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Reproductive II - Exam 2 > Drugs for male GU disorders and Urinary Incontinence - (Martin) SRS > Flashcards

Drugs for male GU disorders and Urinary Incontinence - (Martin) SRS Flashcards

1
Q

Tell me what the Gonadotropin-releasing hormone analogs are. one bold

A
  1. Leuprolide (prototype)
  2. Gonadorelin, goserelin, histrelin, nafarelin, triptorelin
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2
Q

What do the Gonadotropin-releasing hormone antagonists end in?

A
  • relix
    1. Abarelix, cetrorelix, degarelix, ganirelix
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3
Q

What are the two categories of

A
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4
Q

What are the Androgen receptor inhibitors We need to know?

one prototype

A
  1. Cyproterone
  2. Flutamide
  3. Bicalutamide
  4. Nilutamide
  5. Spironolactone
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5
Q

What are the 5α-reductase inhibitors we need to know? 2 both bold

A
  1. Finasteride
  2. Dutasteride
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6
Q

What categories of drugs are used for BPH?

A
  1. 5α-reductase inhibitors (see above)
  2. α-adrenergic antagonists
  3. Saw palmetto
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7
Q

What are the alpha adrenergic antagonists used for BPH? 6, all bold

A
  1. Prazosin (prototype α1-selective antagonist)
  2. Terazosin
  3. Doxazosin
  4. Alfuzosin
  5. Tamsulosin
  6. Silodosin
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8
Q

What are the two categories of drugs used for ED?

A
  1. PDE-5 inhibitors
  2. Alprostadil
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9
Q

What are the PDE-5 inhibitors used in the tx of ED? 2 bold five tots

A
  1. Sildenafil [Viagra]
  2. Tadalafil [Cialis]
  3. Vardenafil [Levitra, Staxyn]
  4. Avanafil [Stendra]
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10
Q

What are the drugs used to urinary incontinence? one bold and 5 otherss

A
  1. Darifenacin
  2. Fesoterodine
  3. Oxybutynin
  4. Solifenacin
  5. Tolterodine
  6. Trospium
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11
Q

In Leydig cells, the 11 and 21 hydroxylases (present in adrenal cortex) are absent but what is present?

A

CYP17 (17 -hydroxylase)

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12
Q
  1. Conversion of testosterone to estradiol by aromatase occurs primarily in the liver and adipose tissue and is executed by what enzyme?
A
  1. CYP19 P450 aromatase
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13
Q

ADRs of androgens include masculinizing actions (most noticeable in women and prepubertal children) although rare, sodium retention and edema are more common in patients with heart and kidney disease. What impact may they have on the liver?

A
  1. Many synthetic androgens cause hepatic dysfunction
    1. Often occurs early in the course of treatment (degree is proportional to the dose)
    2. Bilirubin levels may increase until clinical jaundice is evident
    3. Cholestatic jaundice is reversible upon cessation of therapy
    4. Prostatic hyperplasia may develop in older males, causing urinary retention
  2. Hepatic adenomas and carcinomas
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14
Q

When used for hormone replacement in men, androgens may cause acne, sleep apnea, erythrocytosis, gynecomastia, and azoospermia. What do supraphysiologic doses do?

Is/are these/this thing(s) reversible?

A

Azoospermia and decreased testicular size

Reversible possible months after discontinuation

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15
Q

What types of cancers have been noted with androgen use?

A

Hepatic adenomas and carcinomas

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16
Q

What type of behavioral effects have been reported with androgen use? 3

A
  1. psychologic dependence
  2. increased aggressiveness
  3. psychotic symptoms
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17
Q

Are androgens CI in pregnant women?

A

Yes, and in those who may become pregnant during therapy

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18
Q

What cancer scenarios could men have that would be CI for androgen use?

A

Carinoma of the prostate or breast

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19
Q

Androgens should not be used in infants and young kids. What should be used instead?

A

Somatropin

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20
Q

If used in a patient with renal or cardiac disease, what should these patients be warned of before beginning androgen therapy?

A

Edema (use diuretics if this develops)

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21
Q

What are the options for suppression of androgens?

A
  1. Gonadotropin-releasing hormone (GnRH) and analogs
  2. GnRH receptor antagonists
22
Q

What are the toxicities of leuprolide and friends in men?

A
  1. hot flushes
  2. sweats
  3. edema
  4. gynecomastia
  5. decreased libido
  6. decreased hematocrit
  7. reduced bone density
  8. asthenia
23
Q

What is the MOA of the -relixes?

A
  1. GnRH receptor antagonists
    1. MOA: synthetic competitive antagonists of GnRH receptors inhibit the secretion of FSH and LH in a dose-dependent manner
24
Q

ANTIANDROGENS are Useful in the treatment of individuals producing excessive amounts of testosterone. An example of this type of agent is ketoconazole. What are some uses for this drug?

A
  1. antifungal d/t inh. of CYP450 enzymes for cell wall synth
  2. experimentally to treat prostate cancer
25
Q

What is the MOA and timeline of the 5α-reducatase inhibitors?

A
  1. MOA: inhibition of 5α-reductase reduces levels of dihydrotestosterone within 8 hours of administration
26
Q

Finasteride and dutasteride were developed to treat BPH,. What are some common ADRs?

A

Impotence

Decreased libido

27
Q

What type of 5α-reductase(s) does finasteride inhibit?

