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Information about ED

Published on February 27, 2014

Author: minwoldu

Source: authorstream.com

ERECTILE DYSFUNCTION: ERECTILE DYSFUNCTION Minyahil A. Woldu B.Pharm, Msc, Clinical Pharmacy Unit Pharmacy Dept Ambo University PowerPoint Presentation:  “Man survives earthquakes, experiences the horrors of illness, and all of the tortures of the soul. But the most tormenting tragedy of all time is, and will be, the tragedy of the bedroom.” Tolstoy 2 Objectives : Objectives At the end of the session students be able to Describe both the pharmacologic and non-pharmcologic treatment for erectile dysfunction Select appropriate drug therapy for patients with ED 3 Introduction : Introduction Erectile dysfunction: the failure to achieve a penile erection to allow for satisfactory sexual intercourse. Patients may refer to it as impotence. 4 PowerPoint Presentation: 5 EPIDEMIOLOGY: EPIDEMIOLOGY Incidence is low in men younger than 40 years Age-related 12.4% in men aged 40 to 49 years 46.4% in men aged 60 to 69 years. 6 PHYSIOLOGY OF A NORMAL PENILE ERECTION: PHYSIOLOGY OF A NORMAL PENILE ERECTION A normal penile erection requires: vascular, nervous, and hormonal The patient also must be psychologically receptive to sexual stimuli Arterial flow into the corpora is enhanced by acetylcholine mediated vasodilation Acetylcholine produces an erection probably through two different pathways 7 PowerPoint Presentation: enhances the production of nitric oxide by endothelial cells and nonadrenergic–noncholinergic neurons Nitric oxide enhances the activity of guanylate cyclase  cGMP cGMP decreases intracellular calcium concentrations in smooth muscle cells of penile arteries and cavernosal sinuses enhances arterial blood flow to and blood filling of the corpora  erection 8 PowerPoint Presentation: acetylcholine stimulates a smooth muscle cell membrane receptor to enhance the activity of adenyl cyclase Psychogenic stimulations  patient sees an attractive partner, hears sweet words, smells a particular scent, or tastes or touches a pleasant object dopamine exerts a proerectogenic effect, whereas, α2-adrenergic stimulation causes the penis to become and/or remain flaccid 9 PowerPoint Presentation: The erection is prolonged by a decrease in venous outflow from the corpora, which is caused by compression of subtunical venules by the swollen corpora Detumescence occurs with sympathetic discharge after ejaculation 10 HORMONAL SYSTEM: HORMONAL SYSTEM Normal range 300–1,100 ng/dL  sexual drive is normal Approximately one third of men older than 50 years have hypogonadism, which is characterized by subphysiologic serum testosterone levels. Patients complain of loss of energy, loss of muscle strength, depressive mood, and decreased libido 11 PowerPoint Presentation: The relationship between erectile dysfunction and serum testosterone levels is complicated. Patients with normal serum testosterone levels may have erectile dysfunction, and patients with subnormal serum testosterone levels may have normal sexual function 12 Risk factors: Risk factors Organic erectile dysfunction due to dysfunction in either of vascular, neurologic, or hormonal etiologies(80%) Patients who do not respond to psychogenic stimuli have psychogenic erectile dysfunction 13 PowerPoint Presentation: Diseases that compromise vascular flow to the corpora cavernosum (e.g., peripheral vascular disease, arteriosclerosis, and essential hypertension) Diseases that impair nerve conduction to the brain (e.g., spinal cord injury or stroke) conditions that impair peripheral nerve conduction to the penile vasculature (e.g., diabetes mellitus) hypogonadism 14 PowerPoint Presentation: cigarette smoking The vasoconstrictor effect of cigarette smoking may compromise blood flow to the corpora and decrease cavernosal filling Excessive ethanol intake Medications are estimated to be responsible for approximately 10% to 25% of cases of erectile dysfunction 15 PowerPoint Presentation: 16 Medications…: Medications… 17 CLINICAL PRESENTATION: CLINICAL PRESENTATION General Men are affected emotionally Depression Performance