Pharmacology in pregnancy Flashcards
Approximately what % of women of child-bearing age take some sort of medication?
80%
Why may a woman be on medicines during pregnancy, childbirth and lactation?
Hypertension
Asthma
Migraine
Epilepsy
Diabetes
Mental health disorders e.g depression/anxiety
Long-term anticoagulant therapy use e.g warfarin
Pregnancy may affect any of the 4 basic kinetic processes. What are these?
Absorption
Distribution
Excretion
Metabolism and elimination
Why might a pregnant women be unable to take oral medication?
Morning sickness - nausea and vomiting
Decrease in gastric emptying and gut motility - This is unlikely to be a problem with regular dosing, but may affect single doses
How might the absorption of an IM drug be altered in pregnancy?
Blood flow may be increased, so absorption may also increase using this route
How might the absorption of inhaled medication be altered during pregnancy?
During pregnancy a woman has increased cardiac output and increased tidal volume.
This may cause increased absorption of inhaled drugs
Drug distribution changes during pregnancy
Increase in plasma volume and fat will change distribution of drugs. So the volume of distribution will increase meaning more drug will be distributed to tissues (Esp fatty tissue)
Greater dilution of plasma decreases the relative amount of plasma proteins => results in increased fraction of free drug (unbound drug = active drug)
The hormones oestrogen and progestogen can inhibit which enzymes and ultimately alter drug metabolism?
They can induce or inhibit liver P450 enzymes which can increase or reduce metabolism
Give examples of medications affected by Oestrogen and progestogen?
Phenytoin - epilepsy medication - levels reduced during pregnancy due to induction of metabolism
Theophylline - COPD - levels increased due to inhibition of metabolism
By what % does the GFR increase in pregnancy?
50%
What changes to medication may be required due to the increased GFR in pregnant women?
May need to increase the dose of the drug in order to obtain the required/correct plasma concentration of the drug
What passes through the placenta from foetus to mother? (2)
CO2
Urea and other waste products
What passes through the placenta from mother to foetus?
O2 Glucose Amino acids Lipids, FA's and glycerol Vitamins Ions Alcohol, nicotine, drugs Viruses Antibodies
Look
Safest to assume all drugs will cross placenta
The placenta may also metabolise some drugs
How the drug affects the foetus depends on…
Rate at which drug crosses placenta and amount reaching the fetus
Duration of drug exposure
Distribution in different foetal tissues
Stage of placental and fetal development
Effects of drugs when used in combination
What does placental transfer depend on?
Molecular weight (smaller sizes will cross more easily)
Polarity (non-ionised molecules cross more readily)
Lipid solubility (lipid soluble drugs will cross)
How is drug distribution different in the foetus?
Circulation is different (e.g. Umbilical vein to liver)
Less protein binding than adults therefore more “free” drug available
Little fat, so distribution different
Relatively more blood flow to brain
How is drug metabolism different in the foetus?
Reduced enzyme activity, although this increases with gestation.
Foetus exhibits different P450 isoenzymes to adults.
How is drug excretion different in the foetus?
Excretion is into amniotic fluid – which the foetus swallows leading to recirculation.
Drugs and metabolites can accumulate in amniotic fluid.
Placenta not functioning at delivery so can be issues with excretory function,
Principles of prescribing in pregnancy
If you can, try non-pharmacological treatment first. If you have to use a medication… SAFEST DRUG, LOWEST DOSE POSSIBLE, SHORTEST TIME POSSIBLE (INTERMITTENT IF POSSIBLE)
Avoid the first 10 weeks of pregnancy if possible.
Consider stopping or reducing dose before delivery.
Never under treat disease which may be harmful to the mother or fetus
Principles of 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
What are the 2 major risks of medication use in pregnancy?
Teratogenicity (first trimester)
Fetotoxicity (second and third trimester)
Look
Maternal chronic illness must be treated as under-treatment of maternal illness due to fear of using medicines during pregnancy may cause greater foetal risk!
When is the highest risk of teratogenicity?
3-8 weeks (organogenesis)
Mechanisms of drug teratogenicity
Folate Antagonism
Neural Crest Cell Disruption
Endocrine Disruption: Sex Hormones
Induce foetal oxidative stress - imbalance of free radicals and antioxidants in the body
Vascular Disruption
Specific Receptor- or
Enzyme-mediated teratogenesis
What process is key in DNA formation and new cell production?
Folate metabolism
2 groups of drugs can affect folate metabolism. How do they work?
Block the conversion of folate to THF by binding irreversibly to the enzyme (eg methotrexate, trimethoprim)
Block other enzymes in the folate pathway (e.g. phenytoin, carbamazepine, valproate)
What is normally the result of using folate anatogonistic drugs during pregnancy?
Tend to result in neural tube, oro-facial or limb defects
Which types of drugs are Neural crest cell disruptions associated with?
