PPT Flashcards
When is the period of organogenesis in pregnancy?
Between 3-12 weeks
Important prescribing considerations during pregnancy and breastfeeding?
Changes to the mother’s physiology
Drugs passing through placenta to foetus
Drugs passing through breast milk to baby
Less available licensed medications
Minimal evidence base
Patient/healthcare professional anxiety surrounding prescribing in pregnancy
Dose alterations required in pregnanc
Physiological changes occurring in pregnancy: cardiovascular system
Increases in plasma volume, CO, stroke volume and HR
Decreases in serum albumin concentration and serum colloid osmotic pressure
Increases in coagulation factors and fibrinogen
Compression of IVC by uterus
Physiological changes occurring in pregnancy: kidneys
Increases in renal blood flow and GFR
Physiological changes occurring in pregnancy: liver
Changes in oxidative liver enzymes e.g. CYP450
Can alter oral bioavailability
E.g. CYP1A2 is responsible or caffeine metabolism and during pregnancy the activity is reduced which can cause caffeine plasma concentrations to double
Physiological changes occurring in pregnancy: lungs
Increases in tidal volume and minute ventilation
Physiological changes occurring in pregnancy: stomach and intestines
N+V more common
Delayed gastric emptying
Prolonged small bowel transit time
GI reflux
How can the physiological changes occurring in pregnancy affect the absorption of a drug?
Nausea and vomiting can affect the ability to administer medication
Delayed gastric emptying and prolonged transit time can extend the time it takes to reach peak concentration, decreases the maximum concentration of the drug and more absorb more of the drug than normal
How can the physiological changes occurring in pregnancy affect the distribution of a drug?
Increases in plasma volume increases the volume of distribution so higher drug doses are required
Reduction in plasma protein levels decreases protein binding which increases the free fraction of the drug
How can the physiological changes occurring in pregnancy affect the metabolism of a drug?
Altered liver enzymes e.g. CYP450 = increases, decreases or remains unchanged
This can alter the oral bioavailability
How can the physiological changes occurring in pregnancy affect the elimination of a drug?
Increased renal blood flow and GFR increases renal clearance so there are shorter half lives
E.g. clearance of lithium is doubled in the third trimester = sub-therapeutic drug concentrations
Background risk of birth defects?
2-3% of the general population will have a baby with a major malformation
Risk of birth defects in those who have epilepsy and take anti-epileptic drugs vs those who dont take anti-epileptic drugs?
Epilepsy and dont take AEDs = 3% will have a baby with a major malformation
Epilepsy and do take an AED = up to 10% will have a baby with a major malformation
What are the potential problems and risks of using medications during pregnancy?
Teratogneesis
Effects on growth and development even post-delivery
Effects on neonate during delivery
Passage of drug through breast milk
Long term effects on IQ or behavioural problems
Prescribing principles in pregnancy?
Pre-pregnancy counselling involving:
- Risks vs benefit discussion
- minimise drug use in first trimester
- smallest effective dose
- opt for well-known meds for which we have historical data
- mono therapy wherever possible
- consider non-drug options wherever possible
Carefully monitor meds and their effects
No drug is safe beyond all doubt: absence of evidence is not evidence of absence!!
Exposure to potential teratogens often precedes conception and first contact with a HCP so if exposure has already occurred it may not convey any added benefit to stop Tx
Which women are at higher risk of having a baby with neural tube defects and therefore should recieve 5mg of folic acid to 12 weeks gestation?
either partner has a NTD, they have had a previous pregnancy affected by a NTD, or they have a family history of a NTD
the woman is taking antiepileptic drugs or has coeliac disease, diabetes, SCD or thalassaemia trait.
the woman is obese (defined as a body mass index [BMI] of 30 kg/m2 or more).
Sources of information for the prescriber for prescribing in pregnancy?
National teratology advisory service
UKTIS
TOXBASE
BNF
NICE/RCOG guidelines
Local guidelines
Which anti-epileptics are options in pregnancy?
Lamotrigine, levetiracetam, carbamazepine - lower risk of malformations (2-5%)
Sodium valproate has a higher risk of malformation (up to 10%) and 40% of these children’s have developmental problems
What factors affect the rate of placental transfer of drugs?
Physical:
- placental SA
- placental thickness
- pH of maternal and foetal blood
- Placental metabolism
- uteroplacental blood flow
- presence of drug transporters
Pharmacological:
- molecular weight of drug (e.g. heparin is much larger than warfarin so can be used in pregnancy)
- lipid solubility
- protein binding
- concentration gradient
Which drugs can pass freely through the placenta?
Only drugs with a molecular weight of >1kDa
Risk of metoclopramide in women under 20?
Risk of acute dystonia
What is thalidomide? What did it cause?
