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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
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
26
Interaction between fluvoxamine and warfarin
Warfarin plasma levels nearly double - dose requires adjustment
27
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
28
Time that should be left after stopping irreversible MAOI before starting a drug which may interact
2 weeks
29
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
30
Interaction between trazadone and digoxin
Trazadone can increase digoxin levels
31
Interaction between trazadone and phenytoin
Trazadone can increase phenytoin levels
32
Interaction between trazadone and warfarin
Trazadone can increase warfarin levels
33
Percentage decrease in baseline symptoms for the therapeutic effect of an antidepressant to be called non-response
<25%
34
Percentage decrease in baseline symptoms for the therapeutic effect of an antidepressant to be called partial response
25-50%
35
Percentage decrease in baseline symptoms for the therapeutic effect of an antidepressant to be called partial remission
>50% but some symptoms evident
36
Percentage decrease in baseline symptoms for the therapeutic effect of an antidepressant to be called remission
100% increase - no symptoms left
37
Time frame for antidepressant response to be called remission vs. recovery
Remission if <6 months from previous episode | Recovery if >6 months
38
Difference between relapse and recurrence in depression
Relapse - return to fully symptomatic state while in remission Recurrence - new episode of depression while in recovery
39
Oral bioavailability of mirtazapine
50%
40
Interaction between mirtazapine and carbamazepine
Carbamazepine reduces mirtazapine levels by 60%
41
CYP enzyme which largely metabolises agomelatine
CYP1A2
42
Medications which increase lithium levels
``` ACE inhibitors Loop diuretics - furosemide, bumetanide Fluoxetine NSAIDs Thiazide diuretics - bendroflumethiazide ```
43
Substances which decrease lithium levels
Osmotic diuretics - mannitol, isosorbide Caffeine Aminophylline, theophylline Carbonic anhydrase inhibitors - acetazolamide
44
Medications which increase lithium toxicity even at normal levels
``` Carbamazepine Haloperidol Clozapine Calcium channel blockers Metronidazole Phenytoin ```
45
Interactions between carbamazepine and calcium channel blockers
Verapamil and diltiazem increase carbamazepine levels | Carbamazepine reduces nimodipine and felodipine levels
46
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
47
Interaction between carbamazepine and warfarin
Carbamazepine reduces warfarin efficacy
48
Interaction between carbamazepine and erythromycin
Erythromycin can cause carbamazepine toxicity
49
Impact of changing dose on gabapentin's bioavailability
Decreases as the dose increases
50
Interactions between lamotrigine and carbamazepine
Carbamazepine reduces levels of lamotrigine | Lamotrigine increases levels of the metabolite of carbamazepine - carbamazepine-10,11-epoxide
51
Antipsychotic which is known for having a highly variable absorption rate between different people
Chlorpromazine
52
Interaction between antacids and antipsychotics
Antacids can decrease absorption of phenothiazines - e.g. chlorpromazine
53
Medications which are enzyme inducers and can decrease antipsychotic levels
Carbamazepine Phenytoin Ethambutol Barbiturates
54
Medications which are enzyme inhibitors and can increase antipsychotic levels
``` SSRIs TCAs Cimetidine Erythromycin Ciprofloxacin Ketoconazole ```
55
Anti dementia drug with 100% oral bioavailability
Donepezil
56
Psychotropic medication affected by contact with moist air
Valproate
57
Benzodiazepines which undergo phase 2 metabolism but not phase 1 metabolism
Lorazepam Oxazepam Temazepam
58
Psychiatric drugs which undergo significant first pass effect
Imipramine Morphine Diazepam Buprenorphine
59
Psychiatric drugs which undergo little to no first pass effect
Pregabalin | Lithium
60
Interaction between MAOIs and OTC cold medication e.g. dextromethorphan
Causes a hypertensive crisis
61
Drugs which can reduce the contraceptive effect of the oral contraceptive pill
``` St John's Wort Carbamazepine Phenytoin Topiramate Barbiturates ```
62
Antibiotic that can cause serotonin syndrome in combination with MAOIs
Linezolid
63
Interaction between fluoxetine and clozapine
Fluoxetine increases clozapine levels and can increase seizure risk associated with clozapine
64
Interaction between carbamazepine and phenytoin
Carbamazepine increases levels of phenytoin
65
Interaction between clozapine and carbamazepine
Increases the risk of clozapine induced agranulocytosis
66
Antidepressants to avoid in patients on tamoxifen due to their inhibition of tamoxifen's metabolism to its active metabolite
Fluoxetine | Paroxetine
67
Interaction between sumatriptan and SSRIs
Can increase the risk of serotonin syndrome

Pharmacology (34 decks)

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