ABHINAV SAWHNEYM.PHARMACY (PHARMACOLOGY)

AMITY INSITUTE OF PHARMACY,

AMITY UNIVERSITY

NOIDA

Evaluation and Treatmentof Erectile Dysfunction

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“Man survives earthquakes, experiences the horrors of illness, and all of the tortures of the soul. But the most tormenting tragedy of all time is, and will be, the tragedy of the bedroom.”

Tolstoy

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Goals and ObjectivesDefine erectile dysfunction (ED)Discuss the most common causes of EDReview a practical evaluation of men with

EDReview the treatment optionsProvide suggestions for urologic referral

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What is ED?ED is the inability to achieve and maintain an

erection adequate for intercourse to the mutual satisfaction of the man and his partner.

Remember, both partners in a relationship are affected.

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Incidence20-30 million American men suffer EDAge dependent

2% men age <40 years25% men age 6575% men >75 years

Not a necessary occurrence of the aging process

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How Does an Erection Occur?The brain controls all sexual functions, from

perceiving arousal to initiating and controlling the psychological, hormonal, nerve, and blood flow changes that lead to an erection.

Hormones, including testosterone, control the male sex drive

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How Does an Erection Occur?(cont.)Nerve impulses relay signals of arousal and

sensation to and from the penisArteries deliver extra blood to the penis

that causes it to stiffen. Veins then drain the blood out of the penis

after intercourse.

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Physical orPsychological Stimuli ResultsSacral parasympathetics (S2,3,4)

stimulation to the penile nervesDilation of the penile arteriesRelaxation of the smooth muscle in the

corporal bodies of the penisDecrease venous outflow

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An Erection Requires a Coordinated Interaction of Multiple Organ SystemsPsychological

Endocrine

Vascular

Neurologic

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Mechanism ofSmooth Muscle RelaxationRelease of Neurotransmitters-nitric oxide

Conversion of GTP to cGMP - erection

Breakdown of cGMP by PDE type 5 - detumesence

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Cause of EDPsychogenic Causes:

AnxietyDepressionFatigueGuiltStressMarital DiscordExcessive alcohol consumption

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Causes of EDOrganic Causes

Cardiovascular diseaseDiabetes mellitusSurgery on colon, bladder, prostateNeurologic causes (lumbar disc, MS, CVA)PriapismHormonal deficiency

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Causes of ED

Treated heart disease

Treated diabetes

Treated hypertension

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Causes of EDOther risk Factors ²Diabetes 27% - 59%Chronic renal failure 40%Hepatic failure 25% - 70%Multiple Sclerosis 71%Severe depression 90%Other (vascular disease, low HDL, high

cholesterol)

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Causes of EDHormone DeficiencyEnd Organ FailureBlockage of Blood VesselsVenous Leak

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Causes of EDSpinal cord injuries: 5% - 80%Pelvic and urogenital surgery and radiationSubstance abuseAlcohol: >600ml/wkSmoking amplifies other risk factorsMedications may be responsible for ~25%

of cases of EDBicycle riding

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Causes of EDMedication:

Most common cause of ED in men >50

Many men are polymedicated

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Causes of EDMedications (cont.)

Anti-hypertensive drugsAll capableCommon: thiazides and beta blockersUncommon: calcium channel blockers, alpha-

adrenergic blockers, and ACE inhibitors

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Causes of EDMedications (cont.)CNS drugs:

Antidepressants, tricyclics, SSRIsTranquilizersSedativesAnalgesics

H1 and H2 receptor blockers

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Causes of EDMedications (cont.)AnticholinergicsLHRH agonists (Lupron, Zolladex)AlcoholTobaccoDrug abuseEstrogens, Ketoconazole

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A Practical Evaluation of Men with EDBasic evaluationMedical History

Cardiovascular history

Endocrine history

Sexual history/questionnaire

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A Practical Evaluation of Men with EDBasic evaluation (cont.)Physical exam:

Focused neurovascular examSize of testis

Lab testsUATestosterone, Lipid panel

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A Practical Evaluation of Men with EDSexual HistoryPremature ejaculationRetarded ejaculationPainful intercourseAnorgasmiaDecreased LibidoDissatisfaction with sex life

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A Practical Evaluation of Men with EDPhysical ExaminationBlood pressureExamine penis ( Peyronie’s disease)Determine size and consistency of testesFocused vascular exam/peripheral pulsesFocused neurologic exam

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A Practical Evaluation of Men with EDLaboratory TestsUA (glycosuria) – Fasting if elevatedTestosterone (best to draw in A.M.)Prolactin, Thyroid function, Lipid profile,

Liver function, Creatinine

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Treatment OptionsGoal directed therapy4

Find out what the patient wantsTry to tailor the treatment to the patients

needs and wantsEtiology rarely affects treatment choice for

the patient

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Treatment OptionsNonpharmacologicNon-invasiveMinimally invasiveInvasiveCounseling and/or sex therapy

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Treatment OptionsOral medications - Viagra, Levitra, CialisUrethral suppositories (MUSE)Injection therapy - Caverject, Trimix, BimixVacuum constriction deviceSurgerySex therapy

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Counseling and/or Sex TherapyRule out depressionTry oral medication in patient with

psychogenic impotenceRefer to sex therapist or psychiatrist for

sever psychopathology

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Nonpharmacologic Treatment OptionsLifestyle changes:Reduce fat and cholesterol in dietDecrease or limit alcohol consumptionEliminate tobacco use and substance abuseWeight loss if appropriateRegular exercise

