Men's health

Question 1

Erectile dysfunction

Answer 1

• Increased incidence with age (lower in males

Question 2

ED Treatment Options

First line: PDE5-I
Sildenafil (Viagra)
Vardenafil (Levitra)
Tadalafil (Cialis)

Second line: Alprostadil (synthetic PGE-1); Trazodone, yohimbine

Answer 2

• Address RF (HTN, hyperlipidemia, DM, smoking, EtOH)
• First line: Phosphodiesterase-5 inhibitors (PDE5-I)– used to be to treat pulmonary HTN
• Second line: Alprostadil (synthetic PGE-1); Trazodone, yohimbine (not recommended; Testosterone (not recommended if level normal)

Question 3

Alprostadil

Answer 3

• Intraurethral suppositories
• Intracavernosal injections (high potential for prapism)
• Not good initial tx
• Rapid onset, effective
• Plaque/fibrosis development, pain

Question 4

PDE-5 Inhibitors

Sildenafil (Viagra)
Vardenafil (Levitra)
Tadalafil (Cialis)

Answer 4

• MOA: Inhibit phosphodiesterase-5 found in genital tissue; prevents PDE-5 from breaking down cGMP (increases smooth muscle relaxation, increases blood flow, think NO)
• Need sexual arousal to work

Question 5

Sildenafil (Viagra)

Answer 5

• Administration: 1 hr prior to intercourse
• Peak effect: 30-60 mins
• Fatty meal decreases effect
• T1/2: 3.7hr
• Duration of effect: 4 hr
• No more than one dose daily

Question 6

Vardenafil (Levitra)

Answer 6

Similar to Sildenafil

Question 7

Tadalafil (Cialis)

Answer 7

• Administration: prior to intercourse or once daily
• Peak effect: 2 hr
• Meal: unaffected (fatty meal does not decrease effect)
• Half life much longer (18hr)
• Duration of effect 24-37 hr
• Also indicated for BPH

Question 8

Counseling points

Answer 8

• 30-40% pt fail PDE5-I
• Important to engage in sexual stimulation
• No response with first dose– increase to max dose; continue 6-8 doses before declaring tx failure
• Check testosterone levels (prolactin/LH)
• Lower doses in age > 65yo, severe renal/hepatic impairment

Question 9

PDE5i ADR

Answer 9

• Mild to moderate AEs, self limiting
• Dose related
• HA, facial flushing, dyspepsia, nasal congestion, dizziness (inhibition of PDE-5 in peripheral vascular tissue, plts, tracheal smooth muscle)
• Hypotension: not big problem; seen with Sildenafil and Vardenafil; NOT seen in Tadalafil, multiple anti-HTN meds
• Visual disturbances: increased light sensitivity, blurred vision, loss of blue-green color; inhibition of PDE-6 in photoreceptor cells of retina (less likely with Vardenafil, NOT seen with Tadalafil)
• Back/muscle pain: inhibition of PDE-11 in skeletal muscle (ONLY with Tadalafil)
• Priapism: caution with Tadalafil (unlikely with Sildenafil and Vardenafil–> shorter T1/2)

Question 10

PDE5i Drug Interactions

Answer 10

• Nitrates: increase hypotension; 24-48 hr separation
• Anti-HTN meds: Additive effects (use lower doses of both initially); Alpha blockers (Tamsulosin, Doxazosin, Prazosin, Terazosin)
• Vardenafil– Can prolong QT, avoid w/ antiarrhythmics

Question 11

HTN management

Answer 11

• Lifelong lifestyle modification (focusing on limiting overall caloric intake, improving their nutrition, and becoming physically active)
• Sexual function should be assessed in all men prior to initiation and follow-up of anti-HTN meds
• ARBs should be the DOC in sexually active/ED hypertensive men
• If ED developed during anti HTN tx, prescription of PDE5I suggested unless CI (in concurrent use of nitrates)

Question 12

BPH

Answer 12

• PDE-5 inhibitors: can improve lower urinary tract sx secondary to BPH, erectile fxn, quality of life
• Absolute indiction for intervention: renal complication due to BPH, bladder stones, persistent or recurrent urinary retention, chronic UTIs

Question 13

BPH Treatment options

Answer 13

1. Alpha-1 antagonists
   - Nonselective: Terazosin (Hytrin), Doxazosin (Cardura), Prazosin (Minipres)
   - Selective: Tamsulosin (Flomax), Alfuzosin (Uroxatral), Sildosin (Rapaflo)

