Reproductive system related drugs

Uterine muscle:

Oxytocin:
MoA:
uterus: increases contractions from fundus to Cervix with complete relaxation (estrogen sensitizes)
Postpartum: Breast ejaculates milk
At high doses: ADH like effects
Not given orally, either iv (from seconds to 20 minutes) or spray
Indication: pre or post mature in toximea, diabetic, erythroblastosis, rupture, placental insufficiency
post-partum bleeding, relieving impaired milk ejection
ADR: distress, placental or uterine abruption, water intoxication (long term)
Contraindications.: conditions that harm the baby (uterine or placental abnormality, prematurity
without a reason)

Ergot alkaloids
Ergometrine, methylergometrine (p)
Mote: May act on a1 receptors or serotonin ripening to the cervix, titanic contractions
Uses: to prevent the haemorrhage or atony (caused by ceasirian, instrumental)
ADR: high bp, vasospasm, blurred vision, Gi upset
Contraindicated in: HTN, toximia, liver and kidney disease

Prostaglandin’s analogue
Dinoprostone (intravaginally), carboprost (IM), misoprostol
Indications: first Contraction & ripening of cervix with no retention of water for preeclampsia
Second: post-partum haemorrhage after other first agents
Third: with mifepristone for mid trimester abortion
Contra: obstruction, distress, or rupture

Uterine relaxants

B2 adrenergic receptors
Ritodrine, isoxsuprine
Relaxation by receptors
Uses: prevent premature labour between 22-33 w, delay by 48 hr to give glucocorticoids, for lungs
threatened abortion
ADR: common with sympathetic, not for hyperthyroidism, HTN, antepartum haemorrhage (dilatation
of uterine arteries may increase bleeding)

Ca channel blocker
Nifedipine
Antagonize so low contractility
Prophylaxis for premature labour

Magnesium sulphate
Replace Ca with mg to lower contractility, anticonvulsant
Used in prevention of seizures in eclampsia, preferred over B when related to HTN, diabetes,
hyperthyroidim, heart disease
ADR: flushing, sweating, palpitations
Atosiban
Antagonize oxytocin receptors
Delay premature labour
ADR: TCh, low bp, GI

Indomethacin
No PST synthesis
Used in dysmenorrhea
ADR: gastritis and closure of ductus arteriosis

Erectile dysfunction
Phosphodieshrase-5 inhibitors
Sildenafil, tadalfil (p)
Inhibit pde-5 ' so high cGMP, protein kinase activation and vasodilation
Needs 30 min & prodrug, second is more potent with less pd-6 effect but longer duration
Also used in pulmonary hypertension
ADR: impaired colour vision due PDE6, nc, low BP, rp, priapism (treatment: aspirate blood, a1
agonist
Contraindication with nitrates, a1 blockers, cyp inducers or inhibitors
Blood condition like sca predispose ↳ priapism, contraindicated in cvs, cavernosal fibrosis, peyronies
disease and liver kidney disease

Testosterone
effective when hypogonadism or hyperprolactinemia

Prostaglandin analogue
Alprostadil
Increases camp causing smooth muscle relaxation vasodilation (erection lasts for 1-2 h)
Intracavernous injection, not likely to cause hypotension nor priapism

Gonadal hormones analogues:

Female:

Synthetic estrogen
S: ethinyl estradiol, NS: Diethylstilbestrol
MoA: binds to ERE to activate gene transcription
Actions: 5: genital, 2nd characteristics, breast, endometrium, cervix (WAT): facilitates entry of sperm
Others: bones 2, HDL, LDL, blood coagulation 2 (2,5,10,11), CVS
Uses: primary hypogonadism, HRT (for vasomotor symptoms, whith progestin to. reduce
endometrial cancer), contacepption, senile vaginitis, dysmenorrhea
ADR: N, breast tenderness, gallbladder and hyperpigmentation, migraine and hypertension, venous
thromboembolism
Contra: neoplasm, vaginal bleeding, liver disease, thromboembolic disease, heavy smokers

Antiestrogens

Serm:

Tamoxifen
Anti on breast, estrogenic on bone, uterus, blood
Uses: breast cancer, postmastectomy or radiation, chemoprevention, gynecomastia
ADR: hot flashes, EH, TE

Raloxifen
Anti on breast and uterus, estrogenic on bone, lipids, blood
Uses: postmenopausal osteoporosis
ADR: same without hyperplasia

Clomiphene
inhibit the negative feedback -> FSH -> Ovulation
Uses: infertility with intact HPO axis, Male infertility
ADR: flushes, visual disturbences, multiple gestation, ovarian cyst or malignancy if used for more
than a year

Aromatase ihibitors
SI: exemestane, letrozole
MoA: reduce peripheral conversion
Uses: postmenopausal with breast cancer (estrogen +), ovulation
ADR: flashes, night sweat, vaginal dryness, muscle pain, osteoporosis, hypercholesteremia