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Ideal Medication for Treatment of EDEffectiveAvailable on demandFree of toxicity and side effectsEasy to administerInexpensive

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Medication(Sidenafil, Tadafill, Vedafill)Mechanism of Action:PDE inhibitor and increases the cGMP that

promotes and sustains smooth muscle relaxation

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Medication(PDE Inhibitors)Indications:Psychogenic EDMild vasculogenic EDNeurogenic EDSide effects from medication(s) patient is

already taking

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Medication (PDE Inhibitors)Side effects:HeadacheFlushingDyspepsiaNasal congestionVisual disturbancesPriapism

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Medication (PDE Inhibitors)Contraindications:Organic Nitrites:

OralSublingual

Severe cardiac diseaseObtain stress testing

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Medication(Yohimbine, Yocon, Erex, Yohimex)Alpha 2 andrenoreceptor antagonistDose: 5.4 mg TIDResults: ~20% (same as placebo)Side effects: increase blood pressure,

tachycardia, anxiety

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MedicationTrazodone(Desyrel)Anti-depressant associated with priapismMechanism of action nor fully understoodNor FDA approved for EDSide effects: drowsiness, dry mouth,

sedation, priapism

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MedicationApomorphine (Spontane)Dopaminergic mechanism with

hypothalamic activitySublingual administration64% to 67% response rate with EDSide effects: nausea, sweating,

hypotension, yawning

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MedicationPhentolamine (Vasomax)Alpha-blockerRelaxes smooth muscle tissue40% efficacy in mild organic EDSide effects: nasal congestion, tachycardia,

dizziness, hypotension

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MedicationSide effectsDiscontinue tobacco, alcohol, and abusive

drugsAlter dosage of drugs with ED side effectsChange to another class of drugs

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Transurethral TherapyAlprostadil - MUSEMechanism of Action: vasodilatorAdministration: 125, 250, 500. 1000ugInsert in the urethraErection occurs 10-15 minutes laterErection lasts 30-45 minutesResults: 10-65%Side effects: Pain, bleeding, priapism

(<3%)

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Penile Injection TherapyCaverject, Edex, Tri/Bi-MixMechanism of action: smooth muscle

vasodilatorAdministration: 10, 20, 40ugInject directly into corporeal bodies of the

penisResults: 70%-90%Dropout rates: 25%-60%Side effects: pain (36%), priapism (4%),

fibrosis

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Androgen Replacement TherapyIndications: hypogonadism (<285ng/dl)Avoid oral estrogens-increase LFTsInjectable – 200mg testosterone

(cypionate, enathate, propionate), q2-3 weeks

TransdermalPatchgel

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Androgen Replacement TherapyAvoid in patients with prostate or breast

cancerSlight increase risk of BPHMonitor all patients with annual DRE and

PSA

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Vacuum Constriction DeviceMechanism of Action:Penis placed in plastic tubeAir evacuated from the tubeBlood trapped in penis with constricting

ring

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Vacuum Constriction DeviceErection limited to 30 minutesResults: 80%-90%Contraindications: bleeding disorders,

sickle cell disease, anticoagulationComplications: coolness, petechiae,

numbness, pain with ejaculationHigh drop out rate

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Vacuum Constriction DeviceWas previously first-line treatment for EDSeldom used now that oral therapy is

availableConsidered an alternative if patient fails

oral therapy and does not want to proceed with surgery

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Penile ProsthesisIndications:Patients who have failed other therapiesPeyronie’s diseaseSevere vasculogenic disease

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Malleable ProsthesisEasy for patient and partner to useFew mechanical partsSame-day surgery usually possibleLeast expensive type of prosthesis

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Penile ProsthesisAdvantages:Low-morbidityLow-mortality surgeryLow complication ratesHigh success rates – 5% malfunction rate at

5 yearsHigh satisfaction rate – 87%High partner satisfaction rate

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Penile ProsthesisAdvantages (cont.)Good rigidityFreedom from medicationsOutpatient/24HR surgeryResume sexual activity 4-6 weeksNo loss of ability to ejaculate or achieve

orgasm

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Penile ProsthesisDisadvantages:SurgeryExpensivePossible mechanical failure

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When to Refer to a Urologist

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Refer Patients to a UrologistPatients who fail medical managementPatients with Peyronie’s diseasePatients with severe vasculogenic EDPatients requesting an implant

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Why Refer to a Urologist?Only specialty that is trained in andrology

and/or management of EDUrologists offer a range of treatment

optionsED represents a significant aspect of many

urologic practicesUrology support staff is comfortable

treating men and their partners who suffer from ED

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SummaryED is a common problem that affects

millions of menED can be treated with oral medicationsPatients that do not respond to medical

therapy should be referred to a UrologistPenile prosthesis is an effective means of

treating ED

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RememberPrimary care physician should consider

early referral to Urologist if initial treatment is not successful

No one needs to suffer the “tragedy of the bedroom”

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REFFRENCES Tripathi K.D. “Essentials of Medical Pharmacology”,

JAYPEE Publishers, 6th edn, 2010(Reprint) 295-296Rang H.P; etal, Rang and Dale Pharmacology,

Elsevier's publication, 7th edn, 429-431Clarke A.M, etal; Lippincott,s Ilustrated Review:

Pharmacology, Wolters Kluwer Health, 5th edn, 2009 363-368

Bruntoun lauraence, etal ; Goodman & Gilman’s Manual of Pharmacology and Therapeutics, The MaCgraw hill companies, 2010, 424,531,546

Joseph T D, etal ; Pharmacotheraphy, The MaCgraw hill companies, 7th edn, 2008, 1369-1386

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