Drug excretion 2 Contents '''

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Drug excretion 2Contents ...

• Other routes of excretion
• Biliary
• Pulmonary
• Mammary
• Salivary

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Routes of excretion
Major routes of elimination

• Renal ?
• Biliary
• Pulmonary

Significant for other reasons

• Mammary - Delivery to baby
• Salivary - Drug monitoring

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Biliary excretion
Bile formed in large volumes in the liver Most
of the water re-absorbed Concentrated bile
stored in the gall bladder Bile secreted into
the upper small intestine
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Biliary excretion

• Similar to kidneys
• Lipid soluble drugs filter initially, but get
  re-absorbed along with the bulk of the water.
  Not excreted efficiently.
• Acids and bases have active secretion mechanisms.
• BUT
• only works effectively if Mol Wt high enough.
  Limit varies for different species. (gt300-500
  for humans)

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Biliary excretion

• Most drugs Mol Wt too low for efficient biliary
  excretion.
• Conjugation to glucuronide often increases Mol Wt
  sufficiently for biliary excretion.
• Acetate or glycine generally too small.
• Bile is significant route of excretion for
• Glucuronide conjugates (e.g. morphine)
• Limited number of ionised drugs with very high
• Mol Wt (e.g. cromoglycate)

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Entero-hepatic circulation
Free
Conjugates in bile
Liver
Conjugates
Free
Small intestine
Colon
Mainly bacteria in colon that hydrolyse the
conjugates
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Pulmonary excretion
Excretion via the lungs and breath. Significant
route of excretion for some volatile molecules -
especially anaesthetics.
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Mammary - (milk)

• No active secretion, just passive diffusion.
• Concentration in milk reflects free
  concentration in blood (apart from ion trapping).
• Milk is slightly acid (pH 7.0) compared to
  blood (pH 7.4).

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Erythromycin in milk
Blood (pH 7.4) Milk (pH 7.0)
Non-ionised Non-ionised
Ionised Ionised
Lipid
Erythromycin concentrations approx 8 times higher
in milk than blood.
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Drugs in milk -clinical significance

• Mainly the effect of the drug on the baby. e.g.
• Chloramphenicol Possible bone marrow
  suppression.
• Diazepam Accumulation and sedation.
• Heroin Prolonged neonatal dependence.
• Methadone Possible withdrawal syndrome if
  breast feeding stopped suddenly.
• Propylthiouracil Suppression of thyroid
  function.
• Tetracycline Permanent staining of infant teeth

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Saliva

• Significant because of possible use in drug
  monitoring.
• Pharmacokinetic experiments often need serial
  blood samples (10 or more). Ethical approval?
  Saliva sampling is non-invasive.
• Neutral molecules - salivary concentrations do
• reflect free concentrations in plasma. Has
  been
• used for antipyrine.
• Ionised drugs are a problem. Saliva pH is
• variable - variable degree of ion trapping.

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Terms with which you should be familiar ...

• Biliary excretion
• Pulmonary excretion
• Mammary excretion
• Salivary excretion
• Enterohepatic circulation

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What you should be able to do

• Describe how drugs may be added to or removed
  from bile, including the significance of
  molecular weight.
• Describe the process of enterohepatic
  circulation.
• Describe the movement of drugs into milk and
  the possible consequences for the baby.
• Describe the potential for replacing blood
  sampling by saliva sampling.