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Advanced Pharmacology > Urology > Flashcards

Urology Flashcards

1
Q

Erectile dysfunction

A

Many causes—vascular disease, diabetes,
medications, depression, complication of
prostate surgery, psychological causes

Many options for therapy—penile implants,
intrapenile injections or intraurethral
suppositories of Aloprostil [MUSE, Caverject,
Edex] and oral phosphodiesterase-5 [PDE-5]
inhibitors

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2
Q

Drugs to treat erectile dysfunction:

Phosphodiestrease-5 (PDE-5)

A

PDE-5 inhibitors

 MOA—sexual stimulation causes smooth muscle relaxation of corpus cavernosum, which increases blood flow. The mediator is nitric oxide [NO], which
activates and helps in the formation of cyclic GMP—this then causes smooth muscle relaxation through a
reduction of intracellular Ca++

PDE-5 inhibits PDE-5 which is the isoenzyme responsible for breaking down of cGMP in the corpus cavernosum—the result is to increase the flow of blood into the corpus
cavernosum—these agents have NO effect in the absence of sexual stimulation

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3
Q

Examples of PDE-5 inhibitors

A

Sildenafil (Viagra)—protype
Tadafil (Cialis)
Vardenafil (Levitra; Staxyn)
Avanafil (Stendra)

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4
Q

Sildenafil (Viagra)

A

Brand name: viagra
 Taken on empty stomach—at least 1 hour before anticipated sexual activity; dosed once a day
 Metabolized by CYP3A4
 Dose reduction when hepatic disease is present
 Dose reduction when severe renal disease is present
 ADE—headache, flushing, dyspepsia, nasal stuffiness, DISTURBANCES IN PERCEPTION OF BLUE AND GREENS, SUDDEN TRANSIENT HEARING LOSS (FROM VASODILATION) can cause
priapism
 Use caution with CV disease and in those at risk for CV disease

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5
Q

Drug interactions/considerations with SILDENAFIL aka VIAGRA

A

 Can potentiate hypotension [if patient on other agents that can lower BP—alpha blockers, vasodilators]
 Contraindicated with nitrates, isosorbide (vasodilators)
 Start at low dose and titrate up as needed for effect
 Reduce dose of these agents if patient on CYP3A4 inhibitors—Biaxin, Ritonavir and other protease inhibitors

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6
Q

Generic: sildenafil

A 
Brand: viagra
Route: PO
Onset of action: 60 minutes
1/2 life: 3-4 hours
Food interaction: yes
Caution with alpha blockers: +
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7
Q

Generic: tadalafil

A 
Brand: cialis
Route: PO
Onset of action: 120 miutes
1/2 life: 18 hours
Food interaction: no
Caution with alphablockers: ++++

**ALSO APPROVED FOR BPH*

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8
Q

Generic: Vardenafil

A 
brand: Levitra
Route: PO
Onset of action: 60 miutes
1/2 life: 4-5 hours
Food interaction: no (do not take with WATER)
Caution with alpha blockers: ++
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9
Q

Generic: Avanafil

A 
Brand: Stendra
Route: PO
Onset of action: 30-45 minutes
1/2 life: 5 hours
Food interaction: no
Caution with alpha blockers: ++
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10
Q

Alprostadil

A

 Synthetic prostaglandin E1
 In the penile tissues, PGE1 allows relaxation of the smooth muscle of corpus cavernosum
 Given intraurethral [supp] or intrapenile [injection]
 Can be used 1st line—but most often used in those who are not candidates for oral agents
 Acts locally, which decreases chance of ADEs
 MOA—smooth muscle relaxants, exact physiological mechanism is unknown
 Systemic absorption is minimal
 Onset 5-10” [supp] or 2-25” [injection]—effects last 30-60”
ADEs—rare; hypotension, headache have been reported; local effects—penile pain, urethral
pain, testicular pain
Priapism may occur

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11
Q

BPH

A

 Nonmaligant growth of the prostate—occurs with age
 Three categories of drugs approved for treating
BPH
-Alpha Blockers
-5 Alpha Reductase Inhibitors
-PDE-5 Inhibitors

