Pharmacology 3: Sex hormones, HRT, and lipid and cholesterol metabolism Flashcards
Serious and common adverse effects of combined OCP?
arterial and venous thromboembolism, PE, GB disease, hypertension- Na+ and H20 retention occurs- RAAS stimulation? exertion of similar effects to aldosterone?
precipitate porphyria, increase risk of stroke in women with focal migraine, MI
abnormal menstruation, breakthrough bleeding, breast tenderness, bloating symptoms, migraine, weight change
when is combined OCP contraindicated?
pregnant- already increased risk of DVT women >35 and smoke- assoc risk of thrombotic CVS events prolonged immobolisation thrombotic disorders CAD endometrial cancer liver tumours
risk if women being treated for TB is only using the combined OCP for contraception?
may get pregnant as rifampicin= CYP 450 inducer, so will cause increased metabolism of COCP, so it may become ineffective.
actions of oestrogens?
mild anabolic
sodium and water retention
raise HDL, lower LDL
decrease bone resorption (so post-meopause- risk of osteoporosis)
impair glucose tolerance
increase blood coagulability
?improve mood, concentration, reduce Alzheimer’s
?avoiding 1st pass effect more favoruable
progesterone actions?
anabolic secretory endometrium fluid retention increased bone mineral density mood changes
SEs of progesterone?
weight gain fluid retention anabolic acne nausea, vomiting irritabolity PMS, depression concentration lack
actions/SEs of testosterone?
*remember, determinative and regulatory effects
anabolic
male secondary sexual characteristics e.g. increased laryngeal size, hair growth, increase bone density, increased muscle and strength
voice deepening
aggression
acne
metabolic adverse effects on lipids
describe the difference between the monophasic and triphasic COCP?
monophasic: constant dose of oestrogen and progesterone every day for 21 days
triphasic: constant dose of oestrogen, with a dose of progesterone which increases each wk during the 21 days of cycle. triphasic allows total amount of progesterone administered each month to be reduced
what are the different generations of progestogens?
relate to androgenic activity, so 3rd generation e.g. desogestrel have lower androgen receptor cross-reactivity compared to levonorgestrel= 2nd generation, highest androgenic activity on molar basis
clinical relevance of COCP being metabolised by CYP 450 (hepatic)?
efficacy reduced by enzyme inducing drugs e.g. PCBRAS phenytoin carbamazepine barbiturates rifampicin alcohol sulphonylureas
example of anti-oestrogen drug used to treat infertility and explain how it works?
clomiphene:
weak oestrogen that blocks receptors, inhibits oestrogen binding to anterior pituitary so stops -ve feedback of oestrogen, so increases GnRH, FSH and LH and induces ovulation
tamoxifen= also a weak oestrogen, used in oestrogen receptor +ve breast cancer
given an example of an anti-progestogen used for medical termination of pregnancy and induction of labour?
Mifepristone
partial agonist to progesterone receptor, inhibits progesterone action
sensitises uterus to PGs- can be used with a PG cervical ripening agent
what can selective oestrogen receptor modulators be used for?
e.g. raloxifene
action different in various tissues so can selectively inhibit and stimulate oestrogen action in particular tissues
protects against OP
no proliferative effects on endometrium of breast
oestrogenic effects on lipid metabolism, bone and blood coagulation
reduced risk of invasive BC in PM women with OP
increases hot flushes
why can testosterone not be given orally to males who are hypogonadal e.g. due to pituitary or testicular disease? what can be used instead?
testosterone rapidly inactivated by liver- heavily metabolises drug
synthetic androgens e.g. mesterolone- active orally
examples of secondary benefits of statin treatment?
improved endothelial cell function
plaque reduction
anti-inflammatory
reduced thrombotic risk
what are fibric acid derivatives?
ampipathic carboxylic acids which increase prod. of lipoprotein lipase- reduce triglyceride prod, some reduction in LDLs, increase FA uptake and oxidation
direct vascular effects
what is the best agent to raise HDL-C?
nicotinic acid
how does nicotinic acid work in lipid lowering tment?
inhibition of lipoprotein (a) synthesis, lowers VLDLs and increases HDLs
risk with using combination statin and fibrate as lipid lowering tment?
increased risk for myopathy and rhabdomyolysis- gemfibrozil may impair glucuronidation of statins- espec. cerivastatin, fenofibrate has less potential for impairment of statin metabolism
why does use of the progesterone only pill increase risk of ectopic pregnancies?
progesterone reduces motility of fallopian tubes, so reduced peristaltic action that normally allows fertilised ovum to be moved along for implantation in posterior uterine wall. Also, thickened cervical mucus makes transport more difficult.
what to do if miss taking COCP?
if missed 1 anywhere in pack, or started a new pack 1 day late, should take forgotten pill straight away, even if that means 2 in 1 day, carry on taking rest of pack as normal and take 7 day free or with placebo as normal. Extra contraception not needed.
If 2 or more missed, or new pack started 2 or more days late, last pill missed should be taken, any earlier ones left, carry on taking rest of pack as normal, and use extra contracpetion e.g. condoms for next 7 days.
emergency contraception e.g. levonorgestrel may be needed if had unprotected sex in previous 7 days and you’ve missed 2 or more pills in 1st week of pack.
what to do if missed POP?
if 3hrs, or >12 with cerazette, take a pill as soon as you remember – only take one, take the next pill at the usual time – this may mean taking two pills on the same day, carry on taking your remaining pills each day at the usual time, use extra contraception such as condoms for the next two days (48 hours) after you remember to take your missed pill, or don’t have sex
if you have unprotected sex during these two days, you may need emergency contraception
other than drugs inducing CYP450, give another example of drugs that can reduce the efficacy of the COCP?
antibiotics- affect gut flora- can alter entero-hepatic uptake of drug.
factors to consider in a patients PMH and FH in assessing them for prescribing COCP?
blood pressure, BMI diabetes FH of cancers, DVTs epilepsy migraines drug history- interactions?
effect of vomiting after taking COCP?
if within 2-3 hrs of taking pill, it will have not been absorbed and so next pill should be taken on same day.
Also affects absorption if severe diarrhoea.
how should a patient taking COCP be monitored?
BP
weight
lipid levels- if RFs for CVD
what can be measured in the blood to exclude a DVT in patients?
D-dimer- if low then defo. not DVT
why are patients at increased risk of cervical cancer when taking COCP?
less likely to use barrier contraception and so increased risk of exposure to HPV.
function of tibolone?
synthetic steroid hormone which mimics actions of oestrogen and progesterone so can be used in post-menopausal women
example of a drug used to control symptoms in menopausal women, but is not an example of HRT?
clonidine- control vasomotor symtpoms by binding to adrenergic receptors to relax smooth muscle of blood vessels, causing them to dilate.
before surgery, what must a patient do if taking HRT?
must stop it 4-6 wks prior to surgery as HRT increases risk of thrombosis, as does surgery and anaesthetic used.
effect of statins on plasma lipid levels?
reduced LDLs
increases HDLs
reduces triglycerides
effect of ezetimibe (cholesterol esterase inhibitor) on plasma lipid levels?
reduces LDLs
increases HDLs
reduced triglycerides
effect of niacin on plasma lipid levels?
reduced LDLs
increases HDLs- main effect, best for this
reduces triglycerides
effect of cholestyramine ( a bile acid sequestrant) on plasma lipid levels?
reduce LDLs
increase HDLs
increase triglycerides
