Transcript Diuretics, ….

Diuretics
Why do we want to know
about diuretics?
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What do kidneys do?
What can go wrong?
Interventions that can be used
how do they work?
Effects, side effects
Functions of the kidney?
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Excretion of waste products
regulation of salt and electrolyte content
and volume of extra -cellular fluid
acid -base balance
How?
• Several hundred litres of plasma filtered/day
• filtrate - very little protein/protein bound
substances
• 99% of sodium is reabsorbed, some
substances secreted
• 1.5 litres voided as urine
• Diuretics increase salt and water excretion
Why diuretics?
• important group of drugs employed for their
effects on the kidney to enhance salt and
water excretion (only when needed)
• when used: heart failure, other causes of salt
and water retention (renal failure, liver
failure), hypertension
Variety of compounds with
diuretic activity
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Xanthines - theophylline, caffeine
osmotic diuretics - urea
carbonic-anhydrase inhibitors
thiazides
loop diuretics
aldosterone antagonists
potassium sparing diuretics
How do they work?
• Direct effect on cells of the nephron..
• where most of the active and selective solute
reabsorption occurs
• ascending loop of Henle
• early distal tubule
• collecting tubules and ducts
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• modifying the content of the filtrate by their
presence
Loop diuretics (Rang and Dale p361-363)
• Frusemide, bumetanide, piretanide
• act on thick segment of ascending loop
• inhibit NaCl transport OUT of tubule by inhibiting
Na+/K+/2Cl- carrier (co-transporter) in luminal
membrane ( acting on chloride binding site)
• Reduces the hypertonic interstitial area in the medull,
so reducing water re-absorption
• increases Na+ solute concentration in the distal tubule
which is exchanged for K+ and H+ (hypokalemia and
alkalosis)
• Can increase the excreted sodium from 1% to 15% of
filtrate
• Also reduce peripheral vascular resistance
Loop diuretics
• Kinetics
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oral and IV preparations
bound to plasma protein, secreted into tubule
metabolised by the liver ( P450)
act within 1 hour
half life about 90 minutes; longer in renal
failure
• duration - 3-6 hours (Lasts Six Hours – Lasix)
Loop diuretics
• Effects
• pass urine – in large amounts!
• Side effects
• electrolyte depletion
• Hypovolemia
• other reactions rare
• Main Use
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Heart failure – particularly acute left ventricular failure
Hepatic cirrhosis
Nephrotic syndrome
Renal failure
thiazide diuretics
• bendrofluazide, hydrochlorothiazide,
indapamide
• act on distal convoluted tubule
• bind to chloride site of Na+/Cl co–transport
system and inhibit action
• decrease active Na resorption
• decrease water resorption
• changes in Ca, magnesium and uric acid
thiazide diuretcis
• kinetics
• rapidly absorbed orally
• secreted into the tubule
• maximal effect 4- 6 hours, duration 8-12 hours
thiazide diuretics
• effects
• increase urine output
• side effects
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electrolyte disturbances
increased cholesterol
impotence
hypersensitivity reactions (rare)
• Main uses
• hypertension
• mild heart failure
aldosterone antagonists
• spirololactone
• inhibits action of aldosterone (intracellular receptor
binding anatagonism), increases sodium and decreases
potassium secretion
• kinetics
• well absorbed orally, active metabolite half life of 16
hours
• effects
• limited diuresis
• Main uses – heart failure and cirrhosis
• side effects
• Hyperkalemia, estrogen like effects
other potassium sparing diuretics
• Triamterene, amiloride
• act on collecting ducts
• inhibit Na resorption, decrease potassium
excretion
• effects
• limited diuresis
• side effects
• electrolyte disturbances
clinical choices
• Uses:
• cardiac failure
• hypertension
• fluid overload
• NOT for everyone with oedema (eg from
venous insufficiency)
• acute versus chronic
• evidence of benefit
references
• Rang & Dale, 5th edition
• Cardiovascular Therapeutic Guidelines
• Australian Medicines Handbook