19 Reproductive system Flashcards
19.01 OESTROGENS AND ANTI-OESTROGENS
Natural and synthetic oestrogens: raloxifene; anti-oestrogens: clomifene, tamoxifen - actions
oestrogen controls the proliferative phase of endometrium and exerts negative feedback on the anterior pituitary
in addition to the reproductive system, oestrogens have metabolic and vascular effects
19.01 OESTROGENS AND ANTI-OESTROGENS
Natural and synthetic oestrogens, raloxifene; anti-oestrogens: clomifene, tamoxifen - MOA
bind to nuclear receptors and exert genomic effects
raloxifene has agonist effects at bone but antagonist on reproductive organs
clomifene is a competitive antagonist of oestrogen receptors at the anterior pituitary, and increases gonadotrophin secretion by preventing negative feedback
19.01 OESTROGENS AND ANTI-OESTROGENS
Natural and synthetic oestrogens, raloxifene; anti-oestrogens: clomifene, tamoxifen - abs/distrib/elim
many different formulations available (oral, topical, implantable, transdermal)
19.01 OESTROGENS AND ANTI-OESTROGENS
Natural and synthetic oestrogens, raloxifene; anti-oestrogens: clomifene, tamoxifen - clinical use
oestrogens are used in primary ovarian failure, menopausal symptoms and in female contraception
raloxifene is for osteoporosis
anti-oestrogens are used for inducing ovulation (clomifene) and for oestrogen-sensitive breast cancer (tamoxifen)
19.01 OESTROGENS AND ANTI-OESTROGENS
Natural and synthetic oestrogens, raloxifene; anti-oestrogens: clomifene, tamoxifen - adverse effects
varies with formulation and clinical setting but may include breast tenderness, water retention, venous thromboembolism
small increase in risk of breast and endometrial cancer in menopausal women
clomifene causes menopausal-like hot flushes, ovarian enlargement
19.02 PROGESTOGENS AND ANTI-PROGESTOGENS
Progestogens: medroxyprogesterone, norethisterone, desogestrel, cyproterone; anti-progestogens: mifepristone - actions
progestogens control the secretory phase of endometrium and exert negative feedback on the anterior pituitary and hypothalamus
weak androgenic action
19.02 PROGESTOGENS AND ANTI-PROGESTOGENS
Progestogens: medroxyprogesterone, norethisterone, desogestrel, cyproterone; anti-progestogens: mifepristone - MOA
bind to intracellular receptors and alter gene expression
cyproterone has weak progestational activity but is a partial agonist at androgen receptors in the hypothalamus
19.02 PROGESTOGENS AND ANTI-PROGESTOGENS
Progestogens: medroxyprogesterone, norethisterone, desogestrel, cyproterone; anti-progestogens: mifepristone - abs/distrib/elim
many different formulations (oral, injectable, implantable device)
examples include levonorgestrel as a SC depot or as an intrauterine contraceptive system
19.02 PROGESTOGENS AND ANTI-PROGESTOGENS
Progestogens: medroxyprogesterone, norethisterone, desogestrel, cyproterone; anti-progestogens: mifepristone - clinical use
female contraception, including post-coital emergency contraception
endometriosis
anti-progestogens (mifepristone) used in medical termination of pregnancy
cyproterone used to suppress hyperandrogenism
19.02 PROGESTOGENS AND ANTI-PROGESTOGENS
Progestogens: medroxyprogesterone, norethisterone, desogestrel, cyproterone; anti-progestogens: mifepristone - adverse effects
acne, fluid retention, weight change, menstrual disturbance
19.03 COMBINED ORAL CONTRACEPTIVE PILL
Oestrogen and a progestogen: ethinylestradiol + norethisterone; ethinylestradiol + desogestrel - actions and use
prevention of pregnancy
19.03 COMBINED ORAL CONTRACEPTIVE PILL
Oestrogen and a progestogen: ethinylestradiol + norethisterone; ethinylestradiol + desogestrel - MOA
oestrogen suppresses the development of the ovarian follicle by inhibiting follicle-stimulating hormone (FSH) release from the anterior pituitary
progestogen prevents ovulation by inhibiting luteinizing hormone (LH) release
together, they make the endometrium unsuitable for implantation of the ovum
19.03 COMBINED ORAL CONTRACEPTIVE PILL
Oestrogen and a progestogen: ethinylestradiol + norethisterone; ethinylestradiol + desogestrel - abs/distrib/elim
given orally
taken cyclically for 21 days out of 28 days
19.03 COMBINED ORAL CONTRACEPTIVE PILL
Oestrogen and a progestogen: ethinylestradiol + norethisterone; ethinylestradiol + desogestrel - adverse effects
