Dr. M.N.

Thareja
Vice President of National Sexology Society State Coordinator of HIV/AIDS Rajasthan Joint Secretary of Council of Sex Education & Parenthood International Executive member of Indian Andropause Society Life member of American Education and Sex education Post Graduate Certificate Course of HIV/ AIDS & STD Management counsellor.

Diagnosis of Male Sexual Dysfunction

1. PME->30% 2. E.DYSFUNCTION->25% 3. MYTHS & MISCONCEPTION->25% 4. INHIBITED SEXUAL DESIRE->20%

20%

30%

25% 25%

COMMON MYTHS AND MISCONCEPTIONS ABOUT SEX

Semen Related Myths. Dhat Syndrome Myths. Masturbation Myths.. Penis Related Myths. Precum Secration Hymen Myths.

Precum Secration

COMMON CAUSES OF PME

1. 2. 3. 4. 5. Excessive Excitement. Sexual Abstinence. New Partner. New Setting and Surrounding. Anxiety States. (i) Will I ejaculate too fast. (ii)Will I be able to satisfy my partner. 6. Early experience with Extra-marital relations. 7. Marital disharmony with partner.

PME CAN BE IMPROVED BY

BEHAVIOUR : Start & Stop method. :- Start & Stop with out lubrication :- Start & Stop with lubrication Squeeze Method. :- Standard Squeeze :- Basilar Squeeze PHARMACOLOGIES :- A. Tramadol B. Clomiparine Anesthetic Agents. C. Fluoxetine Psychotropic Drugs. D. Sertraline E. Dapoxetine

ADAPTED FROM PRINS 2002

 Erectile Dysfunction : Erectile dysfunction is defined as the inability to obtain and / or sustain an erection adequate for vaginal penetration and satisfactory completion of sexual intercourse.

CAUSE OF ERECTILE DYSFUNCTION

I ORGANIC
a. b. c. d. e. Traumatic Endocrinological. Neurological. Arterial. Venous Leakage

II PSYCHOGENIC

PSYCHOGENIC
1. 2. 3. 4. 5. Anxiety or Depression. Religious inhibition. Situational. Sexual Phobias. Lack of physical attraction or poor body image. 6. Traumatic post experience. 7. Lack of knowledge.

NEUROGENIC
-Spinal Cord -Spina bifida accidents -Disc herniation - Syringomyelia -Tumors -Multiple sclerosis-Tabes dorsalis Brain Cerebrovascular Parkinsons disease Alzheimers disease Tumors Brain injuries

Arteriogenic Erectile Dysfunction

1. 2. 3. 4. 5. 6. 7. Hypertension. Hyperlipidemia. Cigarette smoking. Diabetes mellitus. Pelvic trauma. Pelvic irradiation. Disease of Aorta , Common iliac , internal pudendal artery.

Endocrinologic Erection Dysfunction

- Testosterone - LH - FSH - Prolactin - Hyper Thyroid Libido - Hypo Thyroid Testosterone & Prolactin

Venous
-Large veins exit corpus cavernosum (Congenital) -The venous channel are enlarged by the distortion of the tunica albuginea ( Peyronie disease)

Drugs commonly associated with Erectile Dysfunction :Antidepressants ( Tricyclic & serotonin reputake inhibitors) Antiarrythmics ( Digoxin) Antiandrogens ( Gonadotropin releasing Harmon( GnRH) ) H2 - Blockers ( Cimetidine) Recreational Drugs ( Alcohol, Cocaine, Heroin, Marijuana )

Medical History
Detail History of :Diabetes Mellitus. Hypertension. Cardiac disease. Liver disease . Renal disease. Neurological. Vascular disease.

Sexual History
-The nature of onset. -Frequency. -Quality. -Duration of erection. -Presence or absence of nocturnal or morning erection. -Ability to achieve sexual satisfaction.

Physical Examination :-Degree of development of secondary sex characters. -Body hair, facial hairs, external genitals. -Evaluation of testes size and consistency. -Palpation of shaft of penis for Peyronie disease. -PR for size & consistence of prostate.

