1
Q
Classes used for BPH?
A
- alpha 1 blockers (MC)
- 5 alpha reductase inhibitors (MC)
- combo:
Dutasteride-Tamulosin (Jalyn) - Tadalafil (Cialis)
2
Q
Class of Alpha-1 blockers?
A
- Terazosin (Hytrin)
- Doxazosin (Cardura)
- Alfuzosin (Uroxatrol)
- Tamsulosin (Flomax)
- Silodosin (Rapaflo)
- combo 5-alpha reductase inhibitor - alpha 1 blocker: Dutasteride-Tamulosin (Jalyn)
3
Q
Use and MOA of Alpha-1 blockers?
A
- More effective than 5-alpha reductase inhibitors for short and long term sx management***
- MOA: relax smooth muscle in bladder neck and prostatic capsule and prostatic urethra
- Alpha-1 receptors located in base of bladder and in prostate
- all drugs in this class have similar efficacy
4
Q
Efficacy of alpha-1 bockers?
A
- sx scores decreased by 30-40%
- urine flow rates increased by 16-25%
- Doxazosin (Cardura) and Terazosin (Hytrin) more effective than 5-alpha reductase inhibitor Finasteride (Proscar)
- efficacy of Tamsulosin (Flomax) and Finasteride (Proscar) equal
5
Q
MC SE of alpha-1 blockers? What is done to decrease this?
A
- MC: dizziness and orthostatic hypotension- Terazosin (Hytrin) and Doxazosin (Cardura) cause more BP lowering than others - can cause severe hypotension if used with phosphodiesterase 5-inhibitors
- Flomax, Uroxatrol, and Rapaflo have less BP effects
- generally start at small dose at bedtime and titrate up slowly over several weeks
6
Q
Other SEs of alpha-1 blockers?
A
- asthenia (muscle weakness)
- nasal congestion
- problems with ejaculation: mostly Tamsulosin (Flomax), can decrease volume of ejaculate by 90%, 35% may have no ejaculate, and up to 28% have retrograde ejaculation on Silodosin (Rapaflo)
7
Q
Class of 5 alpha-reductase inhibitors?
A
- Finasteride (proscar)
- Dutasteride (avodart)
- combo:
Dutasteride-Tamulsoin (Jalyn)
8
Q
Use of 5-alpha reductase inhibitors?
A
- only agents that provide long term decrease in prostate size** and decreased need for prostatic surgery
- but not as effective at controlling sxs as alpha-1 blockers
9
Q
MOA of 5-ARIs?
A
- competitive inhibitor of both tissue and hepatic 5-alpha reductase
- results in inhibition of conversion of testosterone to dihydrotestosterone and markedly suppresses serum dihydrotestosterone levels - serum dihydrotestosterone decreases by 70% - primary androgen in prostate nad hair follicles
- serum testosterone increases by 10%
- decreases prostatic size
10
Q
Efficacy of 5-ARIs?
A
- may be up to a yr to notice reduction in sxs
- reduced sx scores:
obstructive: 23%
non-obstructive: 18% - increase in max urinary flow rate
- reduction in mean prostatic volume by about 18%
- decreased need for surgery
- decreased development of acute urinary retention
- larger prostate volume the more effective med
- Dutasteride (Avodart) may be more potent than Finasteride (Proscar)
11
Q
Major side effects of 5-ARIs?
A
- decreased libido
- ejaculatory or erectile problems
may only have these effects for 1st yr of therapy - decreases serum PSA by 50% - use a factor of 2 when interpreting PSA results in first 24 months of therapy
use a factor of 2.5 after 24 months
? decreased development of prostate cancer but concern for possible increased incidence of high grade lesions
12
Q
Use of Cialis for BPH? Don’t use with what other meds?
A
- Blocks PDE5 in prostate and bladder - mechanism of how Cialis reduces BPH sxs isn’t completely understood
- Don’t use wth nitrates or alpha-1 blockers
- 5 mg daily dose
- takes 2-4 wks to not sx improvement when used for BPH
13
Q
Drugs used for ED?
A
prostaglandin injectable:
- Alprostadil
phosphodiasterase inhibitors:
- Tadalafil (Cialis)
- Vardenafil (Levitra)
- Sildenafil (Viagra)
- Avanafil (Stendra)
14
Q
Use and MOA of Alprostadil (Caverject, Muse?
