Commercial products and compounded options for the treatment of erectile dysfunction. Brief overview regarding the pathophysiology, medical, and physical causes behind these disorders as well as epidemiology and prevalence of the disease.
Invited lecture delivered by Dr Sujoy Dasgupta in a Webinar organized by Sexual medicine Committee of FOGSI (Federation of Obstetric and Gynaecological Societies of India), held in February, 2022
Modafinil is used to help individuals who have narcolepsy, obstructive sleep apnea/hypopnea problem (OSAHS), or shift work sleep issues (SWSD) to remain aware during the day. Modafinil does not treat these circumstances and will only perform provided that you keep take it.
Invited lecture delivered by Dr Sujoy Dasgupta in a Webinar organized by Sexual medicine Committee of FOGSI (Federation of Obstetric and Gynaecological Societies of India), held in February, 2022
Modafinil is used to help individuals who have narcolepsy, obstructive sleep apnea/hypopnea problem (OSAHS), or shift work sleep issues (SWSD) to remain aware during the day. Modafinil does not treat these circumstances and will only perform provided that you keep take it.
This presentation was made to be presented in the urology morning report at An-Najah University Hospital as one of the topics students rotating in the urology required to present. It discusses erectile dysfunction through a virtual case report simulating what urologists deal with every day.
What is Depression?
(1)Major depressive disorder: Combination of symptoms interfering with person’s ability to work, sleep, study, eat, & enjoy once-pleasurable activities. Disabling & prevents person from functioning normally. Often recurs in persons life.
(2)Dysthymic disorder: Long-term (> 2 years) but less severe symptoms that may not disable a person but can prevent one from functioning normally or feeling well.
(3)Psychotic depression: Severe depressive illness accompanied by some form of psychosis, such as break with reality, hallucinations, & delusions.
(4)Postpartum depression: When new mother develops major depressive episode within one month after delivery. Estimated that 10-15% women with postpartum depression after giving birth.
(5)Seasonal affective disorder (SAD): Depression during winter months, when less natural sunlight, that lifts during spring and summer. Half of these cases do not respond to light therapy alone but responsive to combo antidepressants, light, and psychotherapy.
(6)Bipolar disorder: Aka manic-depression. Cycling mood changes from extreme highs (mania) to extreme lows (depression).
Congenital Adrenal Hyperplasia (CAH)
For 5th Year Medical Students and Endocrinology Modules and Master and MD Degree Internal Medicine and Endocrinology
By Dr Usama Ragab Youssif
References: Oxford Handbook of Endocrinology & Diabetes
Diabetes mellitus and erectile dysfunction by Dr. Mohand Yaghi PgDip (urol) C...Mohand Yaghi
A lecture about the effect of diabetes mellitus on the erectile function. Dr. Mohand Yaghi was an invited speaker in Al-Jahra scientific day, Kuwait 2015.
Exercise is any bodily activity that enhances or maintain physical fitness and overall health, Exercise with its Countless Benefits is the logical salvage for a group of diseases related to inactivity . In view of the prevalence, global reach and health effect of these physical inactivity related diseases, the issue should be appropriately described as pandemic, with far-reaching health, economic, social and Environmental consequences.These diseases include, Obesity, Coronary artery disease, Diabetes, Hypertension, Cancer, Depression and anxiety, Arthritis, Osteoporosis, Etc, etc, etc… I think we have no option except doing regular exercises if we seriously searching for a salvage to escape the bad and serious consequences of these new life style diseases.
This presentation was made to be presented in the urology morning report at An-Najah University Hospital as one of the topics students rotating in the urology required to present. It discusses erectile dysfunction through a virtual case report simulating what urologists deal with every day.
What is Depression?
(1)Major depressive disorder: Combination of symptoms interfering with person’s ability to work, sleep, study, eat, & enjoy once-pleasurable activities. Disabling & prevents person from functioning normally. Often recurs in persons life.
(2)Dysthymic disorder: Long-term (> 2 years) but less severe symptoms that may not disable a person but can prevent one from functioning normally or feeling well.
(3)Psychotic depression: Severe depressive illness accompanied by some form of psychosis, such as break with reality, hallucinations, & delusions.
(4)Postpartum depression: When new mother develops major depressive episode within one month after delivery. Estimated that 10-15% women with postpartum depression after giving birth.
(5)Seasonal affective disorder (SAD): Depression during winter months, when less natural sunlight, that lifts during spring and summer. Half of these cases do not respond to light therapy alone but responsive to combo antidepressants, light, and psychotherapy.