anxiety Marital difficulties and avoidance of sexual intimacy Nonadherence to medications patient believes are causing erectile dysfunction 18 PowerPoint Presentation: Symptoms Impotence or inability to have sexual intercourse Signs Low satisfaction with quality of erectile function . Medical history may identify concurrent medical illnesses, past surgical procedure Medication history may reveal prescription or nonprescription medications Physical examination may reveal signs of hypogonadism 19 DIAGNOSIS: DIAGNOSIS a description of the severity of erectile dysfunction, complete medical and surgical histories, review of concurrent medications, physical examination, and selected clinical laboratory tests A history of nocturnal or early morning erections is useful for distinguishing physiologic from psychogenic ED Laboratory Tests a serum testosterone prostate specific antigen 20 PowerPoint Presentation: To assess the severity of erectile dysfunction, the patient should be asked about the quality of sexual intercourse for the last 4 weeks to 6 months International Index of Erectile Dysfunction (IIED) It includes 15 questions about the quality of erectile function and satisfactoriness of sexual intercourse 21 PowerPoint Presentation: A physical examination of the patient should include a check for hypogonadism (i.e., signs of gynecomastia, small testicles, and decreased body hair). 22 TREATMENT: TREATMENT The goal of treatment is improvement in the quantity and quality of penile erections suitable for satisfactory intercourse. 23 GENERAL APPROACH TO TREATMENT: GENERAL APPROACH TO TREATMENT The first step is to identify and, if possible, reverse underlying causes. hypertension, diabetes mellitus, smoking, or chronic ethanol abuse, should be addressed and minimized physical fitness, weight loss to achieve a normal body mass index, low-cholesterol diets, no excessive ethanol intake, and no smoking 24 PowerPoint Presentation: psychotherapy Counseling which address immediate factors that may be causing performance anxiety or depression, rather than the remote, deep-seated reasons for psychological disorders Specific treatments of erectile dysfunction include vacuum erection devices (VEDs), pharmacologic treatments, and surgery 25 PowerPoint Presentation: The ideal treatment should have Fast onset be effective be convenient to administer be cost effective have a low incidence of serious adverse effects be free of serious drug interactions Least invasive are selected first; more invasive therapies are reserved 26 VACUUM ERECTION DEVICE: VACUUM ERECTION DEVICE has three parts: a pump, which generates a negative vacuum pressure; a cylinder, which is closed at one end and into which the penis is inserted; and tubing, which connects the pump to the cylinder A- cylinder B- pump (manual or battery) C- ring 27 PowerPoint Presentation: slow on set(30 minutes) Overall satisfaction rate is 60% to 80% work best in older patients who are married or have stable sexual relationships 6% to 11% cool & discolored (bluish) 28 PowerPoint Presentation: used as second-line therapy in patients who do not respond to oral or injectable drug treatments contraindicated in patients with sickle cell disease should be used cautiously by patients taking warfarin 29 PHOSPHODIESTERASE INHIBITORS: PHOSPHODIESTERASE INHIBITORS Act by decreasing catabolism of cGMP Phosphodiesterase isoenzyme type 5 is also found in peripheral vascular tissue, tracheal smooth muscle, and platelets First -line therapy for erectile dysfunction, particularly in younger patients The effectiveness of the drugs appears to be dose related 30 PowerPoint Presentation: Approximately 30% to 40% of patients do not respond to phosphodiesterase inhibitors Response rates in the lower range for phosphodiesterase inhibitors have been documented in patients with diabetes mellitus or in patients after radical prostatectomy At least half of nonresponders can benefit from education on proper use of the drugs 31 PowerPoint Presentation: Education of patients should include: Patients must engage in sexual stimulation (foreplay) sildenafil should be taken on an empty stomach, at least 2 hours before meals, for the fastest response taking sildenafil or vardenafil with a fatty meal can decrease the absorption rate 32 PowerPoint Presentation: Patients who do not respond to the first dose should continue with the phosphodiesterase inhibitor for at least five to eight doses before failure is declared Some patients require dosage titration up to 100 mg sildenafil, 20 mg vardenafil, or 20 mg tadalafil for response. 