An immunomodulator - initially marketed as a sedative as it was used to Tx pregnancy-related nausea
Found to cause phocomelia, + deformities of ears heart and kidneys
Mortality rate of 40%
Common teratogenic drugs
ACEi
Anti-thyroid drugs
BB
Lithium
Methotrexate
NSAIDs
Phenytoin
Retinoids
Sodium valproate
Tetracyclines
Thiazide diuretics
Warfarin
Effects of ACEi in pregnancy and when is effect greatest?
Renal abnormalities, PDA, oligohydramnios
2nd+3rd trimester
Effects of anti-thyroid drugs e.g. Carbimazole in pregnancy and when is effect greatest?
Neonatal hypothyroidism
After week 10
(Although this is often used in pregnancy for women with hyperthyroidism)
Effects of beta blockers in pregnancy and when is effect greatest?
IUGR, neonatal hypoglycaemia and bradycardia
All throughout pregnancy
Effects of lithium in pregnancy and when is effect greatest?
Cardiac defects - Ebstein’s anomaly
In first trimester
Effects of methotrexate in pregnancy and when is effect greatest?
Medical termination, craniofacial defects, ear/kidney/lung defects, cardiac abnormalities
Avoid throughout and dont get pregnant for at least 6 months after Tx finished
Note: for MEN + WOMEN
Effects of NSAIDs in pregnancy and when is effect greatest?
Premature closure of ductus arteriosus, oligohydramnios, PPHN
After week 30
Effects of phenytoin in pregnancy?
Craniofacial abnormalities, growth/,mental deficiency
Effects of retinoids in pregnancy and when is effect greatest?
CNS abnormalities, renal/ear/eye/parathyroid abnormalities
Weeks 4-10
Effects of sodium valproate in pregnancy and when is effect greatest?
Neural tube defects
First trimester
Effects of tetracyclines in pregnancy+breast feeding and when is effect greatest?
Tooth discoloration
2nd + 3rd trimester
Effects of warfarin in pregnancy and when is effect greatest?
Foetal warfarin syndrome: CNS defects/eye abnormalities/cranofacial features
Others: haemorrhage of foetus, neonate or placenta
All throughout pregnancy
Safer drugs in pregnancy?
Paracetemol
Beta lactam antibiotics
Steroids
Bronchodilators
Labetalol and nifedipine
Paternal drug exposure in pregnancy:
Antimetabolites drugs can cause genetic abnormalities in sperm -> can lead to malformations in offspring
E.g. methotrexate, azathioprine, mercaptopurine
Delay conception for 6 months after discontinuation
Drugs to avoid in breast feeding?
Amiodarone
Aspirin
Barbiturates
Benzodiazepines
Carbimazole
Codeine
COCP
Cytotoxic drugs
Dopamine agonists
Ephedrine
Tetracyclines
Effect of amiodarone in breast feeding?
Iodine content may cause neonatal hypothyroidism
Effect of aspirin in breast feeding?
Theoretical risk of Reye’s syndrome
Effect of barbiturates in breast feeding?
Drowsiness
Effect of benzodiazepines in breast feeding?
Lethargy
Effect of Carbimazole in breast feeding?
Hypothyroidism - rare this is normally ok to take!!
Effect of codeine on baby in breast feeding?
Risk of opiate overdose
Effect of COCP in breast feeding?
May diminish milk supply and quantity
Effect of cytotoxic drugs on baby in breast feeding?
Immunosuppression and neutropenia
Effect of dopamine agonists in breast feeding?
May suppress lactation
May also be present in milk???
Effect of ephedrine on baby in breast feeding?
Irritability
Effect of tetracyclines on baby in breast feeding?
Risk of tooth colouration
Which drugs cause renal abnormalities if taken during pregnancy?
(PPT-lecture specific question)
ACEi and methotrexate
Which drugs cause parathyroid abnormalities if taken during pregnancy?
(PPT-lecture specific question)
Retinoids
Which drugs cause discoloured teeth if taken during pregnancy?
(PPT-lecture specific question)
Tetracyclines
Which drugs cause neural tube defects if taken during pregnancy?
(PPT-lecture specific question)
Sodium valproate
Which drugs cause persistent pulmonary hypertension of the newborn if taken during pregnancy?
(PPT-lecture specific question)
NSAIDs
MOA of goserelin? what is it used for in women’s health?
A GnRH analogue - a potent inhibitor of pituitary gonadotropin secretion = sustained supression of LH and testosterone
Induces a pseudo menopause due to low oestrogen levels. Can be used as a secondary care Tx for endometriosis or adenomyosis. May also be used to reduce the size of the fibroid in the short term.
Indication and MOA of clomifene?
Used mainly in female infertility due to anovulation to induce ovulation
Stimulates release of gonadotropins FSH and LH which leads to the development and maturation of ovarian follicle, ovulation and subsequent development and function of corpus luteum
Examples of COCPs?