(6)Bipolar disorder: Aka manic-depression. Cycling mood changes from extreme highs (mania) to extreme lows (depression).
Congenital Adrenal Hyperplasia (CAH)
For 5th Year Medical Students and Endocrinology Modules and Master and MD Degree Internal Medicine and Endocrinology
By Dr Usama Ragab Youssif
References: Oxford Handbook of Endocrinology & Diabetes
Diabetes mellitus and erectile dysfunction by Dr. Mohand Yaghi PgDip (urol) C...Mohand Yaghi
A lecture about the effect of diabetes mellitus on the erectile function. Dr. Mohand Yaghi was an invited speaker in Al-Jahra scientific day, Kuwait 2015.
Exercise is any bodily activity that enhances or maintain physical fitness and overall health, Exercise with its Countless Benefits is the logical salvage for a group of diseases related to inactivity . In view of the prevalence, global reach and health effect of these physical inactivity related diseases, the issue should be appropriately described as pandemic, with far-reaching health, economic, social and Environmental consequences.These diseases include, Obesity, Coronary artery disease, Diabetes, Hypertension, Cancer, Depression and anxiety, Arthritis, Osteoporosis, Etc, etc, etc… I think we have no option except doing regular exercises if we seriously searching for a salvage to escape the bad and serious consequences of these new life style diseases.
Androgens & Cardiovascular Diseases in Women: From Basic Research to Clinical...InsideScientific
Join Dr. Licy Yanes-Cardozo as she expands on her research exploring the role of androgens on cardiovascular physiology in cis and transgender patients.
Women have higher plasma concentrations of androgens than estrogens, yet the role of androgens in physiological processes and diseases is not completely understood. High levels of androgens in women are associated with a negative cardiometabolic profile, whereas in men, low levels of androgens are associated with an increased incidence of cardiovascular diseases.The biology behind androgens’ sex difference is not completely understood.
In this webinar, Dr. Yanes-Cardozo discusses two clinical situations that are associated with high levels of androgens. Polycystic Ovary Syndrome (PCOS), the most common endocrine disorder in reproductive-aged women, is associated with a modest elevation of plasma levels of androgens. In transmen individuals (female to male), plasma concentrations of androgens are elevated to achieve similar levels found in cisgender men and much higher than in PCOS women. The role that these two different plasma concentrations play in cardiovascular physiology and pathophysiology remains unclear. Gaps and opportunities in basic research and clinical practice are highlighted.
Key Topics Include:
- Review the key role of androgens in cardiovascular pathophysiology
- Discuss potential mechanisms by which androgens mediate a deleterious cardiometabolic profile in females
- Interpret gaps and opportunities in basic and clinical practice in conditions of androgen excess
Personalized medicine involves the prescription of specific therapeutics best suited for an individual based on their genetic or proteomic profile. This talk discusses current approaches in drug discovery/development, the role of genetics in drug metabolism, and lawful/ethical issues surrounding the deployment of new health technology. I highlight some bioinformatic roles in the drug discovery process, and discuss the use of semantic web technologies for data integration and knowledge discovery..
Dr. Ann Steiner, Clinical Professor of OBGYN at Penn Medicine, discusses the changes that happen as a woman's body goes through menopause, as well as treating symptoms that result from these hormonal changes.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
2. TALKING POINTS
