PED1003/L05 Drug Elimination I Flashcards
Give the 3 factors that affect a drug’s distribution.
Blood perfusion of organ/tissue
Ability to cross a cell membrane
Plasma protein binding ability
Describe the blood brain barrier.
Continuous layer of epithelial cells that makes the brain inaccessible to many drugs
What 3 factors does the amount of drug bound to plasma proteins depend on?
Concentration of free drug
Affinity for binding site
Concentration of protein
Describe albumin. (2)
Binds mostly acidic drugs
Binds small number of basic drugs
Describe a1 acid glycoprotein. (2)
Binds most basic and neutral drugs
Increased inflammatory disease
Define apparent volume of distribution (Vd).
Volume of fluid that would be required to contain the amount of drug in the body (Q) at the same concentration as that present in the plasma (Cp)
What is the equation for Vd?
Vd = Q/Cp
What kind of drug is not eliminated by the kidney?
Lipophilic drugs
What occurs to lipophilic drugs before they can be excreted?
Metabolised to more polar products
Describe the 2 phases of drug metabolism in the liver.
Phase I: catabolic, mostly mediated by Cytochrome P450 enzymes
Phase II: anabolic conjugation reactions
Define hydroxylation.
Conversion of a hydrogen to hydroxyl group
Define deamination.
Conversion of an amino group to a carbonyl group
Define dehydrogenation.
Conversion of a hydroxyl group to a carbonyl group
Describe Cytochrome P450s. (3)
Large family of related but distinct enzymes
Embedded in SER
Require oxygen, NADPH & NADPH-P450 reductase
Give 3 reasons for variations in cytochrome P450.
Species differences
Genetic polymorphisms
Environmental factors
Other drugs
What is the function of butrylcholinesterase (plasma cholinesterase)?
Hydrolyses suxamethonium
Overactivates cholinergic receptors on muscles to cause paralysis
What is the function of aspirin esterase?
Hydrolyses aspirin to salicylate
What is the function of alcohol dehydrogenase? (2)
Oxidises ethanol to acetalehdye
Requires NAD+
Where do phase II reactions usually take place?
Liver, also in lungs/kidneys
What are the usual products of phase II reactions?
Inactive
Give 3 methods of elimination.
Mass transport in gut
Water soluble filtered out in kidney
Volatile gases
Secreted into glands
Define clearance (Cl).
Volume of plasma (or blood) cleared of the drug per unit of time to achieve overall elimination of drug from body
What is elimination rate constant?
Fraction of drug eliminated per unit time at any time point
