Drugs and the kidney

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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)

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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)

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Normal handling of drugs

• Mechanisms
• Glomerular filtration
• Active tubular secretion
• Passive diffusion across tubular epithelium

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Which means that.

• 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.

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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

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So what does this mean?

• extended half-life

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Potential for increased toxicity

• Drugs with a narrow therapeutic index will
  require a reduction is dose to prevent toxicity.

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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

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Does it matter?

• Applies to
• Gentamicin
• Methotrexate
• Atenolol
• Digoxin
• Benzylpenicillin
• Lithium

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Managing patients

• Dealing with oedema
• Options?
• Decrease fluid intake
• Increase salt/water excretion
• Others?

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diuretics

• Increase the excretion of Na and therefore water
  from the body at the kidneys
• decrease reabsorption of Na and Cl- from the
  filtrate
• increases the excretion of water due to the
  hypertonicity of the filtrate

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Overview (Rang 5th Edition)
thiazides
amiloride
Loop diuretics
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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)

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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

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Loop Diuretics

• Indications
• Generally fluid overload states
• Pulmonary oedema
• Adjunctive management in cardiac failure
• Electrolyte disturbances where decreased calcium
  or potassium is desirable

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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.

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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

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Potassium sparing diuretics

• Effects
• Limited diuretic efficacy
• Mildly uricosuric
• Indications
• Combination with thiazides to prevent hypokalemia
• Spironolactone in heart failure, liver disease

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references

• Rang Dale Ritter and Moore (5th Edition)
• Australian Medicines Handbook