SPR L10 Drugs in Pregnancy and Extremes of Age

Question 1

Drugs in Pregnancy and Extremes of Age

Learning Outcomes

for general perusal

Answer 1

• Describe the impact of pregnancy on drug pharmacokinetics and pharmacodynamics
• List safety precautions that should be taken when prescribing in pregnancy
• Give examples of common drugs that must be used with caution or contra-indicated in pregnancy
• Discuss the drugs that are commonly prescribed for pregnancy induced symptoms (nausea etc)
• Describe the impact of extremes of age on drug pharmacokinetics and pharmacodynamics
• List safety precautions that should be taken when prescribing in the very young and the elderly
• How may the efficacy and/or safety of a drug be affected by changes in physiology?
• How will these expected changes alter the way you prescribe or monitor these patients
• Remember that when pregnant or breast feeding there are x2 very different patients receiving your prescription
• Common solutions to common problems in pregnancy

Question 2

Drugs in Pregnancy

Pharmacokinetics

1. A: How is absoption affected?
2. D: How is distribution affected?
3. M: How is metabolism affected?
4. E: How is elimination affected?

Answer 2

1. Gastric emptying is delayed for oral preparations
2. 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
3. Increased clearance of drugs which depend on liver enzyme activity- phenytoin, theophylline.
4. Increased renal plasma flow doubling the elimination of renally cleared drugs such as penicillins.

Question 3

Drug effects on the Fetus

Most drugs cross the placenta to varying degrees

What are the factors influencing Placental Transfer?

Which type of molecules cross most easily?

Answer 3

Lipid solubility / Water solubility

Molecular size

Protein binding

Metabolism

small lipid soluble unbound molecule crosses most easily

Question 4

Effects of Drugs on fetal development
Which drug affect the following stages and processes?

1. Blastocyst formation (0-16days), cellular division
2. Organogenesis (17-60 days), Division, Migration, Differentiation, Cell Death
3. Cell and organ Maturation (60 days - term), Division, Migration, Differentiation, Cell Death

Answer 4

1. Cytotoxic drugs, Alcohol?
2. Most known teratogens
3. Alcohol, Nicotine, Radio active iodine, Corticosteroids

Question 5

Drugs known to have adverse effects on the fetus

List the drugs that are known to have an adverse effect on the fetus

Answer 5

• Aminoglycosides
• Carbamazepine
• Cytotoxic Drugs
• Ethanol
• Phenytoin
• Retinoids
• Tetracycline
• Tobacco
• Opioids
• Lithium
• Valporate
• Warfarin

Question 6

Drugs known to have adverse effects on the fetus (1)

What effects are the following known to have on the fetus?

1. Aminoglycosides
2. Carbamazepine
3. Cytotoxic Drugs
4. Ethanol

Answer 6

1. Deafness
2. Spina bifida, reduced head growth
3. Hydrocephalus, neural tube defects, cleft palate, abortion, stillbirth
4. Microcephaly, Retardation, Hypotonia, Septal defects, Tetralogy of Fallot, Craniofacial abnormalities, Low birth weight and increased Neonatal death rate

Question 7

Drugs known to have adverse effects on the fetus (1)

What effects are the following known to have on the fetus?

1. Phenytoin
2. Retinoids
3. Tetracycline
4. Tobacco

Answer 7

1. Microcephaly, Retardation, Hare lip, Cleft palate
2. HydroCephalus, Microcephaly, Septal defects, Tetralogy of Fallot, Facial deformities, Cleft palate
3. Staining of Bones and teeth
4. Impaired growth/low birth weight Abortion^

Question 8

Drugs known to have adverse effects on the fetus (1)

What effects are the following known to have on the fetus?

1. Opioids
2. Lithium
3. Valporate
4. Warfarin

Answer 8

1. Withdrawal symptoms in New born, Growth retardation, Increased peri-natal mortality
2. Hydrocephalus, Septal defects, Ebstein’s anomaly, Floppy baby at birth
3. Spina bifida, Microcephaly, Tetralogy of Fallot, cleft palate and lip, impaired growth
4. Blindness, Deafness, Hydrocephalus, congenital heart disease, scoliosis, impaired growth

Question 9

Drugs known to have adverse affects on the fetus

How can these be remembered?

Answer 9

Seven A’s + DMARDs

1. ACEi / ARBs
2. Anticonvulsants (Phenytoin / carbamazepine / valproate)
3. Antibiotics (tetracyclines / trimethoprim / metronidazole)
4. Antipsychotics (Lithium)
5. Antithyroid (Iodine / propylthiouracil)
6. Anticoagulant (warfarin)
7. Abuse (drugs of) (alcohol / cigs / opiaties / bzds)
8. DMARDS / cytotoxics (methotrexate / cyclophosphamide)

This in an aide memoire it is not a finite list - BNF

Question 10

Prescribing in Pregnancy

All drugs cross the placenta

1. What does the amount of drug that crosses depend upon?
2. Give an example of a drug that was safe in adults but can cause serious adverse effects in the fetus?
3. Most drugs that cause problems increase what?
4. When is there greatest risk when administering drugs in pregnancy?

