Lecture 10 Drugs in Pregnany, Extremities of Age Flashcards
What are the problems in pregnancy surrounding -
Absorption
Distribution
Metabolism
Elimination
Absorption - gastric emptying is delayed by oral preparations (delay absorption of the drug or change the drug if it is affected by the stomach’s acid).
Distribution:
- Total body water and fat are increased resulting in lower concentrations of water soluble and lipid soluble drugs
- Protein binding is reduced increasing free drug concentrations (free drug is active drug, but eliminated quicker)
Metabolism:
Increased clearance of the drugs which depend on liver enzyme activity - phenytoin, theophylline.
Elimination:
Increased renal plasma flow doubling the elimination of renally cleared drugs such as penicillins.
What factors influence placental transfer of drugs ?
- Lipid solubility vs water solubility (lipid cross easier)
- Molecular size (small)
- Protein binding (unbound)
- Metabolism
Fetal development
What processes occur at these stages and name drugs which can affect these processes:
Blastocyst formation (0-16 days)
Organogenesis (17 - 60 days)
Cell and organ maturation (60 days - term)
Blastocyst formation involves cell division. Cytotoxic drugs and alcohol
Organogenesis involves division, migration, differentiation and cell death. Most known teratogens affect this stage.
Cell and organ maturation involves division, migration, maturation and cell death.
Alcohol, nicotine, radioactive iodine, corticosteroids.
Give examples of drugs known to have adverse effects on the foetus (12)
- Aminoglysodes - deafness
- Carbamazepine - spina bifida and reduced head growth
- Cytotoxic drugs - hydrocephalus, neural tube defects, cleft palate, abortion/stillbirth
- Ethanol - microcephaly, retardation, hypotonia, septal defects, tetralogy of fallot, craniofacial abnormalities, low birth weight and increased neonatal death rate
- Phenytoin - microcephaly, retardation, hare lip, cleft palate
- Retinoids - hydrocephalus, microcephaly, septal defects, tetralogy of fallot, facial deformities, cleft palate.
- Tetracycline - staining of bones and teeth
- Tobacco - impaired growth/ low birth weight/ abortion
- Opioids - withdrawal symptoms in newborn, growth retardation, increased perinatal mortality
- Lithium - hydrocephalus, septal defects, Ebstein’s abnormality, floppy baby at birth
- Valproate - spina bifida, microcephaly, tetralogy of fallot, cleft palate and lip, impaired growth
- Warfarin - deafness, blindness, hydrocephalus, congenital heart disease, scoliosis, impaired growth.
List the seven As and DMARDs.
- ACEis/ ARBs
- Anticonvulsants (phenytoin, carbamazepine, valproate)
- Antibiotics (tetracyclines, trimethoprim, metronidazole)
- Antipsychotics (Lithium)
- Antithyroid (Iodine/ propylthiouracil)
- Anticoagulant (warfarin)
- Abuse of (alcohol, cigarettes, opioids, benzodiazepines)
- DMARDs/ cytotoxics (methotrexate, cyclophosphamide)
List principles for prescribing in pregnancy
What are the rules for prescribing during pregnancy
- All drugs cross the placenta but the amount depends on their physico-chemical properties
- Drugs which are safe in adults can cause serious adverse effects in the foetus e.g. thalidomide
- Few drugs are clearly teratogenic and most that cause problems increase the background risk
- Administration during the first trimester has the greatest risk
- There must always be sound reasons for prescribing a drug during pregnancy
- Avoid prescribing in the first semester except during the most exceptional circumstances
- If possible choose a drug within a class which has a proven safety record e.g. labetalol rather than an ACEi when treating hypertension
What are the issues surrounding these topics in pregnancy?
Nausea and vomiting
Asthma
Hypertension
Nausea and Vomiting:
- If mild nothing, may consider vitamin or electrolyte support
- Promethazine (antihistamine) 1st line, cyclizine, prochlorperazine or metoclopamide 2nd line
- Methylprednisolone in severe cases
Asthma:
- Maintain good control with inhalers
- Prednisolone ok if needed
Hypertension:
- Older drugs labetalol/ methyldopa/ nifedipine (NICE - experience)
Why is it important for a pregnant woman to be tested for a UTI even if asymptomatic?
Describe how to prescribe for a UTI in pregnancy.
The bacteria of the UTI may cause harm to the foetus.
