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Pharmacokinetic & Pharmacotherapy Changes in Pregnancy: Perinatal & Postpartum
FORUM FOR PSYCHIATRY RESIDENTS :: Psychiatry :: Psychiatry-Neurology-Psychology discussion :: Psychiatry In Depth
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Pharmacokinetic & Pharmacotherapy Changes in Pregnancy: Perinatal & Postpartum
Pharmacokinetic & Pharmacotherapy Changes in Pregnancy:
Perinatal & Postpartum
Perinatal & Postpartum
Pharmacokinetic changes complicates treatment during pregnancy- as this can cause low medications levels and thereby affect treatment efficacy.
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- Further slowing of gastric emptying and small bowel and colonic transit time.
- Increased plasma volume, change in protein binding, and lower ratio of lean muscle to adipose tissue: results in greater volume of drug distribution for lipophilic drugs.
- Increased sex steroids associated with pregnancy may modulate several of the CYP450 and UGT isoforms.
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- Less active in women compared with men and is inhibited by sex steroids.
- The activity of CYP1A2 is reduced by 65-70% at the END OF pregnancy compared with the postpartum period.
- Affected metabolism of following psychotropics: fluvoxamine, duloxetine, amitriptyline, clomipramine, desmethylimipramine, imipraminem, and doxepin.
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- Increased CYP3A4 activity in women (via progesterone effects)
- This can accelerate metabolism and reduce plasma levels of psychotropics medications:
citalopram, escitalopram, fluoxetine, paroxetine, trazodone, venlafaxine, desvenlafaxine, bupropion, mirtazapine, amitriptyline, clomipramine, imipramine, trimipramine, doxepin, and Carbamazepine.
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- CYP2C19 activity is reduced by almost 50%.
- Affected metabolism of following psychotropics:
citalopram, escitalopram, sertraline, fluoxetine, vilazodone, venlafaxine, amitriptyline, clomipramine, trimipramine, imipramine, and desmethylimipramine.
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- Cytochrome P2D6 is generally induced during pregnancy.
- This may affect the metabolism of numerous psychotropics from the SSRIs, SNRIs, and TCA drug classes.
- Maternal CYP metabolic phenotype (eg, poor, intermediate, extensive, and ultrarapid) is an important determinate of metabolism.
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- Rapid decline in sex steroid levels
- Contraction of plasma volume
- Reestablishment of hepatic enzyme activity after a period of metabolic refractory activity
- Return of the GFR to prepregnancy levels.
Note: Because of above changes, increased drug blood levels may result and manifest as adverse effects of toxicity.
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- During pregnancy monthly monitoring of trough drug levels is recommended: most important in the third trimester when dose increases may be necessary.
- In the postpartum period, careful monitoring for adverse effects and tapering to the preconception dose to mitigate adverse effects that may be associated with rising serum levels 2 to 6 weeks after delivery.
- Checking a blood level whenever adverse effects emerge in the early postpartum or at least at week 6 when drug levels have been reported to peak before eventual stabilization around week.
- Dose decrease may be indicated around week 6 to ameliorate adverse effects.
Source: J Clin Psychopharmacol. 2014 April ; 34(2): 244–255.
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