Drug metabolism Flashcards
Define drug metabolism
A biochemical modification to pharmaceutical substances by living organisms, usually through activity of specialised enzymes.
4 main sites of drug metabolism?
Liver
Lungs
Gut linings
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?
- activation (prodrugs)
- deactivation/ loss of activity
- production of toxic metabolites
What does “wide substrate specificty” of metabolic enzymes mean?
Many drugs can be metabolism by more than one enzyme
What are the 3 types of phase 1 metabolism? (HOR)
Hydrolysis
or Oxidation
or Reduction
Whats the functions of phase 1 metabolism?
To increase polarity of the compound and to provide an active site for phase 2 to occur.
What family of enzymes carry out phase 1 metabolism?
P-450 family of enzymes
What is the prefix for the enzymes in phace 1 metabolism?
CYP is the prefix followed by no-letter-no
What are the 3 enzymes in phase 1 metabolism?
CYP3A4
CYP2D6
CYP1A2
Where is CYP3A4 found?
Liver
What does CYP2D6 metabolise?
- antidepressants and antipyschotics
- convert codeine to morphine
How does smoking affect CYP2D6?
CYP2D6 is induced by smoking
What does CYP1A2 metabolise?
Theophylline
Which phase 1 enzyme isn’t induced by smoking?
CYP3A4 isn’t induced by smoking
What phase involves conjugation?
Phase 2 metabolism involves conjugation
What is conjugation?
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?
- Glucoronic acid
- Glutathione
- Sulphate
- Acetate
Does conjugation deactivate all drug metabolites?
Most but not all are inactivated
In what two ways do other drugs/herbal meds affect drug metabolism?
-Enzyme induction
-Enzyme inhibition
, therefore 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 common inducers?
Other drugs, herbals, smoking and alcohol
How long does it take for enzyme induction to become apparent?
Weeks -> months
Is enzyme inhibition reversible?
Some enzyme inhibition is reversible but not all and some are irreversible
What are some common substances that inhibit drug metabolising enzymes?
- Erythromycin
- Clarythromycin
- Grapefruit
What is pharmacogenetics?
The wide genetic variability in pharmacokinetics and pharmacodynamic response 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
- > absence/deficiency in an enzyme.
- > overly high drug level
How can genetic variation lead to therapeutic failure without adverse reactions?
- over production of an enzyme
- overly high metabolic activity
- low drug conc. in blood
- failure of therapy
What two aspect of the liver can effect drug metabolism?
- liver disease
- hepatic blood flow
What are the two main differences in the drug metabolism of infants to adults?
infants have
- reduced or absent drug metabolising enzymes
- reduced renal function
How is a pubescent Childs metabolism different 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
- lower liver weight
- lower renal function
- lower plasma protein
- lower lean body mass
How does chronic disease in the elderly affect drug metabolism?
-Chronically ill elderly people are on multiple medication which can interact or simply overpower the body
How does gender affect drug metabolism?
Affects all 4 areas of pharmacokinetics:
- absorption
- dsitrubtion
- metabolism
- excretion
How does pregnancy affect drug metabolism?
Hormonal Changes in 2nd/3rd trimester induces some Drug metabolsing enzymes
How does ethnicity affect drug metabolism
Variation in expression of P-450 genes leading to different levels of drug metabolising enzymes between races
What is knowing ADME important for?
- choosing method of administration
- choosing safe and effective dosages/frequencies
- making changes based of drugs, illnesses or physiological factrs