Discuss the Epidemiology and Prevalence of Erectile Dysfunction
Brief overview regarding the pathophysiology, medical, and physical causes
behind Erectile Dysfunction
Reveal risk factors and any associated medication contributing to the
development and/or progression of Erectile Dysfunction
Present current treatment options with an emphasis on pharmaceutical
compounding treatment strategies for oral, injectable, and topical use
3. IT’S NOTYOU . . . IT’S ME
Incidence by Race Not Significantly Different (40+)
Whites – 22%
Blacks – 24%
Hispanics – 20%
Increased Incidence
Age
Diabetes Mellitus
Hypertension
Moderate/Severe LUTS
Decreased Incidence
Exercise and college education – vs – less than HS
Journal of Sexual Medicine 2007 Jan:4(1):57:65 Epub 2006 Nov 1
4. SERIOUSLY . . . IT’S ME
National Health & Nutrition Examination Survey (NHANES)
> 18 million men in U.S. over age of 20 (~18.4% of male population)
Never able or sometimes able to get and keep erection for satisfactory intercourse
90% with ED ≥ 1 CV RF; including DM (51%), HTN, ↑LDL/↓HDL, or smoker
Significantly & independently associated with DM, lower education, & ↓ physical activity
The American Journal of Medicine (2007) 120, 151-157
Massachusetts Male Aging Study (MMAS)
Overall rate of any degree of ED = 52% [40+ = 39%; 70+ = 67%]
↑ risk of ED associated with DM, HTN, CVD, PUD, Arthritis, Depression; ↔ smoker
Increased incidence with treatment
↓ with education; ↓ with income
Extrapolation of data reveals ~30 million (white) men in U.S. with some form of ED
The Journal of Urology (2000) 163, 460-463
5. ERECTING AN ERECTION
Complex event involving integration of:
Psychologic
Neurologic
Endocrine/Hormonal
Vascular & Local anatomic systems
Release of NO from NANC nerves and endothelial cells
Stimulates guanylate cyclase enzyme system in penile smooth muscle
↑ levels of cGMP & ↓ Ca2+
Smooth muscle relaxation
Enhancement of arterial inflow / veno-occlusion → adequate firmness
Return to flaccid state: cGMP is hydrolyzed to GMP by phosphodiesterase type 5
6. THE USUAL SUSPECTS &TYPES OF ED
1. Psychogenic Performance Anxiety, Depression Loss of libido, Impaired NO release
2. Neurogenic Stroke, SpinalCord Injury, DR Lack of nerve impulse/transmission
3. Hormonal Hypogonadism, Hyperprolactinoma Inadequate NO release
4. Vasculogenic Atherosclerosis, Hypertension Impaired arterial or venous flow
5. Medication-Induced Antihypertensives,Antidepressants, etc. Central suppression,Vascular Insuff
7. DRUG INDUCED IMPOTENCE
Antipsychotics, Antidepressants
Disruption of serotonergic, noradrenergic, and dopamine neurotransmitter
pathways involved in sexual function
Amitriptyline, Buspirone, Fluoxetine, Sertraline
Antihypertensives
β-adrenergic Blockers – Potentiation of α-1 adrenergic activity in the penis
Atenolol, Metoprolol, Propranolol, etc.
Thiazide Diuretics – Unknown, but thought to be due to increased uric acid levels
Ca2+-channel blockers, ACE-I, A2RBs
JACC Vol 62/18/Suppl C Oct 26-29, 2013
Kubin, M, et.al. IJIR (2003) 15, 63-71
8. DRUG INDUCED IMPOTENCE
Proton Pump Inhibitors
Inhibits DDAH; leads to increase of ADMA (inhibitor of NO) decreases NO synthase
Induction of hepatic CYP-dependent testosterone metabolism in vitro
Conversion to β-hydroxytestosterone
Esomeprazole, Lansoprazole
Rosenshein B et.al. Am J Med Sci 2004;327(5):289-93
Coulson, M et.al. Toxicol App Pharm 2003;192(2):154-63
Ghebremariam, Y et.al Circulation. 2013 Aug 20; 128(8)
H2-receptor Antagonists
↓ libido; ↑ E ↑ prolactin (gynecomastia; galactorrhea)
Erectile failure via an antiandrogenic effect
Erection promoting action of histamine likely due to H2 receptor activation
Cimetidine
http://medlineplus.gov/ency/article/004024.htm
Cará AM Br Jour Urol. 1995 Feb;75(2):220-4
9. COMMERCIALTREATMENT OPTIONS
Phosphodiesterase type 5 (PDE5) Inhibitors in U.S.
