14. Risks of Drug Use in Pregnancy Flashcards
What is Teratogenesis and Teratogens?
Teratogenesis = the process by which congenital malformations (gross, structural foetal malformations) are produced in an embryo or fetus.
Teratogens = any agent that causes an abnormality following fetal exposure during pregnancy.
Of the 3 main stages of foetal development, what is the:
- Gestation period in humans?
- Main cellular processed involved?
- Affected by?
Foetal Development - Main stages
-
Blastocyst formation (0-16 days)
- Cell divison
- Affected by: cytotoxic drugs & alcohol
-
Organogenesis (17-60 days)
- Division, migration, differentiation, death
- Affected by: teratogens
-
Histogenesis & functional maturation (60 days - term)
- As above
- Affected by: miscellaneous drugs - alcohol, nicotine, anti-thyroid, steroids
What is Thalidomide?
Thalidomide
- Thalidomide was introduced in 1957 and marketed as a safe hypnotic and sedative, but it was found to produce sensory peripheral neuropathy
- It was then marketed for the treatment of morning sickness
- In 1961 there were reports of a sudden increase in the incidence of phocomelia (‘seal limbs’) in new born babies (the bones in the arms and legs are shortened or absent)
- Other defects included hypo-plasticity of the bones, external ear and eye abnormalities, facial palsy and heart, alimentary tract, urinary tract and genital malformations
- Thalidomide at therapeutic doses produced virtually 100% malformed infants if it was taken by mothers in the first 3-6 weeks of gestation
What are the 7 Australian Categories for Prescribing Medicines in Pregnancy?
Australian Categories for Prescribing Medicines in Pregnancy
- A
- B1
- B2
- B3
- C
- D
- X
What are Category A Medicines in Pregnancy?
3 Examples?
Australian Categories for Prescribing Medicines in Pregnancy
Category A
Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed.
Examples
- Amoxicillin
- Metoclopramide
- Paracetamol
What are Category B1 Medicines in Pregnancy?
2 Examples?
Australian Categories for Prescribing Medicines in Pregnancy
Category B1
- Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed
- Studies in animals have not shown evidence of an increased occurrence of foetal damage
Examples
- Loratadine
- Ranitidine
What are Category B2 Medicines in Pregnancy?
3 Examples?
Australian Categories for Prescribing Medicines in Pregnancy
Category B2
- Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed
- Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of foetal damage
Examples
- Methylphenidate
- Ticarcillin
- Fexofenadine
What are Category B3 Medicines in Pregnancy?
3 Examples?
Australian Categories for Prescribing Medicines in Pregnancy
Category B3
- Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed
- Studies in animals have shown evidence of an increased occurrence of foetal damage, the significance of which is considered uncertain in humans
Examples
- Loperamide
- Pantoprazole
- Trimethoprim
What are Category C Medicines in Pregnancy?
3 Examples?
Australian Categories for Prescribing Medicines in Pregnancy
Category C
- Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human foetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details
Examples
- Atenolol
- Diazepam
- Ibuprofen
What are Category D Medicines in Pregnancy?
3 Examples?
Australian Categories for Prescribing Medicines in Pregnancy
Category D
- Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human foetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details
Examples
- Atorvastatin
- Candesartan
- Ramipril
What are Category X Medicines in Pregnancy?
1 Example?
Australian Categories for Prescribing Medicines in Pregnancy
Category X
- Drugs which have such a high risk of causing permanent damage to the foetus that they should not be used in pregnancy or when there is a possibility of pregnancy
Example = Vitamin A derivatives e.g. isotretinoin
What are HMG-CoA Reductase Inhibitors also known as?
What do they do?
What Pregnancy category are they in and why?
HMG-CoA Reductase Inhibitors (Statins) = Category D
- Cholesterol and other products of cholesterol biosynthesis are essential components for foetal development (including synthesis of steroids and cell membranes)
- HMG-CoA reductase inhibitors (statins) decrease cholesterol synthesis
- They may cause foetal harm when administered to pregnant women in the first trimester
- Neurological defects, foetal deaths and spontaneous abortions
- Statins are pregnancy Category D
What do ACE inhibitors do?
What do ARBs do?
Renin-Angiotensin-Aldosterone System
- Angiotensin converting enzyme (ACE) inhibitors reduce the formation of angiotensin II
- Angiotensin II receptor antagonists act as competitive antagonists of angiotensin II at angiotensin II type I receptors
- Both reduce the effects of angiotensin II
What pregnancy category are ACE inhibitors and ARBs in and why?
Angiotensin Converting Enzyme (ACE) Inhibitors and Angiotensin II Receptor Antagonists = Category D
- Angiotensin II is involved in the regulation of blood pressure, and fluid and electrolyte levels
- When ACE inhibitors and angiotensin II receptor antagonists have been used during the second and third trimesters of pregnancy, there have been reports of neonatal hypotension, renal failure, skull hypoplasia and oligohydramnios which has been associated with foetal limb contractures, craniofacial malformations, hypoplastic lung development and intrauterine growth retardation. Neonatal deaths have occurred
- ACE inhibitors and angiotensin II receptor antagonists are pregnancy Category D
What pregnancy category are Vitamin A derivative in and why?
(Explain how Roaccutane can cause permanent damage to the foetus)
Vitamin A Derivatives - Category X
- Vitamin A derivatives are used in the treatment of severe cystic acne e.g. isotretinoin (Roaccutane)
- Vitamin A is metabolised to retinoic acid which is a controller of gene transcription
- In the treatment of acne, it affects cell-cycle progression, sebaceous gland differentiation, sebum secretion, comedogenesis, cell survival and apoptosis
- This results in an anti-inflammatory effect, a significant reduction in sebum production, and a reduction in surface and ductal Propionibacterium acnes
- Vitamin A derivatives may also cause human foetal abnormalities including microcephalus, eye and external ear abnormalities, cardiovascular abnormalities, cleft palate, thymus and parathyroid defects and cerebellar malformation
- Pregnancy must be excluded for female patients, and an effective form of contraception should be used for at least one month before therapy, throughout therapy, and for one month following discontinuation of therapy
What are 5 Clinical Features of Foetal Alcohol Syndrome?
Foetal Alcohol Syndrome - Clinical Features
- Abnormal facial development, with wide-set eyes, short palpebral fissures and small cheekbones
- Reduced cranial circumference
- Retarded growth
- Mental retardation and behavioural abnormalities, often taking the form of hyperactivity and difficulty with social integration
- Other anatomical abnormalities, which may be major or minor e.g. congenital cardiac abnormalities, malformation of the eyes and ears
What are 8 risks of smoking during pregancy to the baby?
Smoking and Pregnancy
Risks to the baby include:
- Dying from Sudden Infant Death Syndrome (SIDS)
- Premature birth
- Reduced birth weight
- Delayed development
- Birth defects such as cleft palate
- Feeding problems
- Middle ear infections or permanent hearing impairment
- Long term damage to the lungs, brain and blood
