Drugs affecting reproductive system

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Basic Clinical Pharmacology
Drugs affecting reproductive system
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Drugs affecting male reproductive system

• Classification
• A. Androgens and antiandrogens
• 1. testosterone(?? )
• 2. methyltestosterone(???) orally effective
• 3. testosterone propionate (?????) most
  commonly used
• 4. mesterolone (?????,???)
• 5.fluoxymesterone(????)
• 6.testosterone phenyl-acetate(??????)
• 7.tristeronum compositum
• testosterone propionate 25mg
• estradiol benzoate(??????) 1.25mg
• progesterone 12.5mg,i.m
• B. Antiandrogens
• cyproterone(????,??????)
• C. Drugs used to treat erectile dysfunction
• sidenafil(????)

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A. Androgens and antiandrogens

• Androgens

Testosterone ??
Testosterone undecanoate ?????
Nandrolone phenylpropionate ?????
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A. Androgens and antiandrogens

• Pharmacological effects
• (1) Development of the male sexual apparatus and
  secondary sex characteristics
• (2) Necessary for normal spermatogenesis (????)
• (3) Increasing protein anabolism
• (4) Promoting growth of blood cells in bone
  marrow, especially for red blood cells (EPO ?)
• (5)Other effects immune regulation,
  antiinflammation effects,CVS effects

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A. Androgens and antiandrogens

• Clinical uses
• (1) Replacement therapy in men hypogonadism
• (2)Female disorders dysfunctional uterine
  bleeding, endometriosis (???????), advanced
  breast and ovarian cancers
• (3) Anemia aplastic or other anemia (largely
  replaced by recombinant erythropoietin )
• (4) Infirmity (????) anabolic steroids (????)
• (5) Others male contraception,
  osteoporosis(either alone or in conjunction with
  estrogens. Replaced by bisphosphonates) etc.

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A. Androgens and antiandrogens

• Adverse effects
• - due largely to their masculinizing actions
  and are most noticeable in women and prepubertal
  children.
• (1) Sex dysfunction
• virilisation in female(hirsutism, acne,
  amenorrhea, clitoral enlargement, and deepening
  of the voice, testosteronegt 200300 mg of per
  month)
• increased libido in male
• (2) Hepatic toxicity
• occurs early in the course of treatment, the
  degree is proportionate to the dose. bilirubin
  levels ?

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A. Androgens and antiandrogens

• Contraindications
• pregnant women, infants and young children
  (somatotropin is more appropriate to produce a
  growth spurt).
• male patients with carcinoma of the prostate or
  breast.
• renal or cardiac disease predisposed to edema
• Caution Several cases of hepatocellular
  carcinoma have been reported in patients with
  aplastic anemia treated with androgen anabolic
  therapy. Erythropoietin and colony-stimulating
  factors should be used instead.

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A. Androgens and antiandrogens

• Classic anabolic hormones
• Growth hormone
• IGF1 and other insulin-like growth factors
• Insulin
• Testosterone and analogs
• Estradiol

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Anabolic-androgen steroids (AAS)
A. Androgens and antiandrogens

• Drugs which mimic the effects of the male sex
  hormones testosterone and dihydrotestosterone.
• They increase protein synthesis within cells,
  which results in the buildup of cellular tissue
  (anabolism), especially in muscles.
• Anabolic steroids also have androgenic and
  virilizing properties, including the development
  and maintenance of masculine characteristics such
  as the growth of the vocal cords, testicles, and
  body hair (secondary sexual characteristics).

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Androgens Preparations Available and Relative
AndrogenicAnabolic Activity in Animals. Drug
Androgenic Anabolic Activity Testosterone
11 Testosterone cypionate 11 Testosterone
enanthate 11 Methyltestosterone
11 Fluoxymesterone 12 Oxymetholone
13 Oxandrolone 13113 Nandrolone decanoate
12.514
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A. Androgens and antiandrogens
Agents 1. Nandrolone phenpropionate(duraboli
n ,?????) 2. Nandrolonedecanoate(????) 3.
Metandienone (?????,???) 4. Danazol (???) 5.
Stanozolol(????)
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A. Androgens and antiandrogens
Antiandrogens
Cyproterone ????

