Obs and gynae

Question 1

Goserelin

Answer 1

Gonadorelin analogue

Use: testosterone reduction in prostate cancer, preparation for IVF

Question 2

Infertility drugs

Answer 2

Human menopausal gonadotrophin, Clomifene

Question 3

Oestrogen based combined oral contraceptives

Answer 3

E.g. Gedarel, Mercilon, Yasmin, Femodene, Cilest, Microgynon
Suppress LH/FSH release and therefore ovulation. Some can reduce menstrual pain and bleeding, and improvements in acne.
Can cause irregular bleeding and mood changes. Oestrogens double the risk of VTE but the absolute risk remains low. They also increase the risk of CVD and stroke. May also be assoc. with increased risk of cervical and breast cancers.
CI in breast cancer.
Avoided in those with increased risk of VTE (personal or family Hx, known thrombophilia) or CVD (>35, other RFs, migraine with aura, heavy smoking Hx).
Cytochrome P450 inducers (rifampicin, carbamazepine) may reduce contraceptive efficacy. Absorption of lamotrigine may be reduced.

Question 4

Progesterone-only oral contraceptives

Answer 4

Desogestrel or Levonorgestrel based
Suppress LH/FSH release and therefore ovulation. Also have a local effect at the cervix/endometrium which contribute to their contraceptive affect.
Can cause irregular bleeding and mood changes.
CI in breast cancer.
Cytochrome P450 inducers (rifampicin, carbamazepine) may reduce contraceptive efficacy. Absorption of lamotrigine may be reduced.

Question 5

Long-acting reversible contraceptives

Answer 5

Nexplanon implant (3 years), Depo-Provera IM injection (3 years)

Question 6

Spermicidal contraceptives

Answer 6

Nonoxinol

Question 7

Contraceptive devices and intra-uterine systems

Answer 7

Mirena IUS (5 years, levonorgestrel based), Jaydess IUS (3 years, levonorgestrel based), Nova-T 380 (copper coil, 5 years), TT 380 slimline (copper coil, 10 years)

Question 8

Emergency contraception

Answer 8

Levonorgestrel, ulipristal, copper intra-uterine contraceptive device

Question 9

Induction of abortion

Answer 9

Gemeprost (PGE1 analogue), Mifepristone (progesterone receptor antagonist)

Question 10

Hormonal therapy for HRT

Answer 10

Oestradiol alone or with progestogens, Raloxifene, Tibolone
The relative risks are higher than with oral combined contraceptives.
CI in breast cancer.
Avoided in those with increased risk of VTE (personal or family Hx, known thrombophilia) or CVD (>35, other RFs, migraine with aura, heavy smoking Hx).
Cytochrome P450 inducers (rifampicin, carbamazepine) may reduce contraceptive efficacy. Absorption of lamotrigine may be reduced.

Question 11

Antidepressants for peri-menopausal symptoms

Answer 11

Fluoxetine, citalopram, venlafaxine

Question 12

Induction and augmentation of labour

Answer 12

Oxytocin, Dinoprostone (exogenous PGE2)

Question 13

Prevention and treatment of PPH

Answer 13

Ergometrine, oxytocin (Syntometrine), Carboprost (PG)

Question 14

Preterm labour

Answer 14

Atosiban (oxytocin receptor antagonist), nifedipine (CCB), salbutamol (beta2 agonist)

Question 15

Pregnancy-related nausea

Answer 15

Promethazine, cyclizine (both 1st line), metoclopramide, ondansetron (both 2nd line)

Question 16

What are the considerations in pregnancy?