Laboratory Test

-Complete blood count (CBC), Urine analysis, Blood Urea Nitrogen(BUN), Creatinine. -Serum glucose or Glycosylated hemoglobin. -Lipid Profile. -Total Serum Testosterone. -Prolactin , FSH. -Thyroid Function Profile. - Prostate Specific Antigen (PSA)

Special Test
-NPTR ( Nocturnal Penile Tumescence & Rigidity ) -ICIVAD -Penile Sonography. -Rigiscan. -Electro Penilegraphy(EPG) -Corpus Cavernosum Electromyography ( CCEMG) -Penile Blood Pressure.

DRUGS USED FOR ICIVAD :-

1.PAPAVERINE 2.PAPAVERINE+PHENTOLAMINE BIMIX 3.PAPAVERINE+CHLOROPROMAZINE BIMIX 4.PROSTAGLANDIN E-I 5.PAPAVERINE+PHENTOLAMINE +CHLOROPROMAZINE(TRIMIX) 6. PAPAVERINE+PGE 1+CHLOROPROMAZINE ( TRIMIX ROUTINE USE)

- PENILE SONOGRAPHY -AT FLACCID STATE - GIVE ICIVID -SONOGRAPHY -PSV is > 30 cm/sec -EDV is <3 cm/sec. -RI= Resistivity Index => 0.91

Quit smoking Exercise regularly Reduce stress Minimize alcohol use Eliminate drugs

Specific endocrinologic conditions Psychosocial issues Prescription and nonprescription drug use

MANAGEMENT OF E.D
=>Direct Methods =>Indirect Methods 1. Pharmacotherapy a. Oral Drugs b. Local Drug c. Intra Cavernosal Injection( Vasoactive Injection) d. Medicated urethareal system for erection ( Muse). 2. Vacuum Erectile Device 3. Surgical Prosthatic Devices

First Line Therapy

Easy to administer. Reversible. Non-invasive. Low-risk. Appropriate for a broad range of patients in the primary-care setting.

COMMONLY USED ORAL

.Yohimbine. .Trazodone. .Apomorphine. .Phentolamine. .Sildenafil Citrate. .Tadalafil Citrate. .Verdanafil Citrate. Local Drug L. Arginine

Mechanism of Action
Sexual stimulation No release in Neurons & endothelium of corpus cavernosum Inhibition of PDE5 by Sildenafil citrate Tadalafil citrate Increase in the level of CGMP ( Cyclic guanosine Monophosphate) in Corpus Cavernosum Smooth muscle relaxation & inflow of blood in Corpa cavernosa

Sildenafil & Tadalafil citrate effective in

Coronary artery disease. Hypertension. Peripheral vascular disease. Diabetes mellitus. Depression. Coronary artery bypass grafts. Radical prostatectomy. Transurethral resection of the prostate. Spinal cord injury. Taking medications such as :-- Anti depressant , Antihypertensive agents. - Antipsychotic agents , Diuretics.

Contraindication of Sildenafil & Tadalafil Citrate 1. 2. 3. Nitrates. Hypotension. Leukemia, Sickle cell Anemia / Multiple Myolema. Retinosa Pigmentosoa. Recent attack of MI. Pt. Hyper sensitive to drugs. Peyronie disease. Apomorphine should be used with caution with Antidepresent & Antipsychotics drugs

4. 5. 6. 7.

Faster Onset of Action

60 50 40
Min

60

30 20 10 0 Tadalafil Sildenafil 16

36 Hrs. Action
36 30 24 Hrs. 18 12 6 0 Tadalafil Sildenafil Up to 4 hrs Up to 36 hrs

Adverse Effect
Headache Flushing Dizziness Dyspepsia Nasal Congestion Rash
Abnormal Vision Back ach Nausea & Vomiting Diarrhea Myalgia

Why PDE5's Fail

Severity of ED at presentation

Deterioration of Endothelial Function

Progressive penile atherosclerosis Post - radical prostatectomy ED Hypogonadism Lack of Patient Education Improper use of medication Psychological issues

PHYTO ANDROGEN

Latin Name Tribulus terrestris

Common Name Gokhru

PHYTO ANDROGEN
Effect of Tribulus terrestris Treatment on Impotence and Libido Disorders

1000 Patient on clinical trial 880 (88%) Patient shows marked improvement Errection, Prolonged duration of errection after treatment 64 (6.4%) Patient shows some improvement in both 30 (3%) Patient does not show any improvement 26 (2.6%) Patient drop out

Administered in average daily doses of 1.5 g in the course of 30 to 40 days, it restores and improves libido. Studies shows that it is non-toxic & non -carcinogenic.

