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

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.

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.

Tache Pharmacy Price PDE5 Inhibitors Drug Strength Quantity Price Viagra®/Generic 100mg 4 $54.83/$44.83 Levitra® 20mg $73.43 Cialis® $78.32 5mg 28 $146.50 ($20.93/4)

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

Tache Pharmacy MUSE® Prices Quantity Price 250µg 1 $48.53 500µg 1000µg

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

Tache Pharmacy Prices Intraurethral Gel Quantity Price Alp 250/Pap 0.3/Phe 0.2/0.2ml 6 Dose $149.46 1 Dose* $24.98 Muse 1000µg 1 $48.53 *If 1 single dose ordered the price would be higher

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 $13.70/$11.20 MUSE 1000µg $48.53 Intraurethral Gel 250/0.3/0.2 $24.98*** Caverject 20ug $40.56* Tri-Mix $3.94** *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 10ml vial a person would get 24 doses ***Need to order 6 doses to get this price

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

Automatic Vacuum Pumps Androvacuum Premium No warranty - $295.00 Osbon ErecAid Esteem 5 Year Warranty - $495.00 30 day money back guarantee

Vacuum Devices Bonro Medical Vacurect® Retails $245.00

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

Actis Adjustable constriction loop