Progestins
original derivitaves: hydroxyprogestrone, medroxyprogestrone
Testosterone derivatives: A: norethisterone, less: norgestimate
MoA: binds to PRE to activate gene transcription
Actions: endometrium, pregnancy, cervix (VAT), breast acini, fat and water retention, high temp
Uses: contraception, HRT with estrogen to prevent cancer, postpone periods, uterine bleeding,
endometriosis, infertility
ADR: acne and hirsutism (TD), exacerbation of actions

Antiprogestin
Mifeprostone
MoA: blockes receptors, anti-glucocorticoids
Uses: abortion (first 7 weeksm with misoprostol given 48 hr later), post coital contraceptives,
cushing
ADR: bleeding, Abd pain, infection

Ulipristal acetate: SPRM -> PC contraception

Danazol
MoA: inhibits gonadotropin secretion-> estrogen synthesis, CYP450 in gonadal steroid synthesis
Uses: endometriosis, fibrocytic breast, gyncemostia, hereditary angioedema
ADR: menopausal symptoms and virilization
Contra: pregnancy and lactation

Androgens
Androgenic: testosterone, methyltestosterone
MoA: Dihydrotestosterone activate gene transcription and protein synthesis
Actions: genital, 2nd characteristics, maintain infertility and lipido, male pattern baldness
Uses: hypogonadism, refractory anemia, AIDs muscle wasting
Anabolic: Nandrolone, oxandronole
Actions:muscles, bone, closure of epiphysis, water retention, erythropoiten, maintains bone density
Uses: improve apetite and recovery from chronic illness

ADR:
Children: short, masculinization
Female: virilization
Males: gynecomastia and testicular atrophy
pregnancy: masculization or under masculization in fetus
Common: jaundice, high liver enzymes, hepatocellular carcinoma
Coontra: in all and prostate cancer

Antiandrogens
Finasteride
inhibits 5-reductase so no active form
Uses: BPH, alopecia
ADR: erectile dysfunction, infertility, ejaculatory disfunction

Receptor anta
Flutamide:
prostate Ca

Cryproterone acetate
Uses: hirsutism in women, reduce libido
ADR: impotence, hot flushes, gynecomastia

Spironolactone
above + reduce alpha hydroxylase level
For hirsutism in women
ADR: hyperkalemia, gynecomastia, menstrual irregularity

Ketokonazole
inhibits adrenal and gonadal synthesis
Uses: prostate CA, cushing syndrome
ADR: impotency and gynecomastia
** interacts with CYP 3A4 inhibitos
needs low PH of stomach

GNRH receptor agonist: leuprolide, goserelin

OCP
combined
MoA: affecting FSH (ovulation), GnRH (midcycle LH), cervix (VAT), tubual motility and peristalisis.
21/7

Progestin only: norethisterone, levonorgestrel, desogestrel (potent, less andronergic)

No effects on ovulation
Advantajes: estrogen ADR avoided
disadvatages: non reliable
ADR: headache, bloating, weight gain, irregular bledding
Uses: ovarian cyst, primary hypogonadism, acne and hirsutism, endometriosis, PCOS, abnormal
bleeding, dysmenorrhea
benefits: reversible, reduce risk of previous conditions in addition to benign breast disease, PID,
ectopic pregnancies, iron deficiemcy, rheumatoid arthritis
ADR: neasuea, mastalgia, edema, migraine, weight gain, pigmentation, high BP, vaginal infections, TE
especially in old women who smokes, stroke, cancers, gall bladder disease
Interactions: anticonvulasants (inducers, but some don’t) and rifampicin, AB, Antiretrovirals,
concurrent use of OCP (alternative barrier and increase dose)
Contraindications: TE, adolescents, stroke, neoplasms, vaginal bleeding, gall bladder
relative: age and smoking, breast feeding, HTN, mirgraine, surgeries

Post coital
before LH surge -> inhibits ovulation. effects cervical mucus, tubal infections, endometrial lining
ADR: headache, Abd pain, mentural irregularities
Plan B one step: levonorgestrel (within 72 h)
Uliprstal: SPRM (120 hr)
Copper IUD

Parentral:
Depot medroxyprogestrone (3 months)
Transdermal (ethynyl estradiol and norelgestromin)- each week for 3 weeks
Vaginal ring (ethynyl estradiol and etonogestrel)- 3 weeks
SC implant (norgestrel)- 2-4 years

IUD:
progestins- levonorgestrel
long acting 3-5 years
effective as sterilizations
MoA: thickening of mucous and sterile actions
Contra: Uterine distortion, abnormal bleeding, PID, ectopic pregnancy

copper non hormonal

MoA: releasing Co that causes inflammatory reaction and impairs: sperm motility and fertilization
Uses: reversible contraception (10 years)
Contra: same, wilson