ADME Flashcards
(26 cards)
Why are some drugs administered in their inactive prodrug form?
- Active drug has very low oral bioavailability.
- Prodrug has greater oral bioavailability.
- Prodrug is metabolised to form greater [active drug] in plasma that what would have been achieved by taking active drug directly.
Where in the body does drug metabolism occur?
- Mainly in the liver.
- Can occur in plasma (e.g. suxamethonium, a drug used in anaesthesia to produce relaxation of the muscles)
- Can occur in intestine (e.g. cocaine).
What happens in Phase I metabolism?
Drug derivative is formed by oxidation, reduction or hydrolysis. Often introduces / exposes a reactive site on drug molecule.
What is the benefit of drug derivatives produced in Phase I metabolism being more reactive?
- More chemically reactive derivative makes phase II reaction more energetically favourable.
What happens in Phase II metabolism?
Conjugation of species formed in phase I with very polar molecules.
Makes metabolite less lipid soluble - more of it excreted in urine.
Reaction often occurs in cytosol of liver cell.
What are microsomal enzymes?
Drug metabolising enzymes found in the ER of liver hepatocytes.
Name the five factors that affect drug metabolism.
- Enzyme Induction
- Enzyme Inhibition
- Genetic Polymorphisms
- Disease
- Age
How do genetic polymorphisms affect drug metabolism?
- Mutations in genes that code for microsomal enzymes (involved in drug metabolism) affect rate of drug metabolism.
What are the consequences of enzyme induction?
- Failure of drugs to produce therapeutic effect.
- Increased clearence, decreasing half-life of drug.
- Steady state plasma concentration of drug (Css) will be less.
Which of the following will have a quicker effect on drug metabolism?
- Enzyme Induction
- Enzyme Inhibition
Enzyme Inhibition
What is the effect of disease on drug metabolism?
Hepatitis, Liver Cancer and cirrhosis will reduce liver function (slower metabolism of drugs).
Diseases that reduce renal function (drugs excreted without metabolism).
Overactive / underactive thyroid (increased thyroid activity = increased rate of metabolism).
Cardiovascular diseases will affect rate of delivery of drug delivery in blood to liver / kidneys.
Give 3 examples are parenteral routes of administration.
- IV
- IM
- Subcutaneous Injection
What is an advantage of the subcutaneous route of drug administration?
Easier than IV or IM so can-self-administered, ideal for drugs like insulin: cannot be taken orally as stomach will digest drug molecule.
What does the oral bioavailability value (F) represent?
Fraction of oral dose that reaches the systemic circulation.
Give 3 factors that affect the oral bioavailbility of a drug.
- Poor absorption from the gut.
- Breakdown of drug in gut.
- First pass effect.
What is the most important factor affecting drug absorption at a membrane?
Lipid solubility of the drug.
Why may the apparant volume of distribution for a drug be greater than the total body volume?
Drug may have accumulated in tissues leading to a relatively low plasma concentration, but a large amount of drug in the body.
What are the 3 key pharmokinetic parameters?
- Volume of Distribution (Vd)
- Plasma half-life of drug (t0.5)
- Clearance (Cl)
Define the term excretion.
The movement of drug from inside to outside of body.
Define the term elimination in terms of drugs.
Overall removal of drug from body. Includes excretion and metabolism.
What does the half-life of a drug represent?
Time it takes for the [Drug] in the plasma to fall to half its initial value from where it is measured.
What does it mean for a drug to be pseudo-zero order?
At high [Drug] it is zero order (when elimination process is saturated), at low [Drug] it is first order.
How many half-lives (roughly) does it take to achieve steady state (Css)?
5 half lives
How would a greater rate of infusion influence the Css of a drug?
Css would be higher.
