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Pharmacology > Clinically relevant kinetics and interactions > Flashcards

Clinically relevant kinetics and interactions Flashcards

1
Q

Percentage of Caucasians who are slow TCA metabolisers

A

7-9%

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2
Q

Reason some Caucasians are slow TCA metabolisers

A

CYP2D6 polymorphism

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3
Q

Timing to take TCA plasma levels to assess therapeutic dosing

A

After 5-7 days when steady state is reached

8-12 hours after last dose

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4
Q

Therapeutic window for nortriptyline - due to lack of effect at higher doses, not due to side effects

A

50-150ng/ml

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5
Q

TCAs which decrease the metabolism of morphine and can lead to opioid toxicity

A

Amitriptyline

Clomipramine

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6
Q

Medications which inhibit TCA metabolism and can increase plasma TCA levels

A 
Quinidine
Cimetidine
Fluoxetine
Paroxetine
Phenothiazines e.g. chlorpromazine
Disulfiram
Methylphenidate
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7
Q

Medications which induce TCA metabolism and can reduce TCA levels

A

Phenytoin
Carbamazepine
Oral contraceptives
Barbiturates

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8
Q

Interaction between TCAs and phenothiazines e.g. chlorpromazine

A

Mutual inhibition of metabolism - both phenothiazine and TCA levels increase

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9
Q

Effect of smoking on TCA metabolism

A

Induces metabolism, TCA levels increase

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10
Q

Effect of TCAs on warfarin levels

A

Increase warfarin levels

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11
Q

Effect of TCAs on clonidine levels

A

Reduce clonidine levels, can cause a hypertensive crisis

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12
Q

Interactions between TCAs and MAOIs

A

Synergistic serotonin enhancement especially with clomipramine - higher risk of serotonin syndrome
TCAs reduce tyramine entry via monoamine reuptake channels - lower risk of cheese reaction

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13
Q

Interaction between TCAs and l-dopa

A

TCAs reduce absorption of l-dopa and lower efficacy

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14
Q

Mechanism by which amitriptyline and clomipramine decrease the metabolism of morphine

A

UDP glucuronyl transferase interaction

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15
Q

SSRI with the greatest linearity of kinetics and most predictable side effects

A

Fluvoxamine

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16
Q

SSRI with the greatest non-linearity of kinetics and most unpredictable side effects

A

Paroxetine

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17
Q

Least protein bound SSRI

A

Escitalopram

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18
Q

SSRIs without active metabolites

A

Fluvoxamine

Paroxetine

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19
Q

SSRIs which can inhibit their own clearance

A

Fluoxetine

Paroxetine

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20
Q

Most selective SSRIs

A

Citalopram

Escitalopram

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21
Q

Most potent SSRI

A

Paroxetine

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22
Q

SSRI which has significant anticholinergic effects at higher doses

A

Paroxetine

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23
Q

SSRI which impairs the clearance of diazepam and should not be co-prescribed

A

Fluvoxamine

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24
Q

Interaction between SSRIs (not sertraline and citalopram) and TCAs

A

Increases levels of TCAs and can cause toxicity or can be associated with therapeutic benefit

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25
Q

Interaction between fluvoxamine and theophylline

A

Fluvoxamine reduces the clearance of theophylline through CYP1A2 inhibition
If co-administered theophylline dose should be one third normal dose

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26
Q

Interaction between fluvoxamine and warfarin

A

Warfarin plasma levels nearly double - dose requires adjustment

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27
Q

Reason the half life of irreversible MAOIs does not correlate with the duration of effects

A

New enzyme needs to be made for normal activity to be resumed - takes 5-7 days

28
Q

Time that should be left after stopping irreversible MAOI before starting a drug which may interact

A

2 weeks

29
Q

Interactions between MAOIs and pethidine (also called meperidine)

A

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

30
Q

Interaction between trazadone and digoxin

A

Trazadone can increase digoxin levels

31
Q

Interaction between trazadone and phenytoin

A

Trazadone can increase phenytoin levels

32
Q

Interaction between trazadone and warfarin

A

Trazadone can increase warfarin levels

33
Q

Percentage decrease in baseline symptoms for the therapeutic effect of an antidepressant to be called non-response

A

<25%

34
Q

Percentage decrease in baseline symptoms for the therapeutic effect of an antidepressant to be called partial response

A

25-50%

35
Q

Percentage decrease in baseline symptoms for the therapeutic effect of an antidepressant to be called partial remission

