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1
Q

Overall medications

A

BPH
1.Alpha 1 antagonists
2. 5-Alpha-Reductase inhibitors (5-ARIs)
3.Phosphodiesterase type - 5 (PDE-5)
4. Antimuscarinic agent
Urinary incontinence
1. Anticholinergics/antimuscarinics
2. Beta-3-agonists
3. Duloxetine
Interstitial cystitis/bladder pain syndrome
1.pentosan polysulfate
2. Amitriptyline
Erectile dysfunction
1. Phosphodiesterase-5 (PDE-5)
2. Alprostadil
Priapism
1. Phenylephrine
Testosterone replacement therapy

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2
Q

Benign Prostatic Hyperplasia

A

Clinical p:
-lower urinary tract symptoms= obstructive/voiding symptoms and irritative/storage symptoms
-enlarged prostate-> DRE OR ULTRASOUND TO RULE OUT PROSTATE CANCER-> large is >40 mL
-elevated PSA level

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3
Q

BPH drugs: Culprits for drug-induced LUTS (lower urinary tract symptoms)

A
  1. Testosterone replacement therapy
  2. alpha-adrenergic agents-> pseudoephedrine
  3. Anticholinergic drugs
  4. Antihistamines
  5. Tricyclic antidepressants (TCAs)
  6. Inhaled anticholinergic agents
  7. Diuretics
  8. Caffeine
  9. Alcohol
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4
Q

Initial tx of BPH

A

bph- >
-Mild LUTS
1. Watchful waiting
-Moderate/severe LUTS
1.Prostate <40 g or PSA< 1.4 = Alpha 1 adrenergic antagonist
2. Prostate > 40 g or PSA > 1.4= 5 alpha-adrenergic antagonist OR 5 alpha-reductase inhibitor + alpha 1 adrenergic antagonist
3. Erectile dysfxn= Phosphodiesterase inhibitor OR 5 alpha-reductase inhibitor to alpha 1 adrenergic antagonist
4. Predominant irritative voiding symptoms= Add anticholinergic agent or beta 3 agonist to alpha 1 adrenergic antagonist OR 5 alpha reductase inhibitor

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5
Q

BPH: Alpha1 Antagonist

A

-osin
1ST LINE FOR MODERATE AND SEVERE BUT W/OUT COMPLICATIONS
improve urinary flow and symptoms
Interactions: CYP3A4, PDE-5 inhibitors

  1. Uroselective- days onset, less SE
    -Tamsulosin (Flomax)
  2. Nonselective- weeks onset, more SE
    -Terazosin
    -Doxazosin

MOA: Block alpha 1 and Beta1 receptors-> sm relaxation in bladder neck, prostate capsule, and prostatic urethra-> improve urinary flow
-A&B blockers-> decrease PVR in arterial and venous= lower BP
-Alpha1-> uroselective and decreased effect on bp

pharmacokinetics: well absorbed for oral, better with food
Silodosin requires dose adjustment in renal impairment/dysfxn –stopsign

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6
Q

BPH: alpha 1 antagonist Patient ed, AE, special notes, other features

A

Pt E: “first dose effect”- exaggerated orthostatic Hypotn= SYNCOPE
-minimize by adjust first dose to 1/3-1/4of normal dose
-admin at bedtime
AE:
dizziness- least tamsulosin and most terazosin
Hypotn- best tamsulosin, worst terazosin
Syncope- none w/ tamsulosin and silodosin
intraoperative floppy iris syndrome- every med
ejaculatory dysfunction-> silodosin and tamsulosin
Notes:
terazosin and doxazosin NOT TAKEN W/ ERECTILE DYSFXN MEDS-> dilodosin minimal SE for ejac
other:
Benefit: improve lipid profiles adn glucose metab
HT: decreases BP but not used as monotherapy for HTN

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7
Q

BPH: alpha 1 antagonists drug interactions

A
  1. drugs that inhibit cytochrome p450- increase plasma conc of doxazosin, alfuzosin, tamsulosin, silodosin
  2. drugs that induce CYP450-> decrease plasma conc bc body metabolizes it faster
  3. alfuzosin may prolong QT interval-> cautious w/ other drugs that prolong
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8
Q

BPH: 5-alpha- reductase inhibitors (5-ARIs)

A

1st LINE FOR MODERATE TO SEVERE SYMPTOMS-> PROSTATE MUST B ENLARGED (>40 ML)
Ex: Dutasteride (Avodart) and Finasteride (Propecia) + for male pattern baldness
Benefits: reduce prostate size, reduce BPH progression, prevent complications, improve urinary symptoms
Onset of actions: 3-6 months SLOWEST
combining w. alpha1 antagonist= IMPROVES RESULTS
MOA: Inhibit 5-alpha reductase enzyme which is the enzyme that converts testosterone into DIHYDROTESTOSTERONE (DHT) -> more active form
-DHT= stim prostate growth-> inhibit then shrinks prostate and urine flow improves
Dutasteride= more potent than finasteride= greater decrease in DHT