A
- drug category: prostaglandin, vasodilator
- forms: intracavernosal injections, urethral pellets
- MOA:
causes vasodilation by means of direct effect on vascular and smooth muscle, relaxes trabecular smooth muscle by dilation of cavernosal arteries when injected along penile shaft, allowing blood flow to and entrapment in lacunar spaces of penis (corporeal veno-occlusive mechanism) - onset and duration of action:
onset 5-20 min
duration: less than 1 hr
15
Q
CIs and SEs of Alprostadil (Caverject, Muse)?
A
- CIs:
conditions that predispose the pt to priapism, anatomic or fibrotic conditions of penis,
for pellets (Muse): urethral stricture, perineal pain - SEs:
syncope
priapism
may cause BP lowering
16
Q
Class of Phosphodiasterase inhibitors?
A
- Tadalafil (Cialis)
- Vardenafil (Levitra)
- Sildenafil (Viagra)
- Avanafil (Stendra)
17
Q
MOA of phosphodiasterase inhibitors?
A
- phsyiologic mechanism of erection of penis involves release of nitrous oxide in corpus cavernosum during sexual stimulation
- NO then activates enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP) producing smooth muscle relaxation and inflow of blood to corpus cavernous
- enhances effect of NO by inhibiting phosphodiesterase type 5 (PDE-5) which is responsible for degradation of cGMP in corpus cavernosum
- don’t directly cause penile erections (still need stimulation)
18
Q
CIs of phosphodiasterase inhibitors use?
A
- men taking nitrates (long acting, can still have SL - wait so many hours)
- caution with alpha-1 blockers due to risk for severe hypotension
19
Q
Adverse rxns of phosphodiasterase inhibitors?
A
- severe hypotension (w/ nitrates or alpha-1 blockers)
- common: flushing, HAs, dyspepsia
- visual effects: transient blue vision with sildenafil (Viagra), may increase risk for nonarteritic ischemic optic neuropathy
- hearing loss
- priapism
- drug interactions: CYP3A4 inhibitors may increase serum concentration of PDE-5
20
Q
Administration of phosphodiasterase inhibitors?
A
- in general take 60 min prior to intercourse
- Vardenafil (levitra) and Avanafil (Stendra) have quicker onset of action (30 min)
- food and ETOH delay onset of action of Sildenafil (Viagra) and Vardenafil (Levitra)
- daily dose Tadalafil (Cialis) is available
21
Q
Cost per pills of phosphodiasterase inhibitors?
A
- Cialis: 10 mg 37.98
- Levitra 10 mg 33.32
- Viagra 50 mg 34
- Stendra 100 mg 29.04
22
Q
How long should you hold nitrates for after use of PDE-5?
A
- for 24 hours after use or 48 hrs if used Cialis
23
Q
Why is there testosterone replacement?
A
- to tx low testosterone levels in primary and secondary hypogonadism
- primary: testes fail to produce testosterone
- secondary: pituitary or hypothalamus malfxn
24
Q
MOA of testosterone replacement?
A
- direct action by binding to androgen receptor
- act in tissues that express enzyme 5-alpha reductase - converts to dihydrotestosterone - binds more readily to androgen receptor than testosterone
- can act as an estrogen after converting to estradiol via an aromatase and bind to estrogen receptor
25
What men should be tx with testosterone? What sxs are being tx? Goal of therapy? When should it not be used?
- only for use in men who are hypogonadal
- sxs that are tx:
decreased libido, decreased AM erections, loss of body hair, low bone density, gynecomastia, small testes, decreased muscle mass
- 3-6 months of therapy needed to note improvement in sxs
- 2 yrs for improvement in BMD
- goal of therapy: return testosterone levels back to normal range
- shouldn't be used to tx impaired spermatogenesis: testosterone therapy suppresses pituitary gonadotropin secretion and leads to more impairment of spermatogenesis
26
Prior to starting testosterone therapy - what needs to be done?
- screen for prostate cancer in men over 50 or in men over age 40 if any risk factors
- screen for erythrocytosis
- if sleep apnea is present - make sure it is being tx
27
SEs of testosterone therapy?
- polycythemia
- worsening of BPH sxs
- acne
- increase in PSA
- oral and prolonged IM doses assoc with multitude of liver issues (jaundice, hepatitis, elevated LFTs)
- increased risk of prostate cancer
- decreased spermatogenesis
- fluid retention
- worsening of sleep apnea
- possible increased risk of CV events (shouldn't start if had event in last 6 months)
28
CIs to testosterone therapy?
