5. Drug therapy in pregnancy.

Pregnancy
Most women are already taking meds when pregnant and therefore it is said to be
most vulnerable period.

As pregnancy evolves, profound changes occur in physiology, including fluid and

tissue composition.

Absorption. Despite reduced gastrointestinal motility, there appears to be no major

defect in drug absorption except that slow gastric emptying delays the appearance
in the plasma of orally administered drugs, especially during labour. Absorption
from an intramuscular site is likely to be efficient because vasodilatation increases
tissue perfusion.
Slowed enteric motility can affect erythromyocin.

Distribution. Total body water increases by up to 8 L, creating a larger space within

which water-soluble drugs may distribute. Plasma albumin (normal 33–55 g/L)
declines by some 10 g/L from haemodilution. While this gives scope for increased
free concentration of drugs that normally bind to albumin, unbound drug is also
available to distribute, be metabolised and excreted. With phenytoin, for example,
the free (and pharmacologically active) concentration does not alter, despite the
dilutional fall in the total plasma concentration. Thus therapeutic drug monitoring
interpreted by concentrations appropriate for non-pregnant women may mislead.
A useful general guide during pregnancy is to maintain concentrations at the lower
end of the recommended range. Body fat increases by about 4 kg and provides a
reservoir for lipid-soluble drugs.

Hepatic metabolism increases due to increased progesterone, although not blood

flow to the liver. There is increased clearance of drugs such as phenytoin and
theophylline, whose elimination depends on liver enzyme activity. Drugs that are
so rapidly metabolised that elimination depends on delivery to the liver, i.e. on
hepatic blood flow, have unaltered clearance, e.g. pethidine.

Elimination. Renal plasma flow almost doubles and there is more rapid loss of
renally excreted drugs, e.g. amoxicillin, the dose of which should be doubled for
systemic infections (but not for urinary tract infections as penicillins are highly
concentrated in the urine).

Placenta. Maternal blood bathes the chorionic villi, which consist of a layer of
trophoblastic cells that enclose fetal capillaries. Their large surface area and the high
placental blood flow (500 mL/min) are essential for gas exchange, uptake of nutrients
and elimination of waste products. Thus a lipid barrier separates the fetal and
maternal bloodstreams, allowing the passage of lipid-soluble substances but
excluding water-soluble compounds, especially those with a molecular weight
exceeding 600.
This exclusion is of particular importance with shortterm use, e.g. tubocurarine
(mol.wt. 772) (lipid insoluble) or gallamine (mol. wt. 891) used as a muscle
relaxant during caesarean section do not affect the infant; with prolonged use,
 however, all compounds will eventually enter the fetus to some extent.

The ph of the blood changes during delivery at low ph during delivery the bases
ionise more then acids, during delivery ph of the fetus decreases below the
mother and drugs get ionised but after delivery ph normalises and the drug goes
to unionised active form and can cause adverse effects.

Pain management in pregnancy afentanyl is the opiod of choice.

Teratology-
First 2 weeks- blastogenesis- all or none
15-60 days- embryonal period- toxic effect on organ dependant on exact date
4months onwards- foetal period- sensitivity to drugs decreases. Usually functional
disorders and growth retardation.

Teratogenic drugs- antiepileptics, benzodiazepines, rifampicin

No teratogenicity- b-lactams, macrolides, beta-blockers, h1- blockers.

FDA risk categories-

Group A- 8 meds no risk controlled studies vitamin A,C,D, folic acid)
Group B- 250 drugs animal studies no risk- penicillin, erythromyocin etc…
Group C- 700 meds- animal studies show teratogenic effects no human trials
Group D- positive evidence of fetal risk but in life threatening could use
Group X- serious risk definitely outweigh risks!

Weigh up risks

Hypertension in pregnancy-
Methyl dopa,
Beta blocker- best is metoprolol? Selective beta 1 dues to bet2 receptors in uterus=
contraction.
Alpha blocker

Antibiotics-
Penicillin
Amoxicillin- 50% more dose
Erythromyocin- 50% increased dose (only macrolide)
Cephalosporin 2nd gen

No diuretics in pregnancy.

Breast feeding-
ADr with penicillin, tetracycline.
Lipid soluble drugs are in higher conc, weak bases are concentrated. (coffee is a
base, therefore decrease intake can go to child!!!!)
Betablocker- bradycardia of baby
Diuretics suppress milk formation
Metronidazole unpleasant taste.

Drugs to avoid in breast feeding- nicotine, amphetamines, lithium, anticancer,

quinolone, aspirin, benzodiapines.