Pharm of Male Urogenital disorders

Question 1

Explain the MOA of degarelix

Answer 1

GnRH antagonist (receptor antagonist) – decrease FSh and LH release and thus decrease androgen and Testosterone that which prostate cancer cells needs to thrive. Upon degarelix injeciton, circulating T levels drop promptly after injection.

Question 2

what receptors do Leuprolide act on?

Answer 2

Leuprolide is an GnRH receptor agonist.

Question 3

What is the rational differences in the use of Leuprolide vs Degrarelix for prostate cancer?

Answer 3

Degarelix is an antagoist that which eventually decreases androgens. Studies have shwon that androgen deprivation therapy alone does not cure prostate cancer. Leuprolide is an agonist such that when given there is an initial surge of androgen. But the idea is that with continued administration of an GnRH agonist such as lueprolide, will desensitize receptors for GnRH and LH. With desensitization, the receptors will not be able to recognize GnRH when its released due to a deprivation of androgen.

Question 4

What are some off LHRH analogs available in the US?

Answer 4

Leuprolide, goserelin, triptorelin and histrelin

Question 5

Administration of leuprolide and related GnRH receptor agonists are associated with bone flares due to the surge of T initially. To avoid to this flare up, what can be given concomitantly?

Answer 5

Anti-androgens for a few weeks when starting treatment with leuprolide or related GnRH receptor agonists.

Such anti-androgen drugs include: Bicalotamide (qd), p.o.; Flutamide (tid, po); Nilutamide, (PO).

Nilutamide is an high end drug that is also cused in combo with surgical castration

Question 6

Explain the mechanism of Flutamide, Bilutamide and bicalutamide

Answer 6

They are non-steroidal anti androgens that compete with T and DHT for receptor thus AR dimerization, AR transport and transcription are all inhibited.

Question 7

Aside from using with leuprolide to suppress effects of residual adrenal testosterone or testoserone flare from GNRH agonist, what else can anti-androgens use approved for?

Answer 7

Palliative for metastic prostate cancer to reduce bone pain, better performance status increased sense of welling being

Question 8

Which anti-androgen used with leuprolide to suppress flare up is favored today?

Answer 8

Bicalutamide cuz it’s once a day tablet.

Question 9

GnRH antagonists and agonists halt androgen biosynthesis by testicles, but not other cells int he body. Prostate cancer cells can make small amounts and so can the adrenal gland. To deal with this issue, can drugs can be administered?

Answer 9

Abiraterone and ketoconazole

Question 10

What is the MOA for abiraterone and ketoconazole?

Answer 10

Blocks CYP17 (17a-hydroxylase/C17,20-lyase), in testicular, adrenal, and prostatic tumor tissues that is required for androgen biosynthesis.

Normally CYP17 catalazes two reactions: 1)conversion of pregnenolone and progesterone to their 17a-hydroxy derivatives and 2) formation of DHEA and androstenedione via C17,20lyase. These androgens are precursor of testosterone.

Question 11

Abiraterone and ketoconazole can’t be used alone and must be used with prednisone or other corticoids. why?

Answer 11

CYP17 working at the adrenals also blocks corticoid production, thus the corticoids must be replaced.

Question 12

Both ketoconazole and abiraterone work similarly to have the same affect. however, ketoconazole is not widely used due to it’s toxicity on _

Answer 12

hepatocytes. Causes significant hepatoxicity. it is not used at all if the pt doesn’t have a good performance status.

Question 13

Finasteride and Dutasteride are used to treat BPH which works by blocking SAR. Why can’t this be used to treat/prevent prostate cancer?

Answer 13

They do prevent tumor formations in 22% of the cases, but the problem is that those that do get the tumors present with much higher grade seen with the finasteride group in a randominzed study.

Question 14

Secondary hypogonadism leading to male infertility is associated with decreased secretion of the gonadotropins, LH and FSH, causing decreased testosterone secretion and sperm production. In this situation will testosterone replacement restore spermatogenesis?

Answer 14

NO. T replacement alone will not fix it. FSH and/or LH is also needed to correct infertility.

Question 15

_ is an analog of LH with an alpha subunit identical to LH, FSH and has a unique beta subunit. this alone may suffice for stimulation of spermatogenesis where FSH replacement is not effective.

Answer 15

HCG

Question 16

In the setting of secondary hypogonadism and infertility due to abuse of misuse of anabolic steroids can lead to distortion of estrogen synthesis where there is an abnormally elevated estrogen and diminished T and shrink the testes. What drugs can these abuse take to mask the effects of estrogen?

