Metabolism & Excretion Flashcards
drug metabolism is
chemical reaction that occurs inside the body to reduce lipid solubility, alters biological activity thereby converting the drug into water-soluble to facilitate excretion from the body.
organs involves in metabolism are
Liver (the main organ of metabolism) Kidney Intestine Lungs Skin Adrenal gland Brain
aims of drug metabolism are
To convert active drug into inactive substances.
To convert active drug into active metabolite. E.g. codeine morphine
To convert inactive drug (prodrug)into active drug. E.g. Levodopa dopamine
To convert active drug to toxic substances. E.g. Paracetamol N-Acetyl Benzoquinone (hepatotoxic)
What is half life?
In general, a drug will be eliminated after___half lives?
Time taken by a drug to become half of its initial concentration.
Generally, a drug will be eliminated after 6 half-lives.
Outline drug metabolizing enzymes
Microsomal enzymes
Located in SER of liver, kidney, lungs & intestine.
Catalyse oxidation, reduction, hydrolysis and glucuronide conjugation
Ex: cytochrome P450, glucoronyl transferase
Non-microsomal enzymes
Present in cytoplasm and mitochondria of the liver, plasma, brain and kidney.
Ex: MAO (Mono amine oxidase), COMT (Catechol-o-Methyl transferase)
Describe cytochrome system
Consists of more than 100 different isoenzymes that divided in families
Most significant: CYP1, CYP2, CYP3
Subfamilies:
CYP3A –causes about 50% biotransformation
CYP2D -causes about 20% biotransformation
CYP2C -causes about 15 % biotransformation
_____ inhibit drug metabolising enzymes thereby decreasing the metabolism of drug
cimetidine
____ induce drug-metabolizing enzymes by enhancing the rate and extent of enzymes synthesis
rifampicin
drugs are eliminated from the body either converted to ___ or ____
metabolites, unchanged form
define drug excretion
transportation of unaltered or altered drug out of the body
renal, hepatobiliary and pulmonary are
major routes of drug excretion
drug elimination processes are
glomerular filtration, active tubular secretion, tubular reabsorption
free drug that are not bound to plasma protein are excreted through
glomerular filtration
at proximal tubule,
charged molecules are transferred from plasma to tubular fluid
reabsorption results in
increase half life of the drug
lipid-soluble drug will be reabsorbed at
distal convoluted tubule
gaseous and volatile substances are absorbed and excreted through lungs by
simple diffusion
weak basic drugs such as ____ are excreted through breast milk
tetracycline, morphine
a constant amount of drug is eliminated per unit time
zero order kinetics
first-order kinetics
a constant fraction of drug is eliminated er unit time
oxidation involves two types
microsomal and non-microsomal oxidation
addition of O2/ -ve radical or removal of H+/+ve radical are involves in
oxidation process
pentosil is reduced to sulphonamide are example of
reduction process of drug metabolism in phase 1
hydrolysis
cleavage of drug molecule by taking up a molecule of water
phase 2 involves
glucoronidation, acetylation, methylation, sulphating, glycine conjugation
factors affecting drug metabolism
genetic factors, age, gender, diseases
grapefruits juice inhibits
CYP3A metabolism of co-administered drug substrates
lipid soluble drugs are not readily eliminated until
they are metabolises to more polar compounds
____ will greatly impairs the elimination of drugs especially those that are primarily excreted by kidney
renal dysfunction
decreased pharmacological effects of drugs are effects of
enzyme induction
if primaquine, aspirin, and sulfonamides are given in glucose-6-PO4 deficiency person, it can cause
severe haemolysis