Males Infertility and Impotence

Increased the efficiency of testosterone conversion to dihydrotestosterone (DHT)
DHT plays an important role in erythropoiesis as well as muscle development, contributing to the sense of physical well-being

Indirectly, these effects also added to the improvement in sexual functions, including libido, erection, and orgasm

 Latin Name Mucuna pruriens Common Name Kapikachhu

Mucuna pruriens - A Comprehensive Review

Mucuna pruriens is a popular Indian medicinal plant, which has long been used, in traditional ayurvedic Indian medicine for diseases including parkinsonism. This plant is pharmacologically studied for various activities like antidiabetic, aphrodisiac,antineoplastic, antiepileptic, antimicrobial activities etc. Biological activities Aphrodisiac Activity (L-dopa & 5-HT) Anti-Parkinsons activity Hypoglycaemic and Hypocholesterolemic activity Antioxidant activity Neuroprotective effect Antimicrobial activity

NANO-LEO
L-Arginine 500 mg

Tribulus terrestris extract powder

Mucuma pruriens extract powder Ginkgo biloba extract powder Zinc (as Zinc sulphate monohydrate) Yohimbe bark extract powder

200 mg
20 mg 20 mg 10 mg 1 mg

SECOND-LINE THERAPY .Vaccume Pump. .ICIVAD .Trans Uretheral Devices

THIRD-LINE THERAPY
- Penile Prostheses. - The malleable or positional Rod - Inflatable Penile Prostheses - Vascular Surgery - Arterial Revascularization - Venous Legation Surgery

Sexual Response Cycle

Desire Phase Excitement Phase

Plateau Phase
Orgasm Phase Resolution Phase
Masters & Johnson and H. S. Kaplan model

Human Sexual Response Cycle

1. Desire

Phase - Lasts Minutes To Hours

- Sexual Fantasies & The Desire For Sexual Intimacy

2. Excitement

Phase - Foreplay

- Early Phase = Minutes To Hours = - Penile Erection = - Vaginal Lubrication, Nipple Erection, & Vasocongestion Of The External Genitals - Late Phase = Seconds To Minutes = - Drops Of Fluid At Penile Urethral Meatus - Swelling Of Outer 1/3 Of The Vagina & Breast Engorgement

Human Sexual Response Cycle

3. Orgasm

Phase - 5 15 Seconds
- Ejaculation & Involuntary Muscular Contractions Of Pelvis Obligatory Refractory Period

- Contractions Of The Outer 1/3 Of The Vagina & Involuntary Pelvic Thrusting

4.

Resolution Phase-Detumescence,Feelings Of Relaxation &

Well being

Basic Mechanisms Of Penile Erection

 Subtunical veous pelxus compression Increase ICP leading to

ELONGATION AND INCREASE OF GIRTH & RIGIDITY

Erection Physiology

Penile Erection Is A Neurovascular Phenomenon That Depends Upon Neural Integrity, A Functional Vascular System, And Healthy Cavernosal Tissues Normal Erectile Function Involves 3 Synergistic And Simultaneous Processes:

- Neurologically Mediated Increase In Penile Arterial Inflow

- Relaxation Of Cavernosal Smooth Muscle

- Restriction Of Venous Outflow From The Penis

Penile erection is understood to be a neurally regulated physiologic event The classical autonomic parasympathetic and sympathetic nervous systems are involved The process of erection does not appear to require cholinergic or adrenergic mechanisms Nitric oxide (NO), a gaseous messenger molecule, has been rapidly advanced to fulfill this elusive role

Female Sexual Dysfunction

43% of American women suffer from sexual dysfunction. (50 million American women!) Highest proportion occures between the ages of 18 and 29. Most women can reach orgasm when the clitoris is stimulated, but only about half of women regularly reach orgasm during sexual intercourse. About 1 of 10 women never reaches orgasm. The WHO International Classifications of Diseases has divided Female Sexual Dysfunction into four disorders: (1) Desire disorder: a persistent absence of desire for sexual activity. (2) Arousal disorder: a persistent inability to attain or maintain sufficient sexual excitement. (3) Orgasm disorder, a persistent difficulty, delay or absence of orgasm after sufficient stimulation. (4) Pain disorder, persistent genital pain associated with sexual intercourse or stimulation.

