pharmacology in pregnancy

Question 1

Medical conditions during Pregnancy

Answer 1

Hypertension
Pain
Nausea and Vomiting
Gestational Diabetes
Anticoagulant Therapy
Herpes Virus
Mental Health Disorders
Migraine
Asthma
Epilepsy

Question 2

Pharmacokinetics during Pregnancy

absorbtion

Answer 2

Absorption

Oral route may not be an option for women suffering N&V (consider buccal).
Decreased gastric emptying and gut motility – higher incidence of constipation, may not affect regular drug therapies but could impact once off treatments.
Increased absorption of intramuscular drugs due to increased blow flow.
Increased cardiac output and reduced tidal volume may cause increased absorption of inhaled drugs.

Question 3

pharmokinetics in pregnancy

distribution

Answer 3

Increase in plasma volume and fat will change the distribution of drugs; increasing the volume of distribution.

Greater dilution of plasma will decrease the relative amount of plasma proteins, increasing the amount of free drug in circulation (less protein bound).

Question 4

pharmokinetics in pregnancy

metabolism

Answer 4

Altered enzyme actions due to oestrogen and progesterone levels.
Liver P450 enzymes may be induced or inhibited which can lead to increased or reduced metabolism – drug dependent.
Examples
Phenytoin levels are reduced in pregnancy due to metabolism being induced (sped up).
Theophylline levels increase during pregnancy due to metabolism being inhibited resulting in more free drug in circulation for longer.

Question 5

pharmokinetics in pregnancy

excretion

Answer 5

GFR is increased in pregnancy by 50% leading to an increased excretion of many drugs.

This can result in a reduction in plasma concentration and can require for higher medication doses being required for renally cleared drugs; eg. Gentamicin and Digoxin.

Question 6

Pharmacodynamics

Answer 6

Pharmacodynamics is defined as the response of the body to the drug. This is less understood in pregnancy.
Pregnancy may affect the site of action and receptor response to drugs
Efficacy of medicine may be different
Adverse effects may also be different

Question 7

Drug therapy during Pregnancy

Answer 7

The placenta is not a barrier to drugs, nearly all drugs except those with a high molecular weight (eg. insulin and heparin) will cross the placenta to the fetus. In practice, virtually all drugs have the ability to affect the unborn baby.
The placenta is a membrane which allows for the exchange of materials between mother and baby. The mother provides oxygen, glucose, fat, vitamins, and antibodies among other things to baby; baby transfers urea, CO2, and other waste products back to mother.
Alcohol and nicotine (smoking) passes through the placenta to the unborn baby. Often in practice now come across cocaine use and other recreational drugs.
Factors affecting placenta transfer of medicine depend on the drug type, lipid-soluble unionised drugs cross more readily than polar drugs; length of exposure, stage of pregnancy.

Question 8

Fetal pharmacokinetics
distribution

Answer 8

Circulation is different.
Less protein binding than adults, more free drug.
Little fat, so distribution different.
More blood flow to brain.

Question 9

fetal pharmacokinetics
metabolism

Answer 9

Less enzyme activity, this increases with gestation.

Question 10

fetal pharmacokinetics
excretion

Answer 10

Drug excretion is into amniotic fluid and then swallowed and re-circulated.
Drugs and metabolites can accumulate in amniotic fluid due to this.

Question 11

Teratogenicity

Answer 11

Teratogen is an agent or factor which can cause congenital malformation.

A teratogen can prevent implantation of the conceptus (embryo), cause abortion, produce intrauterine growth restriction or cause fetal death.

Less than 2% of newborns born have major malformations, and less than 5% of these are caused by medications or toxins. Data is small but very hard to prove single agent cause, may be a magnitude of factors, genetic also.

Biggest risk of exposures during the organogenesis period (3-10weeks). When organs are being formed.

Question 12

Fetotoxicity

Answer 12

‘Toxic effects to the fetus’

Drugs given after the first 2 months of pregnancy are more likely to cause general growth retardation, or interfere with functional development of organs.
Examples –
Warfarin may cause intracranial haemorrhage if given in 2nd and 3rd trimester
NSAIDs taken in the 3rd trimester can cause premature closure of ductus arteriosus resulting in neonatal pulmonary hypertension
Beta Blockers given in late pregnancy may result in neonatal hypoglycaemia

Question 13

Prescribing principles for women of child-bearing age

Answer 13

Always consider the possibility of pregnancy (planned or not)
Warn women of potential risks
If planning a pregnancy, advice to discuss treatment options prior to stopping medication
Always discuss contraception
Pregnancy Prevention Programmes – legal requirement for some treatments, eg. Isotretinoin, valproate. MHRA guidance, confirmed with negative pregnancy test prior to prescribing
Valproate medicines (Epilim▼, Depakote▼): contraindicated in women and girls of childbearing potential unless conditions of Pregnancy Prevention Programme are met - GOV.UK (www.gov.uk)

Question 14

Principles for prescribing during pregnancy

Answer 14

Consider non-pharmacological treatments
Avoid all drugs in the first trimester if possible
Avoid drugs that are known to be harmful
Use the medicine with the best safety profile (avoid new drugs unless deemed safe)
Use the lowest effective dose for the shortest period of time
Consider the need for dose changes and additional therapeutic monitoring for some drugs
Don’t under treat a condition, this may be more harmful to mum and baby