Pharmacology of Androgens Flashcards
1
Q
Major Male Androgens
A
- Testosterone
- Androstenedione
- Dehydroepiandrosterone (DHEA)
2
Q
Androgen Biochemical Synthesis Graph
A
3
Q
Organs that produce androgens
A
- Testis
*Leydig cells
- Adrenal glands
- Ovary
*theca cells
4
Q
Cytochrome P450 role in testosterone production
A
- Progesterone is converted to androstenedione by cytochrome P450
5
Q
Testosterone metabolization product
A
- 5-alpha dihydrotestosterone (DHT) in prostate
*the end product; the form of testosterone this will actually make changes occur
- Unchanged in onther tissues
*muscle
*kidney
6
Q
DHT Synthesis
A
- Dihydrotestosterone; Androstanolone
- Most potent androgen required for sex development
- Synthesized from testosterone in the prostate gland, testes, hair follicles and adrenal glands by 5-alpha reductase
7
Q
Androgens production is regulated by
A
- Luteinizing Hormone (LH)
*LH synthesized by anterior pituitary
- Leydig cells contain receptors for LH
8
Q
Hormonal Control of Testicular Function Graph
A
9
Q
Androgen Release Process
A
10
Q
Sertoli Cells are primarily regulated by what hormone?
A
- FSH
11
Q
Sertoli Cells factors released
A
- Release androgen-binding (transferrin) and inhibin
12
Q
Adrenal glands secrete
A
- Dehydroepiandrosterone
- Androstenedione
- Testosterone
13
Q
Adrenocorticotropin stimulates adrenal to secrete
A
- Cortisol
- Sex steroids
14
Q
Sex Hormone Binding Globulin (SHBG)
A
- Serum glycoprotein
*88,000 daltons
- Derived from liver
- Strong binding of testosterone
15
Q
Sex Hormone Binding Globulin (SHBG) is increased by
A
- Estrogens
*females 2-3x more than males
- Thyroxine
16
Q
Sex Hormone Binding Globulin decreased by
A
- Androgens
- Growth hormone
- Insulin
17
Q
Androgens Pharmacological Actions
A
- Stimulates production of sperm
- Erythropoiesis
- Pos. nitrogen balance
- Growth/development of:
*hair
*bone
*muscle
18
Q
Testosterone Injections
A
Intramuscular injections
- Cypionate
*DEPO-testost.
- Enanthate
*Delatestryl
- Propinate
19
Q
Androgen Products (Drugs)
A
- Fluoxymesterone (Halotestin)
- Oxandrolone (Anavar)
- Oxymetholone (Anadrol)
- Methyltestost. (Metandren)
- Nandrolone (Durabolin)
20
Q
Anabolic Steroids Effects
A
- Synthetic derivatives of testost.
- Anabolic action > Androgenic
- Increases:
*muscle mass
*physical performance
*linear growth: children
21
Q
Anabolic Steroids
A
- Anabolic action > Androgenic
- Oxandrolone
- Oxymetholone
- Stanozolol
22
Q
Androgens Therapeutical Uses
A
- Primary testicular failure
*Increases expression of secondary sex characteristics
*does not fix infertility
- Secondary testicular failure
*insufficient stimulation of testes by pituitary gonadotropins
*hypogonadotropic hypogonadism
- Short children and teenagers to increase height
- Aplastic anemia
*erythropoiesis
- Inoperable breast cancer
- Postpartum:
*breat pain
*engorgement
- Malnutrition
23
Q
Androgen Therapy for short children/teenagers
A
- Controversial
- Role of androgens not completely established
- ADRs
*premature closure of epiphyseal plates
*virilization
- Preferable combined w/ growth hormone
24
Q
Danazol (Danocrine)
A
- Weak androgen
- Treatment of:
*endometriosis
*fibrocystic breast disease
*PMS
25
Androgens ADRs
Usually dose-related
- Priapism
- Suppression of gonadotropin
- Gynecomastia
- Decreased size of testis and spermatogenesis
- Weight gain
- Na+ retention (edema, hypertension)
- Decreased HDLs (possible atherogenesis)
- Hepatotoxic (jaundice, peliosis hepatitis, hepatocellular carcinoma)
26
Androgens specific ADRs in females
- Virilization (discontinue when appears since it may become irreversible)
- Pregnancy category X
27
Anabolic drugs ADRs
All the same ADRs as androgens as well as...