Causes of FSD
Arousal and orgasmic disorders can be caused by a lack of blood circulation to the clitoris and genital area and may be related to medical conditions such as: Menopause Vascular disease High blood pressure Diabetes Pelvic trauma Other conditions related to poor blood flow

Causes of FSD
. Fluctuations in the levels of estrogen and testosterone hormones, which occur monthly and during pregnancy, can affect sex drive. In postmenopausal women, sex drive may be reduced because estrogen levels decrease. Sex drive may also be reduced in women who have had both ovaries removed. A reduction in sex drive may result from depression, anxiety, stress, or problems in a relationship. Use of certain drugs, including anticonvulsants, chemotherapy drugs, -blockers ( Antihypertensive Drugs), and oral contraceptives, can also reduce the sex drive. Drinking excessive amounts of alcohol. Treatment: vasoactive agents (pills, Arginine Gel), herbal drugs, EROS clitoral therapy device, psychological therapy

The EROS clitoral therapy device is a handheld device that increases blood flow to the clitoris. The plastic cup is placed directly over the clitoris.

NO in Female Sexual Response

Genital arousal, an early physiologic event in the overall sexual response, is a neurophysiological process comprising of Central and Peripheral components The peripheral component is characterized by an increase in genital blood flow coordinated with clitoral and vaginal smooth muscle relaxation, engorgement of the clitoris and vaginal wall, vaginal lubrication and lengthening Increased clitoral and vaginal blood flow during sexual arousal is primarily mediated by the nitric oxide NO

J Sex Med. 2009 March 1; 6(S3PROCEEDINGS): 247253

Physiological Similarities Between Male & Female Sex Organs

The Nitric Oxide Pathway in the Female Vaginal & Clitoral Region

Oestrogen
Endothelial Nitric Oxide Synthase (Ser1177) (eNOS)

eNOS(Endothelial Nitric Oxide)

Caveolin -1

Improvement of Blood Flow

Clitoral and vaginal smooth muscle relaxation Engorgement of the clitoris and vaginal wall Vaginal lubrication and lengthening

Conclusion: The use of topic hydrogel as a donor drug in the clitoris of women resulting in a local vasodilatation, without systemic effects. These findings suggest that this preparation may be useful in the management of selected cases of female sexual dysfunction

Clinical Trial Study

To assess efficacy and marketability of a topical personal care vaginal lubricant/moisturizer containing L-arginine and Menthol
Treatment Duration: 8 Sexual Encounters The test agent is a topical personal care vaginal lubricant/moisturizer containing 2.0% L-arginine and 0.25% menthol.

Treatment Groups
Group 1: 0.5 ml per sexual encounter Group 2: 2.0 ml per sexual encounter Age Group Involved 20 57 Years Study Parameters Lubrication -Time and Quality Measures, Orgasm -Intensity & Orgasm Frequency , Time to achieve an Orgasm ,Multiple Orgasms
Kirstin LaVolette (Study Coordinator, FL) Ronald J. Thompson MD (Principal Investigator) Central Florida, U.S.A.