Answer 10

1. physico-chemical properties
2. thalidomide
3. most that cause problems increase the background risk (few drugs are clearly teratogenic)
4. Administration in the FIRST TRIMESTER

Question 11

Phocomelia due to thalidomide

See attached picture

Answer 11

Question 12

Rules for prescribing during pregnancy

Give the 3 main rules

Answer 12

• There must always be sound reasons for prescribing a drug during pregnancy
• Avoid prescribing during the first trimester 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 ACE Inhibitor when treating hypertension

Question 13

List the conditions that could lead to prescribing issues in pregnancy

Answer 13

• Nausea and vomiting
• Asthma
• Hypertension
• UTI and other infections
• Anticoagulation
• Anticonvulsants

Question 14

Common drug issues in pregnancy

How could the following conditions be treated in pregnancy?

1. Nausea and vomiting
2. Asthma
3. Hypertension
4. UTI and other infections
5. Anticoagulation
6. Anticonvulsants

Answer 14

1. If mild nothing – consider vitamin/electrolyte support. Promethazine (antihistamine) 1st line, cyclizine, prochlorperazine or metoclopamide 2nd line. Methylprednisolone in severe cases.
2. Maintain good control with inhalers - Prednisolone ok if needed
3. Older drugs labetalol / methyldopa / nifedipine (NICE)
4. Treat all UTIs - amoxicillin or other (nitrofurantoin), NOT quinolones / tetracyclines / trimethoprim
5. Heparin / LMWHeparins are relatively safe, AVOID Warfarin should be avoided
6. Seizure more risk than drug - Refer to specialist

Question 15

Prescribing to a nursing mother

Most drugs are detectable in breast milk through concentration is very low - consider timing

Which drugs should there be caution with?

Answer 15

Most drugs are detectable in breast milk though concentration very low – consider timing

• Diazepam
• Alcohol
• Lithium
• Iodine / propylthiouracil
• Opiates
• Tetracyclines
• Corticosteroids

Question 16

Drugs and the Neonate

Pharmacokinetics

How are the following affected?

1. Absorption
2. Distribution
3. Metabolism
4. Elimination

Answer 16

1. Skin - Surface Area/ Body weight is greater so the absorption of topical agents is increased e.g. Steroids. Intramuscular absorption is impaired due reduced mass. Rectal absorption is relatively efficient e.g. diazepam, theophyllines
2. Body water, as a %, is greater than older children so that the loading dose is greater for aminoglycosides, digoxin and aminophylline based on body weight Albumin binding is decreased increasing free concentrations of highly bound drugs and increasing the risk of drug/bilirubin interactions
3. (~ 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)
4. Glomerular Filtration/tubular secretion and reabsorption are all impaired, requiring dose reduction for renally cleared drugs based on body weight- aminoglycosides, digoxin and penicillins.

By 6 months renal function is usually normal and standard doses based on body weight can be used.

Question 17

Inherited conditions affecting drug response

What consequences can the following have?

1. Oxidation/acetylation
2. Glucose-6- phosphate dehydrogenase deficiency
3. Pseudocholinesterase deficiency

Answer 17

1. Slow- exaggerated or toxic responses Fast- failure to respond to standard dose
2. Develop acute haemolysis following treatment with a number of drugs
3. Prolonged apnoea after neuromuscular blockade

Question 18

Rules for Prescribing to neonates

1. What should doses be based on where possible?
2. What can assist you?
3. When are special adjustments especially needed?
4. What should be avoided if possible?
5. What can often differ from adults?

Answer 18

1. on estimated body surface area.
2. Use a paediatric formulary
3. especially those who are premature
4. Avoid new drugs if possible and remember that most drugs are not licensed for use in children and that information is often poor
5. Adverse effects are often different from adults

Question 19

Drug treatment in the elderly

Prescribing for the elderly

1. What results in increased drug prescribing, what are the concerns?
2. What tends to be worse in the frail elderly?
3. What alters with age, meaning that dose modification is necessary?
   
   1. What does this result in in most situations?

Answer 19

1. Increased number of diseases - the potential for adverse effects and interactions is increased.
2. Compliance with medication
3. Drug disposition
   
   1. a reduction of the maintenance dose

Question 20

Drug Treatment in the Elderly

Pharmacokinetics

How are the following affected?

1. Absorption
2. Distribution
3. Metabolism
4. Elimination

Answer 20

1. delayed due to reduced motility and blood flow. (of little importance)
2. 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
3. generally slower due to reduced liver mass and blood flow, therefore: Drugs undergoing metabolism act longer, enzyme induction is impaired
4. Elimination by the kidney is 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

Question 21

Pharmacodynamics - Prescribing for the Elderly

1. What are elderly patients more sensitive to?
   
   1. What may this predispose to?
2. Response to what drug is impaired in the elderly?
3. What function is impaired, thus increasing the risk of postural hypotension for drugs which reduce blood pressure?

Answer 21

1. the effects of centrally acting drugs
   
   1. may predispose to falls, confusion hypothermia and respiratory depression
2. Responses to beta blockers are impaired in the elderly and are not as effective as other antihypertensive drugs
3. Baroreceptor function

Question 22

Rules for prescribing in the elderly

Outline the key principles

Answer 22

• Carefully weigh up benefits and risks before prescribing. Is drug therapy the best option?
• In most cases, start low and go slow in terms of dose, especially if the drug has a narrow therapeutic index.
• Choose the most appropriate formulation.
• Check for possible interactions including ‘’over the counter’’ and herbal medications
• Rationalise existing therapy and discontinue those treatments which are not essential.

Question 23

Summary

Answer 23

• Risk:benefit ratio is more complex
• Only prescribe if necessary
• All women 14-50 should be presumed pregnant until proven otherwise (within reason)
• Consider the efficacy/safety for a given drug in a given patient