Pharmacology Flashcards
How many pregnant women will uses drugs (medications) during pregnancy?
Approximately 50%-90% of pregnant women will take a drug during pregnancy.
- Prescribed 60%
- OTC 90%
Why might a woman be on medication during pregnancy, childbirth and lactation?
- Hypertension
- Migraine
- Asthma
- Mental health disorders
- Epilepsy
- Long term anticoagulant therapy
What are the 4 basic kinetic processes?
- Absorption
- Distribution
- Metabolism and elimination
- Excretion
Why is data very limited for drugs in pregnancy?
Very few studies are carried out during pregnancy
What absorption changes occur via the oral route during pregnancy?
- May be more difficult “morning sickness” nausea/vomiting
- Increase in gastric emptying and gut motility
What absorption changes occur via the IM route during pregnancy?
Blood flow may be increased, so absorption may also increase using this route
What absorption changes occur via the inhalation route during pregnancy?
Increased cardiac output and decreased tidal volume may cause increased absorption of inhaled drugs
What changes occur to distribution during pregnancy?
- Increase Vd: Increase in plasma volume and fat will change distribution of drugs.
- Increase fraction of free drug: Greater dilution of plasma will decrease relative amount of plasma proteins.
What metabolism changes can occur during pregnancy?
Oestrogen and progestogens can induce or inhibit liver P450 enzymes, increasing or reducing metabolism.
Give an example of a drug with increases metabolism in pregnancy?
Phenytoin
Give an example of a drug with decreased metabolism in pregnancy?
Theophylline
What excretion changes occur during pregnancy?
- GFR is increased in pregnancy by 50% leading to increased excretion of many drugs.
- This can reduce the plasma concentration, and can necessitate an increase in dose of renally cleared drugs.
How can pregnancy affect pharmacodynamics?
Pregnancy may affect site of action & receptor response to drugs
- Concentration of drug, metabolites at sites of biological action (changes in blood flow)
- Mechanism of action (changes in receptors)
- Efficacy may be different
- Adverse effects may be different
What are the functions of the placenta?
- Attach the foetus to the uterine wall
- Provide nutrients to the foetus
- Allow the foetus to transfer waste products to the mother’s blood
What materials cross the placenta from mother to foetus?
- Oxygen
- Glucose
- Amino acids
- Lipids, fatty acids & glycerol
- Vitamins
- Ions; Na, Cl, Ca, Fe
- Alcohol, nicotine + other drugs
- Viruses
- Antibodies
What materials cross the placenta from foetus to mother?
- CO2
- Urea
- Other waste products
What does placental transfer depend on?
- Molecular weight (smaller sizes will cross more easily)
- Polarity (non-polar cross more readily)
- Lipid solubility (lipid soluble drugs will cross)
How does foetal distribution differ from adults?
- Circulation 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 does foetal metabolism differ from adults?
- Less enzyme activity, though increases with gestation
- Different isoenzymes to adults
How does foetal excretion differ from adults?
- NB excretion is into amniotic fluid – this is swallowed and can allow recirculation
- Drugs and metabolites can accumulate in amniotic fluid
- Placenta not functioning at delivery so can be issues with excretory function
When is teratogenicity an issue?
During the 1st trimester
When is fetotoxicity an issue?
2nd and 3rd trimester
What problem is there with people who have chronic conditions?
They are often undertreated due to fear that the drugs will affect the pregnancy
What percentage of foetal abnormalities are attributable to drugs?
2%
When is the biggest risk of teratogenicity?
3-8 weeks
What are the mechanisms of teratogenicity?
- Folate Antagonism
- Neural Crest Cell Disruption
- Endocrine Disruption: Sex Hormones
- Oxidative Stress
- Vascular Disruption
- Specific Receptor- or Enzyme-mediated Teratogenesis
What is folate action key process in?
DNA formation and new cell production
What are the mechanisms of folate antagonism?
- Block the conversion of folate to THF by binding irreversibly to the enzyme (eg methotrexate, trimethoprim)
- Block other enzymes in the pathway (eg phenytoin, carbamazepine, valproate)
What does folate antagonism tend to result in?
Tend to result in neural tube, oro-facial or limb defects
What can retinoids cause in pregnancy?
Neural crest cell disruption
What problems can neural crest cell disruption lead to?
- Aortic arch anomalies
- Ventricular septal defects
- Craniofacial malformations
- Oesophageal atresia
- Pharyngeal gland abnormalities
What can NSAIDs cause in pregnancy?
Orofacial clefts and cardiac septal defects
What is enzyme mediated teratogenesis?
Drugs which inhibitor stimulate enzymes to produce therapeutic effects may also interact with specific receptors and enzymes damaging foetal development.
What is fetotoxicity?
Toxic effect on the foetus later in the pregnancy
What possible fetotoxcity issues can occur?
- Growth retardation
- Structural malformations
- Foetal death
- Functional impairment
- Carcinogenesis
What can ACEI/ARBs cause in pregnancy?
Renal dysfunction and growth retardation
How are drugs stages for use in pregnancy?
- A: No foetal risk
- B: Animal studies show no risk but no human studies or animal studies show risk but human do not
- C: No human data
- D: Evidence of foetal risk but benefits outweigh them
- X: Foetal risk outweigh possible benefit
Give examples of known teratogens to avoid during pregnancy.
- Anticonvulsants
- Anticoagulants
- Antihypertensives
- NSAIDs
- Alcohol
- Retinoids
What is the teratogenic effect of anticonvulsants?
Valproate is associated with neural tube defects, as is carbamazepine and phenytoin
What is the teratogenic effect of anticoagulants?
Warfarin is associated with haemorrhage in the fetus, as well as multiple malformations in the central nervous system and skeletal system.
What is the teratogenic effect of antihypertensives ?
ACE inhibitors cause renal damage and may restrict normal growth patterns in the unborn child.
What is the teratogenic effect of NSAIDs?
Premature closure of the ductus arteriosus.
What is the teratogenic effect of alcohol?
Foetal alcohol syndrome/effects
What is the teratogenic effect of retinoids?
Ear, CNS, cardiovascular, and skeletal disorders
What are the issues with drugs and lactation?
- Most drugs will be present at lower doses through breast-feeding than in utero
- Important to know what concentration will be in breast milk
What drugs should be avoided when breast feeding?
- Cytotoxics
- Immunosuppressants
- Anti-convulsants (not all)
- Drugs of abuse (especially opiates)
- Amiodarone
- Lithium
- Radio-iodine
What are the 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 principles of prescribing pregnancy?
- If you can, try non-pharmacological treatment first
- Use the drug with the best safety record
- Check the SPC for the most up to date information
- Use the lowest effective dose
- Use the drug for the shortest possible time, intermittently if possible
- Avoid the first 10 weeks of pregnancy if possible
- Consider stopping or reducing dose before delivery
- Don’t under treat disease which may be harmful to the fetus
What are the principles of prescribing in breast feeding?
- Again avoid unnecessary drug use
- Check on up to date drug information
- May be a lack of information
- If licensed and safe in paediatric use (esp under 2 years), a drug is likely to be safe in breast feeding
- Choose drugs with pharmacokinetic properties that reduce infant exposure (eg highly protein bound)
