Impotence. Pathophysiology

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MSc. Clinical Pharmacology Class Presentation 2.

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  • This will be a SMALL presentation talking about the impotence, what and how impotence happens, and what are the factors behind it. Mind you, It is not a HUGE presentation, I wont be talking much about the treatments because they will be talked by other classmates next time.
  • Impotence, is a robbery, robbery of a man’s manhood. Actually, sorry about that, is a deleted old slice that I have no idea why it showed up here.Please allow me to start over!Penile erection is a neurovascular event modulated by neurotransmitters and hormonal status. The penis is innervated by autonomic and somatic nerves. In the pelvis, the sympathetic and parasympathetic nerves merge to form the cavernous nerves, which enter the corpora cavernosa to regulate blood flow during erection and detumescence. The parasympathetic visceral efferent fibers arise from sacral roots 2-4 to supply the pelvic plexus located on the lateral wall of the rectum. The cavernous nerves leave the pelvic plexus and travel in the lateral pelvic fascia on the posterolateral surface of the prostate gland to supply the corpora cavernosa of the penis.The somatic component, the pudendal nerve, is responsible for penile sensation. Autonomic denervation followed by blunt pelvic or perineal trauma, radical pelvic surgeries (eg, for colon or prostate cancer) affect poor smooth muscle relaxation, arterial insufficiency, and venous abnormalities, thus preventing adequate erection.[3] Both surgery and radiation therapy appear to affect this mechanism.that can involve disruptions in neural, vascular, and hormonal signaling. Research on central neural regulation of penile erection is progressing rapidly with the identification of key neurotransmitters and the association of neural structures with both spinal and supraspinal pathways that regulate sexual function. In parallel to advances in cardiovascular physiology, the most extensive efforts in the physiology of penile erection have focused on elucidating mechanisms that regulate the functions of the endothelium and vascular smooth muscle of the corpus cavernosum. Major health concerns such as atherosclerosis, hyperlipidemia, hypertension, diabetes, and metabolic syndrome (MetS) have become well integrated into the investigation of ED.Conclusions.  Despite the efficacy of current therapies, they remain insufficient to address growing patient populations, such as those with diabetes and MetS. In addition, increasing awareness of the adverse side effects of commonly prescribed medications on sexual function provides a rationale for developing new treatment strategies that minimize the likelihood of causing sexual dysfunction. Many basic questions with regard to erectile function remain unanswered and further laboratory and clinical studies are necessary. Gratzke C, Angulo J, Chitaley K, Dai Y-T, Kim NN, Paick J-S, Simonsen U, Ückert S, Wespes E, Andersson KE, Lue TF, and Stief CG. Anatomy, physiology, and pathophysiology of erectile dysfunction. J Sex Med 2010;7:445–475.
  • ED is a multifaceted disease that underliedcomplex mechanisms that involved many different pathologies, which are psychological,neurological, hormonal, and vascular pathologies,or combinations of these factors.George F. Lasker, Jason H. Maley, and Philip J. Kadowitz, “A Review of the Pathophysiology and Novel Treatments for Erectile Dysfunction,” Advances in Pharmacological Sciences, vol. 2010, Article ID 730861, 10 pages, 2010. doi:10.1155/2010/730861http://books.google.co.uk/books?id=P0SRP8Sp1Y4C&lpg=PA17&ots=R7HLaxxhLp&dq=impotence%20pathophysiology&lr&pg=PP1#v=onepage&q&f=falsehttp://www.nlm.nih.gov/medlineplus/maleinfertility.html
  • Why do we care about ED?EDis not a HUGE disease, at least it not fatal, but it is not a small diases too.Multinational MALESis well established and ED can be considered an early marker for cardiovascular disease. CONFIRM THAT The association between ED and major risks to men's health to diabetes, and cardiovascular risk :hypertension, hyperlifactorspidemia, and angina. 1.Men's Attitudes to Life Events and Sexuality (MALES) (2001 – 2004)Europe, North and South America~ Phase I,27839 respondents~Phase II, 2912 respondentshttp://informahealthcare.com/doi/abs/10.1185/030079904125003467%202.The Massachusetts Male Aging Study MMAS (1987-2004) Boston Area, US~1709 respondents3. ENIGMA study in 2004 Netherlands~  2452 respondents
  • This condition has been estimated to affect 150 million individuals worldwide.Imagine many of the man like him, especially the middle age man, and of course the unhappy woman,Many manymany unhappy men and women, that’s why we care about erectile dysfunctionThe association between ED and major risks to men's health to diabetes, and cardiovascular risk :hypertension, hyperlifactorspidemia, and angina. 1.Men's Attitudes to Life Events and Sexuality (MALES) (2001 – 2004)Europe, North and South America~ Phase I,27839 respondents~Phase II, 2912 respondentshttp://informahealthcare.com/doi/abs/10.1185/030079904125003467%202.The Massachusetts Male Aging Study MMAS (1987-2004) Boston Area, US~1709 respondents3. ENIGMA study in 2004 Netherlands~  2452 respondents
