Pharmacology in pregnancy Flashcards by Anna Coull

Approximately what % of women of child-bearing age take some sort of medication?

80%

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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

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Pregnancy may affect any of the 4 basic kinetic processes. What are these?

Absorption
Distribution
Excretion
Metabolism and elimination

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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

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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

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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

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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)

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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

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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

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By what % does the GFR increase in pregnancy?

50%

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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

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What passes through the placenta from foetus to mother? (2)

CO2

Urea and other waste products

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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

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Safest to assume all drugs will cross placenta

The placenta may also metabolise some drugs

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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

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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)

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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

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How is drug metabolism different in the foetus?

Reduced enzyme activity, although this increases with gestation.

Foetus exhibits different P450 isoenzymes to adults.

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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,

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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

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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

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What are the 2 major risks of medication use in pregnancy?

Teratogenicity (first trimester)

Fetotoxicity (second and third trimester)

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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!

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When is the highest risk of teratogenicity?

Study These Flashcards

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, except metformin, 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.

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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)

Pharmacology in pregnancy Flashcards

(58 cards)