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12
Q

Alpha Blockers

A 
 Blocking Alpha1A & Alpha1B receptors in the prostate cause the smooth muscles in the gland to relax, which leads to improved urine outflow 
 Selective agents only block Alpha1B—have no BP effects— nonselective ones decrease peripheral vascular resistance and lower BP
 Five agents in this class approved for BPH, a sixth one may be used but not FDA approved 
 4 nonselective and 2 selective alpha blockers—real prototype drug hard to identify
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13
Q

Generic Name: Terazosin

A 
Trade name: Hytrin
FDA approved for BPH: yes
NONSELECTIVE alpha blocker
NO food effect
Metabolized in liver but not CYP450
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14
Q

Generic Name: Doxazosin

A 
Trade Name: cardura
FDA approved for BPH: yes
NONSELECTIVE alpha blocker
No food effecr
CYP450 metabolism? yes
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15
Q

Generic Name: Alfuzosin

A 
Trade name: Uroxatral
FDA approved for BPH: yes
NONSELECTIVE alpha blocker
Food HELPS with absorption
CYP450 metabolism? yes
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16
Q

Generic: Prazosin

A 
Trade name: minipress
FDA approved for BPH: NOOOO
NONSELECTIVE alpha blocker
No effect with food
CYP450: yes
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17
Q

Generic: Tamulosin

A 
Trade name: Flomax
FDA approved for BPH: yes
SELECTIVE alpha blocker
Food helps with absorption
CYP450 metabolism: yes
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18
Q

Generic: Silodosin

A 
Trade name: rapaflo
FDA approved for BPH: Yes
SELECTIVE alpha blockers
Food helps with absorption
CYP450: yes** (also substrate for P-glycoprotein)
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19
Q

Alpha Blockers

A

 ½ life—8-22 hours
 Peak effects seen in 1-4 hours
 Rapaflo must be dose reduced for renal disease—avoid in severe CKD
 ADEs—dizziness, fatigue, nasal congestion, HA, drowsiness and orthostatic hypotension [these effects are less with selective agents]; nonselective agents given at HS
 Alpha blockers can effect ejaculatory ducts and impair smooth muscle contractions—inhibition of ejaculation and retrograde ejaculation have been reported with all of these drugs—these agents do NOT affect male sexual function severely like phenoxybenzamine and phentolamine [OraVerse]

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20
Q

Drug interaction with Alpha Blockers

A

 Drugs that inhibit CYP3A4 and CYP2D6—Verapamil, Diltiazem may increase the drug levels of Cardura, Flomax, Rapaflo and Uroxatrol
 Drugs that induce CYP450—Tegretol, Dilantin and St. John’s Wort may decrease the plasma concentrations of the aforementioned agents
 Uroxatrol may prolong QT interval, use caution when giving other drugs that can prolong QTc—Biaxin, Levaquin, Cipro, Avelox, class III antiarrhymthics
 Cyclosporine increases levels of Rapaflo because it is a
substrate for P-gp

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21
Q

5 Alpha Reductase Inhibitors

A

 2 agents in this class—both agents work slowly—over 9-12 months [unlike alpha blockers that work in 7-10
days]—these agents reduce the size of the gland

 Prostate MUST be enlarged for these agents to work, these agents are used in COMBINATION with alpha blockers

Types:

  1. finastride (proscar)
  2. dutasteride (avodart)
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22
Q

MOA of 5 alpha reductase inhibitors

A

inhibit 5 alpha reductase—which converts
testosterone to dihydrotestosterone[DHT], the more
potent, active compound that stimulates the prostate
to grow. By decreasing DHT the gland shrinks and urine
outflow improves.

