B.14

Question 1

Androgens, anabolic steroids, antiandrogens. Agents affecting the sexual activity

Answer 1

1. Androgens: Testosterone-undecanoate
2. Anabolic steroids: Nandrolone
3. Antiandrogens: Bicalutamide, Finasteride
4. Agents affecting sexual activity: Sildenafil
5. GnRH agonist: Goserelin
6. GnRH antagonist: Degarelix

Question 2

Adverse effects of androgens and related steroids

Answer 2

• Masculinizing action in women and children
• Some androgens with progestational activity →increased cardiovascular risk, endometrial bleeding upon discontinuation in women
• Na+ retention → edema
• C-17-alkyl-substituted steroids (most anabolic agents) → Hepatic dysfunction (AST, bilirubin, cholestasis, hepatic tumors)
• older men- prostate hyperplasia

Question 3

Progestational effects

Answer 3

the progestin stimulates the progesterone-Rs (thereby helping to prevent ovulation and to lessen menstrual bleeding)

Question 4

Testosterone-undecanoate

Answer 4

MOA: Testosterone analog→ binds its receptor and activates it;
Kinetics: p.o adm.;
IND: androgen replacement (→hypogonadism in men, after castration);
SEs: masculinizing action in women and children (hirsutism, acne, deep voice etc.), older men-prostate hyperplasia, hepatic dysfunction (AST, bilirubin, cholestasis, hepatic tumors);
Contra-IND: pregnancy, prostate cancer, infants and young children, breast cancer in males

Question 5

Bicalutamide

Answer 5

MOA: strong and pure androgen-R antagonist;
IND: treatment of metastatic prostate cancer;
Kinetics: p.o adm., good absorption, ↑PPB, hepatic metabolism (partly glucoronidaiton, partly oxidation)

Question 6

Finasteride

Answer 6

MOA: 5α-reductase (type II) competitive inhibitor (→↓serum DHT) ;
IND: Moderately effective in reducing prostate size in men with BPH (symptomatic), may be useful in male baldness and female hirsutism;
Kinetics: p.o adm., ↑PPB, hepatic metabolism (CYP3A4), urine/fecal excretion

Question 7

Goserelin

Answer 7

MOA: GnRH agonist (continuous exogenous GnRH→ GnRH-R downregulation→ Inhibition of pituitary-gonadal axis);
IND: hormone-dependent tumors (prostate, breast), Endometriosis, Preterm puberty, Assisted fetilization (→stopping pituitary function) during the preparation, Diagnostics (LH, FSH procuction capacity), Hormone replacement (hypothalamic hypogonadism, Kallmann sy.);
SEs: at the beginning of administration it can transiently worsen certain symptoms (i.e. pain from bone metastasis), secondary amenorrhea, reduced libido, erectile dysfunction, hypogonadism, hot flashes, osteoporosis

Question 8

Degarelix

Answer 8

MOA: GnRH antagonist;
IND: Advanced hormone-dependent prostate cancer; SEs: erectile dysfunction, glucose tolerance↓, osteoporosis, QT↑, increased cardiovascular risk

Question 9

Sildenafil

Answer 9

MOA: PDE5 (+6) inhibitor (→↑cGMP→vasodilation); Kinetics: p.o adm., hepatic metabolism (CYP3A4), excreted with feces;
IND: Pulmonary hypertension, erectile dysfunction;
SEs: headache, dizziness, color vision disturbances (PDE6 mediated), insomnia, hypotension (especially if combined with other vasodilators!), QT↑, epistaxis, dyspepsia, diarrhea, muscle pain;
Contra-IND: co-adm. with organic nitrates, severe cardiovascular disease, unilateral vision loss, severe liver damage, hypotension, history of stroke/MI, hereditary retinal degeneration

Question 10

Nandrolone

Answer 10

MOA: anabolic steroid;
IND: increases bone density and muscle mass in patients with osteoporosis

Question 11

Antiandrogens Steroid synthesis inhibitors:

Answer 11

1. Ketoconazole: MOA: inhibits adrenal and gonadal steroid synthesis + antifungal drug (C14-α-demethylase inhibitor);
   IND: Clinical trials in hirsutism (women) and prostate cancer;
   SEs: sexual disturbances during antifungal treatment
2. Abiraterone: MOA: 17-hydroxylase inhibitor;
   IND: Treatment of prostate cancer

Question 12

Antiandrogens

Answer 12

1. Androgenic suppression with GnRH-analogs
2. Steroid synthesis inhibitors
3. 5α-reductase inhibitors
4. Androgen-R antagonists

Question 13

Testosterone

Answer 13

• Intracellular receptor: gene activation
• Kinetics: good absorption, low BAp.o (first pass metabolism); ROA: injection/ T.d use; Testosterone-undecanoate →also p.o adm.
• Pharmacological actions: androgenic and anabolic effects
  
  • In young men: development of secondary sex characteristics
  • In adult women: facial and body hair, deeping of the voice, enlargement of clitoris, frontal baldness
  • In adult men: maintenance of libido, spermatogenesis
  • Anabolic effects: reduced nitrogen excretion, increased protein synthesis, decreased proteolysis (more pronounced in women and children