Use if

• Bothersome or moderate to severe sx
• AUA-SI score of > 8
• 4-6 point reduction on AUA-SI
• Considered equally effective
• Differ in side effect profile

2. 5 alpha reductase inhibitor
3. Combination therapy (Alpha 1 antagonists + 5 alpha reductase ihibitor)
4. Antimuscarinic
5. PDE5i
6. Sae Palmetto (no evidence of efficacy)

Question 14

Alpha 1 Antagonist

Answer 14

• MOA: work by blocking NE effects on alpha 1 receptors on vascular smooth muscle
• Stromal tissue: NE causes contraction, compression around urethra and affects bladder emptying
• Capsule: outer shell of prostate, NE causes contraction around urethra
• Relax urethra sphincter/prostate tissue, increase urine flow
• DO NOT decrease prostate size

Nonselective

Question 15

Nonselective

Terazosin (Hytrin)
Doxazosin (Cardura)
Prazosin (Minipres)

Answer 15

• Work on prostate, vascular, CNS alpha 1 receptors (vascular/CNS effects occur at doses for BPH)
• AUA: do not use to treat BPH and HTN; Prazosin NOT recommended due to lack of evidence
• All effective; full effect in 2-4 wks

ADR: related to blocking of alpha 1b, 1d– CNS and vasculature

• First dose syncope
• Orthostatic hypotension, dizziness (decrease dose, titrate slowly)
• 10% of pts stop these medications secondary to AEs
• Syncope, dizziness, hypotension > than selective

Question 16

Selective

Tamsulosin (Flomax)
Alfuzosin (Uroxatral)
Sildosin (Rapaflo)

Answer 16

Selective for alpha 1 receptors on prostate tissue

• AUA: equal efficacy as nonselective alpha 1 antagonists
• No effect on BP
• Good for combination with anti-HTN meds
• Effect see within days to 1 wk

Question 17

Tamsulosin (Flomax)

Answer 17

• Take dose anytime during day
• Take on empty stomach
• No dose change in renal failure, use with caution in liver failure

ADR–unavoidable, should not lead to d/c: tiredness, asthenia, ejaculatory dysfxn (reduced force or volume of ejaculate), nasal congestion

DRUG INTERACTION:

• Avoid with diltiazem (Cardizem)– reduced met of diltazem
• Reduced effectiveness with phenytoin, carbamazepine

Question 18

Alfuzosin (Uroxatral)

Answer 18

• Take dose after the same meal each day
• No dose change in renal failure
• CI in moderate-severe liver failure

ADR– unavoidable, should not lead to d/c: dizziness, HA, tiredness, hypotension

DRUG INTERACTION: caution with 3A4 inhibitors– increase alfuzosin

Question 19

Silodosin (Rapaflo)

Answer 19

• More potent alpha-1 antagonist
• CrCl 30-50mL/min–> 4 mg/d
• CrCl CI
• CI in liver failure with a child-pugh> 10

ADR: abnormal ejaculation, dizziness, orthostatic, hypotension, HA

DRUG INTERACTION:

• 3A4 substrate: Fluconazole, verapamil, diltiazem can increase silodosin levels (Hypotension– orthostasis, tachycardia)
• PDE5inhibitors: orthostatic hypotension

Question 20

5 alpha reductase

Answer 20

• Converts testosterone to DHT: 2 enzymes
• Type 1: found in hair, liver, skin; acne, body/facial hair, baldness
• Type 2: found in prostate, genital tissue, scalp; prostate enlargement and growth

Question 21

5 alpha reductase inhibitors

Finasteride (Proscar)
Dutasteride (Avodart)

Answer 21

Finasteride: specific for type 2 enzyme
Dutasteride: non-specific for type 1 and 2

• MOA: block effect of 5 alpha reductase
• Efficacy: both considered equally efficacious, no known benefit from dual enzyme blockade
• USE: prostate > 30g (PSA level= 1.5ng/mL); CV or CV AEs from alpha 1 antagonists)
• EFFECT: not seen for 6 months; 4-6 point reduction on AUASI; Reduce prostate 25%/PSA levels 50%; improve urine flow, decrease CXs, surgery; stopping will cause prostate size/sxs return
• ADR: ejaculatory dysfunction (reversible with drug d/c); ED; N/abd pain, asthenia
• Pregnancy cat X: women of child bearing age– avoid pill contact, semen when male is on medication

Question 22

Combination therapy

Answer 22

• Alpha 1 antagonists + 5 alpha reductase inhibitor
• Jalyn (dutasteride + tamsulosin)

