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Group 3 ธนวัต จางคกูล 43076140 กนกพร ตั้งจิตติพร 43076173 เฉลิมพล ธวัชราภรณ์ 43076199 Erectile Dysfunction Meaning : “ The inability to achieve and maintain a penile erection satisfactory for sexual intercourse” (Does not include ejaculation disorders) History • The first description of erectile dysfunction, about 2000 B.C., was set down on Egyptian. • Hippocrates concluded that too much horseback riding was the cause of disease. • Aristotle, air influx into penis. Anatomy of the penis • Tunica Albuginea • Corpora Cavernosa -- Sinusoid • Corpus Spongiosum -- Sinusoid • Glans Penis • Artrial supply • Venous drainage • Nerve Arterial Supply • Internal iliac artery • internal pudendal artery [main] – Dorsal artery – Bulbourethral artery – Cavenous artery • External iliac, Obturator, vesical and femoral artery. [accessory] Venous drainage • Emissary veins, transformed from peripheral sinusoids • Deep dorsal vein [main] • Bulbourethral vein, Cavernous vein [ accessory] Mechanism of erection : Dilatation arterioles&arteries expanding of sinusoids compression of subtunical venular plexuses Emissary veins enclosed increasing of intracavernous pressure to raise the penis Mechanism of Detumescence Transient intracorporeal pressure increase [smooth muscle contraction] Pressure decrease slowly [slow reopening of the venous channels] Pressure decrease fast [venous outflow capacity is fully restored] Neuroanatomy of penile erection • Peripheral pathways Sympa, - NE release Parasym, + NO & Ach release Somatic, +Ach release – autonomic [ C. Cavenosa & C. Spongiosum] – somatic [ Glans Penis & C. Spongiosum] Neuroanatomy of penile erection • Supraspinal pathways [ hypothalamus, limbic system and cerebral cortex] dopaminergic & adrenergic recepters serotonin recepters promotes sexual drive inhibits sexual drive Classification of Erectile Dysfunction • • • • • • • Psycogenic Neurogenic Endocrinologic Arteriogenic Cavernosal (Venogenic) Drug-induced Erectile dysfunction associated with aging, systemic disease & others Cause of Erectile Dysfunction Alcohol Abuse Anxiety or Depression Coronary Artery Disease Diabetes Hormonal Abnormalities Hypertension Peripheral Vascular Disease Renal or Hepatic Failure Anemia Smoking Surgery(Pelvic or Perineal) Trauma to pelvic or spine Medication : AntiHT, Antidepressant, Antiarrhythmic,Antipsychotics Diuretics, Anticonvulsants, Antiandrogen, Narcotics Treatments of Erectile Dysfunction Treatments of Erectile Dysfunction Drug Therapy : Orally Administration Intracarvernous Injection MUSE or Intraurethral Suppository Vacuum Devices Horrmone Replacement Therapy Surgery Others Treatments of Erectile Dysfunction • Drug Therapy : Orally Administration Yohimbine Phentolamine Apomorphine Sildenafil Treatments of Erectile Dysfunction Drug Therapy : Orally Administration Yohimbine alpha 2 -antagonist Side effect : anxiety, ปัสสาวะบ่ อย, tachycardia, เพิม่ arterial pressure Treatments of Erectile Dysfunction Drug Therapy : Orally Administration Phentolamine vasoactive Drug Side effect : orthostatic hypotension, tachycardia Treatments of Erectile Dysfunction Drug Therapy : Orally Administration Apomorphine (Sublingual) Stimulate brain dopaminergic mechanism Side effect : nausea, vomit, yawn Treatments of Erectile Dysfunction Drug Therapy : Orally Administration Sildenafil Phosphodiesterase Inhibitor Side effect : headache, flushing, dyspepsia visual disturbance Contraindication : co-administration with nitrate MI, CHF Treatments of Erectile Dysfunction Intracavernous Injection ใช้ vasoactive agents ในการฉีดเข้ า corpora cavernosa ทาให้ เส้ นเลือดขยายตัว เกิดการคัง่ ของเลือดที่ penis ทาให้ เกิด erection Vasoactive Agent Papaverine Phentolamine Alprostadil Treatments of Erectile Dysfunction Intracavernous Injection Side effect : priapism, small nodule, subcutaneous hemorrhage, pain, trauma, scar *combination therapy จะให้ ผลการรักษาทีด่ กี ว่ า monotherapy *การเพิม่ oral alpha-blocker (Doxazosin) จะเสริมฤทธิ์ในการ ขยายหลอดเลือด Treatments of Erectile Dysfunction Intraurethral suppositories “MUSE” (Medicated urethral system for erection) มีหลอดบรรจุ alprostadil สาหรับสอดเข้ าทาง urethra โดยจะออก ฤทธิ์ภายใน 8-10 