A

> 50% but some symptoms evident

36
Q

Percentage decrease in baseline symptoms for the therapeutic effect of an antidepressant to be called remission

A

100% increase - no symptoms left

37
Q

Time frame for antidepressant response to be called remission vs. recovery

A

Remission if <6 months from previous episode

Recovery if >6 months

38
Q

Difference between relapse and recurrence in depression

A

Relapse - return to fully symptomatic state while in remission
Recurrence - new episode of depression while in recovery

39
Q

Oral bioavailability of mirtazapine

A

50%

40
Q

Interaction between mirtazapine and carbamazepine

A

Carbamazepine reduces mirtazapine levels by 60%

41
Q

CYP enzyme which largely metabolises agomelatine

A

CYP1A2

42
Q

Medications which increase lithium levels

A 
ACE inhibitors
Loop diuretics - furosemide, bumetanide
Fluoxetine
NSAIDs
Thiazide diuretics - bendroflumethiazide
43
Q

Substances which decrease lithium levels

A

Osmotic diuretics - mannitol, isosorbide
Caffeine
Aminophylline, theophylline
Carbonic anhydrase inhibitors - acetazolamide

44
Q

Medications which increase lithium toxicity even at normal levels

A 
Carbamazepine
Haloperidol
Clozapine
Calcium channel blockers
Metronidazole
Phenytoin
45
Q

Interactions between carbamazepine and calcium channel blockers

A

Verapamil and diltiazem increase carbamazepine levels

Carbamazepine reduces nimodipine and felodipine levels

46
Q

Interaction between valproate and carbamazepine

A

Valproate displaces carbamazepine from proteins, increasing free carbamazepine levels
Can cause neurotoxicity from carbamazepine toxicity even though plasma levels appear normal

47
Q

Interaction between carbamazepine and warfarin

A

Carbamazepine reduces warfarin efficacy

48
Q

Interaction between carbamazepine and erythromycin

A

Erythromycin can cause carbamazepine toxicity

49
Q

Impact of changing dose on gabapentin’s bioavailability

A

Decreases as the dose increases

50
Q

Interactions between lamotrigine and carbamazepine

A

Carbamazepine reduces levels of lamotrigine

Lamotrigine increases levels of the metabolite of carbamazepine - carbamazepine-10,11-epoxide

51
Q

Antipsychotic which is known for having a highly variable absorption rate between different people

A

Chlorpromazine

52
Q

Interaction between antacids and antipsychotics

A

Antacids can decrease absorption of phenothiazines - e.g. chlorpromazine

53
Q

Medications which are enzyme inducers and can decrease antipsychotic levels

A

Carbamazepine
Phenytoin
Ethambutol
Barbiturates

54
Q

Medications which are enzyme inhibitors and can increase antipsychotic levels

A 
SSRIs
TCAs
Cimetidine
Erythromycin
Ciprofloxacin
Ketoconazole
55
Q

Anti dementia drug with 100% oral bioavailability

A

Donepezil

56
Q

Psychotropic medication affected by contact with moist air

A

Valproate

57
Q

Benzodiazepines which undergo phase 2 metabolism but not phase 1 metabolism

A

Lorazepam
Oxazepam
Temazepam

58
Q

Psychiatric drugs which undergo significant first pass effect

A

Imipramine
Morphine
Diazepam
Buprenorphine

59
Q

Psychiatric drugs which undergo little to no first pass effect

A

Pregabalin

Lithium

60
Q

Interaction between MAOIs and OTC cold medication e.g. dextromethorphan

A

Causes a hypertensive crisis

61
Q

Drugs which can reduce the contraceptive effect of the oral contraceptive pill

A 
St John's Wort
Carbamazepine
Phenytoin
Topiramate
Barbiturates
62
Q

Antibiotic that can cause serotonin syndrome in combination with MAOIs

A

Linezolid

63
Q

Interaction between fluoxetine and clozapine

A

Fluoxetine increases clozapine levels and can increase seizure risk associated with clozapine

64
Q

Interaction between carbamazepine and phenytoin

A

Carbamazepine increases levels of phenytoin

65
Q

Interaction between clozapine and carbamazepine

A

Increases the risk of clozapine induced agranulocytosis

66
Q

Antidepressants to avoid in patients on tamoxifen due to their inhibition of tamoxifen’s metabolism to its active metabolite

A

Fluoxetine

Paroxetine

67
Q

Interaction between sumatriptan and SSRIs

A

Can increase the risk of serotonin syndrome

Pharmacology (34 decks)

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