  • Technology of an ErectionWhen you want to move nearly any part of your body, you do it using muscles. You think to move a part of your body, the muscle is contracted and your body move.The male organ, on the other is a completely different thing, there is no bone, no muscle contraction . The technology of erection is purely based on pressure.The male sex organhas two cigar-shaped structures, called corpora cavernosa (singular: corpus cavernosum), it is the key component in erection. Because , when a man is aroused, the arteries over there will be dilated, causing massive inflow of blood to the organ, while the veins are constricted so the blood leave the organ is very limited. So all these pressurised blood is trapped in the corpora cavernos, causing the organ to be elongated and strengthen. There you go, The erection!!In a non-erect state, the arteries that transport blood into the corpora cavernosa are somewhat constricted, while the veins that drain the blood from the penis are open. There is no way for pressure to build inside the penis. In this state, the penis is limp.When a man becomes aroused, the arteries leading into the penis open up so that pressurized blood can enter the penis quickly. The veins leaving the penis constrict. Pressurized blood is trapped in the corpora cavernosa, and this blood causes the penis to elongate and stiffen. The penis is erect.
  • So, you know, is not rocket sciencewhen you cannot launch at the right time, that is erectile dysfunction.
  • So what causes ED??interfere with libido, and therefore thebrain’s perception of arousalSexual stimulation and transmission of nerve impulses from the brain to the penile tissueDilation of arteries in the cavernous body and inflow of bloodBlock of blood outflow in the veins of the penisPsychological. Psychological factors such as stress,depression, schizophrenia, and a lack of sexual arousabilitylead to difficulty in achieving an erection. ED may be causedby diseases that interfere with libido, and therefore thebrain’s perception of arousal, such as Alzheimer’s, stroke,Parkinson’s, or brain trauma. Injury to the spinal cord mayinterrupt neural pathways to the sacral region, preventing orinhibiting the process of achieving an erection
  • ACTH acts on GPCR, releasesgluco- and mineralo-corticoster from adrenal cortexplays a significant role inerectile dysfunction as it is believed that a oids and androgenic steroidsFurther contribute to EDWhen was the man stronger?
  • Source: 3D 4 Medical.comhttp://images.3d4medical.com/search-results_penis_YTowOnt9-1.htmlBreakdowns and terminate
  • The pharmacology behind the therapy for osteoporosis is simple:We either A or BSo, it is not rocket science to figure out that therapeutic options for osteoporosis are:Drugs preventing resorption - They are Anti-resorptive treatment, which target the osteoclast to decrease bone reabsorptionDrugs Stimulating new bone formation (they are used in Anabolic therapy), they stimulate osteoblast to increase bone formation
  • The pharmacology behind the therapy for osteoporosis is simple:We either A or BSo, it is not rocket science to figure out that therapeutic options for osteoporosis are:Drugs preventing resorption - They are Anti-resorptive treatment, which target the osteoclast to decrease bone reabsorptionDrugs Stimulating new bone formation (they are used in Anabolic therapy), they stimulate osteoblast to increase bone formation
  • The pharmacology behind the therapy for osteoporosis is simple:We either A or BSo, it is not rocket science to figure out that therapeutic options for osteoporosis are:Drugs preventing resorption - They are Anti-resorptive treatment, which target the osteoclast to decrease bone reabsorptionDrugs Stimulating new bone formation (they are used in Anabolic therapy), they stimulate osteoblast to increase bone formation
  • The pharmacology behind the therapy for osteoporosis is simple:We either A or BSo, it is not rocket science to figure out that therapeutic options for osteoporosis are:Drugs preventing resorption - They are Anti-resorptive treatment, which target the osteoclast to decrease bone reabsorptionDrugs Stimulating new bone formation (they are used in Anabolic therapy), they stimulate osteoblast to increase bone formation
  • The pharmacology behind the therapy for osteoporosis is simple:We either A or BSo, it is not rocket science to figure out that therapeutic options for osteoporosis are:Drugs preventing resorption - They are Anti-resorptive treatment, which target the osteoclast to decrease bone reabsorptionDrugs Stimulating new bone formation (they are used in Anabolic therapy), they stimulate osteoblast to increase bone formation
  • Impotence. Pathophysiology

    1. 1. Impotence.Pathophysiology.Vincent Chang
    2. 2. Impotence = Manhood Missing!Difficulty in initiating or maintaining penile erectionadequate for sexual relations.
