Week 4: Reproductive pharmacology: Pregnancy Flashcards
Considerations of Pregnancy and Drug Distribution
What are the phases of drug distribution?
Physiologic Changes in pregnancy that affect drug absorption
- Increased GI transit time
- Decreased gastric acid secretion
- if present, frequent vomiting
- Vasodilation and increased cardiac output increased blood perfusion of the periphery
Describe the features of transplacental distribution of drugs
- passive diffusion: non-ionized and lipophilic molecules
- Active transport: drugs that are structurally related to endogenous compounds
- Transcytosis: of minor importance
Metabolism of drugs by placental enzymes
*
Physiologic Changes in pregnancy that affect drug distribution
- increase in body fat
- expanded plasma volume and total body water increase the volume of distribution of drugs
- Reduced maternal plasma albumin concentration: α1-acid glycoprotein concentration is either reduced or unchanged
- Fetal pH is slightly lower than maternal pH, “ion-trapping” of weak bases in the fetus
Physiologic Changes in pregnancy that affect drug metabolism
- Alterations in the activities of hepatic cytochrome P450 (CYP) isozymes:
- increased CYP3A4, CYP2D6, CYP2A6 and CYP2C9 activities
- Decreased CYP1A2 and CYP2C19 activities
- Increased activities of certain uridine 5’-diphosphate glucuronosyltransferase isoenzymes (UGT1A1, UGT1A4 and UGT2B7)
- Increased hepatic blood flow leads to increased first-pass clearance
Physiologic Changes in pregnancy that affect drug elimination
- increased glomerular filtration rate: up to 80% at the beginning of gestation due to increase in renal blood flow, decreased renal vascular resistanceand larger cardiac output
- Glomerular filtration rate decreases during the last 3 weeks of pregnancy
What are the potential effects of an administered drug on fetus
FDA categories for drug use during pregnancy
FDA category A for drug use during pregnancy
FDA category B for drug use during pregnancy
FDA category C for drug use during pregnancy
FDA category D for drug use during pregnancy
FDA category X for drug use during pregnancy
Treatment of opioid addiction in pregnant women
Treatment of NV in pregnancy
Pharmacotherapies for NV in pregnancy
Use of antinausea medications and antidepressants during the first trimester of pregnancy
Drugs used to treat hypertension, pregnancy-induced hypertension and pre-eclampsia
- Methyldopa
- Labetalol
- Nifedipine
- Hydralazine
- Magnesium sulfate
Methyldopa MOA in anti-HTN
- centrally acting α-adrenergic receptor agonist
- Considered first-line therapy by many guideline groups
Methyldopa side effects as an anti-HTN
commonly produces somnolence which limits its tolerability
Short acting agents used to treat severe HTN in pregnancy
- Hydralazine, labetalol and short acting (sublingual or orally administered) nifedipine are commonly used to control acute, very high blood pressure in women with severe HTN in pregnancy
Labetalol MOA in severe HTN in pregnancy
Combined α and β-adrenergic receptor antagonist with relatively few side effects
Labetalol side effects for severe HTN in pregnancy
relatively few side effects
Hydralazine MOA in severe HTN in pregnancy
↑ cGMP leads to smooth muscle relaxation (vasodilation)
Hydralazine side effects in severe HTN in pregnancy
- HA
- Nausea
- Vomiting
*Pregnancy Category C*
Hydralazine pregnancy category
Pregnancy category C
Nifedipine pregnancy category
Category C
Nifedipine Clinical use in pregnancy
- Given orally for the acute management of severe HTN during pregnancy
- Also used in postpartum patients with preeclampsia for BP control