ADME part 3 Flashcards
What are the sites of drug excretion?
The kidney (which is the most important site)
Biliary excretion for drugs with high molecular weight
The lungs for anaesthetic gas
What is enterohepatic recirculation?
Drugs which are excreted in the bile may be reabsorbed as enzymes like beta-glucuronidase from the gut microflora can reverse the metabolism of a drug so it can be reabsorbed
What is the relationship between the molecular weight of a drug and its excretion method?
An increased molecular weight will mean an increase in the amount of the drug which is excreted in the faeces
What are the three processes of renal excretion?
Glomerular filtration of the unbound drug
Active secretion of both free and protein bound drug by transporters
Filtrate is 100-fold concentrated in the tubules with a favorable gradient for drug reabsorbtion (passive diffusion)
What are the factors that alter the renal excretion of drugs?
Competitive inhibition of tubular secretion (acts on transporters)
Influence of pH
Influence of urinary flow rate
How does pH influence renal excretion?
Sodium Bicarbonate can be used to alkalinise urine and increase the excretion of weak acidic drugs as a higher proportion of them will be ionized inside the tubule preventing them from diffusing out of the tubule
Ammonium Chloride can be used to acidify the urine to have the same effect for basic drugs
What is the influence of urinary flow rate?
In increase in urinary flow results in a decrease of the concentration of drug in the tubule resulting in decreased gradient for reabsorption and therefore results in increased excretion of drug
What is glomerular filtration rate?
It is the total volume of filtrate produced per unit time by all functioning nephrons (roughly 10% of renal blood flow or 20% of plasma flow)
How is glomerular filtration rate used in dose adjustment?
It can be used as an index of renal function so that potentially toxic drugs which are primarily excreted by this method can have their dosage adjusted to prevent adverse effects
In what situations may the glomerular filtration rate be altered?
It can be decreased by renal disease, reduction in renal blood flow or old age potentially leading to the accumulation of drugs and metabolites excreted by these routes
It can be increased by preganacy
How can glomerular filtration rate be measured?
Inulin (an inert polysaccharide) can be used however the process is invasive as it requires it to be injected and may also require 24 hour urine collection which is impractical
Creatine is an endogenous product from muscle catabolism is more commonly used as it simply requires the taking of a single blood sample and the measurement of creatine in this sample