Conclusions

Lubrication Speed (81.2%) Quality (71.6%) Rating (88.2 %) Orgasm Percentage 20 29 years 71% 30 39 years 68.2 % 40 + years 47. 2 % Orgasm Speed

Decrease in time 69%

Average time 2.94 3.15 minutes

Conclusions Cont'd

Orgasm Intensity 20 -29 years 81 % 30 39 years 60 % 40 + years - 76.2% Multiple Orgasm Percentage 20 29 years 49.3 % 30 39 years 80 % 40 + years 38 %

Indications & Mode of Application

Indications Male Erection FSAD Mode of Application st Digit of the Index Finger 1-3 gms of the Gel taken on the 1 and applied gently to the circumference of the penis 1-3 gms applied on the Clitoral Hood and surrounding areas gently
A slight feeling of warmth at the site of application on the tissue may be experienced due to increased vascular supply

Contraindications Genital Sores, Herpes, Infections due STDs Safety & efficacy of the Gel not established in paediatric class of patients Safety & Efficacy of the Gel not established in Pregnancy Drug Interactions No known drug intercations are reported with the use of LArginine Gel Adverse Drug Reactions The gel is aqua based (pH 7- 7.5) and the adverse drug reactions may include mild irritation at the site of application, which can removed by washing the area with water S/E -Minimal side-effects reported in Clinical Trials

Oral vs Gel Formulation

Oral The amount of oral L-Arginine formualtion required for acheiving erectile responses in males & clitoral stimulation in females has not been established dosages ranging from 10 -15 gms have been used for improving erectile function and clitoral stimulation but have met with little success and the S/E profile reported included Severe Abdominal Pain, Bloating,Nausea & Vomiting, Hypotension Gel The Aqueous based Gel Formulation containing 5% L-Arginine is a better option with minimal or no S/E unlike oral formulation Faster Onset of action due to topical application and absorption (3 5 mins) Minimal Sytemic Absorption

Summary
Relaxation of corpus cavernosum was mediated by nonadrenergic-noncholinergic (NANC) neurons and attributed to the generation and release of NO as the primary neurotransmitter The L-Argine Gel formulation is a better tolerated alternative as compared to the oral formulation with a favourable Pharmacokinetic profile The gel formulation can be co-prescribed along with PDE5 Inhbitors The gel formulation can also be prescribed along with prosexual nutrients

The Quadruple of Atreya

According to ancient sage Athreya, there are 4 components for a successful treatment namely: 1. The Physician. 2. Drugs. 3. The Patient. 4. Attendants It is told that all the 4 components have to be efficient to achieve successful treatment.
Charka Samhitha

Take

home

message

1.ICIVAD & penile sonography is best tool to Diagnose & give the moral support in psychosocial patient of erectile dysfunction. 2. Where we want permanent treatment cure without side effect phytoandrogen are the drug of choice. 3. There is established role of L-Arginine in male Strong Erection & Sexual Arousal in Female by release of NO.

Thank You for Your Kind Attention

RNT Medical College & Hospital Court Circle, Udaipur (Raj.)

Contact Us RNT Goldfest Secretariat, Room No. 6, Department of Physiology, RNT Medical College, Udaipur Rajasthan, INDIA. Phone : +91-294-2528811-18 Ext. 490 Email: info@rntgoldfest.com

NO in Female Sexual Response Cont'd

NO is a potent vasodilator of clitoral tissue, reminiscent of its effects on penile cavernosal tissue The clitoral cavernosal tissue consists of 4045% smooth muscle and blood-filled sinusoids The increase in clitoral blood supply is a result of arterial vasodilation and smooth muscle relaxation in the corpus cavernosum Clitoral tumescence occurs mainly because of the arterial inflow over-whelming blood drainage in the absence of veno-occlusion

J Sex Med. 2009 March 1; 6(S3PROCEEDINGS): 247253

Fig. 1: Anatomy and mechanism of penile erection

Fazio, L. et al. CMAJ 2004;170:1429-1437

Copyright 2004 Canadian Medical Association or its licensors

Role of Nitric Oxide in the Physiology of Erection

Penile erection is understood to be a neurally regulated physiologic event The classical autonomic parasympathetic and sympathetic nervous systems are involved The process of erection does not appear to require cholinergic or adrenergic mechanisms Nitric oxide (NO), a gaseous messenger molecule, has been rapidly advanced to fulfill this elusive role

Role of Nitric Oxide in the Physiology of Erection Cont'd

The nitric oxide (NO) pathway is of critical importance in the physiologic induction and maintenance of erections The constitutive endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) isoforms are tightly regulated and produce physiologically relevant levels of NO in endothelial cells & autonomic nerve endings of the penis Although neurally derived NO is well established as a mediator of penile erection, the role of eNOS in penile erection is becoming increasingly recognized
Society for Experimental Biology and Medicine