    3. 3. Impotence = Erectile DysfunctionDifficulty in initiating or maintaining penile erectionadequate for sexual relations. •Psychological •Neurological •Hormonal •Vascular combinations.
    4. 4. Comorbidities and Risk factors Large population-based studies: 1. Mens Attitudes to Life Events and Sexuality (MALES) (2001 – 2004) Europe, North and South America 2.The Massachusetts Male Aging Study (MMAS) (1987-2004) Boston Area, US 3. ENIGMA study in 2004 Netherlands, Europe Major risks to mens health such as diabetes, and cardiovascular risk : hypertension, hyperlipidemia, and angina. - Well established early markerED had a significant negative influence on the happiness of life.
    5. 5. Comorbidities and Risk factors Large population-based studies: 1. Mens Attitudes to Life Events and Sexuality (MALES) (2001 – 2004) Europe, North and South America 2.The Massachusetts Male Aging Study (MMAS) (1987-2004) Boston Area, US 3. ENIGMA study in 2004 Netherlands, Europe Major risks to mens health such as diabetes, and cardiovascular risk : hypertension, hyperlipidemia, and angina.ED had a significant negative influence on the happiness of life. This condition has been estimated to affect 150 million individuals worldwide.
    6. 6. The technology oferection is purely basedon pressure.
    7. 7. 1. Psychological and Neurological Pathologies: •Anxiety – Teenagers and young men •Stress – Middle Age men •Depression •Lack of sexual arousability Interfere with brain’s perception of arousal: oSchizophrenia oAlzheimer’s oStroke oParkinson’s obrain traumaInjury to the spinal cord may interrupt neural pathways to thesacral region, preventing erection
    8. 8. 2. Hormonal factor •Adrenocorticotropic hormone ACTH - corticosteroids •Oxytocin •Prolactin •Androgens •Testosterone Hypogonadism - threshold level of testosterone is necessary for erection to occurNatural aging process - decline in testosterone production level
    9. 9. 3. Vascular and NO pathologies contributed to ED•Peripheral arterial disease and endothelial/smooth muscledysfunctionseen in diabetes mellitus, atherosclerosis, coronary•Nitric Oxidethe main vasoactive neurotransmitter involved in the erectileresponse •Arousal stimulates NO released from nonadrenergic, noncholinergic (NANC) neurons • Shear forces also stimulate NO production by eNOS in the endothelium
    10. 10. NO Mechanism & Erection Erecting Erected Flacid PDE 5 phosphodiesterase•Arousal stimulates NO released from (NANC) neurons
    11. 11. Therapeutic approaches for ED•Current standard of care for ED consists oflifestyle changes such as management of diet, weight loss•Appropriate treatment for diabetes, hypertension•The current gold standard treatment is the use ofPDE 5 inhibitors such as sildenafil citrate. •Hydraulic pump •ED pump therapy
    12. 12. Therapeutic approach for ED•Current standard of care for ED consists oflifestyle changes such as management of diet, weight loss•Appropriate treatment for diabetes, hypertension•The current gold standard treatment is the use ofPDE 5 inhibitors such as sildenafil citrate. •Hydraulic pump •ED pump therapy
    13. 13. Therapeutic approach for EDcurrent standard of care for ED consists of lifestylechanges such as management of diet, diabetes, hypertension,and weight loss, along with pharmacotherapies. The currentgold standard treatment is the use of phosphodiesterase5 inhibitors such as sildenafil citrate.
    14. 14. Therapeutic approach for EDcurrent standard of care for ED consists of lifestylechanges such as management of diet, diabetes, hypertension,and weight loss, along with pharmacotherapies. The currentgold standard treatment is the use of phosphodiesterase5 inhibitors such as sildenafil citrate.
    15. 15. Therapeutic approach for EDcurrent standard of care for ED consists of lifestylechanges such as management of diet, diabetes, hypertension,and weight loss, along with pharmacotherapies. The currentgold standard treatment is the use of phosphodiesterase5 inhibitors such as sildenafil citrate.
    16. 16. Q?
    17. 17. Thank you! :)

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