Follow LOCAL GUIDELINES. Preference:
- Nitrofurantoin
- Trimethoprim - give folic acid 5mg a day in the first trimester and do not give if the mother is folate deficient, taking a folate antagonist or has been treated with trimethoprim in the first year (although inhibits bacterial DHFR enzyme there is some action on the human one)
- Ceflaxine
- NOT AMOXICILLIN (resistance), QUINOLONES, TETRACYCLINES (may be harmful)
- For asymptomatic bacteruria you may use amoxicillin.
What are the drug issues in pregnancy surrounding:
Anticoagulation?
Anticonvulsants?
Anticoagulation: Needed because there is an increased risk of DVT in pregnancy due to altered blood flow from the legs.
- Heparin/ LMWHs are relatively safe.
- Warfarin should be avoided
- Follow protocols for anticoagulation medication during vaginal delivery or caesarian section to prevent excessive blood loss.
Anticonvulsants: Drug risks around facial abnormalities and neural tube formation
- Seizure more risk to the foetus than the drug
- Refer to specialist - changing guidance (joint obstetric and neurology clinics)
- Why should you be cautious in prescribing to a nursing mother?
- List drugs which should be used with caution in breastfeeding.
- Most drugs are detectable in the breast milk though concentration very low.
- Caution with:
- Diazepam
- Alcohol
- Lithium
- Iodine/ propylthiouracil (depress the baby’s thyroid function, which has effects on GH, vital for brain and musculoskeletal system development)
- Opiates
- Tetracyclines (bones and teeth)
- Corticosteroids
What are the pharmacokinetic issues in prescribing to a neonate?
Absorption
Distribution
Metabolism
Elimination
Absorption
- Skin: SA/body weight is greater so the absorption of topical agents e.g. steroids is increased.
- IM absorption is impaired due to reduced muscle mass
- Rectal absorption inefficient e.g. diazepam, theophylline.
Distribution:
- Body water as a percentage is greater than in older children and so the loading dose is greater for ahminoglycosides, digoxin and aminophylline based on body weight
- Albumin bindin is decreased increasing free concentrations of highly bound drugs and increasing the risk of drug/ bilirubin interactions.
Metabolism (around 50% of an adult)
- Impaired oxidation increasing the concentration of drugs such as warfarin, diazepam and theophylline.
- Impaired glucuronidation increasing the risk of toxicity to drugs which are metabolised by this mechanism e.g. chloramphenicol (grey baby syndrome)
Elimination:
- Glomerular filtration/ tubular secretion and reabsorption are all impaired, requiring dose reduction for renally cleared drugs based on body weight - ahminoglycosides, digoxin and penicillins.
- By 6 months renal function is usually normal and standard doses based on body weight can be used.
Name three inherited conditions and how they affect drug response in neonates.
- Oxidation / acetylation
- Slow: exaggerated or toxic responses
- Fast: failure to respond to standard doses - Glucose-6-phosphate dehydrogenase deficiency:
Develop acute haemolysis following treatment with a number of drugs. - Pseudocholinesterase deficiency:
Prolonged apnoea after neuromuscular blockade.
List rules for prescribing to neonates:
- When possible base doses on estimated body surface area
- Use paediatric formulary
- Special adjustments are necessary in neonates especially those who are premature (lung function)
- Avoid new drugs if possible and remember the most drugs are not licensed for use in children and information is often poor.
- Adverse effects are often different from adults (e.g. grunting and tummy pain presenting with pneumonia)
Give 3 issues concerning prescribing in the elderly
- Increased number of diseases results in increased drug prescribing. The potential for adverse effects and interactions is increased
- Compliance with medication tends to be worse in the frail elderly.
- Drug disposition and responsiveness alter with age requiring dose modification. In most situations this results in a reduction of the maintenance dose.
What are the issues surrounding:
Absorption
Distribution
Metabolism
Elimination
Absorption: absorption of orally administered drugs is delayed due to reduced motility and blood flow. Of little importance.
Distribution: lean body mass/ total body water and albumin binding tend to decrease, increasing the plasma concentrations of tissue bound drugs, water soluble drugs and drugs with high albumin binding.
Metabolism: generally slower due to reduced liver mass and blow flow. Therefore drugs undergoing metabolism act longer and enzyme induction is impaired (there is generally a balance of enzyme inhibitors and inducers because of POLYPHARMACY in the elderly >5 drugs)
Elimination by the kidney reduced so that the risk of drug toxicity is increased for drugs that have a narrow therapeutic index and are mainly eliminated by the kidney.
