Obstetric Pharmacology Flashcards
List some circumstances in which the inclusion of pregnant women in clinical studies would be considered ethically appropriate
Where there are no other available effective therapies for treatment of a serious or life-threatening condition (e.g. in pregnant women with drug resistance, intolerance, contraindication or allergy) Where pregnant women are already using the drug or class of drugs in the post-marketing setting, plus an established safety profile Where the drug is being developed specifically to treat pregnancy-related conditions
List 2 primary factors relating to the distribution of a drug within a pregnant woman and foetus
Ability to cross capillary membranes
Ability to cross lipid membranes
List 4 secondary factors relating to the distribution of a drug within a pregnant woman and foetus
Blood flow
pH differences between the 2 compartments
Protein binding
Binding of other tissue components
What is important to consider in terms of drug excretion in a lactating woman?
The drug may be excreted via breast milk, and will then be absorbed, distributed, metabolised and excreted by the neonate or infant
Need to consider whether the drug will be safe in its excreted form
List 7 important cardiovascular changes in pregnancy
Increased SV Increased HR Increased CO (by ~40%) Decreased TPR Decreased MAP Increased blood volume Increased O2 consumption
Which 8 other symptoms besides cardiovascular are affected in pregnancy?
Respiratory Haematology and coagulation Immune GI (including liver) Renal Endocrine Nervous Musculoskeletal
List 6 maternal factors that determine transfer of drugs to the foetus
Drug dose Route of administration Maternal metabolism and excretion Maternal protein binding Maternal pH and ionisation of the drug Uterine blood flow
What is the general formula for flow?
Pressure differential/resistance
What is the formula for uterine blood flow (UBF)?
UBF = (uterine artery pressure - uterine venous pressure)/uterine vascular resistance
List 4 factors that decrease UBF
Decreased BP
Hypovolaemia
Aortocaval compression
Vasoconstrictors (endogenous/exogenous)
What are the 4 main functions of the placenta?
Transport of substances, gases (especially O2 and CO2), nutrients, waste products and drugs
Immunological
Metabolic including inactivation of drugs
Endocrine
What are 3 drug characteristics influencing placental transfer of any drug?
Molecular weight
Lipid solubility
Degree of ionisation
What 3 aspects of foetal physiology which are relevant to the way the foetus deals with a particular drug?
Foetal uptake (absorption) of drug
Foetal distribution of drug (dependent on blood flow)
Foetal metabolism of drug (immature organ systems may not be able to adequately metabolise certain drugs)
What are the 3 principles of prescribing a drug to a lactating woman?
Minimising the amount of drug in the milk
Minimising disruption to breastfeeding
Effectively treating the woman’s condition
What is teratogenicity and what is required for teratogenicity?
Any significant postnatal change in function or form after prenatal treatment; includes morphological, biochemical and behavioural changes
Teratogenicity occurs when the teratogenic dose is administered at the teratogenic time in gestation with a teratogenic agent of the correct species
List 4 classes of human teratogens and give examples of each
Environmental and physical agents (e.g. nuclear radiation, radioiodine, hyperthermia)
Infection (e.g. rubella, CMV, herpes)
Maternal metabolic imbalance (e.g. diabetes, obesity, folic acid deficiency)
Drugs and chemicals (e.g. ACEI, warfarin, tetracyclines, valproic acid, diethylstilbestrol)
List the 7 categories used in Australia for prescribing medications in pregnancy
A - taken by a large number of pregnant women without causing malformations or harm to the foetus
B1 - taken by only a limited number of pregnant women without causing malformations or harm to the foetus (studies in animals have not shown increased foetal damage)
B2 - taken by only a limited number of pregnant women without causing malformations or harm to the foetus (studies in animals are lacking/inadequate but available data does not show increased foetal damage)
B3 - taken by only a limited number of pregnant women without causing malformations or harm to the foetus (studies in animals have shown increased foetal damage but the significance is uncertain in humans)
C - drugs which have caused or are suspected to cause increased harmful effects on the foetus without causing malformations (damage may be reversible)
D - drugs which have caused or are suspected to cause increased foetal malformations or irreversible damage
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
What are the main causes of maternal mortality?
