Diuretics Flashcards
What is a diuretic?
a drug that increases excretion of both fluids and electrolytes
Natriuretic
increases Na+ secretion
Kaliuretic
increases K+ secretion
Aquauretic
increases water secretion
Most diuretics act by
- increased excretion of Na+ and
water by the kidneys - natriuretic
- decreased reabsorption of Na+ from
filtrate, and increasing water loss
secondary - generally on luminal side of
nephron - some modify the content of the
filtrate
When do we use diuretics?
- chronic heart failure
- cirrhosis
- nephrotic syndrome
- glaucoma (high pressure in the eye)
Is water a diuretic?
under normal conditions, increased water intake leads to increase in volume of urine excreted
process controlled by ADH
Results of reduced expression of aquaporin 2 channels results in
- water excretion
- if on apical surface of DCT and
collecting duct
Drugs that act via ADH:
- alcohol (inhibit ADH, urinate
more) - nicotine and morphine (increase
ADH) - demeclocycline (ADH
antagonist’(SIADH)) - Tolvaptan (SIADH)
Nephron and fluid re-absorption
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5 drug classes of diuretics and where they act:
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Where do diuretics act?
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Core Drug: Furosemide: Which drug class?
Loop Diuretics
Core Drug: Furosemide: Molecular Mechanism of Action:
- blockage of Cl- channel of
NA+/K+/2Cl co- transported in thick
ascending limb of loop of henle - prevents Na+ and Cl- entering
interstitial fluid - increased loss of Na,K,Cl and water
- hence water also remains in LOH
lumen - very powerful
Core Drug: Furosemide: Pharmacological Effect Lasts:
6 hours
Core Drug: Furosemide (loop Diuretic): Side Effects:
- **hypokalaemia (arrhythmias)
- **ototoxicity (auditory nerve
damage) - Hyperuricaemia (gout)
- dehydration
- renal impairment
Core Drug: Furosemide (loop diuretics): Cause of hypokalaemia:
- increase Na+ delivery to DCT where
it is exchanged for K+, which is then
excreted in the urine
Core Drug: Furosemide (loop diuretics): most used for:
- peripheral oedema
- pulmonary oedema
Core Drug: Bendroflumethiazide: Drug Class:
- Thiazide Diuretic
Core Drug: Bendroflumethiazide (thiazide diuretic): Molecular Mechanism of Action:
- blocks apical Na+/Cl- co-transported
both leaving lumen into interstitial
space) in DCT - K+ is also involved
- less powerful than loop diuretics
Core Drug: Bendroflumethiazide (thiazide diuretic): Molecular Mechanism of Action:
- blocks Na+/Cl- co-transported (both
leaving lumen into interstitial space) - K+ is also involved
Core Drug: Bendroflumethiazide (thiazide diuretic):
Core Drug: Bendroflumethiazide (thiazide diuretic: Effect lasts for:
Upto 24 hours
Core Drug: Bendroflumethiazide (thiazide diuretic): Clinical Uses:
antihypertensive
Core Drug: Indapamide: Drug Class:
Thiazide-like diuretics
Core Drug: Indapamide (thiazide-like diuretic): Molecular Mechanism:
- activates K+ATP channels in smooth
muscle of blood vessels to dilate
arterioles: decreased BP - in kidney acts upon Na/Cl co-
transporter:
- increased Na+ loss
- increased water loss
- decreased blood pressure
Core Drug: Indapamide (thiazide-like diuretic): Side Effects:
Kidney:
- hypercalcaemia (high Ca2+)
- hyponatraemia and kalaemia
- gout
Insulin Resistance:
- increase glucose (diabetes)
Lipids:
- increases lipids (arterial disease)
Core Drug: Indapamide (thiazide-like diuretic): Clinical Uses: (thiazide too)
- urinary tract stones
- nephrogenic diabetes insipidus
Why are thiazides better for hypertension then furosemide?
have a vasodilator effect too; sometimes more than the renal effect
Core Drug: Spironolactone: Drug Class:
aldosterone antagonist/potassium sparing diuretic
Core Drug: Spironolactone: (aldosterone antagonist/potassium sparing diuretic): Molecular Mechanism:
- blocks the upregulation of Na+
channels in the DCT by aldosterone - prodrug: metabolised to active form
canrenone
-
Core Drug: Spironolactone: (aldosterone antagonist/potassium sparing diuretic): effect:
takes a few days to develop
Core Drug: Spironolactone: (aldosterone antagonist/potassium sparing diuretic): Clinical Use:
- add on in resistant hypertension
- first line in hyperaldosteronism
- first line in cirrhosis
helps those with poor LV function and post MI
Core Drug: Spironolactone: (aldosterone antagonist/potassium sparing diuretic): Side Effects:
- impaired renal function
- hyperkalaemia
- gynaecomastia (breasts) and
testicular atrophy (similar structure
to oestregen)
Amiloride is a direct inhibitor of epithelial Na+ channels in the DCT. Amiloride is a potassium sparing diuretic and is mostly used in a fixed dose combination with furosemide.
Explain why.
Furosemide will decrease potassium levels, amiloride will increase potassium
Osmotic Diuretics:
- mannitol
- IV
- undergoes glomerular filtration and
is not re-absorbed; does not cross
BBB - increases water in circulating
plasma and urine - increase in blood vol
Osmotic diuretics are used for cerebral oedema:
- swelling of the brain
- sucks fluid out of the brain into the
blood - lowers intra-cranial pressure