Sildenafil Citrate – 1998
25/50/100mg – max dose: 100mg*
$30-$45
Vardenafil HCl – 2003;2010
2.5/5/10/20mg – max dose: 20mg*
~$45
Tadalafil – 2003; (qd use, 2008)
2.5/5/10/20mg – max dose: 20mg*/5mg daily
~$60
Avanafil – 2012
50/100/200mg – max dose: 200mg*
~$70 *Assuming no CYP3A4 inhibitors
10. IN CLINICAL DEVELOPMENT
Compound Company Development Stage Mechanism of Action
RX 10100; (Zoraxel®)
Clavulanic Acid
Rexahn Pharmaceuticals Phase IIa Enhancement of Dopamine Release in CNS
PT-141; Bremelanotide Palatin Technologies Phase IIb Melanocortin-receptor agonist
Udenafil (Zydena®) Dong-A Pharmaceuticals
Warner Chilcott (US)
Phase III (US)
Launched (S. Korea)
PDE5-I t ½ : 12hr Tmax: 1 - 1.3hr
SK3530; Mirodenafil (Mvix®) SK chemical Launched (S. Korea) PDE5-I t ½ : 2.4hr Tmax: 1.5hr
Lodenafil Carbonate Cristalia/Quimicos Phase III PDE5-I t ½ : 2.3hr Tmax: 1.2hr
SLX-2101 Surface Logix Phase IIa PDE5-I t ½ : 9-14hr Tmax: 1hr
Icariin n/a Herbal Preparation PDE4-I, PDE5-I
HA-1077; Fasudil Asahi Kasei Pharma Launched for other ROCK Inhibition (rho-kinase inhibition)
SAR-407889 Sanofi-Aventis Phase IIa ROCK Inhibition
BMS-223131 Bristol-Myers Squibb Phase IIa Maxi-K channel opener
Adapted from: Expert Opin Emerg Drugs. 2010 September;15(3): 467-480
11. COMMERCIALTREATMENT OPTIONS
Prostaglandin E1
Alprostadil
Physicians who prescribe intracavernous injection therapy should:
(1) inform patients of the potential occurrence of prolonged erections
(2) have a plan for the urgent treatment of prolonged erections and
(3) inform the patient of the plan.
(See AUA guideline on priapism: http://www.auanet.org/guidelines/priapism.cfm)
Alternative Options
Papaverine, Pumps, Prosthesis/Implants
Arginine, Yohimbine, Maca, Ginko biloba, Panax Ginseng
Trazodone, Apomorphine, VIP, Testosterone, DHEA
12. COMPOUNDED MEDICATIONS
Sildenafil Compounds (C22H30N6O4S · C6H8O7; MW – 666)
Combined with Oxytocin (and/or Paroxetine for PE)
Oxytocin Benefits (125u – 250u)
Paroxetine Benefits (5mg)
Tablets, Gelatin-based Troches
Extremely bitter; not water soluble
Vardenafil Compounds (C23H33CIN6O4S; MW – 488)
Combined with Oxytocin and/or Paroxetine
Sublingual Tablets, PEG-based mini-troches, or ODT
Very water soluble; reduced bitterness
15. COMPOUNDED MEDICATIONS
Lyophilized Trimix
Ideal for travel use
No refrigeration required before reconstitution
Single-use or Multi-dose vials
Oxytocin Nasal Spray
60-120iu; 15-30 minutes prior to sexual intercourse
Study results suggest that oxytocin induces penile erection by activating NO synthase in the
paraventricular nucleus of the hypothalamus
Argiolas A, Melis M Adv Exp Med Biol 1995;395:247-254
Alprostadil 1% Topical Gel
0.25mL (2.5mg) applied to glans
39% efficacy (P=0.005) Goldstein, I et.al. UROLOGY 57:301-305, 2001
16. SUMMARY
ED is becoming increasingly prevalent and
reported cases are expected to rise (+600k/year)
Highly related to other disease states and may
be preventable via non-pharmacologic
interventions and lifestyle changes
Drug Utilization Review should be considered
when diagnosing/treating ED as many drugs can
contribute to ED
Commercial options are currently limited, but
quickly growing
Partnering with a compounding lab can provide
several alternatives and has ability to customize
therapy while improving and/or maximizing
patient outcomes
18. REFERENCES
• Selvin, Elizabeth, Arthur L. Burnett, and Elizabeth A. Platz. "Prevalence and Risk Factors for Erectile Dysfunction in the US." The American Journal of Medicine 120 (2007): 151-57.
• Laumann EO, West S, Glasser D, et.al “Prevalence and correlates of erectile dysfunction by race and ethnicity among men aged 40 or older in the United States: from the male attitudes regarding sexual health survey”
Journal of Sexual Medicine 2007 Jan;4(1):57-65. Epub 2006 Nov 1
• Johannes C, Araujo A, Feldman H, et.al. “Incidence of Erectile Dysfunction in Men 40 to 69 years old: Longitudinal Results from the Massachusetts Male Aging Study” The Journal of Urology 2000 Feb Vol. 163 460-463
• Ponholzer A, Temml C, Mock K. et.al Prevalence and Risk Factors for Erectile Dysfunction in 2869 Men Using a Validated Questionnaire” European Urology 47 (2005) 80-86
• Kubin M, Wagner G, Fugl-Meyer AR “Epidemiology of Erectile Dysfunction” International Journal of Impotence Research (2003) 15, 63-71
• Aribas, Alpay, Mehmet Kayrak, and Seref Ulucan. "The Relationship among Thiazide like Diuretic, Uric Acid, and Erectile Dysfunction in Hypertensive Subjects." OP-037 N.p., 26 Oct. 2013. Web. 4 Nov. 2016.