- known prostate cancer
- known breast cancer
- severe lower urinary tract sxs
- HCT over 50%
- untx severe sleep apnea
- PSA over 4 mcg/L
- PSA over 3 mcg/L w/ any prostate CA RFs
- CV in last 6 months - relative CI
29
Why is testosterone on FDA watch list - may be assoc with increased risk of what?
- may be assoc with risk of stroke, heart attack, and death in men taking FDA-approved testosterone products
- FDA evaluating 2 diff studies that suggest an increased risk of CV evetns among groups of men Rx testosterone, although agency hasn't concluded that these products increase the risk of stroke, heart attack or death
30
Diff routes of delivery for testosterone?
- oral (hepatic SEs)
- buccal tablet (BID)
- subq pellet (replace 3-6 months)
- nasal gel (TID)
- parenteral (IM): long acting, extra long acting (restricted prescribing)
- transdermal/topical: patch or gel
31
What is a good first choice formulation of testosterone therapy? Labs drawn first?
- transdermal gel:
well tolerated, achieves normal testosterone levels in most, patch is another option
- educate pt regarding transfer of gel onto others
- some prefer injections of long-acting testosterone
- labs:
serum testosterone, hematocrit, PSA prior to initiating therapy
32
Diff Testosterone gels used?
- Androgel - metered pump or packets (MC)
- Testim: dispensed in tubes of 50 or 100mg
- Fortesta: metered dose pump, apply to front and inner thighs
- Axiron: metered dose pump, apply to each axilla
33
What is Androderm? Why isn't it well tolerated?
- patch worn on torso or arm
| - significant skin irritation and 1/3 of men d/c use due to this SE
34
Diff types of IM testosterone?
- testosterone enanthate (Delatestry)
- testosterone cypionate (depo-testosterone)
- gluteal injections:
once weekly (50-100mg) or
once q 2 wks (100-200 mg)
35
What needs to be monitored throughout testosterone replacement?
- serum testosterone:
2-3 months after starting tx or changing dose, if primary hypogonadism check for normalization of serum LH (should decrease)
- Bone density: recheck q 2 yrs until normalizes or stabilizes
- PSA and DRE: 3-6 months after starting tx, yearly, problematic if: prostate nodule, increase in PSA over 1.4 in a yr, PSA velocity greater tahn 0.4/year for 2 or more yrs
- HCT:
3-6 months after starting therapy then yearly
D/C if HCT 54 over greater
36
Use of phenazopyridine (Pyridium)? When can't this be used? Other formulations available OTC?
urinary tract analgesic- sx relief of urinary burning, itching, frequency and urgency assoc with UTI or post urologic procedures
- Don't use if GFR less than 50
- OTC formulations: Azo-Gesic, Baridium, urinary pain relief
37
Prescribing considerations with Phenazopyridine? SEs?
- don't use for more than 2 days
- can turn skin and or sclera yellow
- turns urine bright orange
- only used for sx relief, doesn't tx infection
- other than orange urine: MC adverse rxns are HA, dizziness, stomach cramps
38
What is Pentosan (Elmiron) used for? MOA?
- urinary analgesic - used for interstitial cystitis
- 100 mg TID
- trial for 3-6 months to determine efficacy
- MOA: drug appears to adhere to bladder wall mucosa where it may act as buffer to protect the tissues from irritating substances in urine - low molecular wt heparinoid
39
SEs of Pentosan (Elmiron)?
adverse rxns: sig 1% to 10% -
- CNS: HA (3%), dizziness (1%)
- derm: alopecia (4%), rash (3%)
- GI: rectal hemorrhage (6%), diarrhea (4%), nausea (4%), abdominal pain (2%), dyspepsia (2%)
- hepatic: LFT abnormalities (1%, dose related)
- cost for 100 mg tablets: $814.98
40
Drugs used in tx of incontinence?
Muscarinic antagonists/antispasmodics:
- oxybutynin (ditropan)(Ditropan XL) (oxytrol transdermal patch)
- Tolterodine (Detrol) (Detrol LA)
- Trospium (Sanctura), (Trospium XR)
- Solifenacin (Vesicare)
- Darifenacin hydrobromide (Enablex)
- Fesoterodine (Toviaz)
41
Antimuscarinic agents used for? CIs? MOA?