The physiology of erection includes the understanding that a non-

Thought Touch Visual Erotic Stimuli

Mechanism of Action

Vascular Medicine 2002

Role of Nitric Oxide in the Physiology of Erection Cont'd

There is considerable evidence that NO functions as a neurotransmitter It is an unusual transmitter, in that it is a labile free-radical gas that is not stored in synaptic vesicles NO is synthesized by NO synthase (NOS) from L- arginine, and simply diffuses from nerve terminals,

Kim N N et al. J. Nutr. 2004;134:2873S-2879S, The Journal of Neuroscience, September 1994, M(9): 51475 - 5159

2004 by American Society for Nutrition

Cellular Perspective of the Erection Pathway

Sexual arousal activates the NO-cGMP pathway, leading to cavernosal smooth muscle cell relaxation, lacunar space engorgement and erection
Adapted from Lue TF. N Engl J Med 2000; 342: 1802-1813.

Basic Mechanisms Of Clitoral Stimulation

NO in Female Sexual Response

Genital arousal, an early physiologic event in the overall sexual response, is a neurophysiological process comprising of Central and Peripheral components The peripheral component is characterized by an increase in genital blood flow coordinated with clitoral and vaginal smooth muscle relaxation, engorgement of the clitoris and vaginal wall, vaginal lubrication and lengthening Increased clitoral and vaginal blood flow during sexual arousal is primarily mediated by the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway

J Sex Med. 2009 March 1; 6(S3PROCEEDINGS): 247253

Physiological Similarities Between Male & Female Sex Organs

NO in Female Sexual Response Cont'd

NO is a potent vasodilator of clitoral tissue, reminiscent of its effects on penile cavernosal tissue The clitoral cavernosal tissue consists of 4045% smooth muscle and blood-filled sinusoids The increase in clitoral blood supply is a result of arterial vasodilation and smooth muscle relaxation in the corpus cavernosum Clitoral tumescence occurs mainly because of the arterial inflow over-whelming blood drainage in the absence of veno-occlusion

J Sex Med. 2009 March 1; 6(S3PROCEEDINGS): 247253

The Nitric Oxide Pathway in the Female Vaginal & Clitoral Region

Oestrogen
Endothelial Nitric Oxide Synthase (Ser1177) (eNOS)

eNOS(Endothelial Nitric Oxide)

Caveolin -1

Constitutive eNOS Activation

Improvement of Blood Flow

Clitoral and vaginal smooth muscle relaxation Engorgement of the clitoris and vaginal wall Vaginal lubrication and lengthening

FSAD(Female Sexual Arousal Disorder)

Female sexual arousal disorder (FSAD) is the inability to attain or maintain sufficient sexual excitement and pertains to Impairment in Hemodynamic Changes during Sexual Response Resulting in Decreased Clitoral Engorgement Lack of Vaginal Wall Relaxation & Diminished Vaginal Lubrication

J Sex Med. 2009 March 1; 6(S3PROCEEDINGS): 247253

Conclusion: The use of topic hydrogel as a donor drug in the clitoris of women resulting in a local vasodilatation, without systemic effects. These findings suggest that this preparation may be useful in the management of selected cases of female sexual dysfunction

Clinical Trial Study

To assess efficacy and marketability of a topical personal care vaginal lubricant/moisturizer containing L-arginine and Menthol
Treatment Duration: 8 Sexual Encounters The test agent is a topical personal care vaginal lubricant/moisturizer containing 2.0% L-arginine and 0.25% menthol.

Treatment Groups
Group 1: 0.5 ml per sexual encounter Group 2: 2.0 ml per sexual encounter Age Group Involved 20 57 Years Study Parameters Lubrication -Time and Quality Measures, Orgasm -Intensity & Orgasm Frequency , Time to achieve an Orgasm ,Multiple Orgasms
Kirstin LaVolette (Study Coordinator, FL) Ronald J. Thompson MD (Principal Investigator) Central Florida, U.S.A.

