Treatment of Erectile Dysfunction Gregory Harochaw Robin Coulter Tache Pharmacy 400 Tache Avenue Winnipeg, MB R2H 3C3 Phone: (204) 233-3469

What is Erectile Dysfunction? The persistent or recurrent inability to obtain or maintain an erection sufficient for sexual activity1 > 50% of men aged 40 – 70 will have fairly marked erectile problems2,3 Incidence is on the rise due to aging population & and  prevalence of conditions that are the root of the problem (i.e. diabetes, cardiovascular disease)2 Hatzimouratidis K, and Hatzichristou D. Sexual dysfunctions: Classifications and definitions. Journal of Sexual Medicine 2007;4:241-250. Fazio L, Brock G. Erectile dysfunction: management update. CMAJ 2004;170(9):1429-1437 Feldman HA, Goldstein I, Hatzichristou D, et al. Impotence and its medical and psychosocialcorrelates: results of the Massachusetts Male Aging Study. J Urol 1994;151:54-61

Men With ED ED can have a major impact on the quality of life and self-esteem of men who suffer from it Men often draw a link between their masculinity and their ability to have an erection Some men with ED may begin to think that they are no longer a “real” man This can lead also to affected relationships with partners

Pathophysiology: Mechanism of an erection A normal erection relies on the coordination: Vascular Neurological Hormonal Psychological An erection can occur following direct genital stimulation or auditory or visual stimulation, aspects that contribute to the influx of blood to the penis

Pathophysiology: Mechanism of an erection An erection occurs when the amount of blood rushing to the penis is greater than the amount of blood flowing from it A massive influx of blood accumulates in the sinusoidal spaces due to relaxation of smooth muscle & dilatation of arteries  corpora cavernosa to swell (tumescence) Tumescence compresses the veins that normally drain the penis  prevents blood outflow & maintains penile rigidity

Pathophysiology: Mechanism of an erection Usually following ejaculation: A reduction in arterial inflow due to contraction of the smooth muscle cells Combination of increased venous return loss of erection (detumescence)

Erectile Dysfunction ED is most often an organic origin (up to 80%) Can also have psychogenic causes In several cases, it is both organic/psychogenic in origin  mixed-type ED Anatomy and physiology of erection: pathophysiology of erectile dysfunction. Int J Impot Res 2003;15 Suppl 7:S5-S8.

Main Organic Causes Vascular Roughly 40% of cases of ED in men over 50 Vascular problems can impede arterial blood flow into the penis Examples: diabetes, cardiovascular disease (hypertension ,dyslipidemia), Peyronie’s disease, smoking, and trauma affecting blood circulation Feldman HA, Goldstein I, Hatzichristou D, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994;151:54-61

Main Organic Causes Neurological conditions Can lead to interruption in nerve impulse transmission or the failure to conduct nerve impulses Examples: diabetic or alcoholic neuropathy, MS, stroke, trauma or surgical procedures involving the spinal cord or pelvis Brock G. Issues in the assessment and treatment of erectile dysfunction: Individualizing and optimizing treatment for the “silent majority”. www.medscape.com/viewprogram/1826 Accessed January 20, 2009

Main Organic Causes Hormone disorders ED that is hormonal in origin can be related to low circulation blood levels of testosterone (hypogonadism), hyperprolactinemia (drug-related or non-drug related), hypothyroidism, adrenal insufficiency or glucocorticoid excess Brock G. Issues in the assessment and treatment of erectile dysfunction: Individualizing and optimizing treatment for the “silent majority”. www.medscape.com/viewprogram/1826 Accessed January 20, 2009

Psychogenic Origin Can be cause by: Anxiety Depression or psychosis Possibly with a loss of self-esteem If causes of erectile dysfunction are completely psychological, the patient will continue to have nocturnal erections Men with psychogenic ED often lose interest in sex Anatomy and physiology of erection: pathophysiology of erectile dysfunction. Int J Impot Res 2003;15 Suppl 7:S5-S8.

Risk Factors1,2,3 Aging Diabetes (vascular or neurological problems) Cardiovascular disease (vascular issues) Stress, anxiety & depression (low libido or self-esteem) Medications or illicit substances Prostatectomy (neurological problems) Smoking (exacerbates vascular problem) Hatzimouratidis K, and Hatzichristou D. Sexual dysfunctions: Classifications and definitions. Journal of Sexual Medicine 2007;4:241-250. Fazio L, Brock G. Erectile dysfunction: management update. CMAJ 2004;170(9):1429-1437 Feldman HA, Goldstein I, Hatzichristou D, et al. Impotence and its medical and psychosocialcorrelates: results of the Massachusetts Male Aging Study. J Urol 1994;151:54-61

Diabetes ED About 35 – 75% of men with diabetes will experience at least some degree of ED (impotence) during their lifetime Men with diabetes develop ED 10 – 15 years earlier than men without diabetes Often 1st symptom men notice even before they are diagnosed as a diabetic Above age of 50, the likelihood of having difficulties with an erection occurs in approximately 50 – 60% of men Above the age of 70, there is a 95% likelihood of having some difficulty with erection function www.WebMD.com