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9
Q

BPH: 5-alpha-reductase inhibitors: pharmkinet, AE, contraind, warning, notes

A

Pharmacokinetic= food-> no effect on absorp
AE: Sexual SE - decreased ejaculate, libido, ED, oligospermia (low), gynecomastia
Contrain: FINASTERIDE & DUTASTERIDE TERATOGENIC
-no prego, or childbearing age= serious birth defects on male fetus genitalia
-avoid semen of men on meds, men can’t donate blood until 6 mo after last dose
Warnings: Not idea w/ Testosterone therapy bc drug decreases testost effectiveness-> increased risk of male breast cancer
Special notes:
-Monotherapy= months for full effect
-GREAT FIRST LINE CHOICE IN PT W/ ENLARGED PROSTATE and psa >1.4-> usually in combo therapy
-More sexual dysfxn than alpha1 adrenergic

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10
Q

BPH: contrasting Alpha 1 antag and 5-alpha-reductase inhib

A
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11
Q

BPH tx- combo options

A

Dutasteride 05 mg + Tamsulosin 0.4 mg= Jalyn
-taken 30 min after same meal every day
-significant drug interactions

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12
Q

Other BPH tx options

A
  1. Phosphodiesterase 5 (PDE-5) inhibitor
    -Tadalafil (cialis) -> mono for BPH or BPH+ED
    moa: PDE-5 is w/in Prostate and Bladder-> inhibit causes vd and relaxation of sm of prostate and bladder= improves bph symp
  2. Antimuscarinic agent
    -Off label (tolterodine-Detrol)
    -anticholinergic- increased risk of SE espec in elderly
    May b useful AFTER CONVENTIONAL THERAPY in those w/ urge incontinence symp-> w/out elevated postvoid residuals
  3. Herbal therapies- only in europe
    -Saw palmetto- no studies
    -Beta-sitosterol- som improvement
    -Cernilton- rye grass pollen no improvement
    -PYGEUM AFRICANUM- extract of bark from an african plum tree-> some efficacy 23% increase in peak urinary flow
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13
Q

BPH summary of recommendations

A

1st line: Alpha blocker-> if inadequate response/cant tolerate
2. if urgerncy predom- OAB tx
2. trial of PDE5
2.Adding 5ARIs if large prostate

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14
Q

Urinary incontinence types

A
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15
Q

Incontinence tx

A

drug tx should be combined w. behavioral/nonpharm
-pelvic floor exercises (kegels), biofeedback, weight loss, bladder retraining, avoidance of caffeine, carbonated beverages, alcohol, drink water in small amounts
Look for reversible causes
Remove meds causes if possible:
-functional: diuretics, opioids, benzo, alcohol, antipsyhc, anticholin
-stress: diuretics, alpha 1 antag, ACE inhib
-Overflow- diuretics, anticholin, TCAs, CCBs
-OAB:diuretics, anticholinergics, cholinesterase inhibitors

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16
Q

reversible causes

A
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17
Q

Common types of UI and drug induced causes

A
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18
Q

Meds that can contribute to Urinary incontinence

A
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19
Q

Initial management of UI

A
  1. Stress, urgency, mixed, or overactive bladder OAB
    -lifestyle mods: weight loss, dietary changes, constipation, smoking cessation
    -pelvic floor musc: kegels
    BLADDER TRAINING= MOST EFFECTIVE FOR URGENCY INCONTINENCE
    tx for 6 weeks to 6 months prior to new therapies
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20
Q

UI: tx of OAB

A
  1. Antimuscarinic/Anticholinergic agents
    -Oxybutinin (Oxytrol) high SE of elderly)
  2. Beta 3 agonists
    -Mirabegron (Myrbetriq)
    -Vibegron (Gemtesa)
  3. Onabotulinumtoxin A (Botox)
  4. Duloxetine (Cymbalta)- SNRI may be effective= off label use
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21
Q

UI tx: Anticholinergics/Antimuscarinics- moa, pharmaco

A

MOA: Competitively block muscarinic receptors in the bladder= decrease intravesical pressure, higher bladder capacity, adn frequency of bladder contractions reduced
pharmac: all in oral, Oxybutynin= patch and gel, all but trospium metab by CYP450

