics block the Na-K-2Cl cotransporter on the luminal side → Na, K, Cl cannot be reabsorbed → all excreted in urine.
• More Na reaches the DCT → exchanges with K → K is lost (hypokalaemia risk).
• Also increases excretion of Ca²⁺ and Mg²⁺.
• Furosemide also weakly inhibits carbonic anhydrase → slight HCO₃ loss too.

Pharmacokinetics:

• Rapidly absorbed orally
• IV onset: 2–5 min | IM onset: 10–20 min | Oral onset: 30–40 min
• Duration of action: 2–4 hours (short)
• Routes: Furosemide & Bumetanide — oral, IV, IM | Torsemide — oral, IM

Uses:

1. Cardiac & renal oedema — First choice in initial stages
2. Hepatic oedema — Useful but avoid vigorous diuresis (risk of hepatic coma)
3. Hypercalcaemia — IV Furosemide + isotonic saline promotes Ca excretion
4. Cerebral oedema — Loop diuretics can be used (IV mannitol preferred though)
5. ❌ NOT preferred in uncomplicated hypertension — too short-acting

Adverse Effects:

• Hypokalaemia (most important) → fatigue, muscle weakness, cardiac arrhythmias. Prevent with K-sparing diuretic or K supplements.
• Hyponatraemia — low sodium
• Hypocalcaemia + Hypomagnesaemia → Mg loss can cause cardiac arrhythmias

• Hyperglycaemia — decreased insulin secretion
• Hyperuricaemia — decreases uric acid excretion → can trigger gout
• Hyperlipidaemia — raises triglycerides + LDL

• Usually reversible on stopping drug
• Risk ↑ with renal impairment or combined with cyclosporine/aminoglycosides

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4. Thiazides (Medium Efficacy)

Drugs: Hydrochlorothiazide, Metolazone, Chlorthalidone

Site of Action: Early Distal Convoluted Tubule (DCT)

How it works (Simple):

• Thiazides block Na-Cl symport in early DCT → Na and Cl excreted in urine.
• More Na delivered to late DCT → more Na-K exchange → K is lost.
• They reduce urinary Ca excretion (opposite to loop diuretics — useful in kidney stones!).

Uses:

Adverse Effects:

• Hypokalaemia — more common than loop diuretics (longer acting)
• Hyponatraemia, Hypomagnesaemia
• Hypercalcaemia — opposite of loop diuretics

• Hyperglycaemia
• Hyperlipidaemia
• Hyperuricaemia (gout risk)

• Impotence — not preferred in young males for hypertension
• Skin rash, photosensitivity, nausea, vomiting, diarrhoea

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5. Potassium-Sparing Diuretics — Spironolactone

Site of Action: Late DCT + Collecting Duct (CD)

How it works (Simple):

• Aldosterone normally enters cells in late DCT/CD → binds to mineralocorticoid receptors (MR) → signals the cell to retain Na and excrete K.
• Spironolactone is a synthetic steroid that competitively blocks MR → so aldosterone can't work → result: Na is excreted, K is retained.
• Most effective when aldosterone levels are high.
• Also increases Ca²⁺ excretion.

Uses:

Main Adverse Effect:

• Hyperkalaemia (high potassium) — most important and dangerous side effect

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Quick Exam Comparison Table

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Key Points to Remember for MUHS Exams:

1. Furosemide = most commonly used loop diuretic; fastest IV onset (2–5 min)
2. Acetazolamide is used for glaucoma + mountain sickness, NOT as diuretic
3. Mannitol = only osmotic diuretic given IV; used for raised ICT and IOP
4. Thiazides retain calcium → used in calcium kidney stones; Loop diuretics lose calcium
5. Spironolactone = potassium-SPARING (retains K); all others cause K loss
6. Hypokalaemia is the most common adverse effect of both loop + thiazide diuretics
7. Ototoxicity = loop diuretics (furosemide) → risk ↑ with aminoglycosides
8. Loop diuretics are not preferred in hypertension (too short-acting)
9. Metolazone is the only thiazide that works even when GFR is low
10. Spironolactone prevents cardiac remodelling in heart failure