Recommended

• Appropriate/effective for pts with LUTS and prostate enlargement
• Rapid relief with alpha 1 and sustained relief with 5 alpha
• greater reductions in complications and progression than monotherapy
• d/c 6-9 months following sx improvement

Question 23

Antimuscarinic agents

Answer 23

• Role of M2 and M3 muscarinic receptors
• AUA: data are lacking, use with caution (concern may worsen urinary retention)
• May be best as add-on tx for men with predominantly storage sx

Question 24

PDE-5 inhibitors

Answer 24

• Role of PDE-5 enzyme in bladder/urinary tact

- Produce smooth-muscle relaxation + block proliferation of prostate and bladder smooth-muscle cells

Question 25

Saw Palmetto

Answer 25

- Extract from raw fruit - Must be lipid extract, water extraction not effective - Antiandrogenic: inhibits 5 alpha reductase; inhibits conversion of testosterone to DHT - Antiproliferative, antiinflammatory properties - USES: BPH, mild diuretic, sedative, antiinflammatory, antiseptic, aphrodisiac, prostatitis, prostate cancer, stimulate hair growth - ADRs (mild): dizziness, HA, N/V/D/C, asthenia - Potential anticoagulant interaction - Potential interaction with estrogen

Question 26

Yohimbine

Answer 26

Don't use due to lots of ADRs

Question 27

Testosterone replacement

Answer 27

- For male hormone replacement for hypogonadism Goals of therapy - Restore sexual fxn, libido, well being and behavior - Produce and maintain virilization - Optimize bone density and prevent osteoporosis - In elderly men, possibly normalize growth hormone levels - Potentially affect the risk oc CVD - In cases of hypogonadotropic hypogonadism, restore fertility

Question 28

Testosterone CI

Answer 28

- Breast/prostate cancer - Palpable prostate nodule - PSA > 4 or > 3 in men at high risk of prostate CA - Hematocrit above 50% - Untreated sleep apnea - Uncontrolled HF - Those desiring fertility

Question 29

Testosterone ADRs

Answer 29

- Increased Hematocrit (Baseline, then q6months x 18months, then annually; clots) - Acne, oily skin - Mood swings - Sleep apnea - Infertility - Worsening of BPH (why prostate CA is concerning-- baseline PSA, at 3-6 months, then annually in men over 40; need digital rectal exam to check size) - Gynecomastia - Risk of stroke, AMI and death

Question 30

Delivery mechanisms

Answer 30

NOT given orally (T1/2 too short)-- concerns for liver damage Give IM: Depotestosterone or Delatestryl - Levels peak then drop fast - Check 1 week after the dose Transdermal testosterone: Androgel, Fortesta, Testim, Axiron, Androderm

Question 31

AVEED

Answer 31

- Testosterone undecanoate - Long acting, depot formulation for IM - Injection every 10 weeks - Box warning for risk of serious pulmonary oil microembolism (Acute cough after injection) - Associated with anaphylaxis

Question 32

Androgel

Answer 32

- Need to make sure to clean hands/table once it is applied - Need to be careful not to expose it to anyone else - Don't let anyone apply it for you!!!!

Question 33

Axiron

Answer 33

- Testosterone axillary solution | - Attempt to help limit secondary

Question 34

Guidelines

Answer 34

- No recommendation for general screening - Test men with symptoms - Check PSA for baseline - Consider treatment for total testosterone levels 4 ng/ml, PSA > 3 ng/ml in AA males) - Breast cancer - HCT > 50% (worry about polythythemia) - Untreated sleep apnea - Poorly controlled HF - Severe lower urinary tract symptoms

Question 35

Prostate Cancer Treatment

Answer 35

Androgen Deprivation Therapy: - Luteinizing Hormone Releasing Hormone (LHRH) analogs - LHRH antagonists - Anti-Androgen

Question 36

LHRH analogs Leuprolide Goserelin Triptorelin Histrelin

Answer 36

- Lower androgen levels as well as orchiectomy | - Testicles shrink over time

Question 37

LHRH Antagonist Degarelix

Answer 37

- Suppresses androgen production | - Reduce testosterone levels more quickly

Question 38

Anti-Androgens

Answer 38

- Androgen receptor blockers at tissues: Bicalutamide, Flutamide, Nilutamide, Enzalutamide - Ketoconazole : blocks androgen production

Question 39

After ADT

Answer 39

- Monitor pts for osteoporosis - Watch for anemia - ED - Gynecomastia - Decreased muscle mass, weakness - Mood changes - Fatigue