Gedarel - ethinylestradiol with desogestorel
Mercilon - ethinylestradiol with gesgestorel
Yasmin - ethinylestradiol with drospirenone
Femodene - ethinylestradiol with gestodene
Cilest - ethinylestradiol with norgestimate
Microgynon 30 - ethinylestradiol with levonorgesterol
Examples of desogestrel-based POPs?
Cerelle
Ceravette
Examples of levonorgestrel-based POPs?
Norgeston
What is the implant called?
Nexplanon - etonogestrel
What is in the depo-provera?
Medroxyprogesterone
What is the progesterone base of the IUS coils?
Levonorgestrel
2 names of IUS and how long they last?
Mirena - 5 years
Jaydess - 3 years
Kyleena - 5 years
What are the 2 types of copper coils and how long do they last?
Nova-T 380 - 5 years
TT 380 slimline - 10 years
Options for emergency contraception?
Levonorgestrol
Ulipristal
Copper IUD
Moa of levonorgestrol for emergency contraception?
Acts both to stop ovulation and inhibit implantation
Moa of ulipristal for emergency contraception?
Selective progesterone receptor modulator
Inhibits ovulation
What is misoprostol?
An analogue of prostaglandins E1
Causes uterine contractions. Can be used for medical miscarriage to expel the products of conception OR for medical termination of pregnancy OR for inducing labour if bishop score <=6
What is mifepristone moa?
Competitive progesterone receptor antagonist
Used in combination with misoprostol to terminate pregnancies and for medical management of a miscarriage
What is tibolone?
A synthetic compound with both oestrogenic, progestogenic, and androgenic activity
A type of HRT!
Moa of ergometrine?
An ergot alkaloid used as an alternative to oxytocin in active management of the third stage of labour
It stimulates alpha adrenergic, dopaminergic and serotonigeric receptors which constructs vascular smooth muscle of the uterus and can decrease blood loss
Moa of dinoprostone?
This is vaginal prostaglandin E 2. Causes stimulation of mymetrium to contract
Used to stimulate labour if bishop score <=6
Moa of syntocinon? Indication?
a synthetic version of oxytocin that is used in the active management of third stage of labour.
It stimulates the contraction of the uterus reducing the risk of postpartum haemorrhage. It is also used to induce labour.
Moa of syntometrine?
This is ergometrine-oxytocin together
It stimulates the myometrium. More effective than syntocinon in reducing blood loss during third stage of labour
Moa of carboprost?
A synthetic prostaglandin E2 - causes myometrial contraction causing induction of labour or helps with third stage of labour
Moa of atosiban
A synthetic peptide oxytocin antagonist
Used for tocolysis
How does the COCP work?
Inhibits ovulation as oestrogen and progesterone act on the HPA axis to reduce LH and FSH and without the surge to stimulate the ovaries, ovulation does not occur
Risks of COCP?
Increased risk of VTE, breast Cancer, cervical cancer, stroke, IHD
No proitection to STIs
moa progesterone only pill
Thickens cervical mucus making it difficult for sperm to enter the uterus and fertilise the egg
Also inhibits ovulation
Moa of injectable contraception?
Inhibits ovulation
Also thickens cervical mucus
MOA of implantable contraceptive?
Inhibits ovulation
Also thickens cervical mucus
MOA of IUD?
Decreases sperm motility and survival
MOA of IUS?
Prevents endometrial proliferation
Also thickens cervical mucus
Moa of desogestrel?
A type of POP but it inhibits ovulation as its primary action
When must levonorgestrel be taken to work as emergency contraception?
Within 72 hours of UPSI
When must ulipristal be taken to work as emergency contraception?
<120 hours after UPSI
When must IUD be inserted to work as emergency contraception?
Within 5 days of UPSI or up to 5 days after likely ovulation date
How effective is IUD for emergency contraception?
99%
Which route is best for HRT if risk of VTE?
Transdermal patch
Side effects of HRT?
Nausea
Breast tenderness
Fluid retention and weight gain
Potential complications of HRT?
Increased risk of breast cancer - increased by addition of progesterone
Increased risk of endometrial cancer - reduced by addition of progestogen
Increased risk of VTE - increased by addition of progestogen
Increased risk of stroke
Increased risk of IHD if taken >10 years after menopause
Adverse effect of ergometrine?
Coronary artery spasm
When is carboprost contraindicated?
In asthma
Moa of cabergoline?
Dopamine receptor agonist which inhibits prolactin production causing suppression of lactation
Contraindications to intrauterine systems/devices?
Pregnancy or up to 4 weeks post-partum
Distortion of the uterine cavity e.g. fibroids, bicornuate uterus or gynae malignancy
Current unexplained vaginal bleeding
Pelvic infection - history of PID, recent STI or other infection
Specific to IUD - allergy to copper
Specific to IUS - DVT or PE, current liver disease or history of breast Ca