FIRST LINE FOR TX OF URGE INCONTINENCE IN WOMEN
AE: blurred vision, dry mouth, heart palpitations, drowsiness, anxiety, ams, Dry mouth, eyes, constipation
Contrain: pts with UNCONTROLLED NARROW ANGLE GLAUCOMA- wide angle isnt, Dementia, urinary retention, bowel obstruction
Renal: reduce dose
Hepatic : reduce dose
USE CAUTION IN COGNITIVE IMPAIRMENT AND W/ ELDERLY

22
Q

UI tx: Anticholinergic/antimuscarinic AE on cognition

A

Factors in AE profile:
receptor specificity in CNS, lipophilicity, P-glycoprotein active efflux transport, charge/polarity, molecular weight

Oxybutynin: MOst= IR, MOd= ER, Least= Patch and gel
-Tolterodine= more SE w/ IR than ER
-Trospium=crosses BBB to a lesser extent
-M3 uroselective agents: solifenacin, darifenacin

23
Q

UI OAB: Beta3 agonists

A

MOA: Activates beta3 adrenergic receptors in the bladder resulting in relaxation of the detrusor sm during the urine storage phase= increasing bladder capacity
1. Mirabegron (Myrbetriq)- AE: HTN
2. Vibegron (Gemtesa)
preferred over antimusc in elderly
Indications: overactive bladder and urgency urinary incontinence
AE: htn, nasopharyngitis, UTI, headache, angioedema
NOT FOR PT W/ UNCONTROLLED HTN

