Transcript ocyr4

Oral contraceptive prescribing
• clinical pharmacology
– mechanism of action
– ADME
• interactions
• adverse reactions
• benefits and harms
what are they
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around since late 1950’s
social revolution
progestogen /oestrogen
variety of components and doses
changes over time in both
components
• oestrogen
– ethinyoestradiol
– mestranol
• progestogen
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–
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–
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norethisterone
norgestrel
Levonorgestrel
medroxyprogesterone
ethynodiol diacetate
gestodene
desogestrel
doses
• monophasic
• oestrogen - up to 50g/day
• progestogen - up to 1mg/day
• biphasic
• oestrogen: constant
• progestogen: eg 11 days @50, 10 @125 g
• triphasic
• oestrogen 30/40/30
• progestogen 50/75/125
clinical pharmacology
• mechanism of action
– inhibit secretion of FSH, LH - inhibit ovulation
– additional actions on endometrium tubal
motility, cervical mucosa
clinical pharmacology
• absorption
– well absorbed orally
• distribution
– bound to plasma proteins
– albumin, SBG, others
metabolism
• Oestrogens
– 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
excretion
• urinary
• remember the bile duct
STO
HV
PV
CBD
About 40-60 % of estrogen removed
in the first pass through the liver
HMW conjugates are excreted in bile
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)
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
adverse reactions
• estrogen excess
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late cycle breakthrough bleeding
menorrhagia/dysmenorrhoea
nausea/vomiting
fluid retention
breast tenderness
adverse reactions
• progestogen excess
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amenorrhoea
acne/oily skin
weight gain
mood changes
depressed libido
breast tenderness
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
big picture risks
• endometrial cancer
– progestogen is protective
• ovarian cancer
– protective
• breast cancer
– jury out /data unconvincing
• cervical cancer
– confounded
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
risk of nonfatal VTE
AR
(per
100000
women
years)
RR
Pregnancy 3rd gen
Ist gen
60
30
15
Nonusers
5
12
6
3
1
99.97
99.985
99.995
% of
99.94
women
free of VTE
other issues
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compliance
gastro.
missing pills
alternative forms of hormonal contraception
balance sheet
• benefits
– effective contraception
– other health benefits
– long-term health and
social impact
• harms
– immediate adverse
effects
– risk of failure
– long-term health
effects
other uses
• morning after pill
– EE 100mcg + norgestrel 1mg within 72 hours,
2 doses
– Failure rate of about 1%