Androgens & Male Gu Drugs

Front 1

What two drugs are androgen receptor antagonists?

Back 1

1. Bicalutamide
2. Flutamide

Front 2

What is the MOA of Bicalutamide & Flutamide?

Back 2

Competitively block androgen receptors

Front 3

What is the effect of Bicalutamide blocking androgen receptors in the Hypothalamus?

Back 3

Lose feedback inhibition

Plasma LH & Testosterone are increased markedly

Increase in plasma Testosterone limits the anti-androgenic effects of Bicalutamide

GnRH analog is given w/ Bicalutamide in order to treat prostatic carcinoma

Front 4

Why is Bicalutamide preferred over Flutamide?

Back 4

1. Less hepatic toxicity
2. Can be taken once a day

Front 5

What is the MOA of Spironolactone & its therapeutic use?

Back 5

MOA: competitive antagonist of Aldosterone receptors; partial agonist at androgen, estrogen, and progesterone receptors

Also partially inhibits CYP17 which synthesizes testosterone

Use: treat Hirsutism in females

Front 6

What drugs are GnRH analogs?

Back 6

1. Leuprolide
2. Goserelin

Front 7

How are Leuprolide & Goserelin administered?

Back 7

Leuprolide: 3-4 mth. depot prep for i.m. injection

Goserelin: i.m. implant that lasts 3 months

Front 8

What is the MOA of the GnRH analogs?

Back 8

Initially stimulate the release of FSH & LH in males & females; plasma Testosterone initially rises in males

Continuous stimulation of GnRH receptors (non-pulsatile stimulation) leads to downregulation

Leads to decreased secretion of LH

Plasma Testosterone is suppressed to about 10% of normal values w/ in two weeks

Front 9

What are the medical uses of the GnRH analogs?

Back 9

Prostatic carcinoma--initial increase in plasma Testosterone can cause a flare-up of prostatic tumor activity and symptoms (such as bone pain from mestastases)

Endometriosis/Uterine fibroid tumors

Central precocious puberty

Front 10

What drug is given w/ GnRH analogs to prevent the effects of the initial increase in plasma Testosterone and resulting flare-up of prostate tumor activity?

Back 10

Bicalutamide

Front 11

What are the adverse effects of Leuprolide & Goserelin?

Back 11

1. hot flashes & sweating
2. edema
3. gynecomastia
4. decreased libido

Front 12

What drugs are a1-adrenoreceptor antagonists?

Back 12

1. Doxazosin
2. Terazosin
3. Tamsulosin

Front 13

What is the MOA of Doxazosin & Tamsulosin?

Back 13

Alpha-1 antagonists

Receptors are found in the smooth muscle of the prostate, prostatic capsule, prostatic urethra, and bladder neck

(70% of these receptors are alpha-1A subtype)

Pharmacologic blockade of these receptors causes relaxation of this smooth muscle resulting in decreases urethral resistance to flow

Patient has a more rapid initiation of urination, greater peak flow rate, more complete bladder emptying

Front 14

Doxazosin & Terazosin improve the symptoms of urgency, hesitancy, weak stream & nocturia within __________

Back 14

2 weeks

*some pts. obtain almost immediate relief

Front 15

Terazosin & Doxazosin produce identical therapeutic effects and side effects. ____________ has a half life of 22 h whereas _____________ has a half life of 12 h

Back 15

1. Doxazosin
2. Terazosin

Front 16

Doxazosin & Terazosin are efficacious for treating both ____________ & ___________ in the same patient.

Back 16

1. Hypertension
2. BPH

Front 17

What are the adverse effects of Doxazosin?

Back 17

"PIS PAD"

Postural hypotension
Impotence (failure to ejaculate)
Somnolence

Peripheral edema
Asthenia (fatigue)
Dizziness

Front 18

What is are the benefits of Tamsulosin over Doxazosin? What are the cons of Tamsulosin over Doxazosin?

Back 18

Benefits: less dizziness & orthostatic hypotension

Cons: increased incidence of ejaculatory dysfunction due to increased receptor selectivity for alpha1a-adrenoreceptors

Front 19

What does ejaculatory dysfunction consist of?

Back 19

1. Failure to ejaculate
2. Decreased volume of ejaculation
3. Retrograde ejaculation

Front 20

What enzyme converts testosterone to dihydrotestosterone?

Back 20

5alpha-reductase

Front 21

Where are the type 1 & type 2 forms of 5-alpha-reductase found?

Back 21

type 1: liver & skin

type 2: prostate

Front 22

What is the MOA of Finasteride?

Back 22

Selectively inhibits type 2 5-alpha-reductase enzyme

Plasma DHT concentration falls by 70% & plasma testosterone concentration rises by 10%

Concentration of DHT within the prostate gland decreases by more than 70%

Plasma LH is not changed

Front 23

What is the MOA of Dutasteride?

Back 23

Inhibits both type1 & type 2 forms of 5-alpha-reductase

Front 24

A dose of ___ mg of __________ ( Finasteride/Dutasteride) is necessary for a clinical effect to be seen in patients w/ BPH

Back 24

1. 5
2. Proscar

Front 25

What are the clinical effects seen in patients w/ BPH treated with Finasteride/Dutasteride?