weight gain, flushing, mood changes, dizziness, acne or skin pigmentation, transient rise of blood pressure
some risk of thromboembolism
19.04 GONADOTROPHINS
GnRH analogues (gonadorelin, leuprorelin) and inhibitors (danazol) - actions and MOA
pulsatile regimens of gonadotrophin-releasing hormone (GnRH) analogues stimulate gonadotrophin release but have inhibitory effects when given continuously
danazol is a modified progestogen that inhibits gonadal function by suppressing the mid-cycle surge of gonadotrophins
19.04 GONADOTROPHINS
GnRH analogues (gonadorelin, leuprorelin) and inhibitors (danazol) - abs/distrib/elim
GnRH analogues are given by SC injection or nasal spray intermittently, or through a depot injection for continuous use
danazol is given orally
19.04 GONADOTROPHINS
GnRH analogues (gonadorelin, leuprorelin) and inhibitors (danazol) - clinical use
GnRH analogues are used in infertility
longer term use for gonadal suppression in prostate cancer and endometriosis
danazol is used in the treatment of endometriosis and gynaecomastia
19.04 GONADOTROPHINS
GnRH analogues (gonadorelin, leuprorelin) and inhibitors (danazol) - adverse effects
adverse effects of GnRH analogues vary depending on whether treatment is used for stimulation (hypergonadism) or inhibition (hypogonadism)
moderate effects are common with danazol: weight gain, acne, hot flushes, amenorrhoea, masculinisation (hirsutism, deepening of voice, etc.)
19.05 UTERINE STIMULANTS
Oxytocin - actions
contracts the uterus causing coordinated contractions that travel from fundus to cervix with complete relaxation between contractions
has vasodilator action
19.05 UTERINE STIMULANTS
Oxytocin - MOA
acts on oxytocin receptors in the smooth muscle of the myometrium
contracts myoepithelial cells in the breast to release milk
vasodilator and antidiuretic action
19.05 UTERINE STIMULANTS
Oxytocin - abs/distrib/elim
usually given by IV infusion
can be given IM
inactivated by the liver and kidneys and by circulating oxytocinase
19.05 UTERINE STIMULANTS
Oxytocin - clinical use
induction or stimulation of labour when the uterine muscle is not functioning adequately
prevention and treatment of post-partum bleeding
treatment of incomplete abortion
19.05 UTERINE STIMULANTS
Oxytocin - adverse effects
dose-related hypotension due to vasodilatation
water retention and hyponatraemia due to an antidiuretic hormone-like effect
19.06 UTERINE STIMULANTS
Ergometrine - actions
contracts the relaxed uterus
has vasoconstrictor action
19.06 UTERINE STIMULANTS
Ergometrine - MOA
not understood
may act partly on α adrenoceptors, partly on 5-HT receptors
19.06 UTERINE STIMULANTS
Ergometrine - abs/distrib/elim
given orally, IM or slow IV
rapid onset of action
duration: 3-6h
a combined IM preparation of oxytocin and ergometrine is available
19.06 UTERINE STIMULANTS
Ergometrine - clinical use
to treat post-partum haemorrhage
19.06 UTERINE STIMULANTS
Ergometrine - adverse effects
nausea and vomiting due to action on dopamine receptors
increase in BP and in some cases angina (due to vasoconstriction)
headache, dizziness
dysrhythmias
19.07 UTERINE STIMULANTS
Analogues of prostaglandins E and F: carboprost, dinoprostone, misoprostol, gemeprost - actions
cause coordinated contractions of the pregnant uterus
relax the cervix
19.07 UTERINE STIMULANTS
Analogues of prostaglandins E and F: carboprost, dinoprostone, misoprostol, gemeprost - MOA
carboprost activates PGF2α (FP) receptors on uterine smooth muscle, whilst dinoprostone, misoprostol and gemeprost act on PGE receptors
19.07 UTERINE STIMULANTS
Analogues of prostaglandins E and F: carboprost, dinoprostone, misoprostol, gemeprost - abs/distrib/elim
carboprost is given by deep IM injection, whereas dinoprostone and misoprostol are given intravaginally
19.07 UTERINE STIMULANTS
Analogues of prostaglandins E and F: carboprost, dinoprostone, misoprostol, gemeprost - clinical use
carboprost for the treatment of post-partum haemorrhage unresponsive to oxytocin or ergometrine
dinoprostone (PGE2) or misoprostol used intravaginally to augment or induce labour
gemeprost (PGE1 analogue) used in pessary form for medical induction of abortion
19.07 UTERINE STIMULANTS
Analogues of prostaglandins E and F: carboprost, dinoprostone, misoprostol, gemeprost - adverse effects
