Diuretics

Name of Drug Subdivisions/ Mechanism of Action Clinical Uses Side Effects Other Notes
Site of Action
Loop Diuretics Thick ascending Inhibit Na/K/Cl co-transporter Oedematous state decreases 1. Hypokalaemia Strongly plasma
loop of Henle (NKCC2)  Reduce pulmonary oedema of 2. Hypocalcaemia protein bound.
 Furosemide (Lasix) reabsorption of Na/K/Cl. congestive heart failure 3. Hypomagnesia Acts within 1 hour
 bumetanide (Bumex) 4. Hypovolemia  orally.
(oral, IV, parenteral) Bind to Cl site. Reducing intracranial pressure. reduced blood volume, Very rapid onset
hypotension, shock when given IV.
Hypercalcaemia: arrhythmias
Increases tubular Ca2+ secretion
thus decreasing Ca2+ conc. in 5. Hyperuricaemia  gout
blood. 6. Hyperglycaemia

7. Ototoxicity (rare) 
Permanent damage in
hearing; worsens with
aminoglycoside
antibiotics.

Thiazides Distal Tubule Inhibit Na/Cl co-transporter Hypertension 1. Hypokalaemia Orally and IV.
(NCC) on the luminal membrane. 2. Hypercalcemia
 chlorothiazide/ diuril Reduce extracellular volume in Take 1-3 weeks
(potent) Bind to Cl site. mild/moderate CHF 3. Hyperuricemia  gout for stable
 hydrochlorothiazide 4. Hyperglycaemia reduction in BP.
(more potent) Promote loss of K+ and Prevents recurrent kidney stone 6. With continued use 
 chlorthalidone reabsorption of Ca2+ into blood formation in idiopathic reduced peripheral Used in
(oral) (increases strength of normal hypercalciuria vascular resistance due to combination with
process). relax of arteriolar smooth thiazides.
Diabetes Insipidus (can replace muscle.
Inhibit secretion of Ca2+. ADH) 7. Dizziness due to volume
depletion
8. Hypersensitivity - bone
marrow suppression &
dermatitis.
K-sparing diuretics Distal tubule Spironolactone: aldosterone
antagonist. Competes with
 Spironolactone aldosterone for intracellular
[synthetic Collecting receptors, prevents
aldosterone duct translocation of receptor complex
antagonist] into nucleus preventing
(oral) transcription, translation of
mediator proteins that normally
 Triamterene stimulate Na+/K+ exchange
 Amiloride  prevents Na+ reabsorption
and K+ and H+ secretion.
Triamterene & Amiloride: inhibit
luminal Na+ channels in DCT/CD.
Osmotic Diuretics Filtrate Substances filtered in the
glomerulus but not reabsorbed
 Mannitol increase osmolarity of filtrate to
 Urea promote urinary water retention.
Carbonic Anhydrase Proximal Sulphonamide without
Inhibitors Convoluted antibacterial activity.
Tubule
Inhibiting intracellular and
 Acetazolamide luminal carbonic anhydrase.
Decreased ability to exchange H+
and Na+ causes mild diuresis.
Spironolactone: Spironolactone: Spironolactone
1. Hyperkalaemia rapidly
Hypertension 2. Nausea, lethargy, metabolised to
confusion canrenone.
Promote K+ retention w/ loops or 3. Gynecomastia (Male)
thiazides. 4. Menstrual irregularities
Secondary Hyperaldosteronism.
Reducing intracranial pressure
(iv mannitol increases blood
osmolality relative to the brain --
pulling water from the brain to
restore osmolar balance)
Acute Renal Failure
Non-renal uses: Only a weak diuretic effect
since loop of Henle
Chronic glaucoma: reabsorbs large amounts
Reduce the elevated intraocular of Na+.
pressure. Decreases production
of aqueous humour, by blocking
carbonic anhydrase in ciliary
body of eye.
Prophylaxis of acute
mountain sickness:
given nightly 5 days before
ascent above 10,000ft prevents
weakness, breathlessness,
dizziness, nausea and cerebral
& pulmonary oedema.
Efficacy:
Increase in excretion of Na+ varying from:
 ~0.1 - 2% control (no diuretic)
 ~2 - 3% for weak potassium-sparing diuretics
 ~10% thiazides
 ~20-30% for potent loop diuretics

Recall:
 K+ sparing diuretics reduce K+ loss.
 Thiazides reduce Ca2+ loss.

Recall Relevant Drug Targets:

 SGLT2 is the target for Gliflozins (e.g., Dapagliflozin) which are used to lower blood glucose in diabetes