24
Q

UI: tx of stress and overflow incontinence

25
UI: Bladder botox
indications: Refractory overactive bladder (OAB)- 3rd line MOA: blocks actions of acetylcholine adn paralyzes bladder musc No effect right after injection-> muscle paralysis slowly over next few days (7-10 best) and lasts 6-12 mo AE: dysuria, hematuria, procedure related uti, increase in post void residual volume leading to urinary retention Procedure: bladder filled w/ sterile water- small injections in bladder wall away from trigone area
26
UI: management in geriatrics
1. Hx 2. Reversible 3. Care giver involvement/non pharm 4. Drugs -Men= alpha blocker or 5 alpha reductase inhibitor
27
Dysuria
Phenazopyridine (Azo) Indications: symptomatic relief of dysuria (pain, burning, urgency, frequency) MOA: urinary anesthetic -> azo die is local anesthetic by unknown mech Special notes: only used for 2 days and urine= ORANGE
28
Interstitial cystitis/Bladder pain syndrome
-unpleasant sensation w/out infection or identifiable causes- Symp: intermittent, severe suprapubic pain, urinary freq, urgency, hematuria, dysuria Labs: Cystoscopy= mucosal fissues and punctate hemorrhages, Biopsy= rule out carcinoma TX: Pentosan polysulfate (Elmiron) Amitriptyline
29
IC: Pentosan polysulfate (Elmiron)
indication: relief of bladder pain secondary to IC MOA: low molec weight Heparinoid-> acts as a buffer of bladder wall to protect tissues from irritating substances expensive SE: bleeding comp Cautions: increased bleeding risk, Ocular effects= Pigmentary changes in retina Contraind: hypersens to pentosan polysulfate and heparin
30
IC: Amitriptyline
Indications: off label indications for IC MOA: increase synaptic conc of serotonin and norepi in CNS by inhibiting reuptake by presynaptic neuronal mem pump Class: tricyclic antidepressant SE/contrain: Sedation, overdose, orthostatic hypotn, suicidal ideation, many interactions START LOW AND GO SLOW, 10 mg hs, increase weekly
31
Erectile dysfxn
1 of mc male sexual dysfxn= 1/3 of adult men, coexist with other sexual dysfxn, often w/ htn, hypercholesterolemia, dm or bph TX: penile implants, intrapenile injections of alprostadil, intraurethral suppositories of alprostadil, PDE-5 inhibitors, vacuum devices
32
ED tx
1st line: PDE-5 or testosterone replacement for hypogonadism 2nd line: vacuum constriction device -contra for sickle cell, warfarin, DOAC 3rd: injected vd 4th: unapproved agents= supplements
33
ED tx: PDE inhibitor
1. Sildenafil (viagra) 2. Vardenafil (levitra) 3. Tadalafil (cialis) 4. Avanafil (stendra) all effective w/ similar AE Sildenafil adn tadalafil= tx pulmonary HTN but different dosing MOA: allows prolonged cGMP activity on vd 65% effective
34
ED tx: PDE Inhibitor chart
35
ED tx: PDE AE, contraindications, precautions, notes
AE: HA, hyptn, PRIAPISM (medical emergency), CP INHERENT CV risk W/ SEXUAL ACTIVITY even w/out PDE-5 tx Contraindications: NO NITRATE BC OF HYPOTN RISK NO VARDENAFIL AND DRONEDARONE TOGETHER= PROLONGS QT INTERVAL Precautions: Concomitant alpha1 antagonist therapy-> use uroselective alpha1 antag to avoid hypotn avoid high fat foods w/ sildenafil and vardenafil PRIAPISM IS RARE AND DOES NOT IMPROVE LIBIDO
36
ED tx: Alprostadil
Structure: synthetic prostaglandin E1 (PGE1) MOA: relaxes SM in corpus cavernosum by unknown mech-> increased blood flow-> compresses venous flow-> blood entrapment-> erection Local effect: less AE urethral suppository and injectable Pharmacokinetics: little systemic absorption AE: rare due to systemic-> Hypotn, HA, PRIAPISM-> local penile pain, urethral pain
37
Meds that can contribute to or cause ED
Antihypertensives antidepressants antipsychotics antiandrogens alcohol overview
38
Priapism
AN EMERGENCY-> may result in low blood flow leading to penile ischemia and potential necrosis Management depends on cause med induced= inj of a weak alpha agonist into corpus cavernosum is often effective= PHENYLEPHRINE
39
Low T manifestations
Specific: delayed sexual development, decreased libido, gynecomastia, decreased spontaneous erection, loss of body hair, low sperm counth Nonspecific: decreased energy, depression, anemia, sleep disturbances
40
Testosterone
Schedule 3 Rx- acts thru psychogenic channels to enhane libido To confirm hypogonadism= 2 serum total testosterone conc on diff days PREGNANCY CATEGORY X= TERATROGENIC *Contraindication: *severe renal/cardiac/hepatic disease *male breast cancer *prostate cancer *sleep apnea *peripheral edema Replacement therapy: levels should be <300 ng/dl on 2 separate morning measurements-> follow levels thru tx-> caution w/ topical bc of transfer-> CAUTION W/ EXISTING PROSTATE CANCER AND BPH SE: MAY INCREASE RISK OF HEART ATTACKS and STROKES-> hA, changes in libido, acne, priapism transdermal preparations- gel, patch, spray, solution, IM, implantable pellets *pregnant and lactating women
41
Testosterone replacement therapy Patient Ed
Patch- 4 different areas= front of thighs, back of thighs, stomach, arms, back-> NON HAIRY area changed q 24 hrs and allow 7 days btwn app to same site-> COVER AND TRASH AWAY FROM CHILDREN, PETS, WOMEN Gel- upper arms and shoulders-> never on stomach, penis, scrotum, armpits, or knees->avoid exposure
42
Urinary tract infections
Cystitis, pyelonephritis, urethritis, epididymitis, orchitis, prostatitis Main study sheet Women: acute simple cystitis= macrobid or bactrim
43
Complicated UTIs including pyelonephritis
Men w/ simple cyst= tx like complicated Uptodate: Nirtofurantion, bactrim for empiric tx in a healthy male without neurogenic bladder
44
outpatient uti
Ciprolevofloxacillin
45
inpatient uti tx
Ceftriaxone, piperacillin, cipro/levo
46
Urethritis- STDs
1. Gonococcal-> Neisseria gonorrhea= high dose IM Ceftriaxone 2. Non-gonococcal -> Chlamydia, mycoplasma genitalium, ureaplasma urealyticum, trichomonas-> Empiric= Doxycycline tx the cause -Chlamydia and mycoplasma= doxy -trichomonas- metronidazole
47
Epididymitis and Orchitis
< 35 yoa= likely STI= Chlamydia trachomatis or N. gonorrhea > 35 yoa= gram neg rods= E. coli acute < 6 wks chronic > 6 wks dont have cremasteric reflex Amiodarone-> self limiting epididiymitis Tx: Rest, ice, elevation -> AB for underlying cause Not an STI= use fluoro= levofloxacin
48
Prostatitis
Acute: Ampicillin and gentamicin Chronic: Ciprofloxacin or levofloxacin
49
Seen more frequently
BPH -Tamsulosin -Tadalafil Urinary incontinence -elderly= Mirabegron -not elderly= Oxybutynin ED -PDE-5 inhibitors
50
Pt taking a PDE-5 inhibitor for ED is diagnosed w/ angina. Which antianginal med would be concerning?
Nitroglycerin
51
Which is CORRECT regarding the local administration of alprostadil? A. local administration of alprostadil allows for low systemic absorption B. increases chance of drug interactions c. accomplished by application of a cream D. Causes changes in color vision
A. low systemic absorption
52
Which is correct regarding finasteride? A. assoc w. significant hypotension B. assoc w/ birth defects C. effective within 2 weeks of initiation D. renally eliminated
B. birth defects= prego cat x

Pharm 2 (15 decks)

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