Conclusions

Lubrication Speed (81.2%) Quality (71.6%) Rating (88.2 %) Orgasm Percentage 20 29 years 71% 30 39 years 68.2 % 40 + years 47. 2 % Orgasm Speed Decrease in time 69% Average time 2.94 3.15 minutes

Conclusions Cont'd

Orgasm Intensity 20 -29 years 81 % 30 39 years 60 % 40 + years - 76.2% Multiple Orgasm Percentage 20 29 years 49.3 % 30 39 years 80 % 40 + years 38 %

The aim of this study was to determine whether a patent pending modified topical L-Arginine cream could improve female sexual dysfunction when applied to the clitoral hood prior to intercourse Conclusion This study demonstrated a significant improvement in sexual response with the topically applied proprietary modification of L-Arginine

Indications & Mode of Application

Indications Male Erection FSAD Mode of Application st Digit of the Index Finger 1-3 gms of the Gel taken on the 1 and applied gently to the circumference of the penis 1-3 gms applied on the Clitoral Hood and surrounding areas gently
A slight feeling of warmth at the site of application on the tissue may be experienced due to increased vascular supply

Contraindications Genital Sores, Herpes, Infections due STDs Safety & efficacy of the Gel not established in paediatric class of patients Safety & Efficacy of the Gel not established in Pregnancy Drug Interactions No known drug intercations are reported with the use of LArginine Gel Adverse Drug Reactions The gel is aqua based (pH 7- 7.5) and the adverse drug reactions may include mild irritation at the site of application, which can contained by washing the area with water (serious ADR's none reported) S/E -Minimal side-effects reported in Clinical Trials

Oral vs Gel Formulation

Oral The amount of oral L-Arginine formualtion required for acheiving erectile responses in males & clitoral stimulation in females has not been established However studies and anecdotal instances of dosages ranging from 10 -15 gms have been used for improving erectile function and clitoral stimulation but have met with little success and the S/E profile reported included Severe Abdominal Pain, Bloating,Nausea & Vomiting, Hypotension Gel The Aqueous based Gel Formulation containing 5% L-Arginine is a better option with minimal or no S/E unlike oral formulation Faster Onset of action due to topical application and absorption (3 5 mins)

Summary

Chemical and Biological properties of NO endow this potent endogenous mediator with the capacity to act as a local modulator of blood flow and hemostasis Ideal for the local and immediate delivery of this lipophilic and labile vasodilator directly to the underlying smooth muscle as well as to the endothelial cell surface The small size and lipophilic nature of NO are conducive to the rapid diffusion of NO through cell membranes to reach its target cells

JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 2002, 53, 4, 503-.514

Summary
Relaxation of corpus cavernosum was mediated by nonadrenergicnoncholinergic (NANC) neurons and attributed to the generation and release of NO as the primary neurotransmitter Mammalian penile erection is mediated by NO released from NANC neurons and that cyclic GMP serves as the signal transduction mechanismfor smooth muscle relaxation (Arginine-NO - Cyclic GMP

Pathway)

The L-Argine Gel formulation is a better tolerated alternative as compared to the oral formulation with a favourable Pharmacokinetic profile The gel formulation can be co-prescribed along with PDE5 Inhbitors The gel formulation can also be prescribed along with pro-sexual nutrients

Take home message

1.ICIVAD & penile sonography is best tool to Diagnose & give the moral support in psychosocial patient of erectile dysfunction. 2. Tadalafil is far superior than Sildenafil citrate and the newer drug vardanafil citrate is not available . 3. Where we want permanent treatment cure without side effect phytoandrogen are the drug of choice.

THANKS

Thought Touch Visual Erotic Stimuli

Mechanism of Action

Vascular Medicine 2002

Role of Nitric Oxide in the Physiology of Erection Cont'd

There is considerable evidence that NO functions as a neurotransmitter It is an unusual transmitter, in that it is a labile free-radical gas that is not stored in synaptic vesicles NO is synthesized by NO synthase (NOS) from L- arginine, and simply diffuses from nerve terminals,

Kim N N et al. J. Nutr. 2004;134:2873S-2879S, The Journal of Neuroscience, September 1994, M(9): 51475 - 5159

2004 by American Society for Nutrition

Cellular Perspective of the Erection Pathway

Sexual arousal activates the NO-cGMP pathway, leading to cavernosal smooth muscle cell relaxation, lacunar space engorgement and erection
Adapted from Lue TF. N Engl J Med 2000; 342: 1802-1813.