Back 25

Decrease in size of prostate gland is noted by 3 months; shrinkage continues for the next 1-2 years

Average reduction in size of the prostate gland is 25%; shrinkage is associated w/ a decrease in the symptoms of BPH

Decrease in size is maintained as long as the patient continues to take Finasteride or Dutasteride

The larger the prostate, the greater the response

Front 26

Treatment with a 5-alpha-reductase inhibitors decreases the need for a ________ or a ________.

Back 26

1. TURP
2. TUNA(town)

Front 27

To treat male pattern baldness, you would give ___ mg of _________ (Finasteride/Dutasteride).

Back 27

1. 1
2. Propecia

*inhibition of 5-alpha-reductase in hair follicles can prevent hair loss

Front 28

What are the adverse effects of Finasteride/Dutasteride?

Back 28

1. Impotence
2. Decreased libido
3. Suppression of plasma concentration of PSA

Front 29

Finasteride given at ____ mg p.o. does not suppress the PSA whereas a ____ mg does given p.o. suppresses the plasma concentration of PSA by up to 50%?

Back 29

1. 1
2. 5

*Dutasteride suppresses the serum PSA by 50% also

Front 30

What must you do one year after beginning treatment of BPH with a 5-alpha-reductase inhibitor?

Back 30

Obtain a new baseline PSA

Front 31

What drug is used for the treatment of voiding dysfunction (nocturnal enuresis in children & adults)?

Back 31

DDAVP aka Desmopressin

Front 32

DDAVP is a long-acting synthetic analog of:

Back 32

AVP = ADH

Front 33

What is the duration of action of DDAVP?

Back 33

6-20 h

Front 34

What is DDAVPs ratio of V2:V1 receptor activity? What is the significance of this ratio?

Back 34

4000:1

Drug is selective for the V2 receptor found in Principal Cells of the late distal tubule & collecting duct

Front 35

What is the route of administration of DDAVP?

Back 35

Nasal spray given before bedtime

*pts w/ allergic rhinitis or nasal congestion may have slow absorption

Front 36

What is the mechanism of DDAVP?

Back 36

Enhances the renal reabsorption of water & thus decreases urinary volume

Front 37

Impotence can result from the inability to achieve an _________ or the inability to __________.

Back 37

1. Erection

2. Ejaculate

Front 38

What are some organic causes of ED?

Back 38

"SAD PAs"

Spinal cord injury
Atherosclerosis
Diabetes mellitus

Prostatectomy
Antidepressant drugs (SSRIs)
Smoking

Front 39

Erectile dysfunction exists in _______ of men worldwide.

Back 39

10-20%

Front 40

What are three pharmacological interventions allowing penile smooth muscle to relax and an erection to be achieved?

Back 40

Inhibition of type 5 phosphodiesterase

Blockade of alpha-1-adrenoceptors

Stimulation of PGE1 receptors

Front 41

What is the MOA of Alprostadil?

Back 41

PGE1 receptor agonist

Front 42

What are the routes of administration of Alprostadil?

Back 42

1. Injection into corpus cavernosa--method no longer used

2. Topical (urethral suppository; cream)

Front 43

When would the use of Alprostadil be indicated?

Back 43

Patients who do not respond to Sildenafil

Front 44

What drugs are selective PDEase5 inhibitors?

Back 44

1. Sildenafil
2. Vardenafil
3. Tadaladil

Front 45

What is the MOA of the selective PDEase5 inhibitors?

Back 45

Prevents the degradation of cGMP by PDEase5

Increased cGMP activates cGMP protein kinase which phosphorylates MLC phosphatase

MLC phosphatase dephorphorylates MLC resulting in relaxation of the SM in the corpus cavernosa

Front 46

How long does it take for Sildeanfil, Vardenafil, Tadalafil to produce an erection & how long does the drug act for?

Back 46

Sildenafil: 30-60 minutes; 4-5 h

Vardenafil: 60 minutes; 4-5 h

Tadalafil: 30-45 minutes; acts for 24h (TADA!!!)

Front 47

Sildenafil taken one hour before sexual activity produces an erection that lasts ____ to ____.

Back 47

30 minutes to 2 hours

Front 48

What are the adverse effects of PDEase5 inhibitors?

Back 48

1. Smurf vision and impairment of blue-green color discrimination--due to partial blockade of PDEase type 6 in the cones of the retina

2. non-arteritic ischemic optic neuropathy (NAION) which results from decreased blood flow to the optic nerve--rare S/E. but can result in the permanent loss of vision in affected eye

3. Headache & flushing

Front 49

Do not use any _________ in any form in the presence of an inhibitor of PDEase type 5 b/c this can result in severe hypotension which in turn precipitates chest pain, MI, or ischemic stroke.

Back 49

Nitrate

Front 50

Do not used inhibitors of PDEase 5 in patients taking ___________ & ___________. However, the inhibitors of PDEase type 5 can be used in patients taking _____________ b/c this drug has little effect to lower BP

Back 50

1. Terazosin / Doxazosin

2. Tamsulosin