Drug Responses During Pregnancy

Drug Responses During Pregnancy
The response to anaesthetic and adjuvant drugs is modified during pregnancy and the early puerperium. The most pertinent alteration is a reduced drug requirement, manifest in both regional and general anaesthesia. Regional Anaesthesia. In the late first trimester to the early puerperium, a smaller dose of local anaesthetic is required to obtain the desired level of spinal or extradural blockade. During the last months of gestation, approximately two-thirds of the normal dose is adequate.

This altered response, which is due to CSF and hormonal changes and an increase in volume of the epidural veins, subsides progressively in the early postpartum period. General Anaesthesia changes in depth of inhalation anaesthesia occur with greater rapidity in pregnant women than in non-pregnant subjects. Pregnancy enhances anaesthetic uptake in two ways. The increase in resting ventilation delivers more agent into the alveoli per unit time, while the reduction in functional residual capacity favors rapid replacement of lung gas with the inspired agent.

In addition, there is a reduction in anaesthetic requirements, with a fall in the minimum alveolar concentrations (MAC) of halogenated vapors. When measured in ewes MAC was 25-40% lower in gravid as compared with nonpregnant animals. Serum Cholinesterase. Serum cholinesterase levels fall by 24-28% during the first trimester without a marked change for the remainder of gestation. However, even lower levels (about 33% reduction) develop during the first 7 postpartum days.

The decreased levels of the enzyme are still sufficient for normal hydrolysis of clinical doses of suxamethonium or chloroprocaine during gestation. Postpartum, however, approximately 10% of women will be at risk of a prolonged reaction to suxamethonium.The decreased functional residual capacity has a further effect on the management of general anaesthesia, the resultant reduction in oxygen storage capacity, together with the elevated oxygen consumption, leads to an unusually rapid decline in arterial oxygen tension in the apnoeic anaesthetised gravida.

Thus, the mean elimination half-life for thiopentone in gravid women is more than doubled in comparison with that in nongravid young patients. There are also alterations in the response to intravenous agents, the resultant reduction in oxygen storage capacityin particular prolongation of their elimination half-lives consequent to the greater distribution volume (resulting from the pregnancy-induced increase in plasma volume).