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23
Q

5 Alpha Reductase Inhibitor

FINASTERIDE (Proscar)

A

 Food does not affect absorption
 ½ life 6-12 hours [terminal ½ life of Avodart is 5 weeks, once the steady state is reached in 6 months]
 ADEs—decreased ejaculate, decreased libido, ED, gynecomastia, oligospermia
 All drugs in this category are teratogenic for women—those of child bearing age or those that are pregnant should not handle or ingest 5 alpha reductase inhibitors as they may lead to birth defects in the
genitalia of male fetus
 Rare drug interactions
 Finasteride is used [in small doses] for alopecia—
reduces DHT in scalp and serum which prevents hair
loss

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24
Q

PDE-5 inhibitors

TADALAFIL (Cialis)

A

FDA approved for s/s of BPH
-inhibition of PDE 5 allow vasodilation and relaxation of smooth muscles of the prostate and bladder-which improves the symptoms of BPH

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25
Q

Effect of BPH urethra

A

 As the prostate enlarges, it can obstruction of the urethra
 As a result, the man can present with urgency, postvoid dribbling or overflow incontinence
 More common in men
Men can have urethral obstruction—from a cystocele, stricture or meatal stenosis [but most common in men]
 Conservative therapy includes bladder retraining and prompted voiding, which can be used if none of the following are present
Hydronephrosis, large PVR, recurrent UTI or hematuria

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26
Q

Alpha blockers that decrease tone in prostatic capsule and urethra-really helpful in BPH

A
  1. Terazosin (hytrin)
  2. Doxazosin (cardura)
  3. Alfuzosin (uroxatral)
  4. Tamsulosin (flomax)
  5. Silodosin (rapaflo)

5 alpha reductase inhibitors are also added

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27
Q

Last resort for BPH

A

intermittent or indwelling catheter then can do a voiding trial and then if that does not work, surgery

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28
Q

Detrusor Underactivity

A

If the patient has a prolonged outflow obstruction, a neurogenic type situation can develop; this patient has a large PVR and overflow leakage

Goals—drain urine from the bladder; decrease UI; present hydronephrosis & urosepsis

Trial of indwelling/intermittent catheterization to decompress bladder, allowing it to recover its contractile ability; left in for 2 weeks; then removed to see if voiding recurs normally

If not, catheter can be reinserted for 4
weeks & a voiding trial reattempted;
Valsalva maneuvers can be tried to induce
bladder contractions

Bethanechol, a cholinergic agonist, can be
tried at 10-50 mg QID

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29
Q

Testosteron Deficiency

A

 Evaluation of ED should include a testosterone level
 Testosterone deficiency can be part of male hypogonadism and can lead to osteoporosis—in addition to sexual issues.
 Refer to URL and EBG cited on slide #2; refer to detail
document that reviews testosterone products

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30
Q

Urinary Incontinence

A

Involuntary loss of urine that leads to hygienic or social problems
Affects at least 10 million Americans
UI is associated with pressure ulcers, skin irritation and falls
UI can lead to anxiety, depression, embarrassment and isolation

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31
Q

Prevalence of UI

A
  • more in men than women

- affects men and women equally after 80 years old

32
Q

Lower urinary tracts (LUT) consists of

A

Detrusor
Internal sphincter
External sphincter

33
Q

Detrusor (bladder)

A

Muscular storage and contractile organ

Smooth muscle that accommodates large volume at low intravesical pressure

34
Q

What makes up the internal sphincter?

A

Essentially smooth muscle in proximal urethra
In men it has no landmarks
In women, ill defined and extends throughout most of urethra

35
Q

What makes up the external sphincter?

A

More distal periurethral striated muscle

Well defined in men with striated muscle arranged in an annular style in urogenital diaphragm

36
Q

Continence is maintained by?