นาที อาการไม่ พงึ ประสงค์ : ปวด อาการบวมแดง อาจมีเลือดออกในท่ อปัสสาวะ Treatments of Erectile Dysfunction Vacuum Devices Pump จะดูดอากาศออกจาก cylinder ทาให้ เกิดสู ญญากาศเกิดแรงดึงเลือดเข้ า penis และ elastic band จะป้องกันไม่ ให้ เลือดไหล ย้ อนกลับ Treatments of Erectile Dysfunction Hormone Replacement Therapy : Testosterone เพิม่ sexual function มีท้ งั ในรู ปแบบการฉี ด การรับประทาน และการทา Treatments of Erectile Dysfunction Surgery - ผ่ าตัดใส่ Paired rod เข้ าใน corpora cavernosa - ผ่ าตัด repair arteries จะช่ วยได้ ใน กรณี obstruction Treatments of Erectile Dysfunction Others : Alprostadil gel ทาที่ glans penis จะทาให้ เพิม่ penile rigidity Comparision of Treatments Use : Oral Intracarvenous Medication Injection AUA guildline : AUA guildline : 1st Line(Now) 1st Line(Old) effective in effective in definable & definable & undefinable cause undefinable cause MUSE Vacuum HRT Surgery Device Injection Oldest alternatives Treatment Andropause Last choice or Arterial revascularize and venous ligament in younger pt. Or prosthetic penile implantation Comparision of Treatments Agents : Oral Intracarvenous Medication Injection Sildenafil Alprostadil Yohimbine Papaverine Phentolamine Phentolamine MUSE Vacuum HRT Surgery Device Alprostadil - Testosterone - 40-65% 90 % up 61 % - Apomorphine Effective : Silden. 65-93% Monotherapy 70-74% Others is lower Combined 90 % Comparision of Treatments Advantage Oral Intracarvenous Medication Injection Comfortable, High effective, Less Non invasive no death evidence Invasive BMD than inj. Improve and sex fn.,mood no death evidence & emotion MUSE Vacuum HRT Surgery Device High effective Maintain Increase muscle strength High effective Comparision of Treatments Dis Advantage Oral Intracarvenous Medication Injection Have Death evidence data 50 % reject the long term treatment cause : lower effective in some case as DM MUSE urethral bleeding problem of self inj. Penile pain(11%) priapism (0.5-5%) More expensive than injection HRT Surgery Use only Expensive, in uncomfort. Device Penile pain Patients and decrease in response less interest in sex Vacuum Partner’s satisfation andropause less than inj. long term : Anemia, increase bl. Viscosity CI in Prostate CA Comparision of Drug Therapy Agents Sildenafil Alprostadil MUSE Papaverine Phentolamine Apo morphine Phosphodies- Alpha 1,2Stimulate terase inhibitors alpha-adrenagic Alprostadil adrenergic Brain : increase NO : Inhibit smooth blocking agent receptor dopaminergic : increase cGMP muscle :Carvenous smooth blocking mechanism contraction muscle relax :Dilate arterial that effect Mechanism Phosphodiesterase inhibitors Effective Syn. PG. E Like :Arterioles smooth vessel muscle relax :inh. Symp. 65-93% Monotherapy 70-74% avg. 75 % Combined 90 % 40-65% 40-60 % 40-45 % erection 65% Comparision of Drug Therapy Agents Sildenafil Alprostadil MUSE Papaverine Phentolamine Apo morphine Admin. oral route intracarvenous injection Intraurethral intracarvenous suppository injection by oral or sublingual Intracarvenous injection applicator usual dose 25-100 mg 5-20 mcg 50-1000 mcg Single 10-60mg Combine 3-5mg (Papa+Phento or Papa+Alpro) 40-80 mg - Comparision of Drug Therapy Agents Sildenafil Alprostadil MUSE Papaverine Phentolamine Apo morphine Use in Definable and Definable and case undefinable undefinable injection such as DM, such as DM, alternative Olderly with HT Olderly with HT spinal cord injury spinal cord injury Contra depression - pt. Use nitrate, indication Heart Disease, Renal&Hepatic Impairments Alprostadil like alprostadil depression Predisposition to priapism eg anemia,leukemia Ab. Penile Anatomy Urethritis Anatomical deformation of penis risk of priapism Heart Disease like Psychogenic alprostadil Type NA.data NA.data Comparision of Drug Therapy Agents Sildenafil Alprostadil MUSE Papaverine Phentolamine Apo morphine ADR 16% Headache 35 % Penile Pain 30 % Penile Papa + Phentolamine Nausea 10% Flushing 2% 0.4 % Penile Pain Vomit 8% Yawn 7% Dyspepsia 3% Visual Disturb Priasism or Fibrosis Pain 5% Urethral bleeding Priapism and fibrosis 6% Drowsiness sweating,Hypot. Dis Advantage Have Death only Alprostadil has approved in USA evidences Phentolamine has carcinogenic potential effect in rat The End