EXAM #5: ANDROGENS, ANTIANDROGENS, ED Flashcards Preview

Pharmacology > EXAM #5: ANDROGENS, ANTIANDROGENS, ED > Flashcards

Flashcards in EXAM #5: ANDROGENS, ANTIANDROGENS, ED Deck (47):
1

Where is Testosterone synthesized?

1) Leydig cells of the Testes (de novo)
2) Adrenal cortex (low potency androgens that get converted)

2

What does the hypothalamus produce in the synthetic pathway of the androgens?

GnRH

3

What does they pituitary produce in the synthetic pathway of the androgens?

LH and FSH

4

What is the function of LH?

1) LH binds Leydig cells in testes
2) Induces the production and secretion of testosterone
3) Testosterone diffuses into the Sertoli cells

5

What is the function of Testosterone in the Sertoli cells?

Stimulation of spermatogenesis

6

What is the function of FSH?

- Induces the synthesis of Androgen Binding Protein (ABP) by Sertoli cells
- ABP concentrates Testosterone at the site of spermatogenesis in the Sertoli cells

7

Describe Testosterone's feedback in the HPA axis.

Testosterone directly inhibits:
1) LSH and FSH from pituitary
2) GnRH from hypothalamus

8

What is the function of 17a-hydroxylase in the synthesis of the androgens?

Converts androstenedione to testosterone

9

What is the function of 5a-reductase in the synthesis of androgens?

Converts testosterone to DHT

*Note that DHT will inhibit the secretion of GnRH and LH

10

What are the two general effects of the androgens?

1) Androgenic
2) Metabolic effects

11

What are the "androgenic" effects of the androgens?

- Growth/ development of male reproductive tract
- Male secondary sex characteristics

12

What are the metabolic effects of the androgens?

Actions on non-reproductive tissue e.g.
- Muscle growth
- Liver production of serum proteins
- Kidney, stimulates EPO
- Bone growth
- Bone marrow stem cell production

13

What are the three therapeutic androgen preparations?

Methyltestosterone
Testosterone enanthate
Testosterone

14

What is the problem with oral Testosterone? How is this combated?

Low bioavailability b/c it undergoes extensive first pass metabolism

*Administered topically in a gel or transdermal patch*

15

Structurally, how does Testosterone Enanthate differ from Testosterone?

Fatty acid conjugated to Testosterone via an ESTER bond

16

How is Testosterone Enanthate administered?

Dissolved in oil and administered IM

17

What is the colloquial name for 17-alkylated derivatives of Testosterone?

Anabolic steroids

*This was an attempt to make a drug with METABOLIC effects and without androgenic effects*

18

What is the hallmark 17-alkyated testosterone derivative?

Methyltestosterone

19

How is Methyltestosterone administered?

Orally, undergoes less first pass metabolism than Testosterone

20

What adverse effects are associated with androgen therapy?

- Reduction in spermatogenesis and testis size
- Acne
- Polycythemia
- Prostatic enlargement
- Na+/ H20 retention--> HTN
- Increased LDL and decrease HDL-->atherosclerosis
- Mood swings, depression, aggression

21

What is the theraputic use of antiandrogens in females?

Hirsutism

22

What are the therapeutic uses for antiandrogens in males?

1) Percocious puberty
2) BPH
3) Prostate cancer
4) Alopecia

23

What are the androgen receptors antagonists?

Flutamide and Biclatumide

24

What is the MOA of the androgen receptor antagonists?

Competitive antagonists of the androgen receptor

25

What is the clinical indication for the androgen receptor antagonists?

Prostate cancer

26

What toxicities are associated with the androgen receptor antagonists?

- Gynecomastia
- Mild liver toxicity

27

What drugs are commonly added to Flutamide and Biclatumide therapy? Why?

Androgen receptor blockade increases LH secretion from the pituitary gland; thus, increase Testosterone

*Given with a GnRH analog*

28

What is the MOA of Enzalutamide?

Competitive androgen receptor antagonist that ALSO:
1) Inhibits nuclear translocation of the androgen receptor
2) Blocks DNA binding
3) Blocks transcriptional coactivator recruitment

29

List the GnRH agonists.

Leuprolide
Goserelin

30

What are the clinical indications for GnRH agonists?

Prostate cancer

31

What is the MOA of the GnRH agonists?

Constantly elevated GnRH:
1) Desesitizes receptors on pituitary gonadotrophs
2) Decreases LH production and secretion
3) Decreases Testosterone

32

What is the major adverse effect of GnRH agonists in the treatment of prostate cancer?

Testosterone surge that can cause growth of the cancer

33

How is the Testosterone surge with GnRH agonists prevented in the treatment of prostate cancer?

AR receptor antagonist coadministration (Flutamide or Bicalutamide)

34

What is the hallmark GnRH antagonist?

Degarelix

35

What are the advantages of Degarelix in the treatment of prostate cancer?

1) Faster onset
2) No LH/ Testosterone surge

36

What class of drug is Abiraterone?

Androgen biosynthetic inhibitor

37

What is the clinical indication for Abiraterone?

Metastatic prostate cancer

38

What is the MOA of Abiraterone?

Inhibits 17a-hydroxylase

39

List the 5a-reductase inhibitors.

Finasteride
Dutasteride

40

What are the clinical indications for 5a-reductase inhibitors?

BPH
Alopecia

41

How do 5a-reductase inhibitors treat alopecia?

- High DHT is thought to cause alopecia by inducing apoptosis of dermal papilla
- 5a-reductase inhibitors prevent formation of DHT from Testosterone

42

What are the adverse effects associated with the 5a-reductase inhibitors?

1) Impotence
2) Gynecomastia
3) LOWER PSA levels leading to FALSE NEGATIVE testing

43

What is the function of PDE-5 in the penile erection?

Converts cGMP to 5'GMP

*cGMP is needed for smooth muscle relaxation and erection*

44

List the PDE-5 inhibitors. What are these drugs clinically indicated for?

Sildenafil
Vardenafil
Tadalafil

1) ED
2) Pulmonary arterial HTN

45

How does Tadalafil differ from SIldenafil and Vardenafil?

- Double the time to peak concentration
- Half-life of 18 hours

46

What is a contraindication of PDE-5 inhibitors?

HIV protease inhibitors and Nitrates (can lead to hypotension)

*CYP 3A4 effects INCREASE efficacy of PDE-5

47

What adverse effects are associated with PDE-5 inhibitors?

1) Cardiac events
2) Priapism
3) Sudden vision loss (blood flow to optic nerve blocked)

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