• Antigonizing androgen receptor inhibiting
  hypothalamus-pituitary axis LH?, FSH?,
  testosterone?
• Used for treatment of prostatic cancer, severe
  acne and hersulism, and contraception

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A. Androgens and antiandrogens

• Adverse effects
• 1. Antiandrogenic action gynecomastia (breast
  growth), galactorrhea (milk outflow), and
  erectile dysfunction.
• 2.Liver toxicity high dose (200300 mg/day).
• 3. Increased risk of DVT ( in combination with
  ethinylestradiol )
• 4. Other reactions
• Depressive mood changes
• Suppression of adrenal function and reduced
  response to ACTH
• Osteoporosis- suppresses production of estrogen
  due to its antigonadotrophic effect

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A. Androgens and antiandrogens
Other antiandrogens

• 1.Other receptor Inhibitors
• Flutamide(????)
• Bicalutamide(????) nilutamide(????)
• Spironolactone
• 2. Steroid synthesis inhibitors-
• Ketoconazole(???)
• 3. Conversion of Steroid Precursors to Androgens
• Abiraterone(????) inhibitor of 17-hydroxylase
• Finasteride(????) inhibitor of 5 -reductase
• Dutasteride(????) similar to but much longer t1/2
  than finasteride

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B. Drugs used to treat erectile dysfunction

• Phosphodiesterase type 5 isoenzyme inhibitors
  (PDE5I)
• Sidenafil (????,???)
• Vardenafil (????,???)
• Tadalafil (????,???)

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B. Drugs used to treat erectile dysfunction
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B. Drugs used to treat erectile dysfunction
Sildenafil citrate(Viagra)

• Acts by inhibiting cGMP-specific PDE5, an enzyme
  that delay degradation of cGMP, which regulates
  blood flow in the penis
• The prime treatment for erectile dysfunction in
  all settings, including diabetes.

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B. Drugs used to treat erectile dysfunction
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B. Drugs used to treat erectile dysfunction

• Clinical uses
• (1) Sexual dysfunction
• (2) Pulmonary arterial hypertension (PAH)
• relaxes the arterial wall, leading to decreased
  pulmonary arterial resistance and
  pressure?workload of the right ventricle ?,
  symptoms of right-sided heart failure?
• acts selectively in the lungs and penis without
  inducing vasodilation in other areas of the body
  ?PDE-5 is primarily distributed within the
  arterial wall smooth muscle of the lungs and
  penis
• (3) Altitude sickness
• prevention and treatment of high-altitude
  pulmonary edema associated with altitude sickness
  -such as that suffered by mountain climbers.

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B. Drugs used to treat erectile dysfunction
Adverse effects 1.Headache, flushing, dyspepsia,
nasal congestion and impaired vision, including
photophobia and blurred (lead to vision
impairment in rare cases) - the most common
adverse effects 2. Priapism, severe
hypotension, myocardial infarction (heart
attack), ventricular arrhythmias, stroke,
increased intraocular pressure, and sudden
hearing loss -rare but serious
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B. Drugs used to treat erectile dysfunction

• Contraindications
• Administration of nitric oxide donors
• Recent stroke or heart attack, or in men for whom
  sexual intercourse is inadvisable due to
  cardiovascular risk factors
• Hypotension (low blood pressure)
• Severe hepatic/ renal function impairment
• Hereditary degenerative retinal disorders
  (including genetic disorders of retinal
  phosphodiesterases)

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• Further reading
• 1.Bertram G. Katzung, Susan B. Masters, Anthony
  J. Trevor
• Chapter 40. The Gonadal Hormones Inhibitors
• Basic and Clinical Pharmacology, 11e. 2010 The
  McGraw-Hill Companies.
• 2. http//www.ncbi.nlm.nih.gov/pubmedhealth/PMH000
  1046/