Diabetes ED To get an erection, men need healthy: Blood vessels Nerves Muscle function Desire to be sexually stimulated Elevated blood glucose levels can cause damage to blood vessels & nerves to the penis Men with coronary artery disease (CAD) & diabetes will be 9 times more likely to develop ED than men with just diabetes www.diabetes..about.com

Diabetes ED Longer a man has diabetes with poor blood glucose levels, complications of accompanying heart disease such as high blood pressure & high cholesterol can also affect ED Diabetic men who smoke also have increased risk of developing ED www.diabetes..about.com

MEDICATIONS ASSOCIATED WITH ED ALTERNATE SOLUTIONS Cardiovascular Antidepressants Betablockers Hydralazine Methyldopa Alpha-blockers ACE inhibitors ACE II inhibitors Ca++ channel blockers SSRI Tricyclic antidepressant MAOI Buproprion Mirtazapine Diuretics Antipsychotic agents Thiazide diuretics Spironolactone Furosemide (loop diurectics) Conventional neuroleptics Risperidone Quetiapine Olanzapine Hormone agents Gastroesophageal reflux & ulcers Anti-androgens (e.g. cyproterone) Corticosteroids Varies depending on indication Cimetidine Other H2 antagonist or PPI Antiparkinsonian agents Anticonvulsants Levodopa At the neurologist’s discretion Carbamazepine Phenytoin Miscellaneous: Phenothiazine antiemetics, opioids (chronic use), digoxin, ketoconazole, lithium Drug-induced male sexual dysfunction.Pharmacist’s Letter/Prescriber’s Letter 2006; 22(9):220907.

Treatment Options PDE5 Inhibitors Intraurethral suppositories Sildenafil - Viagra® Varedenafil - Levitra® Tadalafil - Cialis® Intraurethral suppositories Alprostadil - MUSE® Intraurethal gel Penile injections Vacuum devices

Autonomic spinal erection center The increase in arterial inflow to the penis is dependent upon the autonomic spinal erection center, which sends parasympathetic and sympathetic impulses to the arteries and smooth muscles of the corpora cavernosa. High concentrations of nitric oxide (NO) are released through neural pathways into the smooth muscles of the corpora cavernosa (Figure 2). Nitric oxide activates cyclic guanosine monophosphate (cGMP), resulting in a reduction in cytosolic calcium levels and relaxation of the smooth muscles. Phosphodiesterase type 5 (PDE-5) is responsible for the breakdown of cGMP into an inactive form, 5+cGMP4, which inhibits the effect of NO.

Presence of fatty foods can double the absorption time of Sildenafil and Vardenafil from 1 hour to 2 hours. Absorption is reduced from 20-50%. Take these at 5PM and say dinner is at 7PM then these products will continue to work 8-12 hours later. If taken after meals then people should wait at least 2 hours prior to activity. For diabetics, stomach emptying time is very much delayed so they should take these for sure before meals to get a response. For tadalfil because reponse is 2-4 hours people should take 1st dose at least 4 hours prior to activity to ensure this works for them. Side effects come on with 30-60 minutes of taking the pill and last 30-60 minutes. These are usually mild and disappear after a while. Visual disturbances: sildenafil/vardenafil cross react with an enzyme in the retina known as PDE6, thus causes blurred vision, double vision or loss of colour vision. Not dangerous and does not cause night blindness. Tadalfil can cause pooling of blood in major muscles in the body particularly back buttock’s and leg. 10% discontinuation.

Intraurethral Suppository MUSE® 250ug, 500ug, 1000ug Medicated Urethral System for Erection A choice for people: Who do not respond to oral pills Are afraid of injections Suppository (about the size of a grain of rice) which is placed about 1” inside the urethra using a special applicator

Advantages with MUSE® Fool proof and low incidence of SE’s Gives an erection similar to penile injection therapy Gives the most normal looking erection. The head of the penis doesn’t swell in penile injections/PDE5 inhibitors but does with MUSE®

Disadvantages with MUSE® 50 – 75% of men don’t respond well 50- 60% of men don’t respond consistently May get good erection one time but not the next May develop a lack of confidence because 1 out of every 2 or 3 uses doesn’t work well 2% of men may have dizziness on 1st administration with 1000µg strength. May need to do the 1st dose in the Dr’s office Not with 250µg or 500µg dose

MUSE® Injector

Intraurethal Gels Fool proof and low incidence of SE’s Gives an erection similar to penile injection therapy Possibly stronger than using MUSE® Must be kept in the fridge and has a 30 day expiry date

Intraurethral Gels Many combinations Dispense in 0.2ml single use syringes Expiry date 30 days Dose 0.2 intraurethrally 10 – 15 minutes prior to sexual intercourse Hold penis upright for 30 seconds to allow medication to absorb Rub any excess cream over the forehead of the penis

Penile Injections Intracavernosal injection therapy Around since 1983. Very safe & highly effective Around since 1983. In 1982, a French surgeon injected a vasodilator into the pelvic artery & the patient obtained an erection Shortly after, a British physician injected a drug directly into the penis

