Cytochrome p450 system Flashcards
Where the cytochrome p450 enzymes are mostly located
Liver and small intestine
Importance of the cytochrome p450 SYSTEM
Excretes exogenous toxins
Much of the inactivation of psychotropic drugs is via the hepatic cytochrome system
Ethnic group showing the highest frequency of poor metabolisers of CYP2D6
Africans and African-Americans
CYP group which shows the largest phenotypic variation
CYP2D6
Proportion of Caucasians who are poor metabolisers of CYP2D6
6-10%
Most abundant CYP group
CYP3A
Psychotropics metabolised by CYP2D6
TCAs, fluoxetine, paroxetine, antipsychotics, trazodone, valproate, amphetamines, venlafaxine
Psychotropic inhibitors of CYP2D6
Paroxetine (can inhibit its own clearance), antipsychotics, amitriptyline, clomipramine
Psychotropics which induce CYP2D6
Nil
Drugs metabolised by CYP3A4
Clomipramine, mirtazapine, carbamazepine, fluvoxamine, nefazodone, aripiprazole, quetiapine, clonazepam, donepezil, most benzodiazepines
Psychotropics which induce CYP3A4
Carbamazepine (can cause autoinduction), barbiturates, St John’s Wort
Drugs which inhibit CYP3A4
Calcium channel blockers, fluoxetine, paroxetine
Psychotropics metabolised by CYP1A2
Clozapine, olanzapine, agomelatine
Substances which induce CYP1A2
Smoking, barbiturates
Substances which inhibit CYP1A2
Grapefruit juice, caffeine, fluvoxamine
Effect of smoking on clozapine levels
Lowers levels
Effect of grapefruit juice on clozapine levels
Increases levels
Effect of carbamazepine autoinduction
Rate of metabolism gradually increases over the first few weeks of treatment
Three ways in which drug interactions can influence the CYP system
Induction
Non-competitive inhibition
Competitive inhibition
Part of the body CYP3A4 is most prominent
Gut wall mucosa
The gradual speeding up of the rate of metabolism of a newly started drug because it induces the CYP system which metabolises it
Autoinduction
Medication which classically undergoes autoinduction
Carbamazepine
Type of metaboliser who has more than two copies of fully active CYP450 enzyme alleles
Ultrarapid metaboliser
Type of metaboliser who has more two copies of fully active CYP450 enzyme alleles
Extensive metaboliser
Type of metaboliser who has more one copy of fully active CYP450 enzyme alleles
Intermediate metaboliser
Type of metaboliser who has more no copies of fully active CYP450 enzyme alleles
Poor metaboliser
CYP enzyme which primarily metabolises caffeine
CYP1A2
Psychiatric drugs where levels are most altered by grapefruit juice
Carbamazepine Pimozide Triazolam Midazolam Methylprednisolone Buspirone
Effect of reboxetine on cytochrome P450 enzymes
No impact
