Men’s Health

Men’s Health Bin Deng, PharmD, BCACP, BC-ADM, CDCES Spring 2025 Question 1 What is considered a first line agent for Benigneprostetic Moohyperplasia treatment of moderate to severe BPH? a. alpha 1 blocker O b. 5 alpha reductase inhibitor c. PDE 5 inhibitor d. Anticholingeric agent prostategland enlangeswiobeing concengst  Alpha blockers reduce sx within 4-6 weeks by  Relaxing smooth muscle in the prostate and bladder neck  Increasing urinary flow rate  Reduce PVR to post residualvolume void α- 1 blockers  Onset: within days  Effectiveness and ADR are dose dependent  Considered first line agents for tx of moderatesevere LUTS/BPH  2nd gen vs 3rd gen: urine lowersymptoms tract • Uroselective: 3rd generation alpha blockers have less effect on alpha 1B/1D • Dose titration  The 2nd- and 3rd-gen α1-blockers are considered equally effective They do not shrink prostate and does not affect PSA levels or prostate volume prostate my specific Antigen 3 ORJI OSIIficcontrouedreleaseonaldolivaysusten PIED to Drug Class Drug Usual Dose (mg) Comments 2nd Generation alpha-1 blockers Terazosin (Hytrin) IR: Start 1 mg at HS; titrate slowly 10 mg QD is generally effective (Max 20 mg HS) Doxazosin (Cardura) IR: start 1 mg; titrate slowly up to 4-8 mg daily, usually given at HS These are associated with orthostatic hypotension, especially in older adults. Give first dose at bedtime; patients should rise from sitting or lying down slowly to minimize risk of orthostatic hypotension. Discontinue if angina occurs. XR: start 4 mg QD w/ breakfast; titrate to max 8 mg QD Cardura XL is an OROS formulation ghost shell. α- 1 blockers minipress g Prazosin (2nd gen), NOT recommended due to BIDTID dosing and significant CV effect tardiousailor no III 3rd Generation Alpha-1A blockers Better option toast Alfuzosin (Uroxatral)--clinically uroselective—less CV ADR XR: 10 mg QD immediately after the same meal each day Tamsulosin (Flomax) 0.4 mg daily; 30 min after the same meal each day Avoid tamsulosin in sulfa allergic (max 0.8 mg QD) Tamsulosin/silodosin can cause reversible ejaculation failure/retrograde ejaculation (8-18%) + dutasteride (Jalyn) Silodosin (Rapaflo) Do not use alfuzosin in patients at risk of Qtc prolongation Crcl < 30 ml/min: use w/ caution 8 mg QD w/ meal Crcl 30-50 ml/min: 4 mg QD Crcl < 30 ml/min: do not use W wtf Silodosin can cause reversible retrograde ejaculation (28%) Meal: helps lower risk of hypotensive ADR 4 Question 2 propecia no Which pregnancy category is finasteride? a. A b. B c. C d. X forfinasteride mo women of child bearing • Contraindication: potential, pregnancy, children (Category X) • Warnings: May increase risk of high-grade prostate CA cancer • Side Effects: tprostat Safety Information (3-16%), decreased libido, WIGHT • Impotence ejaculation disturbances, breast staffed enlargement/tenderness, rash • Sexual SE are reversible, decreases with time and are uncommon after 1st yr of therapy • Monitoring • PSA, urinary sx 5-α Reductase Inhibitors • Interactions  Finasteride and dutasteride are minor CYP3A4 substrate; strong inhibitors may increase levels 6 Question 3 Which class of medication shrinks prostate and reduce PSA level? a. alpha 1 blocker b. 5 alpha reductase inhibitor c. PDE 5 inhibitor d. Anticholingeric agent  In the prostate, dihydrotestosterone (DHT) induces growth and enlargement of the gland 5-α Reductase Inhibitors  Inhibit 5- α Reductase enzyme which is responsible for converting testosterone to dihydrotestosterone (DHT)  Shrinks prostate and reduces PSA levels  PSA level falls approx. 