Cardiac disease Indirect neurological conditions Sepsis Pre-eclampsia and eclampsia Thrombosis and thromboembolism Amniotic fluid embolism Psychiatric causes Early pregnancy deaths Haemorrhage Anaesthesia
What are 5 direct causes of maternal mortality in developing countries?
Haemorrhage Pre-eclampsia/eclampsia Infection Unsafe abortion Obstructed labour
What is the risk of severe maternal morbidity?
1 in 200 women
What % of all causes of developmental defects in humans is caused by drug administration in pregnant women?
2%
What are the 9 conditions mentioned specifically in the WHO list of priority life-saving medicines for women and children?
Post-partum haemorrhage Severe pre-eclampsia and eclampsia Maternal sepsis Provision of safe abortion services and/or management of incomplete abortion and miscarriage STIs Management of preterm labour Maternal HIV/AIDS and malaria Prevention of tetanus in mother and newborn Contraception
What % of maternal death is caused by haemorrhage?
25% (most common cause)
What are the 3 goals of acute management of obstetric haemorrhage?
Control the bleeding
Restore adequate O2-carrying capacity
Maintain adequate tissue perfusion
What is the mechanism of action, route of administration and side effects of oxytocin?
Used to stimulate uterine contraction in obstetric haemorrhage
Administered via IV or IM
Side effects include hypotension, tachycardia, H20 intoxication
What is the mechanism of action, route of administration and side effects of ergometrine?
Used to stimulate uterine and vascular smooth muscle contraction in obstetric haemorrhage
Administered via IV or IM
Side effects include hypertension, nausea and vomiting
What kind of IV fluid therapy is administered in obstetric haemorrhage?
0.9% isotonic NaCl
What is delivered in a blood transfusion for obstetric haemorrhage?
Packed RBCs
Coagulation factors
Platelets
What technique can be used to monitor women with obstetric haemorrhage? What are its benefits?
Rapid Obstetric Screening Echocardiography Scan (ROSE Scan)
Provides structural and functional information in real time at the bedside; non-invasive and safe, liked by pregnant women
What is pre-eclampsia?
Hypertension occurring in pregnant women with multi-organ system involvement
What % of pregnant women does pre-eclampsia affect?
5-8%
When does pre-eclampsia generally occur and when does it resolve by?
Occurs at >20 weeks gestation
Resolves by 3 months post-partum
List 5 long term complications of pre-eclampsia
Same as for general population: IHD, cerebrovascular disease, HF, CKD, PVD
List some ways in which pre-eclampsia can cause maternal mortality
Cerebral complications Cardiorespiratory failure Multiple organ failure DIC Renal failure Hypovolaemic shock
How is severe pre-eclampsia defined?
BP >140/90
And 1 or more symptoms affecting cardiorespiratory, haemotalogical, GI or renal systems, CNS, or uteroplacental/foetal circulation (symptomatic disease is severe disease; abnormal biochemistry or haematology is usually severe disease)
What are the 6 general principles of treating severe pre-eclampsia?
Early senior and multi-disciplinary involvement
Standardised guidelines
Regular review and awareness of complications
Control of hypertension with anti-hypertensives
Prevention and treatment of seizures with MgSO4
Meticulous fluid balance
Should ergometrine be administered to a pregnant woman with severe pre-eclampsia? Why/why not?
No, will cause vascular smooth muscle contraction and exacerbate hypertension
At what BP threshold is pre-eclampsia considered a medical emergency?
SBP >180mmHg is classed as a medical emergency
What is the mechanism of action, route of administration and side effects of MgSO4?
Used to treat and prevent seizures in women with pre-eclampsia
Involved in production and utilisation of ATP, reduces IC [Ca2+] and Mg acts as a weak Ca2+ channel antagonist regulating Ca2+ influx via NMDA receptor (may inhibit ischaemic neuronal damage caused by anion flux)
Administered via IV or IM
Side effects include cardiorespiratory depression
How can toxicity with MgSO4 be reversed?
With Ca2+ gluconate
What is the mechanism of action and route of administration of labetalol?
Competitive non-selective B-adrenoceptor antagonist and competitive a1-adrenoceptor antagonist; also has membrane-stabilising properties at higher doses (used to treat hypertension)
Administered orally or via IV