Answer 16

selective estrogen receptor modulator (SERM) such as clomiphene

Or aromatase inhibitors such as anastrazole and letrazole

In sports, they runs tests to check for levels of these drugs that mask abuse.

Question 17

_ is a SERM used for enhanced recovery of testosterone production after anabolic steroid cycles

Answer 17

Clomiphene

Question 18

Clomiphene is an _ antagonists

Answer 18

estradiol

Question 19

Explain the pharmacology of clomiphene

Answer 19

Clomiphene a SERM ocupies binding sites of estrogen receptors of cells without activating them it trisk the hypothalamus to conclude that estrogen levels are low. If androgen levels are not elevated, as they shouldn’t be after an anabolic steroid cycle, the hypothalamus is then stimulated to produce LHRH. This will act to increase LH and restart natural testosterone production.

Question 20

A 75-year-old male is diagnosed with advanced metastatic prostate cancer. After further evaluation and staging, the patient is started on flutamide therapy. Addition of which of the following medications to this patient’s medication regimen would be of greatest benefit in the treatment of this patient’s condition?

1. Leuprolide
2. Anastrozole
3. Clomiphene
4. Tamoxifen
5. Cyproterone

Answer 20

1. Leuprolide

Flutamide is a non-steroidal antiandrogen that acts as a competitive inhibitor at testosterone receptors. It is used in combination with a GnRH agonist, such as leuprolide, in the treatment of advanced prostate cancer.

Question 21

A 57-year-old presents to your clinic complaining of baldness. He is overweight, has been diagnosed with BPH, and is currently taking atorvastatin for hyperlipidemia. The patient has tried several over-the-counter products for hair-loss; however, none have been effective. After discussing several options, the patient is prescribed a medication to treat his baldness that has the additional benefit of treating symptoms of BPH as well. Synthesis of which of the following compounds would be expected to decrease in response to this therapy?

1. GnRH
2. DHT
3. LH
4. Testosterone
5. FSH

Answer 21

2. DHT

Finasteride is a 5-alpha-reductase inhibitor that decreases the peripheral reduction of androgens, specifically suppressing the conversion of testosterone to dihydrotestosterone (DHT). It is commonly used to treat both male-pattern baldness (androgenetic alopecia) and benign prostatic hyperplasia (BPH; associated symptoms include increasing urinary frequency, urinary dribbling, and nocturia).

Question 22

A 19-year-old South Asian male presents to the family physician concerned that he is beginning to go bald. He is especially troubled because his father and grandfather “went completely bald by the age of 25,” and he is willing to try anything to prevent his hair loss. The family physician prescribes a medication that prevents the conversion of testosterone to dihydrotestosterone. Which of the following enzymes is inhibited by this medication?

1. Desmolase
2. Aromatase
3. 5-alpha-reductase
4. cGMP phosophodiesterase
5. Cyclooxygenase 2

Answer 22

3. 5-alpha - reductase

The patient is concerned that he may be going bald; therefore, the physician prescribes finasteride, which inhibits the enzyme 5-alpha-reductase.

Question 23

A 46-year-old female presents with a primary complaint of irregular menstrual bleeding that has persisted for the last several months. Her medical history consists of 2 full-term pregnancies and invasive ductal carcinoma of the breast that was successfully treated one year ago. After an appropriate evaluation, she is given a diagnosis of type 1 endometrioid adenocarcinoma. Which of the following factors most likely increased this patient’s risk for developing this cancer?

1. Administration of raloxifene in the treatment of her previous breast cancer
2. The patient is 46-years-old and has yet to enter menopause
3. Combined oral contraceptive use from the age of 32 to 42
4. The patient’s two previous pregnancies
5. Tamoxifen regimen used to treat her previous breast cancer

Answer 23

5. Tamoxifen regimen used to treat her previous breast cancer

Tamoxifen is a selective estrogen receptor modulator (SERM) used in the treatment of estrogen receptor positive breast cancer. It has a stimulatory effect on the endometrium, leading to an increased risk of developing endometrial hyperplasia and eventually endometrial carcinoma.

Question 24

A 57-year-old male presents with a primary complaint of erectile dysfunction. After proper evaluation, the patient is started on daily administration of sildenafil. This medication directly causes accumulation of which of the following intracellular mediators?

1. Ca2+
2. cGMP
3. AMP
4. NO
5. ANP

Answer 24

2. cGMP

Sildenafil is a selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5). Inhibition of this enzyme leads to a reduction in cGMP degradation and, therefore, an accumulation of cGMP.