<http://content.onlinejacc.org/>.
• "Drugs That May Cause Impotence." MedlinePlus - Health Information from the National Library of Medicine. N.p., n.d. Web. 04 Nov. 2016. <https://medlineplus.gov//ency/article/004024.htm>.
• Ghebremariam, Y et.al. “An Unexpected Effect of Proton Pump Inhibitors: Elevation of the Cardiovascular Risk Factor ADMA” Circulation. 2013 August 20; 128(8)
• Rosenshein B, Flockhart DA, Ho H. “Induction of testosterone metabolism by esomeprazole in a CYP2C19*2 heterozygote” American Journal of Medical Science 2004;327(5):289-93
• Coulson M, Gibson GG, Plant N, et.al “Lansoprazole increases testosterone metabolism and clearance in male Sprague-Dawley rats: implicaitons for Leydig cell carcinogenesis” Toxicological Applications in Pharmacology
2003;192(2):154:63
• Cará AM, Lopes-Martin RA, Antunes E et.al “The role of histamine in human penile erection” British Journal of Urology 1995 Feb;75(2):220-4
• Khan MA, Thompson CS, Sullivan ME, et.al. “The role of prostaglandins in the aetiology and treatment of erectile dysfunction” Prostaglandins, Leukotrienes and Essential Fatty Acids (1999) 60(3), 169-174
• Minhas S, Cartledge J, Eardley I “The role of prostaglandins in penile erection” Prostaglandins, Leukotrienes and Essential Fatty Acids (2000) 62(3), 137-146
• Wright PJ “Comparison of phosphodiesterase type 5(PDE5) inhibitors” International Journal of Clinical Practice August 2006, 60, 8, 967-975
• “Erectile Dysfunction: The Management of Erectile Dysfunction, An Update” American Urological Association AUA guideline on erectile dysfunction Copyright @2005
• Kaufmann, Melissa, Ranjith Ramasamy, and Paul Turek. "Erectile Dysfunction." American Urological Association. American Urological Association, 2016. Web. 4 Nov. 2016. <http://www.auanet.org/>.
• Albersen M, Shindel A, Mwamukonda K, Lue T. “The Future is Today: Emerging Drugs for the Treatment of Erectile Dysfunction” Expert Opinion on Emerging Drugs 2010 September;15(3):467-480
• Goldstein, Irwin, Terry Payton, and Paul Schechter. "A Double-blind, Placebo-controlled, Efficacy and Safety Study of Topical Gel Formulation of 1% Alprostadil (topiglan) for the In-office Treatment of Erectile
Dysfunction." Urology 57.2 (2001): 301-05. Web. 9 Nov. 2016.
• Trissell, Lawrence A., and Yanping Zhang. "Long-Term Stability of Trimix: A Three-Drug Injection Used to Treat Erectile Dysfunction." International Journal of Pharmaceutical Compounding May/June 8.3 (2004): 231-35. Print.
19. What is the reasoning behind having the tadalafil/oxytocin as a rapid dissolve tablet, and the sildenafil/oxytocin as a chewable tablet?
Every drug has a specified solubility profile. Tadalafil has a solubility profile greater than that of Sildenafil. Additionally, the required strength for biological activity has much to do with it’s ability to
with it’s ability to function as a sublingual dosage form. Finally, palatability must be considered for patient use and/or compliance. Sildenafil is an extremely bitter drug as compared to Tadalafil.
Editor's Notes
J Sex Med (2007) ---
N = 2200
7-month (2001)
general community setting . . . 40+ yrs
**617k new cases expected annually
Erection Pressure: 100mm Hg (2psi) = resting BP of average healthy adult
Ejaculation Pressure: 700mm Hg (15psi) = pressure of paint being sprayed from canister or 1kg of force exerted upon 1cm2 (2.2 pounds per 0.15inch)
When the cytoplasmic calcium concentration falls below 500nmol, calcium dissociates from calmodulin (CaM), which in turn dissociates from myosin light chain kinase (MLCK), thus inactivating it.
With its kinase inactivated and its phosphate moiety removed by smooth muscle myosin phosphatase (SMPP-1M), the myosin light-chain (MLC) becomes inactive and can no longer bind the myosin head to actin.