- Benign prostatic hyperplasia
- Prostatic cancer
- Increased risk of atheroslcerosis and peliosis hepatitis
- Acne conglobata
- Atherosclerosis and CV pathology
\*case where a male abuser had to have legs amputated due to severe atherosclerotic development
28
Acne Conglobata
- Development of acne on the chest of anabolic steroid abusers
- Can become very severe w/ lesions that include pauples, pustules, abscesses and deep ulcerations
- Can be treated
29
Androgens Contraindications
- Male:
\*breast carcinoma
\*prostate carcinoma
- Female:
\*pregnancy (known/suspected)
- All pts:
\*serious cardiac, hepatic or renal disease
30
Anti-androgens MOA
- Suppress synthesis of androgen or blockade of androgen receptors
31
Gonadotropin Releasing Hormone (GnRH) Agonist Analogues
- Suppress synthesis of androgen by stimulating feedback inhibition
- Goserelin
- Leuprolide
- Naferelin
32
GnRH Agonist Analogues Therapeutic Uses
- Primarily used to treat men w/ prostate cancer
33
GnRH Agonist Analogues ADRs
- Assoc. w/ small inc. risk for diabetes, heart attack, stroke, and sudden death
- May cause initial inc. in testosterone lvls
34
Leuprolide
- Synthetic non-peptide analog of naturally occurring GnRH
- Overstimulates production of androgens resulting in activation of neg. feedback resulting in dec. testosterone produciton
- Inc. in testosterone lvls at start of treatment may produce new or worsening symptoms for a few wks
35
Leuprolide Therapeutic Uses
- Men: treat symptoms of prostate cancer; not the cancer itself
- Women: treat symptoms of endometriosis (Pregnancy category X)
- Children: treat precocious puberty
36
Goserelin Acetate Implant (Zoladex)
- Anti-androgen
- Suppresses synthesis of androgen
- Synthetic decapeptide analogue of LH releasing hormone (LHRH)
- Also known as a GnRH agonist analogue
37
Goserelin Acetate Implant Therapeutic Uses
- Treatment of advanced prostatic carcinoma
38
Nafarelin
- Anti-androgen
- Suppresses synthesis of androgen
- Nasal spray
- Powerful stimulant (agonist) analogue of GnRH
- Stimulates release of the pituitary gonadotrophins, LH, and FSH
- Initial inc. of gonadal steroidogenesis
- At 4wks dec. gonadal steroidogenesis
39
Nafarelin Therapeutic Uses
- For hormonal management of endometriosis, including pain relief and reduction of endometric lesions
40
Degarelix
- Anti-androgen
- Suppress synthesis of androgens
- LHRH antagonist
- Compared to LHRH agonists it dec. testosterone lvls more rapidly and no tumor flare
41
Ketoconazole
- Anti-androgen
- Suppresses synthesis of androgen
- Decreases cytochrome P450 in testicular microsomes
- Dec. 17-hydroxylation of progesterone or pregnenolone
- Less selective for fungal P450 than newer azoles/systemic ketoconazole rarely used as antifungal
42
Ketoconazole ADRs
- Gynecomastia
- Impotence/oligospermia \>400mg/day
- Can block production of cortisol - may need to add corticosteroids (prednisone, hydrocortisone)
43
Finasteride
- Anti-androgen
- Suppress synthesis of androgen
- Steroid-like inhibitor of 5alpha-reductase
- Orally active; t1/2 = ~8hrs (longer in elderly pts.)
- Dec. dihydrotestosterone lvls within 8hrs
- Duration: 24hrs
- 40-50% metabolized
44
Dutasteride
- Anti-androgen
- Suppresses synthesis of androgen
- Steroid-like inhibitor of 5alpha-reductase
- Slow onset of action
- t1/2 \> finasteride
45
Abiraterone
- Anti-androgen
- Suppresses synthesis of androgen
- Blocks CYP17
- Dec. testicle production of androgens
- Other cells including prostate cancer cells can still produce small amts. = cancer growth
46
Flutamide
- Anti-androgen
- Blockade of androgen receptor
- Nonsteroidal
47
Flutamide Therapeutic Uses
- Used w/ LHRH agonists in Tx of prostatic and metastatic carcinoma
48
Flutamide ADRs
- Hepatic injury
- Not recommended when ALT \> 2x ULN
49
Enzalutamide
- Anti-androgen
- Blocks signals from androgens to cells for growth and division
