Pharmacology in Pregnancy Flashcards
What percentage of pregnant women will take a drug during pregnancy?
50-90%
List some absorption changes in pregnancy?
- Oral route changes due to ‘morning sickness’/Increase in gastric emptying and gut motility
- Intramuscular (Blood flow may be increased -^absorption)
- Inhalation (Increased CO, decreased tidal volume - can increase absorption)
List some distribution changes in pregnancy?
- Increases in plasma volume and fat
- Greater dilution of plasma will decrease relative amount of plasma proteins ^fraction of free drug
List some metabolism changes in pregnancy?
-Oestrogen/Progestogens can induce/inhibit P450 enzymes, increase/reduce metabolism.
(Eg Phenytoin reduced/Tehophylline increased)
List some excretion changes in pregnancy?
- GFR ^ - ^Excretion
- Can reduce plasma conc, so need to increase dose of renally cleared drugs
What are the pharmacodynamic changes in pregnancy?
- May affect site of action and receptor response to drugs
- Efficacy/adverse effects may be different
Do most drugs cross the placenta?
Yes
What does placental transfer depend on?
- Molecular weight
- Polarity (non-polar crosses easier)
- Lipid solubility
- Charge
What are the distribution differences in fetal pharmacokinetics?
- Circulation different
- Less protein binding - more ‘free drug’ available
- Little fat, different distribution
- Relatively more blood flow to brain
What are the metabolism differences in fetal pharmacokinetics?
- Less enzyme activity (increases with gestation)
- Different isoenzymes to adults
What are the excretion differences in fetal pharmacokinetics?
- Excretion into amniotic fluid, swallowed and can allow recirculation
- Drugs and metabolites can accumulate in amniotic fluid
- Placenta not functioning at delivery - can be issues with excretory function
What issues are there with sodium valproate (anti-convulsant) in pregnancy?
Teratogenicity
Neural tube defects
What trimester does teratogenic drugs affect?
First trimester
What trimesters do fetotoxic drugs affect?
Second and Third timester
List some mechanisms of teratogenicity
- Folate Antagonism
- Neural Crest Cell Disruption
- Endocrine Disruption: Sex Hormones
- Oxidative Stress
- Vascular Disruption
- Specific Receptor- or Enzyme-mediated Teratogenesis
What defects are usually seen in folate antagonism?
Neural tube defects
Oro-facial defects
Limb defects
List some drugs involved in folate antagonism
Methotrexate, Trimethprim (Block coversion of Folate to THF)
Phenytoin, Carbazepine, Valproate (Block other enzymes in pathway)
What defects may arise from neural crest cell disruption?
Aortic arch anomalies Ventricular septal defects Craniofacial malformations Oesophageal atresia Pharyngeal gland abnormalities
What class of drugs may be involved in neural crest cell disruption?
Retinoids (eg isotretinonin)
Give an example of drugs involved in enzyme-mediated teratogenesis?
NSAIDs causing orofacial clefts and cardiac septal defects
List some possible issues from fetotoxicity?
- Growth retardation
- Structural malformations
- Fetal death
- Functional impairment
- Carcinogenesis
Give an example of a fetotoxic drug?
ACE inhibitors/ARBs - renal dysfunction and growth retardation
List some examples of known teratogens to avoid in pregnancy?
Anticonvulsants (Valproate) Anticoagulants (Warfarin) Antihypertensive agents (ACE inhibitors) NSAIDs Alcohol Retinoids
List some drugs to avoid in lactation
- Cytotoxics
- Immunosuppressants
- Anti-convulsants (not all)
- Drugs of abuse
- Amiodarone
- Lithium
- Radio-iodine
- Also avoidance of some herbal remedies (Fenugreek, comfrey)
What are the principles to consider when prescribing for women of child-bearing age?
Always consider possibility of pregnancy (planned or not!)
Warn women of possible risks
When treating medical conditions, advise women to attend before getting pregnant if planning to (optimise treatment)
Discuss contraception
If necessary, do not prescribe without contraception
Try non-pharm treatment first.
Use lowest effective dose.
Avoid first 10 weeks of pregnancy if possible.
Dont under treat disease which may be harmful to fetus.
What are the principles to consider when prescribing in breastfeeding?
- Avoid unnecessary drug use
- Check up to date info - if safe in paeds, likely to be safe in breastfeeding
- Choose drugs that reduce infant exposure
What is the first line therapy used in pregnancy for hypertension?
Labetolol
What antihypertensives are used during pregnancy for hypertension?
Combined alpha + beta blockers - eg labetolol
Hydralazine
Nifedipine
Methyldopa
When may labetolol be contraindicated?
Asthmatics
Some cardiac conditions (bradycardias, cardiac failure)
What may be used in women with symptomatic pre-eclampsia to treat/prevent seizures?
Magnesium sulphate
What antihypertensives are CONTRAindicated in pregnancy?
ACE Inhibitors
Angiotensin Receptor Blockers
Spironolactone
What simple analgesias are used in pregnancy?
Paracetamol
Dihydrocodeine/Codeine
Aspirin (But avoid in labour!)
Entonox
What simple analgesias are CONTRAindicated in pregnancy?
NSAIDS - Ibuprofen/Diclofenac
Can cause premature closure of ductus arteriosus, fetal oliguria, oligohydramnios
What drugs make up Entonox?
Oxygen
Nitrous oxide
What opiates are commonly used in labour?
Morphine
Pethidine
Diamorphine
Remifentanyl PCA
Often co-prescribe with anti-emetic
When may local anaesthetic be used in labour?
- Before large bore IV cannula insertion
- After delivery to suture an episiotomy/vaginal tear
- Pudendal nerve block
What are some contraindications to epidural use in labour?
Thrombocytopenia, Coagulopathy Raised ICP Local sepsis Septic shock Allergy to local anaesthetic Recent anticoagulants
When may spinal anaesthesia be used?
Most caesarean sections