uterine pain, nausea, vomiting, diarrhoea, vasodilation
19.08 OXYTOCIN ANTAGONIST
Atosiban - actions
inhibits oxytocin-induced contractions of the pregnant uterus
19.08 OXYTOCIN ANTAGONIST
Atosiban - MOA
antagonises oxytocin action on oxytocin receptors on uterine smooth muscle causing relaxation
19.08 OXYTOCIN ANTAGONIST
Atosiban - abs/distrib/elim
given by IV injection followed by slow IV infusion
19.08 OXYTOCIN ANTAGONIST
Atosiban - clinical use
to delay pre-term labour
19.08 OXYTOCIN ANTAGONIST
Atosiban - adverse effects
nausea, vomiting, vasodilation, hyperglycaemia
19.09 MALE SEX HORMONE
Testosterone - actions
has the same actions as endogenous testosterone
the effects will depend on the age of the patient
19.09 MALE SEX HORMONE
Testosterone - MOA
converted by 5α-reductase to dihydrotestosterone, which interacts with nuclear receptors to initiate transcription of some genes (resulting in DNA-directed RNA and protein synthesis) and repression of others
dihydrotestosterone has greater activity than testosterone
19.09 MALE SEX HORMONE
Testosterone - abs/distrib/elim
given orally, buccal, IM injection or transdermally
oral formulations are rapidly metabolised in the liver
19.09 MALE SEX HORMONE
Testosterone - clinical use
replacement therapy in hypogonadism due to pituitary or testicular disease
19.09 MALE SEX HORMONE
Testosterone - adverse effects
eventual decrease of gonadotrophin release resulting in infertility
oedema due to salt and water retention
19.10 ANTI-ANDROGENS
5α-reductase inhibitors (finasteride, dutasteride) and androgen antagonists (flutamide, bicalutamide, etc.) - actions
reduce the effect of testosterone, particularly at the prostate
19.10 ANTI-ANDROGENS
5α-reductase inhibitors (finasteride, dutasteride) and androgen antagonists (flutamide, bicalutamide, etc.) - MOA
finasteride and dutasteride block intracellular type II 5α-reductase (enzyme that converts testosterone to the more active variant, dihydrotestosterone)
androgen antagonists block the action of testosterone on cell receptors
19.10 ANTI-ANDROGENS
5α-reductase inhibitors (finasteride, dutasteride) and androgen antagonists (flutamide, bicalutamide, etc.) - abs/distrib/elim
given orally
19.10 ANTI-ANDROGENS
5α-reductase inhibitors (finasteride, dutasteride) and androgen antagonists (flutamide, bicalutamide, etc.) - clinical use
finasteride is used in benign prostatic hyperplasia (often in conjunction with α-adrenoceptor blockers), and for male pattern hair loss
androgen antagonists are used to treat prostate cancer
19.10 ANTI-ANDROGENS
5α-reductase inhibitors (finasteride, dutasteride) and androgen antagonists (flutamide, bicalutamide, etc.) - adverse effects
erectile dysfunction
libido loss
gynaecomastia and breast tenderness are particularly common with androgen blockers
19.11 PHOSPHODIESTERASE TYPE V INHIBITORS
Sildenafil, tadalafil, vardenafil - actions
enhance penile erection
relax the non-vascular smooth muscle of the corpora cavernosa
blood at virtually arterial pressure then flows into the cavenosa sinuses resulting in swelling and erection of the penis
do not cause erection independent of sexual stimulation
19.11 PHOSPHODIESTERASE TYPE V INHIBITORS
Sildenafil, tadalafil, vardenafil - MOA
inhibit phosphodiesterase type V (enzyme that normally converts cGMP to 5′-GMP)
this increases the concentration of cGMP, which inhibits the contractile mechanisms of the muscle, allowing relaxation
vascular relaxation also improves perfusion of the prostate and bladder
19.11 PHOSPHODIESTERASE TYPE V INHIBITORS
Sildenafil, tadalafil, vardenafil - abs/distrib/elim
given orally
peak action occurs in 30-120 min
as tadalafil has a longer half-life, the exact timing of administration prior to anticipated sexual activity is less crucial
19.11 PHOSPHODIESTERASE TYPE V INHIBITORS
Sildenafil, tadalafil, vardenafil - clinical use
usually for erectile dysfunction, but sildenafil is also licensed for pulmonary arterial hypertension
tadalafil is also licensed for benign prostatic hyperplasia
19.11 PHOSPHODIESTERASE TYPE V INHIBITORS
Sildenafil, tadalafil, vardenafil - adverse effects
these are due to the action of these drugs on other vascular beds and include fall in blood pressure, headache and flushing