A

the urethra

37
Q

PNS (cholinergic): parasympathetic

A

-nerves come from spinal cord segments S2-S4 & travel by pelvic nerve to bladder
Cholinergic stimulation increases force and frequency of bladder contractions

38
Q

SNS (sympathetic nervous system)(adrenergic)

A

-regulated by presacral or hypogastric nerves in the spine at T10-L2
Bladder base [trigone] and proximal urethra rich in alpha adrenergic receptors and stimulation increases
contraction of internal sphincter

39
Q

How urination occurs

A

Somatic nerves stem from cord at levels S2-S4 and are carried via pudendal nerve to innervate urogenitaldiaphragm and external sphincter

Pons coordinates bladder contraction with sphincter relaxation

Bladder fills passively, sphincters remain closed

Filling is facilitated by CNS inhibition of parasympathetic
activity

At the same time, increase in alpha adrenergic and somatic tone maintains the sphincters in a closed
position

For urination to occur, PNS mediates bladder contraction with coordinated sphincter relaxation

40
Q

Causes of urinary incontinence

A 
 All other causes of UI are from problems in 
bladder, urethral outlet or both 
 Bladder contracts prematurely 
 Detrusor overactivity
 Bladder contracts too weakly 
 Detrusor under activity 
 Urethral outlet resistance too high 
 Obstruction  
 Urethral outlet resistance too low 
Incompetent
41
Q

What happens in detrusor overactivity?

A

 Usual mechanism of urge incontinence
 Most common cause of geriatric UI
 Inhibition of bladder contractions is impaired and bladder contracts on its own, leading to leakage
 Patient feels urge to void and before can get to toilet, wets on self
Moderate to large amounts of urine
 May be associated with nocturia

42
Q

Detrusor hyperreflexia If patient has a neuro lesion, overactivity is

A

Detrusor hyperreflexia

-frequency, urgency, and incontinence

43
Q

If no neuro lesion is present, it is called

A

Detrusor instability

44
Q

What happens in Detrusor overactivity with normal contraction

A

bladder can empty most of its contents

45
Q

what happens in Detrusor hyperactivity with impaired contractility

A

Bladder can’t empty and >100 cc of urine remains in bladder after contraction

46
Q

Detrusor Underactivity

A

Bladder’s contractions so diminished that overflow incontinence ensues
Bladder contracts [if at all] only when patient tries to void
Uncommon in geriatrics
It can be:
-Neurogenic in origin
-Secondary to nerve damage from DM, ETOH or vertebral disease
-From long standing obstruction

47
Q

Outlet Incompetence

A

 Also known as stress incontinence
 Common in women
 Patient has involuntary loss of urine with physical activity or coughing
Leakage is small and rare when patient is recumbent
Usually from weakening of supporting structures of
pelvic floor
Uncommon in men
Except after transurethral surgery or XRT that damages sphincter

48
Q

Outlet Obstruction

A 
Common cause of UI in elderly men 
Can  lead to urinary retention, bladder distention and overflow incontinence 
Post-void dribbling or urge incontinence due to detrusor overactivity
Causes 
-BPH 
-Alpha agonists  
-Tumors  
-Strictures  
-Spinal cord lesions
49
Q

Treatment for detrusor overactivity

A

-voiding trails
-Anticholinergics or smooth muscle relaxants can be used to decrease involuntary contractions of the overactive detrusor and increase volume needed to elicit involuntary contractions
Propantheline: 15-30 mg TID or QID
Dicyclomine : 10-30 mg TID or QID. Has anticholinergic and smooth muscle relaxant properties
TCA (tricyclic antidepressants): Tofranil or Doxepin at 25-50 mg TID or at HS; **Evaluate for orthostatic hypotension and confusion
Ditropan: 2.5-5 mg QD or QID

50
Q

Systemic side effects of anticholinergics

A

Systemic side effects—xerostomia, confusion, constipation, urinary retention

51
Q

Anticholinergics for detrusor overactiviy

A 
 Detrol- 2 mg BID 
 Detrol LA- 4 mg daily 
 Ditropan XL-5-10 mg daily 
 Levbid- 1 tab BID 
 Symax 
 Oxytrol Patch- change twice weekly 
 Gelnique- 1 gram gel q 24 hrs 
 Vesicare 
 Sanctura 
 Sanctura XR 
 Enablex 
 Toviaz
52
Q

Antimuscarinic Medications—

Prototype—Oxybutynin (ditropan)

A

4 formulations:

  • Immediate release: 2.5–5 mg BID–QID, up to 20 mg/day
  • Extended release (ER) (Ditropan XL): 5–20 mg/day
  • Topical patch (Oxytrol): 3.9 mg, applied 2x/week
  • Topical gel (Gel): 1 gram applied every 24 hours
• Side effects (less frequent with ER and topical): 
 Dry mouth 
 Blurry vision 
 Constipation 
 Possibly cognitive

Interactions with CYP34A and 2D6
• Monitor PVR if UI worsens

53
Q

Antimuscarinic Medications—

Tolterodine [Detrol]

A

Initial dose: 1–2 mg BID immediate release, 2–4 mg
QD for ER (Detrol LA)

Side effects similar to those of oxybutynin-ER; possible decreased xerostomia (dry mouth)

Interactions with CYP34A and 2D6

54
Q

Antimuscarinic Medications—

Trospium [Sanctura]

A

 Dose is 20 mg twice daily; can dose once daily in elderly because of renal clearance
 Does come in an extended release form—Santura XR 60 mg daily
 Must be taken on an empty stomach
 Associated with 56%–60% reduction in weekly urge incontinence episodes
 No data in long-term-care populations
 Adverse events: dry mouth, constipation, headache, abdominal pain

55
Q

Antimuscarinic Medications—

Darifenacin [Enablex]

A

Dose is 7.5 or 15 mg/day
Median reduction in weekly UI episodes 55%–58% in patients on 7.5 mg and 60%–70% in patients on 15 mg
No data in long-term-care populations
Adverse events: dry mouth, constipation; may have limited cognitive effects
Interactions with CYP34A and 2D6

56
Q

Antimuscarinic Medications—

Solifenacin [VESIcare]

A

Dose is 5 mg/day; may be titrated to 10 mg/day
Reduction in daily UI episodes 57%–69%, depending on dose
No data in long-term-care populations
Adverse events: dry mouth, constipation, nausea, and blurred vision; possible
QTc
Interactions with CYP34A and 2D6

57
Q

Antimuscarinic

Oxybutynin-Ditropan

A

Cost: generic
Dosing: BID-QID
Considerations: quick onset; P450 interactions

SE: Dry mouth, constipation, cognitive issues

58
Q

Antimuscarinic

Oxybutynin- Ditropan XL

A

Cost: generic
Dosing: QD
Considerations: wide titration range: p450 interactions
SE: dry mouth

59
Q

Antimuscarinic

Oxybutynin- Oxytrol (patch form)

A

Cost: no generic
Dosing: twice a week
Considerations: skin irritation; single dose
SE: dry mouth

60
Q

Antimuscarinic

Tolterodine: Detrol LA

A

Cost: no generic
Dosing: QD
Consideration: titration; p450 interactions
SE: dry mouth, constipation: QTc, and there have been case reports of cognitive issues

61
Q

Antimuscarinic

Trospium-Sanctura

A

Cost: no generic
Dosing: QD-BID
Considerations: renal clearance; must give NPO
SE: dry mouth, constipation, INCREASED HEART RATE, less cognitive issues

62
Q

Antimuscarinic

Darifenacin-Enalbex

A

Cost: no generic
Dosing: QD
Considerations: p450 interactions; titration
SE: dry mouth, constipation, less likely to have cognitive issues

63
Q

Antimuscarinic

Solifenacin-Vesicare

A

Cost: no generic
Dosing: QD
Considerations: P450 interactions; titration; long half life
SE: dry mouth, constipation, effects on QTc

64
Q

Fesoterodine [Toviaz]

A

Atropine like agent that is used to treat OAB—this quaternary amine has the fewest cholinergic effects—working mostly on muscarinic and nicotonic receptors in the detrusor
Increases bladder capacity
For those on drugs that may increase
cholinergic neurotransmitters [agents
for dementia]—this is one of the DOC (drug of choice)
for OAB in those individuals

**first line for person with cognitive deficits

65
Q

β 3 Agonist—Mirabergron [Myrbetriq]

A

 This agent relaxes the detrusor smooth muscle and increases bladder capacity

 Used for OAB [in patients that have failed other agents or have a contraindication to the use of the anticholingergics