A
  1. Preferentially antagonizes type II 5α-reductase
28
Q

What type of 5α-reductase(s) does dutasteride inhibit?

A
  1. Antagonist of types I and II 5α-reductase
29
Q

What are some uses of finasteride apart form the BPH thingy?

A
  1. Also approved for use in the treatment of male pattern baldness (effect presumably mediated via type I)
  2. Been shown to successfully treat hirsutism in women (unlabeled/investigational use)
30
Q

In what patients are finasteride and dutasteride absolutely CI?

A

Women and children

31
Q

What are the MOA of spironolactone?

A
  1. Antagonist effects at multiple nuclear receptors
    • androgen
    • aldosterone/mineralocorticoid
  2. reduces 17α-hydroxylase activity, which lowers plasma levels of testosterone and androstenedione
32
Q

The clinical manifestations of BPH include increased frequency of urination, nocturia, hesitancy, urgency, and weak urinary stream (not all symptoms are specific for BPH and the correlation between symptoms and the presence of prostatic enlargement on rectal examination or by transrectal ultrasonographic assessment of prostate size is poor). Treatment typically occurs only when the symptoms have a significant impact on the patient’s quality of life.

What are the two cornerstone drug classes used to treat BPH?

A
  1. 5α-reductase inhibitors
  2. α1-adrenergic receptor antagonists
33
Q

What are the definite benefits of 5α-reductase inhibitors in the treatment of BPH?

A
  1. Have demonstrated the potential for long-term reduction in prostate volume compared to α-antagonists
  2. Shown to reduce the need for surgery compared to α-antagonists
34
Q

Tamsulosin has been shown in recent studies to have a better effect with fewer side effects than other alpha antagonists. Why?

A

Is specific to α1A, and antagonism of α1A, compared to antagonism of α1B or α1D, treats BPH more effectively and with fewer adverse effects

35
Q

What are some common ADRs of prazosin?

A
  1. Adverse effects include palpitations and orthostatic hypotension (postural hypotension and syncope are sometimes seen 30-90 minutes after a patient takes an initial dose)
36
Q

Describe the effect of tamsulosin on blood pressure.

A

Little effect (primarily α1B mediated in vasculature)

37
Q

Which class, 5 alhpa reductase inhibitors or alpha-antagonists is the best approach to tx of BPH?

A

Trick question…

  1. The use of agents from both classes (5α-reductase inhibitors and α1-adrenergic receptor antagonists) in combination may be superior to using either class alone
38
Q

What is the MOA of sildenafil and taldalafil and the other afils?

A
  1. MOA: selective inhibition of PDE-5 increases intracavernosal cGMP levels and causes relaxation of the nonvascular smooth muscle of the corpora cavernosa
39
Q

Given that PDE-5inhibitors are potent vasodilators, what drug should this not be used concomitantly with?

A

Nitrates - will lead to severe hypotension and syncope (also MI has been reported)

40
Q

In men with BPH treated with alpha antagonists, what is a reported DDI that can occur?

A

symptomatic hypotension

41
Q

What are some rare ADRs for the PDE-5 drugs?

A

Visual changes

  • color change
  • blurred vision
  • increased sensitivity

Hearing loss

42
Q

In what three cases of ED/sexual dysfunction are PDE-5 inhibitors not useful?

A
  1. Loss of potency d/t cord damage
  2. lack of libido
  3. damaged innervation
43
Q

Androgen deprivation therapy (ADT), through either surgical or medical castration, is a mainstay of treatment for advanced prostate carcinoma. Why is this the case?

A

Carcinoma of the prostate is uniquely dependent on hormonal stimulation with androgens

44
Q

What is the prototype antimuscarinic compound?

A

Atropine

45
Q

What is the MOA of atropine?

A
  1. MOA: antagonist at the muscarinic acetylcholine receptor (mAChR)
46
Q

Therapeutic uses for antimuscarinics include

  1. CNS Disorders
    1. Parkinson Disease
    2. Motion Sickness
    3. Blockade of parasympathetic effects during reversal of skeletal muscle relaxation
  2. Ophthalmologic disorders (e.g., mydriasis during examination of the retina)
  3. Respiratory disorders (e.g., COPD)
  4. Gastrointestinal disorders (traveler’s diarrhea)
  5. Cholinergic poisoning (e.g., caused by cholinesterase inhibitors, wild mushrooms, nerve gasses; often paired with the cholinesterase regenerator pralidoxime)

And of course urinary disorders. What kind of selectivity would be preferred for the treatment of urinary dysfunction?

A

M3 subtype selectivity is preferred for agents that reduce urinary frequency - overactive bladder, urinary urge incontinence

47
Q

So what is the protorype antimuscarinic can we use that is selective for the M3 subtype?

A

Oxybutinin, is somewhat M3 selective

48
Q

Given that oxybutinin is “somewhat selective”, what are some of the ADRs?

A

side effects that include dry mouth, dizziness, constipation, blurred vision, dry eyes, and urinary tract infections among others

49
Q

What is a nonselective muscarinic antagonist that is comparable to oxybutinin in both efficacy and side effects?

A

Trospium

50
Q

What are the newer drugs than oxybutinin that are actually selective for the M3 subtype receptor?

A
  1. Darrifenacin
  2. solifenacin
  3. festeroterodine
  4. tolterodine
51
Q

In what patients are antimuscarinic agents CI?

A

Those with glaucoma

(reduced secretions)

52
Q
A

Reproductive II - Exam 2 (4 decks)

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