This leads to relaxation of the cavernous smooth muscle cell vasodilation and enhancement of blood flow into the cavernosal sinusoids occurs, leading to penile erection.
Blood becomes trapped in the corporal bodies by compression of subtunical venules against the tunica albuginea
Digoxin – blockade of Na-K-ATPase pump → net increase in intracellular Ca+ and ↑ tone in coporal smooth muscle
Fibrates/Statins have been reported – very little information
NSAIDs have been reported - prostaglandin inhibitors; may be anti-erectogenic
First-line treatment
All equally effective, insufficient evidence to support superiority of one agent over another
Sild/Vard – Tmax 1hr; t ½ x 4hrs
T – Tmax 2hr; t ½ x 18hrs
Liver metabolism – adjust dose with altered hepatic function (CYP3A4 inhibitors; HIV, itraconazole, cimetidine, erythromycin)
SE profiles - flushing, HA, congestion, dyspepsia
Sild/Vard – PDE6 (visual S/E) - - - not with tadalafil
Vard – QT interval prolongation
Alpha blocker interaction
Contraindicated with Nitrates – time interval for administration of nitrates = 1-2 days
Mirodenafil (Mvix S) – MW = 531
Udenafil (Zydena) – MW = 516
the up-regulation of the contractile RhoA/Rho-kinase (ROCK) signaling pathway is one of the important mechanisms for diabetes-associated erectile dysfunction (ED).
Maxi-K channels:
function as neuronal calcium sensors
contribute to the control of cellular excitability and
regulation of neurotransmitter release
Caverject, Muse, Edex
OXT MW = 1007g/mol …
Oxytocin is one of the many neurotransmitters and peptides involved in controlling erections
Several studies have indicated that OT has a key role in the central regulation of penile erection
OT is released by posterior pituitary at the time of orgasm, mediates contractility in human epididymis
OT also induces release of Endothelin-1 – another potent stimulator of epididymal contraction
Filippi, S, et.al. Role of oxytocin in the ejaculatory process. J Endocrinol Invest 2003;26(3 Suppl):82-6
OXT could contribute to romantic bonds in men by enhancing their partner's attractiveness and reward value compared with other women.
Scheele, D., Wille, A., Kendrick, K., Stoffel-Wagner, B., Becker, B., Gunturkun, O., Maier, W. and Hurlemann, R. (2013). Oxytocin enhances brain reward system responses in men viewing the face of their female partner. Proceedings of the National Academy of Sciences, 110(50), pp. 20308-20313.
PAROXETINE
absorbed into the reticulated vein
transported through the facial veins, internal jugular vein, braciocephalic vein and then drained into systemic circulation.
Pankaj Prajapati, IJPRBS, 2014; Volume 3(2): 1019-1036
Sublingual Tablets:
MW < 500
Small tablet size
Highly soluble in saliva
Biphasic absorption
Potential Side Effects from IC Injections
Bruising at Injection Site
Penile pain / Groin pain
Fibrosis/scarring
Priapism - Phenylephrine HCl 0.5mg – 1mg (1%; 0.1mL)
Papaverine:
80% efficacy psycho-/neurogenic ED 40% efficacy Vasculogenic ED
Priapism risk, 35% Corporal Fibrosis 33%
Atropine:
Atropine effectively relaxes the vessels in the penis and helps in achieving erection.
Used alone is relatively insignificant and in combination with other injectables does not improve the success rates of a mixture without atropine
**It can help reduce the pain PGE1 can cause --- combined with higher concentrations of PGE1
Forskolin: (Not FDA approved)
Adenylate cyclase activator directly stimulates the enzymes responsible for starting and maintaining erections.
Triggers an increase in cAMP which causes smooth muscle relaxation in the penis.
This pharmacologic action enhances penile veno-occlusion and increases the quality of an induced erection.
In combination with other vasoactive agents, has demonstrated safety and efficacy in patients with vasculogenic impotence resistant to standard 3-agent pharmacotherapy.
Lue, T. ERECTILE DYSFUNCTION NEJM Vol 342;24 June 15, 2000 1802-1813
Goal is to achieve an erection that is adequate for sexual intercourse but does not last for more than one hour
The 2 major side effects of IC injections are:
Priapism & Fibrosis (leading to penile deviation, plaque)
To prevent fibrosis compress injection site x 5 minutes after injection
ICI’s are CI in sickle cell, schizophrenia, other psychiatric disorder
High response rate … but not 100% effective 100% of the time … dose adjustments may be necessary with chronic use
No more frequent than once every 24 hours and not more than 3 times per week