Biochemistry of Erection: Contarctile Mechanism

ENOS = endothelial nitric oxide synthase.

NANC = nonadrenergic-noncholinergic. NNOS = neural nitric oxide synthase.

N Engl J Med. 2000

Biochemistry of Erection: Relaxation Mechanism

eNOS=endothelial nitric oxide synthase nNOS=neural nitric oxide synthase.

N Engl J Med. 2000

Fig. 1: Anatomy and mechanism of penile erection

Fazio, L. et al. CMAJ 2004;170:1429-1437

Copyright 2004 Canadian Medical Association or its licensors

Role of Nitric Oxide in the Physiology of Erection

Penile erection is understood to be a neurally regulated physiologic event The classical autonomic parasympathetic and sympathetic nervous systems are involved The process of erection does not appear to require cholinergic or adrenergic mechanisms Nitric oxide (NO), a gaseous messenger molecule, has been rapidly advanced to fulfill this exclusive role

Role of Nitric Oxide in the Physiology of Erection Cont'd

The nitric oxide (NO) pathway is of critical importance in the physiologic induction and maintenance of erections
The constitutive endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) isoforms are tightly regulated and produce physiologically relevant levels of NO in endothelial cells & autonomic nerve endings of the penis

Although neurally derived NO is well established as a mediator of penile erection, the role of eNOS in penile erection is becoming increasingly recognized The physiology of erection includes the understanding that a nonadrenergic,non-cholinergic (NANC) mechanism is principally involved
Society for Experimental Biology and Medicine

Libido & Sexual Arousal

Visual Olfactory Auditory Tactile Temporal Factors linked to Psychological & Physiological Stimulation

Female Sexual Arousal Disorder

Inability to lubricate or stay lubricated Increases with age and is common after 50 Physiological factors: lowered blood flow to the vulva Psychological factors: fear, guilt, anxiety, depression Treatment: vasoactive agents (pills, creams), herbal drugs, EROS clitoral therapy device, psychological therapy

Summary

Chemical and Biological properties of NO endow this potent endogenous mediator with the capacity to act as a local modulator of blood flow and hemostasis Ideal for the local and immediate delivery of this lipophilic and labile vasodilator directly to the underlying smooth muscle as well as to the endothelial cell surface The small size and lipophilic nature of NO are conducive to the rapid diffusion of NO through cell membranes to reach its target cells

JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 2002, 53, 4, 503-.514

L-Arginine Gel

Libido & Sexual Arousal

Human Sexual Response Cycle

1. Excitement Phase response develops from any physical or mental stimulation of erotic nature. This phase may prolonged or cut short lasts minutes to hours sexual fantasies & the desire for sexual intimacy

2. Plateau Phase - foreplay early phase = minutes to hours = - penile erection - vaginal lubrication, nipple erection, & vasocongestion of the external genitalia late phase = seconds to minutes = - drops of fluid at head of penis - tightening of outer 1/3 of the vagina & breast engorgement

Human Sexual Response Cycle

3. Orgasmic stage - 5 15 seconds - ejaculation & involuntary muscular contractions of pelvis obligatory refractory period contractions of the outer 1/3 of the vagina & involuntary pelvic thrusting multiple orgasms 4. Resolution stage - detumescence feelings of relaxation & well-being

Basic Mechanisms Of Penile Erection

Erection a Neurovascular Event

Penile Anatomy

American Family Physician 2000

Mechanics of Erection
(A) In the flaccid state, arterial vessels are constricted and venous vessels are noncompressed. (B) On erection, smooth muscle relaxation in the trabeculae and arterial vasculature results in increased blood flow, which rapidly fills and dilates the cavernosal spaces. Venous outflow drops as the expanding cavernosal spaces compress the venous plexus and the larger veins passing through the tunica albuginea

Physiology of Erection

Basic Mechanisms Of Clitoral Stimulation