Caverject Alprostadil 20µg/0.5ml Works in 60% with all men with ED Prefilled syringe Dosage range 5 – 20µg Works in 60% with all men with ED Will work better with milder erection problems Can cause an aching or burning penile pain in some men with cavernous nerve injury

Caverject

Penile Injections Alprostadil Papaverine Phentolamine Atropine Prostaglandin E -1  cAMP Vasodilator & muscle relaxant of corpus cavernosum & trabecular smooth muscle Papaverine Inhibits phosphodiesterase in smooth muscle cells, which  cAMP & cGMP  relaxation of vascular smooth muscles Phentolamine Blocks -adrenergic receptors in penile blood vessels  relaxation of trabecular cavernous smooth muscles & dilatation of the penile arteries Weak erectile-promoting effect when used alone. Potentiates the effect of papaverine or PGE-1 Atropine Smooth muscle relaxation Chlorpromazine  blocker activity 1:1 mg interchangeability with phentolamine

Penile Injections Products require refrigeration Caverject® is kept at room temperature After 18 months of radical prostatectomy more than 70% of people will  the dose of their injection Duration of injection will be a sign for this i.e. 30 minutes  45 minutes  60 minutes

Price Comparison Medication Cost Per Dose Viagra 100mg/Generic $16.69/$12.79 MUSE 1000µg $40.76 Intraurethral Gel $22.82*** Caverject 20ug $40.17* Tri-Mix $4.10** *Caverject is a single use vial so product. Manufacturer recommends once mixed product to be discarded regardless what dose is used ** Tri-Mix dose used here is 40 units (0.4ml). In a 10.6ml vial a person would get 24 doses ***Need to order 6 doses to get this price Prices January 2013

BD Inject-Ease Will inject needle into the skin but you still need to push the plunger to dispense injection $45.00

Autoject 2 Does a complete injection $69.95

Vacuum Devices Have been used for more than a century 1874 by Dr. John King 1917 Dr. Otto Lederer developed constriction rings for maintenance of erections 1960’s Geddings Osborn developed his version of vacuum device 1974 Osborn’s product became commercially available 1976 FDA withdrew it’s approval 1982 FDA reapproved product

Vacuum Devices Erect penis (especially Caucasian) appears blue or grey 50% of blood from arteries oxygenated 50% of blood from veins  non-oxygenated Arterial blood is warmer than venous blood Penis may not be as warm (1º-2º F lower) Most common complaint of partners Touch penis Upon penetration

Vacuum Devices Takes 2-10 minutes to obtain a functional erection Take on average 4 attempts to use pumps to become proficient Need to place constriction ring as close as possible to base of penis. Penis will be hard on one side of ring and soft on the other side Only wear for maximum 30 minutes

Vacuum Pumps 80-90%of men can obtain an erection Overall patient satisfaction 60-80% In order to achieve enough pressure in the vacuum device, gel will have to be applied to the open end of the device Some men will also have to trim the pubic hair to maximize seal

Vacuum Devices Certain groups of men should avoid using these devices Blood thinners or history of bleeding disorders Coumadin® - Warfarin Plavix® - Clopidogrel Diminshed penile sensation Spinal cord injury Significant penile curvature History of priapism Not ASA 81mg

Osbon Erecaid Classic OTC $395.00 Automatic $495.00 5 Year Warranty 30 day Warranty

Vacuum Devices Bonro Medical Vacurect® Retails $195.00

Osbon Erecaid Constriction Rings Pink = firm fit Beige = Regular fit Each colour comes in 2 sizes small and large

Actis Adjustable constriction loop

Peenuts® Acronym for “Power to Empty Every time while Never Urinating Too Soon” Contains: Vitamin C, E, B6, Selenium, Zinc, Echinacea, Glycine, Alanine, Glutamic Acid, Saw Palmetto (Beta-Sitosterol), Pygrum, Pumpkin Seed, Nettle, Garlic & Ginkgo Biloba Antioxidants, antiinflammatories, beta-sitosterol & immune boosters  EPS & WBC & improved PSA

Neo 40 Daily ED is may be an early warning sign of CVD 80% of men who had ED in beginning of a study were more likely to develop CVD by the end of the 10 year study Neo40 Daily helps restore nitric oxide (NO) levels Safer and more effective than L-arginine

Neo40 Daily 1 Box (30 lozenges/2 test strips) $59.99TAX Depleted or Low Normal Neo40 Daily Dose 2 lozenges daily 1 lozenge daily Testing schedule 2 – 3 times per week Once per week Goal Maintain Normal reading for 2 weeks Maintain Normal reading every other day Dose after reaching goal Reduce to 1 lozenge per day Reduce to 1 lozenge every other day Testing Schedule after reaching goal Test 2 – 3 times per week until restoration is stable at Normal Test once a week to confirm restoration is stable at Normal 1 Box (30 lozenges/2 test strips) $59.99TAX 1 Container (10 strips) $13.35TAX