Clinically relevant kinetics and interactions Flashcards
Percentage of Caucasians who are slow TCA metabolisers
7-9%
Reason some Caucasians are slow TCA metabolisers
CYP2D6 polymorphism
Timing to take TCA plasma levels to assess therapeutic dosing
After 5-7 days when steady state is reached
8-12 hours after last dose
Therapeutic window for nortriptyline - due to lack of effect at higher doses, not due to side effects
50-150ng/ml
TCAs which decrease the metabolism of morphine and can lead to opioid toxicity
Amitriptyline
Clomipramine
Medications which inhibit TCA metabolism and can increase plasma TCA levels
Quinidine Cimetidine Fluoxetine Paroxetine Phenothiazines e.g. chlorpromazine Disulfiram Methylphenidate
Medications which induce TCA metabolism and can reduce TCA levels
Phenytoin
Carbamazepine
Oral contraceptives
Barbiturates
Interaction between TCAs and phenothiazines e.g. chlorpromazine
Mutual inhibition of metabolism - both phenothiazine and TCA levels increase
Effect of smoking on TCA metabolism
Induces metabolism, TCA levels increase
Effect of TCAs on warfarin levels
Increase warfarin levels
Effect of TCAs on clonidine levels
Reduce clonidine levels, can cause a hypertensive crisis
Interactions between TCAs and MAOIs
Synergistic serotonin enhancement especially with clomipramine - higher risk of serotonin syndrome
TCAs reduce tyramine entry via monoamine reuptake channels - lower risk of cheese reaction
Interaction between TCAs and l-dopa
TCAs reduce absorption of l-dopa and lower efficacy
Mechanism by which amitriptyline and clomipramine decrease the metabolism of morphine
UDP glucuronyl transferase interaction
SSRI with the greatest linearity of kinetics and most predictable side effects
Fluvoxamine
SSRI with the greatest non-linearity of kinetics and most unpredictable side effects
Paroxetine
Least protein bound SSRI
Escitalopram
SSRIs without active metabolites
Fluvoxamine
Paroxetine
SSRIs which can inhibit their own clearance
Fluoxetine
Paroxetine
Most selective SSRIs
Citalopram
Escitalopram
Most potent SSRI
Paroxetine
SSRI which has significant anticholinergic effects at higher doses
Paroxetine
SSRI which impairs the clearance of diazepam and should not be co-prescribed
Fluvoxamine
Interaction between SSRIs (not sertraline and citalopram) and TCAs
Increases levels of TCAs and can cause toxicity or can be associated with therapeutic benefit
Interaction between fluvoxamine and theophylline
Fluvoxamine reduces the clearance of theophylline through CYP1A2 inhibition
If co-administered theophylline dose should be one third normal dose
Interaction between fluvoxamine and warfarin
Warfarin plasma levels nearly double - dose requires adjustment
Reason the half life of irreversible MAOIs does not correlate with the duration of effects
New enzyme needs to be made for normal activity to be resumed - takes 5-7 days
Time that should be left after stopping irreversible MAOI before starting a drug which may interact
2 weeks
Interactions between MAOIs and pethidine (also called meperidine)
Can produce a sedative or excitatory reaction - sedative due to opioid toxicity, excitatory due to serotonin excess
Excitatory reaction can be fatal - should never be co-prescribed
Interaction between trazadone and digoxin
Trazadone can increase digoxin levels
Interaction between trazadone and phenytoin
Trazadone can increase phenytoin levels
Interaction between trazadone and warfarin
Trazadone can increase warfarin levels
Percentage decrease in baseline symptoms for the therapeutic effect of an antidepressant to be called non-response
<25%
Percentage decrease in baseline symptoms for the therapeutic effect of an antidepressant to be called partial response
25-50%
Percentage decrease in baseline symptoms for the therapeutic effect of an antidepressant to be called partial remission
> 50% but some symptoms evident
Percentage decrease in baseline symptoms for the therapeutic effect of an antidepressant to be called remission
100% increase - no symptoms left
Time frame for antidepressant response to be called remission vs. recovery
Remission if <6 months from previous episode
Recovery if >6 months
Difference between relapse and recurrence in depression
Relapse - return to fully symptomatic state while in remission
Recurrence - new episode of depression while in recovery
Oral bioavailability of mirtazapine
50%
Interaction between mirtazapine and carbamazepine
Carbamazepine reduces mirtazapine levels by 60%
CYP enzyme which largely metabolises agomelatine
CYP1A2
Medications which increase lithium levels
ACE inhibitors Loop diuretics - furosemide, bumetanide Fluoxetine NSAIDs Thiazide diuretics - bendroflumethiazide
Substances which decrease lithium levels
Osmotic diuretics - mannitol, isosorbide
Caffeine
Aminophylline, theophylline
Carbonic anhydrase inhibitors - acetazolamide
Medications which increase lithium toxicity even at normal levels
Carbamazepine Haloperidol Clozapine Calcium channel blockers Metronidazole Phenytoin
Interactions between carbamazepine and calcium channel blockers
Verapamil and diltiazem increase carbamazepine levels
Carbamazepine reduces nimodipine and felodipine levels
Interaction between valproate and carbamazepine
Valproate displaces carbamazepine from proteins, increasing free carbamazepine levels
Can cause neurotoxicity from carbamazepine toxicity even though plasma levels appear normal
Interaction between carbamazepine and warfarin
Carbamazepine reduces warfarin efficacy
Interaction between carbamazepine and erythromycin
Erythromycin can cause carbamazepine toxicity
Impact of changing dose on gabapentin’s bioavailability
Decreases as the dose increases
Interactions between lamotrigine and carbamazepine
Carbamazepine reduces levels of lamotrigine
Lamotrigine increases levels of the metabolite of carbamazepine - carbamazepine-10,11-epoxide
Antipsychotic which is known for having a highly variable absorption rate between different people
Chlorpromazine
Interaction between antacids and antipsychotics
Antacids can decrease absorption of phenothiazines - e.g. chlorpromazine
Medications which are enzyme inducers and can decrease antipsychotic levels
Carbamazepine
Phenytoin
Ethambutol
Barbiturates
Medications which are enzyme inhibitors and can increase antipsychotic levels
SSRIs TCAs Cimetidine Erythromycin Ciprofloxacin Ketoconazole
Anti dementia drug with 100% oral bioavailability
Donepezil
Psychotropic medication affected by contact with moist air
Valproate
Benzodiazepines which undergo phase 2 metabolism but not phase 1 metabolism
Lorazepam
Oxazepam
Temazepam
Psychiatric drugs which undergo significant first pass effect
Imipramine
Morphine
Diazepam
Buprenorphine
Psychiatric drugs which undergo little to no first pass effect
Pregabalin
Lithium
Interaction between MAOIs and OTC cold medication e.g. dextromethorphan
Causes a hypertensive crisis
Drugs which can reduce the contraceptive effect of the oral contraceptive pill
St John's Wort Carbamazepine Phenytoin Topiramate Barbiturates
Antibiotic that can cause serotonin syndrome in combination with MAOIs
Linezolid
Interaction between fluoxetine and clozapine
Fluoxetine increases clozapine levels and can increase seizure risk associated with clozapine
Interaction between carbamazepine and phenytoin
Carbamazepine increases levels of phenytoin
Interaction between clozapine and carbamazepine
Increases the risk of clozapine induced agranulocytosis
Antidepressants to avoid in patients on tamoxifen due to their inhibition of tamoxifen’s metabolism to its active metabolite
Fluoxetine
Paroxetine
Interaction between sumatriptan and SSRIs
Can increase the risk of serotonin syndrome