Teratogens Flashcards
What is a teratogen
An environmental factor that can disrupt the normal development of the embryo or fetus
Examples
Sodium valproate -
Radiation
Tobacco
Antidepressants
Zika viruses
Hepatitis E
Presentation of harm or damage of teratogens
Timing can be everything
Amoun of exposure is import t for some agents
Early pregnancy where embryo most viunerable
Some teratogens cause recognisable pattern of harm - thalidomide
Risk vs benefit decision
Teratogenic mechanisms
Folate antagonism - disrupts dna synthesis
Endocrine disruption - increase or decrease hormone activity
Oxidative stress - reactive oxygen species
Vascular disruption
History of teratogens
1941 - maternal rubella infection n pregnancy associated with birth defects
Until late 1950s little structures regulation of drugs outside of the USA
19 61 small observation from Australia published in lancet drawing attention to adverse reaction
Pharmacokinetics
What the body does to the drug
Pharmacodynamics
What the drug does to the body
Physiological changes that affect pharmacokinetics during pregnancy
Absorption - gastric mobility is reduced, increased gastric ph, delay in time to reach peak levels in the body
Distribution - increased total body water, increased plasma volume, decreased plasma albumin concentration
Metabolism - considerable chan in the enzymes that breakdown surges during pregnancy
Excretion increased cardiac output
What dictates how and what gets across placenta
Size of drug molecule
Formulation of the drug
Electrical charge
Types and number of transporters
Maternal age
Genetics differences
Presence of other drugs
Maternal and foetal health
Hypertension
Chronical or gestational needs to be managed
Increased risk of PET
Increased risk of preterm delivery
Antihypertensive drugs can be teratogenic
ACE inhibitors should be avoided during pregnancy Excretion increased
Complexity of chronic medication and planned vs unplanned pregnancy
Additional antenatl monitoring. USS and Doppler
Mental health
Depression anxiety and psychotic disorders
Complex management including non pharmacological interventions and support from all medical professional involved in antenatl care
Epilepsy
Can be challenging to manage during pregnancy
AEDs can cause harm to fetus
Sodium valproate and valpric acid containing drug s - 40% developmental disorders and10% risk of birth defects
Non one under 55 should be started on valproate unless two independent specialists agree no other effective treatment
Concentraceptive pill interaction with AEDs which increase chance of pregnancy
Manipulating drug side effect
NSAIDS - evidence of teratogenicity in first trimester including risk of miscarriage
Naiads use after 30 weeks is associated with increased risk of early closure of the foetal ductus arteriosus
Can inhibit slow labour
Pathogens antimicrobials and antifungals
Antiretroviral drugs used in the treatment of hiv may nee close management - important in preventing transmission of hiv
Antifungals - cleft palate, skeletal abnormalities, still birth.
Recreational and illlicit drugs
Use of illicit drugs AED commmn in pregnancy
Education and support services to promote ceasarian
Smoking
Co - inhaled by mum, enters maternal circulation, placenta, foetal circulation
Reduces amount of of oxygen that reaches foetus
Growth restriction, cardiovascular complications, placental abruption
Sids
Neurodivergent]
Alcohol - fetal alcohol syndrome
Most severe with neurological , growth and facial abnormalities
Amount, frequency and window of most exposure correlated to level of harm
Opioids
MDT approach needed to manage these patients and awareness of associated risks
Neonatal abstinence syndrome
Presentation time varies with drug typically between 24 and 72 may be biphasic if multiple drugs are being used
Severe - seizures , tremors even when undistrubted , rigid muscle tone, tachypnoea, watery stools, vomiting and poor swallowing coordination and SIDS
Mild - irrability,, sneezing, yawning, hiccough shrill cry, sweating and weight los
Maternal history important
