Oral contraceptive prescribing

Presentation on theme: "Oral contraceptive prescribing"— Presentation transcript:

1 Oral contraceptive prescribing

2 clinical pharmacology
mechanism of action ADME interactions adverse reactions benefits and harms

3 what are they around since late 1950’s social revolution
progestogen /oestrogen variety of components and doses changes over time in both

4 components oestrogen progestogen ethinyoestradiol mestranol
norethisterone norgestrel Levonorgestrel medroxyprogesterone ethynodiol diacetate gestodene desogestrel

5 doses monophasic biphasic triphasic oestrogen - up to 50g/day
progestogen - up to 1mg/day biphasic oestrogen: constant progestogen: eg 11 g triphasic oestrogen 30/40/30 progestogen 50/75/125

6 clinical pharmacology
mechanism of action inhibit secretion of FSH, LH - inhibit ovulation additional actions on endometrium tubal motility, cervical mucosa

7 clinical pharmacology
absorption well absorbed orally distribution bound to plasma proteins albumin, SBG, others

8 metabolism Oestrogens Progestogens first pass clearance
metabolised in liver, conjugated excreted in the bile - (estradiol vs EE) enterohepatic circulation Progestogens depends on which one - “natural” progestogen extensive first pass metabolism

9 excretion urinary remember the bile duct STO HV PV CBD
About % of estrogen removed in the first pass through the liver HMW conjugates are excreted in bile

10 interactions (1) antibiotics
impaired absorption (effect on gut enzymes) reduced bacterial sulfatase leading to reduced entero-hepatic recycling enzyme induction -> increased clearance, lower plasma estrogen concentrations (eg rifampicin, griseofulvin, anticonvulsants, St John’s Wort)

11 interactions (2) anticonvulsants
Older drugs are enzyme inducers -> increased clearance and reduced concentration and failure (phenytoin, phenobarbitone, primidone, carbamazepine). No effect of sodium valproate Newer drug have variable effects (no change with gabapentin, lamotrigine, tiagabine, levetiracetam) (induction with topiramate and oxcarbazepine) try higher dose estrogen pills, double product dosing valproate less of a problem

12 adverse reactions estrogen excess late cycle breakthrough bleeding
menorrhagia/dysmenorrhoea nausea/vomiting fluid retention breast tenderness

13 adverse reactions progestogen excess amenorrhoea acne/oily skin
weight gain mood changes depressed libido breast tenderness

14 other risks thromboembolic disorder
high dose oestrogen - Inman, dose response relationship worse with other risk factors (age, smoking) ?third generation progestogens differentiating effects on VTE and other cardiovascular disease

15 big picture risks endometrial cancer ovarian cancer breast cancer
progestogen is protective ovarian cancer protective breast cancer jury out /data unconvincing cervical cancer confounded

16 other benefits reduction in menstrual flow - may lower incidence of anemia reduction in dysmenorrhoea possible reduction in auto-immune thyroid disease, rheumatoid arthritis some protection against PID

17 risk of nonfatal VTE

18 other issues compliance gastro. missing pills
alternative forms of hormonal contraception

19 balance sheet benefits harms effective contraception
other health benefits long-term health and social impact harms immediate adverse effects risk of failure long-term health effects

20 other uses morning after pill
EE 100mcg + norgestrel 1mg within 72 hours, 2 doses Failure rate of about 1%