Transcript Drugs and the kidney 2006

Drugs and the kidney
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What does the kidney do to drugs?
What do drugs do to the kidney (in a
therapeutic sense)
Normal kidney function
Excretion of wastes, drugs, drug
metabolites and such as
Urea
Uric acid
Creatinine
Regulation of NaCl and electrolyte content
(aldosterone, natriuretic peptides)
Regulation of water balance (anti-diuretic
hormone)
Normal handling of drugs
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Mechanisms
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Glomerular filtration
Active tubular secretion
Passive diffusion across tubular epithelium
Which means that….
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Most drugs (unless protein bound) cross the
glomerulus
Some drugs are actively secreted into the
tubule (pH-dependant) (eg penicillin –
blocked by probenecid)
Lipid soluble drugs are passively reabsorbed
(not excreted in the urine)
Some important drugs are predominantly
excreted by the kidney – a problem in the
elderly or patients with kidney disease….
clearance
CLr =
CuVu
Cp
Volume of plasma containing amount of
substance removed by the kidney in
unit time
Cu – concentration in the urine
Vu rate of flow of volume of urine
Cp plasma concentration
So what does this mean?
extended half-life
Potential for increased toxicity
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Drugs with a narrow therapeutic index will
require a reduction is dose to prevent toxicity.
In effect
keep the usual dose but prolong the dosing
intervals (eg gentamicin)
decrease the maintenance dose without
changing dosing intervals (eg digoxin)
Monitor blood levels of drug
Does it matter?
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Applies to
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Gentamicin
Methotrexate
Atenolol
Digoxin
Benzylpenicillin
Lithium
Managing patients
Dealing with oedema:
Options?
 Decrease fluid intake
 Increase salt/water excretion
 Others?
diuretics
Increase the excretion of Na+ and
therefore water from the body at the
kidneys
decrease reabsorption of Na+ and Clfrom the filtrate
increases the excretion of water due to
the hypertonicity of the filtrate
Overview (Rang 5th Edition)
thiazides
amiloride
Loop
diuretics
Summary
Sites of effect
Ascending loop of Henle – inhibit Na+
absorption(Loop diuretics)
Distal tubule - inhibit Na+ and Cl(thiazides)
Collecting tubules and ducts - blocks Na+ K+ exchange (amiloride, spironolactone &
triamterene – so called ‘potassium sparing’)
Osmotic Diuretics
Pharmacologically inert substances which
are filtered into the glomerulus (eg
mannitol) and incompletely reabsorbed or
not reabsorbed by the nephron
Prevent the reabsorption of water and Na
due to osmotic pressure
Indications
Cerebral swelling
Loop Diuretics
Indications:
Generally fluid overload states:
Pulmonary oedema
Adjunctive management in cardiac failure
Electrolyte disturbances where decreased
calcium or potassium is desirable
Loop diuretics
effects:
Vigorous diuretic effects
reduces accumulation of oedema – can cause
hypovolaemia, hyponatremia.
decreases potassium and magnesium reabsorption,
hypokalaemia.
Decreases calcium reabsorption → hypercalcinuria,
hypocalcaemia.
Ototoxicity - dose-related hearing loss that is usually
reversible. Most common in patients who have
diminished renal function and high doses.
thiazides
Effects:
 Diuresis – much less marked than with loop diuretics
 Increase potassium excretion
 Decreased excretion of uric acid
 Increased chloride excretion →hypochloraemic
alkalosis
Indications:
 Hypertension
 Less commonly oedema, fluid retention
Potassium sparing diuretics
Effects
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Limited diuretic efficacy
Mildly uricosuric
Indications
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Combination with thiazides to prevent hypokalemia
Spironolactone in heart failure, liver disease
references
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Rang Dale Ritter and Moore (5th Edition)
Australian Medicines Handbook