50% after 6-12 mon  Helps increase urinary flow rate (less effect than alpha antagonist), reduce long term risk of acute urinary retention or need for surgery  Delays sx progression g  Reserved use for patients with • Significantly enlarged prostates—unclear definition • • • • Volume > 25, 30 or 40 ml (AUA, 2010); 40 ml (European guideline, 2014) And/or PSA > 1.4- 1.5 ng/dl (proxy for prostate size) Intolerant or refractory to alpha-1 blockers, Those with hematuria associated with BPH (thru diagnosis of exclusion) 8 Anticholinergics (antimuscarinic) Agents Makespigdry fr  Anticholinergics block acetylcholine in the central and peripheral nervous system  Reduce detrusor muscle contraction reducing urinary freq, urgency and incontinence 5  Used in combination w/ alpha-antagonist or 5ARI am  If the patient has significant irritative storage sx not responsive to either tx alone  Onset: weeks  Anticholinergics may be used off-label if  LUTS predominantly storage/irritative sx AND post-void residual (PVR) is NOT elevated  Caution is PVR > 100-150 ml  Prior to initiation, baseline PVR urine should be assessed  These agents do not improve urinary flow rate or consistently improve AUA symptom scores  Consider total anticholinergic burden (from other concurrent medications)  Anticholinergic: e.g. tolterodine (most studied in BPH), Solifencin, darifencin  Other options:  Beta-3 agonist 9 Its Tadalafil FDA approved for PDE-5 Inhibitor Improvement of BPH sx has been reported to ameliorate ED; and vice versa Minimal reduction in PVR and minimal effect on flow rate • BPH • BPH + ED • ED alone PDE5I considered less effective than alpha blocker for BPH Recommended in the in moderate-severe LUTS in younger male patients by the European guideline Monotherapy or in combination Dosing for BPH +/- ED: • 5 mg daily (NOT PRN) Onset: within 1st week 10 MEFFEG Combination Therapy • Alpha blocker + 5-ARI  Use for men with larger prostates (>40 ml and PSA > 1.41.5 ng/dl) and severe sx  This combination is superior either alpha blocker or 5ARI alone in preventing progression and improving symptoms in men with large prostate (long term treatment) Alpha Blocker + anticholinergic •  For patients with a predominance of irritative/storage symptoms, an anticholinergic agent could be added to an existing drug regimen for BPH PDE5-Inhibitor + Alpha blocker (or 5 ARI)  BPH + ED  Using PDE5I w/ 5-ARI is will effectively treat ED associated w/ 5ARI 11 Question 4 Which of the following agent is associated with more lower back and limb pain? a) sildenafil b) vardenafil c) tadalafil • Mechanism: PDE5 inhibitors increase the concentration and prolong the activity of intracellular cGMP • Drugs: sildenafil, tadalafil, vardenafil, avanafil PDE5 Inhibitors -Sildenafil and vardenafil use is associated with more vascular and ocular adverse effects due to its inhibition of PDE type 1 and 6 respectively, -Sildenafil and vardenafil use is associated with more vascular and ocular adverseiseffects due to its and limb pain Tadalafil associated back inhibition of PDE type 1 and 6 and myalgia due to its greater inhibition of respectively, PDE type 11 -Sildenafil and vardenafil use is associated with more vascular and ocular adverse effects due to its inhibition of PDE type 1 and 6 respectively, • Side Effects: mild-moderate, self-limiting, most are dose related • Side Effects: mild-moderate, self-limiting, most are dose related • • • • • • • • Headache (10%) Flushing (12%) Hypotension (less w/ tadalafil, avanafil) Low back pain (PDE11 inhibition)—up to 30% w/ tadalafil (occurs 1224 hrs after taking, and can last up to 2 days) Ocular side effects e.g. light sensitivity, loss of blue-green discrimination, blurry vision (PDE6 inh)---EXCEPT for tadaladil Vardenafil: Qtc prolongation Priapism (esp sildenafil, vardenfil) Rare: may be permanent • • Hearing loss, ringing of the ear Vision loss • Immediately stop PDE5Inhibitors if vision or hearing loss • NO more than one PDE5 inhibitors taken per day is recommended 13 PDE5 Inhibitors Contraindications Nitrates Guanylate Cyclase (GC) stimulators Viagra • Withhold for 24 hours after sildenafil, avanafil and vardenafil or staxyn • Withheld for 48 hours after tadalafil administration no Adem Am pas • E.g riociguat • Do not give within 24 hr of sildenafil or 24 hrs before or 48 hrs after tadalafil CHF= congestive heart failure 14 Viagra (empty stomach, at Least 2 hrs before meals) Cialis Onset/duration Side effect Caution Quick onset/short duration Hypotension, Visual side effects (PDE6 inh) Renal Dose No muscle pain/back pain adjustment Fatty food reduces Tmax by 1 hr and Cmax by 30% Muscle/back pain (PDE11inhibition) Renal Dose Adjustment Hypotension Qtc prolongation Fatty food reduced No Renal Dose Adjustment Cmax (Levitra/Staxyn) No muscle pain/back pain 18-50% -water reduces Tmax of ODT by 30% Summary Chart Delayed onset/long duration Levitra/Staxyn (empty stomach, at Least 2 hrs before meals) Quick onset/short duration Stendra Quick onset/short duration Advantages No Hypotension Can be dosed daily One pill can last a weekend Absorption not delayed by fatty food Low risk of visual SE & hypotension No Renal Dose Adjustment; although not recommended in crcl < 30 15 Question 5 Which of the following agent is more preferred for a patient with frequent sexual intercourse? a)Sildenafil b) vardenafil c) tadalafil • For a patient with infrequent sexual intercourse, sildenafil (Viagra) or vardenafil(Levitra) is a good choice; • For a patient with frequent sexual intercourse, tadalafil (Cialis) may be preferred (more spontaneity) Eton • For a patient with unscheduled periodic intercourse, a fast-acting agent like vardenafil ODT (Stazyn) may be preferred. • Avanafil is the most selective w/ quickest onset of action and short duration (may be the best tolerated PDE5i Dose Counselling Note Sildenafil (Viagra, Revatio) 25-100 mg (start with= 50 mg) once daily prn (MAX once daily) Take 1 hour prior to sexual activity Tadalafil (Cialis, Adcirca) 1. 2.5-5 mg daily at the same time each day (scheduled)—(clinical trial off label: 10-20 mg daily) PRN dosing: take 30 min prior to sexual activity May be used alone or along with an α-adrenergic antagonist for BPH Staxyn is ODT (take w/ot water for discretion)— higher BA. Do not take ODT w/ water. Levitra (film-coated) is not interchangeable with Staxyn (ODT) 2. 5-20 mg (start with=10 mg) once daily as needed (prn) (MAX: once daily) Vardanafil (Levitra, Staxyn) 5-20 mg (start= 10 mg) prn (MAX once daily) Take 1 hour prior to sexual activity Avanafil (Stendra) 50-200 mg (start with=100 mg) once daily prn (MAX once daily) Take 15-30 min prior to sexual activity • Dose should be titrated to provide optimal efficacy 18 Synthetic prostaglandin E1 • Vasodilator • Mechanism: stimulates adenyl cyclase, resulting in increased production of cAMP resulting in muscle relaxation intoBrand: Caverject, Edex directly Alprostadil Mopeds (intracavernosal Injection-ICI) Max 1x/day; 3x/wk • Erection caused after 5-10 min of injection; should last approx. 1 hour • Duration of erection is dose dependent Adverse drug reactions: • Mostly local (will improve as self-injection technique improves) • Corporal fibrosis or plaques (wait till resolved before injecting again) • Penile pain or burning during erection • Hypotension (high doses), priapism More efficacious than intraurethral alprostadil Does not require NO to produce clinical effect • Preferred in diabetic pts who failed PDE5 inh 19 ALPROSTADIL (INTRAurethral) Intraurethral MUSE ® (Medicated Urethral System for alprostadil Erection) • Micro-suppository administered immediately after urination • Max 2x/day • Refrigerate Adverse Effects • Damage to urethra Urethral pain, Female sexual partners may experience vaginal burning, itching, or pain Priapism, syncope and dizziness—rare (at large doses) Intraurethral alprostadil should be avoided in patients with urethral stricture or urethritis 20 Non-Pharmacological VED Vacuum Erection device (VED)  Onset: 3-20 min; a faster onset of 2-3 min if more experienced use  Available OTC; Purchase once and use repeatedly • Battery operated available  Prescription VED have safety mechanism • Minimizing excessive vacuum pressure  Not discreet  Monotherapy or combination  Better efficacy in combination w/ PDE5i or alprostadil  Contraindications • Sickle cell anemia • Anticoagulants  Create tight seal w/ lubricant  Constriction bands penile pain, injury Pump Negative Vacuum pressure Cylinder Penis is inserted into cylinder 21 Penile Prosthesis Implantation  Invasive  Benefits: erection on-demand and for as long as desired (and as frequently as desired!)  Risks: • Device malfunction • Possible changes in appearance of penis • Infection • Irreversible 22