pharmacogenomics Flashcards
What are the 2 CYPs that affect antidepressants?
and what are the antidepressants
2C19 and 2D6 (2ssri, 1 snri, 1sms)
2C19: Sertraline, Escitalopram
2D6: Fluvoxamine, Paroxetine, Venlafaxine, Vortioxetine
Recommendations for 2C19 for SSRI
Escitalopram IM and PM same as Sertraline
Escitalopram only
UM, RM: change or increase dose
Both Escitalopram and Sertraline
IM: reduce dose
PM: change or reduce dose
gene for carbamazepine
Must test for HLAB 15:02
If (+), dont use if Carbamazepine-naive. Use non aromatic anticonvulsants. Dont use aromatic eg. Phenytoin, Phenobarbital, Lamotrigine
Optional for HLAA 31:01
If (+), use other agents if available. If no other agents available, use cautiously with increased frequency of monitoring
gene for phenytoin
and recommendations
HLAB 15:02 (same as Carbamazepine) and substrate of 2C9
HLAB 15:02
If (+), do not use
2C9
If IM 1.5 → no change
If IM 1.0 → normal initial loading dose, use 25% lower dose for 2nd dose onwards
If PM → normal initial loading dose, use 50% lower dose for 2nd dose onwards
gene for allopurinol
and recommendation
HLAB 58:01
Routine testing not recommended, considered in high risk patients eg. renal impairment and old age
gene for Abacavir
and recommendation
HLAB 57:01
Must screen for Malay and Indian patients with late stage of HIV (CD4 < 200cells/mm3)
If (+), dont use (risk of hypersensitivity reaction)
gene for clopidogrel
and recommendation
2C19
UM, RM, NM: Use standard dose (75mg OD)
IM, PM: Avoid, use Ticagrelor
gene for omeprazole
and recommendation
2C19
UM: increase starting daily dose by 100%
RM, NM: No change, consider increase dose by 50-100% for H.pylori or erosive esophagitis
IM, PM: No change, for chronic therapy (> 12 weeks) and efficacy achieved, consider 50% reduction in daily dose
gene for statins
and recommendation
SLCO1B1, ABCG2, 2C9
decreased function: use Ator 40
poor function: use Rosu 20
SLCO1B1
Decreased function: Atorva 40mg. Combination with non-statin for higher efficacy. Avoid Simvastatin OR use Simvastatin 10mg
Poor function: use Atorva 20mg or Rosu 20mg
ABCG2 (more for Rosu)
Poor function: Rosu 20mg
2C9
Only for Fluvastatin
what is the enzyme for tramadol and hydrocodone?
recommendation
2D6
Tramadol
UM (> 2.25 activity score): avoid use due to toxicity. Use non-codeine opioid
PM (0): Avoid use. Use non codeine opioid
No change for hydrocodone
what are the antidepressants for 2D6
6 - 2 = 4
2 SSRI, 1 SNRI, 1 SMS
Paroxetine, Fluvoxamine, Venlafaxine, Vortioxetine
Paroxetine (SSRI)
UM: change drug
IM: reduce dose
PM: reduce dose
Fluvoxamine (SSRI)
PM: change or reduce dose
Venlafaxine (SNRI)
UM: increase dose
PM: change or reduce dose
Vortioxetine (SMS)
UM: change or increase dose
PM: change or reduce dose
2C19 Inhibitors (antidepressants)
Strong: Fluconazole
Moderate: Fluoxetine, Fluvoxamine, Voriconazole
2D6 inhibitor (antidepressants)
Strong: Buproprion, Fluoxetine, Paroxetine
Moderate: Abitarone, Duloxetine
Not metabolised by 2C19 (antidepressants)
FFP
ssri: Fluoxetine, Fluvoxamine, Paroxetine
DDV
snri: Duloxetine, Desvenlafaxine, Venlafaxine
TCA: Nortriptyline
Others: Agomelatine, Mirtazapine, Trazodone, Bupropion, Vortioxetine
Not metabolised by 2D6 (antidepressants)
SSRI
Escitalopram, Sertraline
SNRI: Desvenlafaxine
TCA: none
Others: (all except Vortioxetine)
Agomelatine, Mirtazapine, Bupropion, Trazodone
Activity score is relevant for which genes (3 points)
2C9
2D6
DPYD
Fluoxetine is a…
Strong 2D6 inhibitor
Moderate 2C19 inhibitor
Which drug is not metabolised by both 2C19 and 2D6
Desvenlafaxine
Agomelatine, Bupropion, Mirtazapine, Trazodone
