Drug Metabolism Flashcards
Define Drug Metabolism:
A biochemical modification to pharmaceutical substance by livin organisms, ususally through activity of specialzed enzymes.
4 main sites of drug metabolism?
Liver
Lungs
Gut Lining
Kidneys
What is a prodrug?
A precursor to a drug which is converted to its active form by metabolism. e.g. Codeine
What are the 3 outcomes of metabolism on a drug?
Production of toxic metabolites
Activation (prodrugs)
Deactivation/loss of activity
What does the “wide substrate specificty” of metabolic enzymes mean?
It means many drugs can be metabolized by more than one enzyme
What are the 3 types of phase 1 metabolism reaction? [HOR}
Hydrolysis
or Oxidation
or Reduction
Whats the function of phase 1 metabolism?
To increase polarity of the compound and provide an active site for phase 2 to occur
What family of enzymes carries out phase 1 metabolism?
P-450 family of enzymes
Prefix for the enzymes in phase 1 metabolism?
CYP- is the prefix followed by no-letter-no.
3 enzymes in phase 1 metabolism?
CYP3A4
CYP2D6
CYP1A2
Where is CYP3A4 found?
In the Liver
What does CYP2D6 metabolize?
CYP2D6 metabolizes antidepressants, antipsychotics & ocnverts codeine to morphine
How does smoking affect CYP2D6?
CYP2D6 is induced by Smoking.
What does CYP1A2 metabolize?
Theophylline
Which phase 1 enzyme isnt induced by smoking?
CYP3A4 isnt induced by smoking
What phase involves conjugation?
Phase 2 metabolism involved conjugation
What is conjugation?
Conjugation is combining drugs with other substances to terminate their activity
How does conjugation make excretion of the drug easier?
Conjugated drugs have an increased water solubility
What substances are used to conjugate the metabolites formed in phase 1?
Glucuronic Acid
Glutathione
Sulphate
Acetate
Does conjugation deactivate all dru metabolites?
Most but not all are inactivated
In what two ways do other drugs/herbal meds affect drug metabolism?
Other drugs & herbals can cause enzyme induction & inhibition. Therfore affecting metabolic rates
What is enzyme induction?
One substance causes an increased synthesis of the enzyme leading to a greater metabolic rate.
What are some commmon inducers?
Other drugs, herbals, smoking & alcohol.
How long does induction take to become apparent?
Weeks -> months
Is enzyme inhibition reversible?
Some enzyme inhibition is reversible but not all
What are some common substances htat imhibit durg metabolizing enzymes?
Erythromycin & Clarythromycin
Grapefruit
What is pharmacogenetics?
The wide genetic variability in pharmcokinetic & pharmacodynamic reponse to drugs between individuals
What are the consequences of ‘bad’ pharmacogenetics?
Therapeutic failure
Adverse reactions
How can genetic variation lead to drug toxicity?
Genetic variation
- > abscence/deficiency in an enzyme
- > Overly high drug level
- > Drug toxicity
How can genetic variation lead to tehrapeutic failure without adverse effectS?
Over production of an ezyme
Overly high metabolic activity
Low drug conc. in blood
Failure of therapy
What two aspects of the liver can effect drug metabolism?
Liver Disease
Hepatic Blood Flow
What are the 2 main differnces in the drug metabolism of infants to adults?
Infants have:
- reduced or absent drug metabolizing enzymes
- Reduced renal function
How is a pubescant childs metabolism differnt to an adults?
By puberty a childs metabolism is faster than an adults
Which parameters affecting drug metabolism are affected in the elderly?
The elderly have a lower liver weight, renal function, plasma protein & lean body mass
How does chronic disease in the elderly affect drug metabolism?
Chronically ill elderly people ar eon multiple meds which can interact or simply overpower the body.
How does gender affect drug metabolism?
It effects all 4 areas of pharmacokinetics:
- Absorption
- Distribution
- Metabolism
- Excretion
How does pregnancy effect drug metablism?
Hormonla changes in 2nd/3rd trimester induce some durg metabolizing enzymes
How does ethnicity effect drug metabolism?
Variation in expression of P-450 genes leading to different levels of drug metabolizing enzymes between races
What is knwing ADME importnat for?
- Choosing methd of administrstion
- Choosing safe & effect Dosaes/Frequency
- Making changes based on drugs, illness or physioloical factors