 Myrbetriq 25-50 mg daily

  • Can increase BP [this effect is more marked at lower doses]
  • It increases digoxin levels; can decrease Metoprolol levels; can inhibit CYP2D6
  • If GFR is <30 cc/min—use the 25 mg dose
66
Q

Other Treatments for OAB

A

Botulinum toxin
Sacral Nerve Stimulation
Percutaneous Tibial Nerve Stimulation

67
Q

Stress Incontinence

A 
Outlet incompetence is manifested by stress incompetence 
Can be treated nonsurgically or surgically 
Nonsurgical therapy 
-Weight loss 
-Kegel exercises 
-Use of vaginal cones 
-Biofeedback  
-Adjusting fluid intake 
-Voiding frequently
68
Q

Nonsurgical treatments for stress incontinence with medication

A

Estrogen
-Especially in females with atrophic urethritis or vaginosis
-0.3-0.625 mg qd and/or 2 grams vaginal cream qod
 Oral—shown to increase UI in randomized trials
 Topical—may reduce atrophic vaginitis, urethritis; impact on UI is unclear

Alpha agonists
-Pseudoephedrine 15-30 mg BID or TID

⍺-Adrenergic Agonists

  • Stimulate urethral smooth-muscle contraction
  • No pure ⍺-agonists are available
69
Q

Stress Incontinence—Post-prostatectomy

A

 Milder cases: pelvic muscle exercises, periurethral injections
 More severe cases: protective garments, catheters
 Artificial sphincter replacement can be effective but has high re-operation rate
 Emerging data on sling operations

70
Q

Mixed Incontinence

A

Many women show evidence of 2 kinds of incontinence

  1. Urge
  2. Stress

Empirical treatment can be based on clinical history

71
Q

Pediatric Enuresis

A

Involuntary discharge of urine at night by children older enough to be expected to have bladder control
Causes: Hormones, bladder problems, genetics, sleep problems, caffeine, medical conditions, psychological problem

Treatment options:
-alarm therapy that teaches children to respond to a full bladder while asleep. Alarm goes off when child starts to void.
-behavior therapy
-avoid caffeine before bed
Medication: desmopressin acetate
Considerations: not rec for children under 6; use caution with children having issues with osmoregulation or fluid balance, cystic fibrosis, no fluids for one hour before and 8 hours after taking desmopressin

72
Q

Phosphodiesterase-5 Inhibitors (PDE-5)

A
  • FOR ERECTILE DYSFUNCTION (ED)

MOA: sexual stimulation causes smooth musclerelaxation of corpus cavernosum, which increasesblood flow. The mediator is nitric oxide [NO], whichactivates and helps in the formation of cyclic GMP—this then causes smooth muscle

PHARMACOKINETICS:  All of these agents inhibit PDE-5 which inhibitsthe isoenzyme responsible for breaking downof cGMP in the corpus cavernosum—the result
is to increase the flow of blood into the corpuscavernosum—these agents have NO effect in the absence of sexual stimulation

ADE: headache, flushing, dyspepsia, nasal stuffiness, disturbances in perception of blues and greens, sudden transient hearing loss [from vasodilation], can cause priapism

DRUG INTERACTIONS:
 Can potentiate hypotension [if patient on other agents that can lower BP—alpha blockers, vasodilators]
 Contraindicated with nitrates, isosorbide
 Start at low dose and titrate up as needed for effect
 Reduce dose of these agents if patient on CYP3A4 inhibitors—Biaxin, Ritonavir and other protease inhibitors

73
Q

Examples of Phosphodiesterase-5 Inhibitors

A
  1. Sildenafil
    2 Vardenafil
  2. tadalafil
  3. Avanafil
74
Q

Which PDE-5 can be FDA approved for BPH as well as ED?

A

tadalafil (Cialis)

75
Q

What can you use to treat BPH?

A
  1. alpha blockers
  2. alpha reductase inhibitors
  3. PDE-5 inhibitors
76
Q

Functional incontinence

A

address behavior, no meds

Advanced Pharmacology (18 decks)

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