Answer 16

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 (due to ethics)
Patient/healthcare professional anxiety surrounding prescribing in pregnancy
Dose alterations required in pregnancy

Question 17

CV/blood physiological changes during pregnancy

Answer 17

Increased plasma vol, CO, SV, HR and coagulation factors
Decreased serum albumin conc. and serum colloid osmotic P
Protects woman from PPH but causes risk of VTE
Bloods: dilution anaemia, leucocytosis, low albumin

Question 18

Renal physiological changes during pregnancy

Answer 18

Increased renal BF and GFR
Results in increased excretion and reduced blood levels of urea and creatinine
Mild glycosuria and proteinuria may occur (increased GFR exceeds ability of tubules to absorb glucose/protein)
Relaxation/dilation of renal pelvis and ureters, increased length of kidneys and relaxation of bladder SM
Increased risk of UTI due to increased capacity of bladder

Question 19

Liver physiological changes during pregnancy

Answer 19

Changes in oxidative liver enzymes e.g. cytochrome P450

Question 20

Lung physiological changes during pregnancy

Answer 20

Increased tidal vol and minute vent.
Due to increased progesterone conc.
Inhaled meds may be more readily absorbed.
State of respiratory alkalosis overall (reduced pCO2, increased O2 and decreased bicarb)

Question 21

GIT physiological changes during pregnancy

Answer 21

Reduced gastric motility allows increased nutrient absorption but can result in constipation
Progesterone causes relaxation of the lower oesophageal sphincter and increased reflux

Question 22

Pregnancy: changes to absorption

Answer 22

Delayed gastric emptying and prolonged transit time alters drug bioavailability, with prolonged time to reach peak levels after oral administration and an overall decrease in maximum concentration achieved
Factors such as nausea and vomiting can also affect absorption, and ability to administer medication orally

Question 23

Pregnancy: changes to distribution

Answer 23

Maternal intravascular fluid vol begins to increase in T1 of pregnancy, as a result of increased production of RAAS which promotes sodium absorption and water retention. Increased total body water/extracellular fluid increases the volume of distribution of water-soluble drugs. Clinically, this could necessitate a higher initial and maintenance dose of drugs to obtain therapeutic plasma concentrations. Lipid-soluble drugs are also affected due to increased fat compartment stores, with an increased volume of distribution.
With increasing plasma vol, there is an assoc. reduction in maternal plasma protein concentration. Decreased plasma albumin concentration leads to decreased protein binding and increases free fraction of the drug. This is important for drugs such as midazolam, digoxin, phenytoin, valproic acid. The free drug concentration is responsible for drug effects but may be off-set by changes in metabolism and elimination

Question 24

Pregnancy: changes to metabolism

Answer 24

Cytochrome P450 is a family of liver enzymes and a major route of drug metabolism
Altered cytochrome P450 activity in pregnancy (unchanged/increased/decreased) alters oral bioavailability and hepatic elimination

Question 25

Pregnancy: changes to elimination

Answer 25

Increased renal BF and GFR increases renal clearance The increase in renal clearance can have significant increase in the elimination rates of renally cleared medications leading to shorter half-lives, requiring higher doses of medications Important for drugs such as penicillin antibiotics, digoxin and lithium

Question 26

Risk of birth defects for epileptic mothers

Answer 26

2-3% in the general population will have a baby with a major malformation (the 'background risk') 3% who have epilepsy and do not take AEDs will have a baby with a major malformation 4-10% who have epilepsy and do take an AED will have a baby with a major malformation

Question 27

Problems of using medications during pregnancy

Answer 27

Teratogenesis Effects on growth and development (neurological or neurodevelopmental abnormalities through early childhood) Effects on the neonate during delivery e.g. premature closure of patent ductus with use of PGs Passage of drug through breast milk Long term effects on IQ or behavioural problems

Question 28

Prescribing principles

Answer 28

Counselling - risk vs. benefit, minimise drug use in T1, small effective dose, use well-know meds, mono therapy if possible, consider non-drug options, monitor meds and their effects Exposure to potential teratogens often precedes conception and first contact with a healthcare professional; it may not convey any added benefit to stop treatment if exposure has already occurred Folic acid - 400 micrograms daily recommended pre-conception to 12 w gestation; 5 mg recommended if higher risk e.g. AEDs, diabetes, FHx of neural tube defects, sickle cell

Question 29

Why drugs cross the placenta

Answer 29

Physical - placental surface area, placental thickness, pH of maternal/foetal blood, placental metabolism, uteroplacental BF, presence of drug transporters Pharmacological - molecular weight of drug (<1 kDa), lipid solubility, protein binding, conc. gradient