33 Adverse Effects: Adverse Effects the most common adverse effects are headache (11%), facial flushing (12%), dyspepsia (5%), nasal congestion (3.4%), and dizziness (3%) Sildenafil and vardenafil produce an 8- to 10-mm Hg decrease in SBP and a 5- to 6-mm Hg decrease in DBP Tadalafil does not produce decreases in blood pressure 34 PowerPoint Presentation: Sildenafil and vardenafil cause increased sensitivity to light, blurred vision, or loss of blue–green color discrimination in 2% to 3% of patients Priapism 35 PowerPoint Presentation: contraindicated in patients taking nitrates given by any route at scheduled times or intermittently nitrates should be withheld for 24 hours after sildenafil or vardenafil administration and for 48 hours after tadalafil administration Manufacturers recommend a 4-hour interval with α-adrenergic antagonists 36 TESTOSTERONE REPLACEMENT REGIMENS: TESTOSTERONE REPLACEMENT REGIMENS correct symptoms of hypogonadism, which include malaise, loss of muscle strength, depressed mood, and decreased libido testosterone may stimulate nitric oxide synthase, thereby increasing cavernosal concentrations of nitric oxide 37 PowerPoint Presentation: do not directly correct erectile dysfunction; instead, they improve libido, thereby correcting secondary erectile dysfunction Prostate cancer is a contraindication to androgen supplementation Testosterone replacement regimens can be administered orally, parenterally, or transdermally 38 PowerPoint Presentation: Injectable testosterone preferred Effective Inexpensive Not associated with the bioavailability problems or hepatotoxic adverse effects of oral androgens. Patches and gels are much more expensive than other forms of androgen replacement 39 PowerPoint Presentation: Natural testosterone: Extensive first-pass hepatic metabolism Oral bioavailability: alkylated derivatives . E.g. methyltestosterone and fluoxymesterone Oral alkylated derivatives : high incidence of hepatotoxicity 40 PowerPoint Presentation: Testosterone buccal system (Striant), which is applied to the gum above the upper incisor teeth twice per day. Testosterone esters (im) Testosterone propionate, which requires dosing tiw Testosterone cypionate or enanthate, which can be dosed every 2-4 weeks Subcutaneous implant for dosing every 3-4 months Topical testosterone replacement regimens can be delivered as once-daily patches or gel. 41 PowerPoint Presentation: Testoderm brand patch was formulated for scrotal application. Androderm and Testoderm TTS patches: the arms, buttocks, or back. Testosterone gel 1% formulation (AndroGel): shoulders, upper arms, or abdomen. 42 Adverse Effects: Adverse Effects cause sodium retention, which can cause weight gain, or exacerbate hypertension, congestive heart failure, and edema 43 ALPROSTADIL: ALPROSTADIL Prostaglandin E1, stimulates adenyl cyclase, resulting in increased production of cAMP Alprostadil is commercially available as an intracavernosal injection (Caverject and Edex) and as an intraurethral insert (medicated urethral system for erection [MUSE]) More effective by the intracavernosal route than the intraurethral route 44 PowerPoint Presentation: Intracavernosal Alprostadil prescribed after patients do not respond to or cannot use the less invasive interventions Alprostadil acts rapidly, with an onset in 5 to 15 minutes. The duration is directly related to the dose. Within the usual dosage range of 2.5 to 20 mcg, the duration of erection is no more than 1 hour efficacy  70% to 90%. 45 PowerPoint Presentation: 46 PowerPoint Presentation: The usual dose of intracavernosal alprostadil is 10 to 20 mcg, with a maximum recommended dose of 60 mcg. Adverse Effects Cavernosal plaques or areas of fibrosis at injection penile pain Priapism injection site hematomas and bruising. 