Antiandrogens
description
Transcript of Antiandrogens
Androgen Suppression Androgen Suppression
& & AntiandrogensAntiandrogens
Male contraceptivesMale contraceptivesDr keliDr keli
Androgens supressionAndrogens supression
Androgens effects can be eliminated Androgens effects can be eliminated by Suppression of gonads byby Suppression of gonads by
Orchidectomy Orchidectomy Large doses of oestrogen !! Large doses of oestrogen !!
GynaecomastiaGynaecomastiaGnRH analogue adminstered GnRH analogue adminstered
contonouslycontonously
Anti-AndrogensAnti-Androgens
Compounds that block the synthesis or Compounds that block the synthesis or action of androgens.action of androgens.
They are useful in the management ofThey are useful in the management ofhyperplasia and carcinoma of the hyperplasia and carcinoma of the
prostate,prostate,acne,acne,male-pattern baldness,male-pattern baldness,virilizing syndromes in women virilizing syndromes in women precocious puberty in boys precocious puberty in boys To inhibit of sex drive in menTo inhibit of sex drive in men
Modes of Antiandrogens Modes of Antiandrogens effectseffects
1. Steroid synthesis inhibition ketoconazole
It inhibits adrenal and gonadol steroid synthesis
it does not affect the ovarian aromatase but affects the
placental aromatase activity
• Not usefull in women due to its toxcity
• Experimetal rx of prostatic ca
It causes gynaecomastia in men due to increased ratio
ofesradiol:testosterone
AntiandrogensAntiandrogens• Androgen Receptor inhibitorsAndrogen Receptor inhibitors
1. Cyproterone and Cyproterone1. Cyproterone and Cyproterone acetateacetate
inhibit androgens at their target organsinhibit androgens at their target organs
Use hirsutism has contraceptive effects, to reduce Use hirsutism has contraceptive effects, to reduce
excessive sexual drive in menexcessive sexual drive in men
2. Flutamide NSAID Rx of ca prostrate behaves like 2. Flutamide NSAID Rx of ca prostrate behaves like
a competitive antagonist of androgen receptors a competitive antagonist of androgen receptors
Ae mild gynaecomastia mild hepatotoxicity ? Mx Ae mild gynaecomastia mild hepatotoxicity ? Mx
of excess androgens in womenof excess androgens in women
Androgen receptor inhibitors3.3. Bicalutamide Nilutamide potent ant Bicalutamide Nilutamide potent ant
androgens for Rx of metastatic androgens for Rx of metastatic
prostrate ca use with GnRH prostrate ca use with GnRH
analogues to reduce tumour flareanalogues to reduce tumour flare
4. Spironolactone competes for 4. Spironolactone competes for
androgen receptors with androgen receptors with
dihydrotestosterone reduces 17 a dihydrotestosterone reduces 17 a
hydroxylase activity lowering hydroxylase activity lowering
testosterone and androstenedione testosterone and androstenedione
Rx of hirsutim in women Rx of hirsutim in women
Conversion of steroid precursors to androgens
This occurs via Inhibition of the conversion of This occurs via Inhibition of the conversion of
progesterone or pregnelone to androgens via progesterone or pregnelone to androgens via
inhibition of 17 hydroxylase by inhibition of 17 hydroxylase by Abiraterone and Abiraterone and
DutasterideDutasteride
Inhibition of 5 a reductase, reduces the levels of Inhibition of 5 a reductase, reduces the levels of
dihydrotestosterone an androgen in the prostratedihydrotestosterone an androgen in the prostrate
Finasteride Rx of prostrate ca Finasteride Rx of prostrate ca Dutasteride Slow OOA & longer DOASlow OOA & longer DOA
Dose 5mg/dDose 5mg/d
Both not approved for use in women or childrenBoth not approved for use in women or children
Spironolactone
A competitive inhibitor of aldosteroneA competitive inhibitor of aldosterone Also competes with DHT for androgen Also competes with DHT for androgen
receptors in target tissuesreceptors in target tissues Also reduces 17Also reduces 17 hydroxylase activity, hydroxylase activity,
lowering plasma levels of testosterone & lowering plasma levels of testosterone & androstenedioneandrostenedione
Treatment of hirsuitism in womenTreatment of hirsuitism in women As effective as other finasteride, As effective as other finasteride, Cyproterone
& Flutamide Dose: 50-200mg/dDose: 50-200mg/d
DanazolDanazol
Uses:Uses:EndometriosisEndometriosisMenorrhagiaMenorrhagiaFibrocystic breast diseaseFibrocystic breast diseaseHereditary angioneuroticHereditary angioneurotic
oedemaoedemaGynecomastiaGynecomastiaInfertilityInfertility
Side effects:Side effects:
Dose related Dose related
Amenorrhea (High doses)Amenorrhea (High doses)
Androgenic side effectsAndrogenic side effects
• FSH & LH release in both sexes
• Binding of steroids to receptors
• Enzymes needed for steroid synthesis
• Weak androgenic, anabolic, progestational & glucocorticoid action
Parasympathetic Sympathetic
Acetyl cholineNoradrenaline
Hypothalamus
ANS
Muscarinic Receptors
vasoconstriction
Penile flaccidityPenile erection
SildenafilSildenafil
Inhibits PDE5 in the corpus cavernosa of the Inhibits PDE5 in the corpus cavernosa of the penispenis
50mg, p.o. 1 h before sexual activity50mg, p.o. 1 h before sexual activity potentiate nitrate’s hypotension activitypotentiate nitrate’s hypotension activity ketoconazole & erythromycin increases its levelketoconazole & erythromycin increases its level renal & hepatic disease increases its levelrenal & hepatic disease increases its level Side effects: Side effects:
headache, flushing, dyspepsia, myalgiaheadache, flushing, dyspepsia, myalgia
MALE CONTRACEPTIONMALE CONTRACEPTION CondomCondom VasectomyVasectomy Male oral contraception with androgensMale oral contraception with androgens
and with cotton seed oiland with cotton seed oil Immunological contraception Immunological contraception
Still at Still at investigative investigative stage.stage.
Do men want new Do men want new options?options?
Over 40% of US couples rely on the Over 40% of US couples rely on the currently available male contraceptivescurrently available male contraceptives
Source: CDC (2006) Health, United States
Chemical Contraception in Chemical Contraception in MenMen
Testosterone and testosterone Testosterone and testosterone enanthate in a dose of 400 mg a enanthate in a dose of 400 mg a monthmonth
Testosterone + Danazole well Testosterone + Danazole well tolerated but not more effective than tolerated but not more effective than testosterone enathatetestosterone enathate
Testosterone enanthate 100 mg Testosterone enanthate 100 mg weekly + levonorgestrel 500 mg weekly + levonorgestrel 500 mg daily produce azoospermiadaily produce azoospermia
Under investigationUnder investigation
Gossypol a cottonseed derivative it Gossypol a cottonseed derivative it destroys semineferpous epithelium destroys semineferpous epithelium
AE Hypokalemia AE Hypokalemia Has been tried as an intravaginal Has been tried as an intravaginal
contraceptivecontraceptiveRisk of lack of normal near normal Risk of lack of normal near normal
reversibility of sperm amountsreversibility of sperm amounts