Pregnancy & lactation

C P E Program

[PREGNANCY & LACTATION]

Continuing pharmaceutical education (CPE) program Alexandria Syndicate of pharmacists

Pregnancy & lactation Prepared by : Ph/Esraa nader Ph/Omnia Abdelrahman Presented by: Ph/Ahmed El-Gewily Alex syndicate of pharmacists

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Pregnancy and lactation Introduction  Critical periods in human development

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 Pharmacokinetics in pregnancy Physiological changes in pregnancy, beginning during the first trimester, and most marked during the third trimester; alter the absorption, distribution and clearance of drugs.

 Absorption

 Gastric emptying and small intestine motility are reduced in pregnancy due to elevation of progesterone. This may increase Tmax and reduce Cmax, although effects on total bioavailability may be relatively minor.  An increase in gastric pH, due to a reduction in H. secretion and an increase in mucus production may increase the ionization of weak acids, tending to reduce their absorption more than that of weak bases.  They may, however, reduce the efficacy of a single dose of an oral drug such as an analgesic or anti-emetic for which Tmax and Cmax are important.

 Distribution

 During pregnancy there is an expansion of intravascular (plasma volume) and extra- vascular (breasts, uterus, peripheral edema) water content. Thus, total body water increases by up to 8 liters, creating a larger space within which hydrophilic drugs may distribute, i.e. increasing Vd.  Total plasma concentration of albumin-bound drugs decreases as a result of haemodilution. There is thus the possibility of a rise in free (active) drug concentration of agents that are normally albumin-bound. This would be expected to produce an increased drug effect.  distribution for lipophilic drugs, but this has little practical importance.

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 Metabolism

 Some enzymes of the hepatic cytochrome P-450 system are induced by oestrogen/ progesterone, resulting in a higher rate of metabolism (and hence elimination) of drugs, for example, phenytoin.  Clearance of drugs, such as rifampicin, that are secreted via the biliary system, may be attenuated due to the cholestatic property of oestrogen.

 Elimination

 Renal blood ﬂow is increased by 60-80% during pregnancy, and glomerular normally excreted unchanged, for example, penicillin and digoxin.  Elimination from the fetus is by diffusion back to the maternal com- partment. Because most drug metabolites are polar, this favours accumulation of metabolites within the fetus.

 FDA pregnancy categories  Category A

Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester (and there is no evidence of a risk in later trimesters), and the possibility of fetal harm appears remote.

 Category B

Either animal-reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women, or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters).

 Category C

Either study in animals has revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women, or studies in Alex syndicate of pharmacists

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women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

 Category D

There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a lifethreatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

 Category X

Studies in animals or human beings have demonstrated fetal abnormalities, or there is evidence of fetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.

Specific drug therapy during pregnancy and lactation 1} headache, migraine & fever

 Chronic tension-type headaches often respond to reIaxation exercises and physical therapy that emphasizes stretching and strengthening of head and neck muscles.  General treatment measures for migraine include maintaining a regular sleeping and eating schedule, and practicing methods for coping with stress. Some patients with migraines benefit from use of ice (ice bags or cold packs) combed with pressure applied to the forehead to reduce pain associated with acute migraine attack.  Paracetamol/acetaminophen , perhaps combined with caffeine(Panadol® Extra tab.) is the analgesic and antipyretic of choice. It can be used at usual dosages and at any stage of pregnancy; paracetamol belongs to the group of analgesics of choice during breastfeeding. Dose : Oral(Abimol® tab. ,Tylenol® cap.) , rectal (Acetaminophen® supp.): 325-650 mg every 4-6 hours or 1000 mg 3-4times/day; do not exceed 4 g/day Alex syndicate of pharmacists

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Pregnancy risk factor: B Lactation:  Excreted into milk in small amounts.  Safe in breast feeding but reported single case of maculopapular rash in exposed infants. I.V. (Perfalgan® vial):