47 PowerPoint Presentation: Intraurethral Alprostadil contains a medication pellet inside a prefilled urethral applicator Effectiveness rate of 43% to 60% a thirdline treatment option The usual dose is 125 to 1000 mcg should be administered 5 to 10 minutes before sexual intercourse 48 PowerPoint Presentation: 49 PowerPoint Presentation: Adverse Effects urethra injury  urethral stricture and difficulty voiding Urethral pain vaginal burning, itching, or pain Priapism Syncope and dizziness 50 UNAPPROVED AGENTS: UNAPPROVED AGENTS Trazodone acts peripherally to antagonize α-adrenergic receptors  a predominant cholinergic effect 50 to 200 mg daily dry mouth, sedation, dizziness and priapism 51 PowerPoint Presentation: Yohimbine a central α2- adrenergic antagonistic that increases catecholamines and improves mood may reduce peripheral α-adrenergic tone The usual oral dose is 5.4 mg three times per day adverse effects  anxiety, insomnia, tachycardia, and hypertension 52 PowerPoint Presentation: Papaverine a nonspecific phosphodiesterase inhibitor that decreases metabolic catabolism of cAMP more often administered in lower doses combined with phentolamine and/or alprostadil 7.5 to 60 mg when used as a single agent for intracavernosal injection 0.5 to 20 mg when used in combination ADE  priapism, corporal fibrosis, hypotension, and hepatotoxicity 53 PowerPoint Presentation: Phentolamine a competitive nonselective α-adrenergic blocking agent administered as an intracavernosal injection used in combination with other vasoactive agents A ratio of 30 mg papaverine to 0.5 to 1 mg phentolamine is typical, and the usual dose ranges from 0.1 to 1 mL of the mixture S/E-hypotension, priapism 54 PowerPoint Presentation: PENILE PROSTHESES malleable and inflatable associated with a greater than 90% patient satisfaction rate 55 Case : Case A 52-year-old man with type 2 diabetes, hypertension, and dyslipidemia returns to your clinic for follow-up on his chronic disease states. When reviewing his history, he describes problems achieving a firm erection. After further questioning, you determine that his dysfunction has progressively gotten worse over the last year. He is quite emotional and states that the problem is distressing and has caused significant marital discord. He wonders about “those ads on television” suggesting a pill. 56 PowerPoint Presentation: PMH Type 2 diabetes for 15 years; not controlled due to his stressful profession; he often works late, eats on the run, and has no time for exercise Hypertension for 8 years, currently uncontrolled Dyslipidemia for 8 years, currently controlled 57 PowerPoint Presentation: FH Father had type 2 diabetes and died of myocardial infarction at the age of 50 years; mother is alive at 75 with no major illnesses SH Works long hours as a business executive; drinks alcohol only occasionally, but smokes 1/2 pack per day; has a 20 pack per year history 58 PowerPoint Presentation: Meds Metformin 1000 mg PO twice daily Metoprolol XL 50 mg PO once daily Zocor 20 mg PO once daily ROS (–) Morning, nocturnal, or spontaneous erections suitable for intercourse; (–) nocturia, urgency, symptoms of prostatitis; (+) significant life stressors; (+) mild pain in feet 59 PowerPoint Presentation: PE VS: Blood pressure 148/90 mm Hg, pulse 85 beats per minute, respiratory rate 18/minute, temperature 37.0°C (98.6°F) CV: Normal exam Genit/Rect: Normal scrotum and testicles w/o masses; penis without discharge or curvature Labs Hemoglobin A1c: 8.0% (0.08), testosterone: 700 ng/dL (24 nmol/L) 60 PowerPoint Presentation: Does he have risk factors for ED? Would his ED most likely be organic or psychogenic? what is your assessment of the patient’s condition? What is/are the most likely causes of his ED? Identify treatment goals for this patient. What pharmacologic and nonpharmacologic alternatives are available for this patient? Which of the above will be your treatments of choice based on degree of invasiveness, side effects, ease of use, and side-effect profile? 61

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