Reproductive and post-reproductive health Flashcards
What are the different drug groups used in reproductive health?
Sex steroid hormones
Inhibitors and antagonists
Mixed agonist/antagonist
Give examples of sex steroid hormones
Oestrogens, progestogens and androgens
Give examples of inhibitors and antagonsists
RU486, finasteride
Give examples of mixed agonists/antagonists
Selective oesterogen receptor modulators
Selective progesterone receptor modulators
What are sex steroids synthesised from?
Cholestrol
What is the difference between Estrone and Estradiol?
Estone is more prevalent in post menopausal women whereas Estradiol is the more potent oestrogen present in reproductive life for follicular maturation
What are the receptors for steroid hormones? How do they exert their effects?
Classic nuclear receptors
Exert effects via gene transcription, as a transcription factor
What additional type of receptor does it have?
Membrane receptor for oestrogen
What are the major actions/effects of estradiol?
Stimulates growth of the endometrium and breast Mild anabolic Na and H20 retention Raises HDL and lowers LDL Decreases bone reposition Impairs glucose tolerance Increased blood coagulability Stimulates production of progesterone
What are the major actions/effects of progesterone?
Stimulates growth of the endometrium and breast Anabolic Increases bone mineral density Fluid retention Mood changes Maintains pregnancy Inhibits production of oestrogen
What are the major effects of testosterone?
Male characteristics Body hair Acne Deep voice Anabolism Aggression
What are the side effects of oestrogen?
Breast tenderness Nausea/vomiting Water retention Increased blood coagulability Thromboembolism Impaired glucose tolerance Emdometrial hyperplasia and cancer Breast hyperplasia and cancer Ovarian metaplasia
What are the side effects of progesterone?
Weight gain Fluid retention Anabolic Acne Nausea/vomiting Irritability, depression, PMS Lack of concentration
What are the side effects of testosterone?
Adverse effects of lipid profiles especially the HDL-c/LDL-c ratio
Increased risk of atherosclerotic disease in males
Pharmacokinetics of oestrogen: What does it’s absorbability mean for administration?
Natural and synthetic oestrogen are well absorbed in the GI tract so can be given in oral root
OR via patches in skin because readily absorbed from skin and mucus membranes
Where is oestrogen metabolised and by what?
Liver by CYP450
How is oestrogen excreted?
In the urine as glucoronides and sulphates
Pharmacokinetics of progesterone: How is it transported in blood and where is it stored?
Injected progesterone if bound to albumin with some stored in adipose tissue
Where is progesterone metabolised and by what?
Liver by CYP450
How is progesterone excreted?
In urine conjugated to glucuronic acid
What are some adverse effects of the combined pill?
Risk of thromboembolism
What risk factors increase the likelihood of the adverse effects?
Smoking
Long term use after 35 years of age
Obesity
Hypertension
What enzyme is involved in COCP and POP metabolism
CYP 450 in the liver
What reduces the contraceptive efficacy?
Enzyme inducing drugs which increase production of CYP450
What are some examples of enzyme inducing drugs?
Anti-epileptics e.g. carbamazepine or phenytoin
Antibiotics e.g. rifampicin and rifabutin
Natural products e.g. St Johns Wort- anti-depressant
What are the effects of soya protein on oral contraceptives?
Enhance oestrogen absorption and reduce its storage in adipose and muscle so cause the T1/2 to bee reduced from 15 to 7 hrs
Why prescribe hormone replacement therapy?
To relieve systemic symptoms that are a result of loss of oestrogen and progesterone
Osteoporosis
What are the routes of HRT administration?
Oral Transdermal Implant Transvaginal Nasal
Risks of taking unopposed oestrogen?
Increased risk of developing endometrial and ovarian cancers
Risks of taking HRT: oestrogen and progesterone?
Increased risk of developing breast cancer
Why is there an increased risk of venous thromboembolism?
Theres increased activated protein c resistance Increased thrombin activation Decreased anti thrombin 3 activity Decreased protein s levels Decreased factor 7 levels Decreased TF pathway inhibitor
What is Mifepristone (RU486)?
Progesterone receptor antagonist so acts as an anti-progesterone
What effect does RU486 have?
Sensitising the myometrium to prostaglandin induced contarctions
What is the use of RU486?
For the termination of pregnancy
What is a SERM?
Selective estrogen receptor modulator, have varying effects in different tissues
What are examples of drugs in the SERM class?
Tamoxifen
Raloxifene
Clomiphene
What is Raloxifene?
Management og post-menopasual osteoporosis- stops acceleration of bone resorption
What is clomiphene, what is its use?
Used in the treatment go anovulation
What is the mechanism of action of Clomiphene
Competes with oestrogen for ER binding
Tricks the pituitary to think there is no oestrogen
This increases oestrogen production, and thus increased follicular development
What is Tamoxifen?
Pro drug
How is Tamoxifen made functional?
Metabolised in the liver to make active derivatives
What is the mechanism of action of active Tamoxifen?
Competes with oestrogen for bidding to the ER
Why is there so much person to person variability in Tamoxifen effects?
Metabolising enzymes come in various isoforms and so have varying metabolisms
Where does Tamoxifen have converse effects?
Breast tissue and endometrial tissue
What effect does Tamoxifen have on the endometrium?
Acts as ER agonist
What effect does Tamoxifen have on the breast?
Acts as ER antagonist, causes the cell to arrest cycle
What is Ulipristal acetate?
Selective progesterone receptor modulator
What is Ulipristal acetate?
Used for emergency contraception and used for uterine fibroids
What does Ulipristal acetate bind to?
Progesterone receptor