- tx of urgency, urgency predominant mixed or over active bladder sxs
- don't use pharm therapy in demented people (stay away from anticholinergic drugs)
- CIs for antimuscarinic agents:
gastric retention
angle closure glaucomea
- MOA:
increase bladder activity, block basal release of acetylcholine during bladder filling resulting in decreased urgency
42
Selecting an antimuscarinic agent? How long does it take for peak efficacy?
- extended release agents have lower rates of adverse effects than immediate release agents
- start with lowest available dose
- eval for response in 4-6 wks
- on average takes at least 4 wks to peak efficacy
- may respond to one agent and not another so ok to try others in same class
43
Adverse effects?
- d/c rate of 58-71% at 6 months b/c:
anticholinergic effects -
dry mouth, constipation, blurred vision to near objects, tachycardia, drowsiness, decreased cognitive fxn, dizziness
44
What are considerations to think about b/f prescribing antimuscarinic agent?
- hepatic metabolism at CYP450 (many interactions) - except for Trospium
- renal failure
- liver failure
- cognitive impairment
- combos to avoid
- adverse effects to avoid
- generally prescribe extended release or transdermal formulations
45
What are drug combos to avoid with antimuscarinic agents?
- 1st gen antihistamines
- muscle relaxants
- some antipsychotics
- TCAs
- ipratropium (Combivent)
_ tiotropium (Spiriva)
- cholinesterase inhibitors (donepezil, rivasatigimine, galantamine)
- Triospoum and ETOH w/in 2 hrs
- mirabegron
- metoprolol and darifenacin
- grapefruit juice (darrifenacin, solifenacin, festerodine, tolerodine)
46
MC Rx antimuscarinic drugs? Goal of these drugs?
- Oxybutynin (Ditropan) (Ditropan XL) (Oxytrol transdermal patch)
- Tolterodine (Detrol) (Detrol LA)
- set realistic expectations prior to Rx:
goal is to reduce number of incontience episodes along with ongoing behavioral therapy, only 30% of pts at best achieve complete bladder control w/ tx, if failure on one med in class - try another if pt willing
47
What are common abx used for tx of UTI?
- ciprofloxacin
- Trimethoprim/sulfamethoxazole (Bactrim/septra)
- Nitrofurantoin (Macrodantin)
- amoxicillin
- ampicillin
48
Ciprofloxacin:
| class, MOA, preg, BBW, indications?
- Fluoroquinolone
- MOA: inhibit DNA gyrase and topoisomerase IV necessary for replication of bacteria
- preg: Assoc risk of tendinitis and tendon rupture in all ages, esp over 60, pts taking corticosteroids, and in pts with kidney, heart and lung transplants
- Adjust dose for renal failure pts
- caution when using in pts with hx of ventricular arrhythmias secondary to QT prolongation
- Preg C
- urologic indications:
cystitis, UTI and prostatitis
49
Trimethoprim/sulfamethoxazole (Bactrim/Septra):
class
MOA
preg?
- sulfonamide
- folic acid synthesis inhibitor
- Major but rare SE: SJS, hemolytic anemia if underlying G6PD deficiency
- Don't use with sulfa alelrgy
- preg C (but CI at term due to development of kernicterus in infants)
50
Nitrofurantoin (Macrodantin):
MOA
preg
urologic indications
- What should be done if decreased CrCl and chronic kidney disease?
- only for tx and prevention of uncomplicated UTIs
- MOA: poorly understood, thought to disrupt bacterial cell wall synthesis through inhibition of bacterial enzymes
- preg B (CI at term due to possibility of causing hemolytic anemia due to immature erythrocytes, don't use in lactaion
- inadequate drug levels in bladder if CrCl is abnormal (GFR less than 60 ml/min), CI in pts with CrCl of less than 60 ml/min
51
```
Amoxicillin:
class
MOA
preg category
urologic indications?
```
- 2nd generation PCN
- MOA: inhibit cell wall synthesis of bacteria
- Preg B, lactation: safe
- urologic indications: infections due to b-lactamase negative E. coli, proteus mirabilis or enterobacter faecalis
52
```
Ampicillin:
class
MOA
preg category
urologic indications?
Forms that it comes in?
```
- 2nd gen PCN
- inhibit cell wall synthesis of bacteria
- preg: B
- UTI
- oral, IM, IV