Retinoid drugs e.g isotretinoin/’accutane’ (acne medication)
accutane is so potent that it can only be given if the woman is on contraception
What problems can Retinoid drugs cause as a result of neural crest cell disruptions
Aortic arch anomalies
Ventricular septal defects
Craniofacial malformations
Oesophageal atresia
Pharyngeal gland abnormalities
Enzyme-mediated teratogenesis
Drugs which inhibit or stimulate enzymes to produce therapeutic effects may also interact with specific receptors and enzymes damaging fetal development.
e.g NSAIDs - causing orofacial clefts and cardiac septal defects
What are possible issues related to fetotoxicity?
Growth retardation Structural malformations Foetal death Functional impairment Carcinogenesis
Common drug example that causes fetotoxicity later in pregnancy and should NOT be given to pregnant women?
ACE inhibitors/ARBs
May cause foetal renal dysfunction and growth retardation
Teratogenic drugs to avoid during pregnancy
Sodium valproate, phenytoin - neural tube defects
Warfarin - associated with haemorrhage in the fetus, as well as multiple malformations in the CNS and skeletal system.
ACE inhibitors - renal damage
NSAIDs - teratogenic and fetotoxic
Alcohol - foetal alcohol sydnrome
Retinoids - potent teratogenic
Drugs and lactation
Almost all drugs/medication the mother takes will be present in breast milk
Important to know what concentration will be in breast milk - what are the potentially toxic effects of those when they move into the baby
When considering drug therapy for a mother who is breast feeding what are the most important factors?
Minimal infant exposure
Treating the mother if completely necessary
How is minimal exposure achieved?
If a drug needs to be used, then the mother should take the medication immediately after feeding the baby
Avoid breast-feeding during peak drug effect
Avoid drugs with long half-life or active metabolites
Drugs that are highly protein-bound are preferred
Extra caution if baby is severely ill or preterm.
What 2 popular herbal galactagogues for nursing mothers pose a health risk to their infants?
Fenugreek
Comfrey
What are considered preventable teratogens?
Alcohol
Smoking
Drugs i.e marijuana, ecstacy and cocaine
What problems can smoking during pregnancy cause in the foetus/baby?
Low birth weight
Pre-term birth
Cerebral palsy
Learning difficulties
What is Pharmacokinetics?
What the body does to a drug
Movement of the drug through, and out of the body
The time course - absorption, bioavailability, distribution, metabolism, and excretion.
Affected by pregnancy
What is the 1st line treatment for nausea and vomiting during pregnancy?
Cyclizine- antihistamine
Prochloroperazine- phenothiazine
Doxylamine/pyridoxine combination product
2nd line treatment for nausea and vomiting
Ondansetron
Metoclopramide
What medication is given for hypertension in pregnancy?
Labetolol, nifedipine, methyldopa or hydralazine
What common hypertensive medication is teratogenic and should NOT be given to pregnant women?
ACE inhibitors
What are the safest drugs to give a pregnant woman to treat Epilepsy?
Carbamazepine and lamotrigine
What should always be given with anti-epileptics in pregnancy?
Folic acid
Diabetic treatment in pregnancy
Insulin = safest
Gestational diabetes / type 2 = metformin
All oral antidiabetic drugs, exceptmetformin, should be discontinued before pregnancy and substituted with insulin therapy.
Treatment is key if benefits from improved blood-glucose control outweigh the potential for harm
Which drug is given to prevent thromboembolism in pregnancy?
Low molecular weight heparin = safe
What is considered safe Asthma treatment during pregnancy?
Risks of medication use are lower than risk of untreated asthma
B2 agonist- albuterol, salbutamol - safe
Inhaled corticosteroid- budesonide
Systemic corticosteroid if severe asthma
What medication is safe to use to treat headaches and migraines during pregnancy?
Paracetamol
Ibuprofen- persistent pulm hypertension- avoid in 3rd trimester!!
Sumatriptan- acute treatment of migraine
Propanolol lowest effective dose
True or false: Morphine is used as labour analgesia
True
Antidepressants and antipsychotics during pregnancy
Need to weigh risk vs benefits of treatment
Selective Serotonin Reuptake Inhibitor (SSRI) - Where the benefits of SSRI use outweigh potential risks, use of SSRIs during pregnancy may be indicated.
What antibiotics are considered safe during pregnancy?
Penicillin- generally safe- check allergy
Macrolide- azithromycin/erythromycin- use only if no alternative
Sulphonamides- teratogenic-avoid in first trimester- folate antagonist
Cephalosporins- generally safe
Is Tetracycline safe during pregnancy? (Antibiotic)
No
Animal studies show it has effects on skeletal development and can cause discolouration of teeth
Are Aminoglycosides safe during pregnancy?
No
Can result in auditory or vestibular nerve damage -The risk is greatest with streptomycin.
Look
Most cytotoxic cancer drugs are teratogenic
Exclude pregnancy before starting these medications
If a woman in labour has had no analgesia but is crying out for pain relief what should be given first (before morphine)?
Inhalation Analgesia (Entonox)
