Pharmacology of pregnancy

 

Beeley (1976) classifies pharmacological causes of embyopathies in relation to different embryonic horizon.

a)                                                                              During the first two weeks before primitive streak formation, embryo is affected in all-or-none fashion. If the agent affects embryo, it dies, if not it survives and develops normally.

b)                                                                              The third week to the 10th week is the main period of organogenesis. Pharmacological and other agents have a more devastating effect on fetal development during this period.

c)                                                                              In the last six months of pregnancy teratogenic agents can affect the growth and functional development of fetal tissues and organs and not the whole organism.

First trimester effects (After Beeley 1976)*

 

Drug

Adverse effect

1

2

Thalidomide

Cytotoxic drugs

High risk of congenital malformations

3

Anticonvulsants

Phenytoin

Phenobarbito

Primidone

Treated maternal epilepsy is associated with an increase incidence of congenital malformation, especially oral clefts. Risk appears to be associated with phenytoin and not phenobarbitone or primidone.

 

Amphethamines

Lithium

Quinine, chloroquine

Hormonal pregnancy test primidos menstrogen

Chronic alcoholism

Warfarin

 

 

Definite but smaller increase in incidence of congential malformations

 

Aspirin

Oral contraceptive

Ethionamide

Diphenylhydramine

Diazepam

Co-trimoxazole pyrimenthamine

Possible risk of congenital malformation. Theoretical risk of congenital malformations. These drugs are folate antagonists. (Pyrimetha-antagonists. (Pyrimethamine has been used on large scale in preventing malaria placentitis amongst pregnant women in malarious areas with little reported effect on the fetus probably because of combination with folic acid). Recent reports claim some definite teratogenic effect. (Akpaffion et al, 1984.

 

Live vaccines

Rubella

Smallpox

Vaccination frequently produces viraemia

 

Androgens

Progestagens

Oestrogens

May produce virilization of female fetus

 

Stillboestriol

High does have been associated with later development of carcinoma of the vagina.

2nd and 3rd trimester effects

 

Drug

Adverse effect

 

Tetracyclines

Deposits in the developing bones and teeth. Affects decidous teeth when given from the 14th week. Permanent teeth are discoloured when given during the last 3 months.

 

Aminoglycosides

Streptomycine

Gentamicin

Kanamycin

Cause auditory or vestibular nerve damage, although serious damage is said to be rare

 

Chloroquine

Causes neonatal choroiretinitis in large doses

 

Thiazide diurectics

May produce diabetes in the fetus

 

Iodides (including cough mixtures) and antethyroid drugs

May produce in the fetus and also neonatal hypothyroidism. Antithyroid therapy should be withheld a week before delivery.

 

Radioactive Iodine

May damage fetal thyroid and cause permanent hypothyroidism.

*Beeley, L. (1976): Safer Prescribing. Oxford: Blackwell Scientific Publications.

 

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