Question 30

3 mechanisms of placental transfer

Answer 30

Complete transfer with drugs rapidly crossing the placenta and equilibrating in maternal and foetal blood Exceeding transfer with drugs crossing the placenta to reach greater concentrations in foetal compared with maternal blood Incomplete transfer with drugs incompletely crossing the placenta resulting in higher concentrations in maternal compared with foetal blood

Question 31

Initial management of N&V

Answer 31

``` Reassurance and rest - this is a normal part of pregnancy and usually resolves by 16-20 w gestation Avoid triggers Eat plain crackers in the morning Eat bland, small and frequent meals Cold meals if nausea if smell-related Drinking little and often Ginger Acupressure ```

Question 32

Hx of thalidomide

Answer 32

This is an immunomodulator It was initially marketed as a sedative, but used to treat pregnancy-related nausea Found to cause phocomelia and deformities of the ears, heart and kidneys 40% mortality rate Now its use is limited to the treatment of multiple myeloma The birth defects caused by this drug varied depending on gestational age

Question 33

Drug teratogenicity effects in the different trimesters

Answer 33

T1 - most susceptible weeks are 3-8, this affects organogenesis T2 or T3 - manifest as growth retardation, respiratory problems, infection of bleeding in the neonate

Question 34

Teratogenic effects of ACEi

Answer 34

Renal abnormalities, patent ductus arteriosus, oligohydramnios T2/3

Question 35

Teratogenic effects of anti-thyroid drugs

Answer 35

Neonatal hypothyroidism | >10 w

Question 36

Teratogenic effects of beta-blockers

Answer 36

IUGR, neonatal hypoglycaemia, bradycardia | Throughout pregnancy

Question 37

Teratogenic effects of lithium

Answer 37

Cardiac defects - Ebstein's anomaly; congenital heart defect in which the septal and posterior leaflets of the tricuspid valve are displaced towards the apex of the RV T1

Question 38

Teratogenic effects of methotrexate

Answer 38

Medical termination, craniofacial defects, ear/kidney/lung defects, cardiac abnormalities

Question 39

Teratogenic effects of NSAIDs

Answer 39

premature closure of ductus arteriosus, oligohydramnios, PPH | >30 w

Question 40

Teratogenic effects of Phenytoin

Answer 40

Craniofacial abnormalities, growth/mental deficiency

Question 41

Teratogenic effects of retinoids

Answer 41

CNS abnormalities, renal/eye/ear/parathyroid abnormalities | Weeks 4-10

Question 42

Teratogenic effects of sodium valproate

Answer 42

NTDs | T1

Question 43

Teratogenic effects of tetracyclines

Answer 43

Tooth discolouration | T2/3

Question 44

Teratogenic effects of thiazide diuretics

Answer 44

electrolyte abnormalities, growth retardation

Question 45

Teratogenic effects of warfarin

Answer 45

foetal warfarin syndrome, CNS defects, eye abnormalities, foetal/neonatal/placental haemorrhage

Question 46

Safer drugs in pregnancy

Answer 46

paracetamol, beta-lactam based antibiotics, steroids, bronchodilators, labetalol, nifedipine

Question 47

Drugs which can cause genetic abnormalities in the sperm

Answer 47

Antimetabolites drugs e.g. methotrexate, azathioprine, mercaptopurine Delay conception for 6/12 after discontinuation

Question 48

Drugs to avoid in breastfeeding

Answer 48

``` Amiodarone - neonatal hypothyroidism due to iodine content Aspirin - Reye's syndrome Barbiturates - drowsiness Benzos - lethargy Carbiazmole - hypothyroidism Codeine - opioid OD Combined oral contraceptive - diminish milk supply and quantity Cytotoxic drugs - immunosuppression DA agonists - suppress lactation Ephedrine - irritability Tetracyclines - tooth discolouration ```

Question 49

Infections in pregnancy

Answer 49

Broad-spectrum antibiotics (cephalosporins), steroids if overwhelming infection (betamethasone IM injections, max of 2 doses)

Question 50

Anaemia in pregnancy

Answer 50

Ferrous sulphate if iron-deficiency | Check B12 and folate for deficiencies