Drug distribution and excretion Flashcards
Distribution
Reversible transfer of a drug between the blood and the extra vascular fluids and tissues of the body eg muscle, fat, brain
What 6 things effect tissue distribution?
Disease and other drugs tissue perfusion Membrane characteristics Plasma protein binding Elimination Transport mechanism
Membrane characteristics
Blood-brain barrier
Blood testes-ovary barrier, lipid soluble drug, active transport
Plasma protein binding
Drug bound to albumin eg phenytoin
Binding is reversible and can be changed in response to renal failure, pregnancy etc.
Is an unbound drug active or inactive
Active
What 3 things effect the therapeutic range
- Clearance
- Volume of distribution
- Half life
Clearance (ml/min)
Theoretical volume of fluid from which a drug is completely removed over a period of time
What is clearance dependent on?
- Metabolism and biliary secretion
- Concentration and urine flow
Volume of distribution (Vd)
Volume in which the amount of drug would be uniformly distributed to produce the observed blood concentration
What does a greater Vd mean?
Greater ability to diffuse into/through membrane
What should the Vd be?
42L
Half life (t1/2)
Time taken for the drug concentration in the blood to decline to half of current value
Depends on Vd and clearance
What does an increased half life mean?
Increased toxicity
To have an effect what should a drugs concentration and half life be?
- Steady concentration between therapeutic range
- 4-5 half lives before stabilisation
Drug elimination
Removal of active drug and metabolites from body
Determines length of action
What does drug elimination depend on?
Drug metabolism (liver) and excretion (kidneys)
What are the primary organs for drug excretion?
Kidneys - renal failure cause toxicity
How much does glomerular filtration filter a day?
190L of unbound drug
Passive tubular reabsorption
Through tubule into circulation - distal tube and collecting duct - unionised eg weak acid
Active tubular secretion
Secrete into proximal tube ( acid and alkali)
Protein bound cationic and anionic drug
How much drug elimination does bilary secretion make up?
5-95%
How much bile does the liver secret a day?
1L
Describe biliary secretion
Drugs secreted into bile and reabsorbed in circulation -enterohepatic circulation
Occurs until drug metabolised in liver or excreted
What does metabolism in liver lead to?
Conjugation of drug - not reabsorbed from intestine
What does liver damage lead to?
Decreased conjugation and biliary secretion
Build up and reabsorption of drug = TOXICITY
