Clinical Case 1 Pharmacology B E. B. Andaya 3/8/07

Introduction A couple came to Fatima Clinic for fertility testing. They have been together for the past 10 years w/2 children. The couple is now in their middle age life. The woman complained of unsatisfied sexual activities for the last 2 years. She claimed her husband has a problem maintaining penile erection. Both underwent different lab procedures including psychological testing. A particular counselor was assigned to access family functions & dynamics. No significant abnormality was noted from the wife’s complete examination

Findings Subjective Findings Unsatisfied sexual activities for 2 years Husband has a problem maintaining penile erection Objective Findings No significant abnormality was noted from the wife’s examination

Diagnosis Erectile Dysfunction (ED) – when men can't get a penile erection or can't keep an erection long enough to finish having sex.

Causes of ED 1.Vascular Disease 2.Medicines/Illicit Drugs: 3.Hormone Disorders 4.Neurological conditions 5.Psychological conditions:

Likely Causes of Erectile Dysfunction Based on Clinical Presentation Psychologic causes Young age with abrupt onset Onset associated with specific emotional event Dysfunction in certain settings while normal function in others Persistence of nocturnal erections Previous history of erectile dysfunction with spontaneous improvement Excessive life stressors--work, relationships Mental status findings suggestive of depression, psychosis or anxiety disorder Organic causes Vasculogenic—arterial Persistent interest in sex Older age with gradual onset Impaired function in all settings Presence of chronic disease (particularly diabetes, hypertension) Use of prescription/over-the- counter medications associated with erectile dysfunction Smoking Elevated blood pressure, evidence of peripheral vascular disease (bruits, decreased pulses, skin and hair changes consistent with arterial insufficiency) Vasculogenic—venous Inability to maintain erection once established Prior history of priapism Local anomalies of the penis Neurogenic History of spinal cord/pelvic trauma or surgery Presence of chronic disease (diabetes, alcoholism) Presence of neurologic condition (multiple sclerosis, stroke) Abnormal neurologic examination of genitals/perineum Hormonal Loss of interest in sexual activity Small atrophic testis Low testosterone, elevated prolactin

Conditions Associated with Erectile Dysfunction Aging Chronic disease Diabetes mellitus Heart disease Hypertension Lipid disorders Renal failure Liver disease Vascular disease 1.Atherosclerosis 2.High blood pressure 3.High cholesterol levels 4.Long term smoking Endocrine abnormalities Hypogonadism Hyperprolactinemia Hypothyroidism/ hyperthyroidism Life style Cigarette smoking Chronic alcohol abuse Neurogenic causes Spinal cord injury Multiple sclerosis Herniated disc Penile injury/disease Peyronie's disease Priapism Anatomic abnormalities Medications Psychologic issues Depression Anxiety Social stressors Trauma/injury Pelvic trauma/surgery Pelvic radiation

Drugs Most Commonly Associated with Sexual Dysfunction MedicationType of sexual dysfunction* Antihypertensive medications Diuretics –Thiazides –Spironolactone (Aldactone) Sympatholytics –Central agents (methyldopa [Aldomet], clonidine [Catapres]) –Peripheral agents (reserpine [Serpasil]) –Alpha blockers Beta blockers (particularly nonselective agents) Erectile dysfunction, decreased libido Erectile dysfunction, ejaculatory dysfunction Erectile dysfunction, decreased libido Psychiatric medications Antipsychotic agents Antidepressants –Tricyclic antidepressants –Monoamine oxidase inhibitors –Selective serotonin reuptake inhibitors Anxiolytic agents - Benzodiazepines Multiple phases of sexual function Decreased libido, erectile dysfunction Multiple phases of sexual function Ejaculatory dysfunction, erectile dysfunction Decreased libido Antiandrogenic Digoxin (Lanoxin) Histamine H2-receptor blockers Decreased libido, erectile dysfunction Others Alcohol (long-term heavy use) Ketoconazole (Nizoral) Niacin (Nicolar) Phenobarbital Phenytoin (Dilantin) Decreased libido, erectile dysfunction

Evaluation of Patient with Erectile Dysfunction

Lab Tests & other Physical Examinations CBC: used to evaluate the presence of anemia. A low level of red cells limits the body’s utilization of O2 & can lead to fatigue & general malaise. The level of blood lipids such as cholesterol & triglycerides may indicate arteriosclerosis, w/c can reduce blood flow to the penis Liver & Kidney function test: Liver & Kidney disease can create hormonal imbalances. The test involve analysis of liver enzyme & serum creatinine levels, w/c are indicators of kidney efficiency Lipid profile: measures the level of lipids (fats) such as cholesterol in your blood. High levels of certain lipids may indicate atherosclerosis, a condition where arteries harden, which can affect blood circulation in the penis. Thyroid function test: thyroid hormones regulate metabolism & the production of sex hormones; a deficiency may contribute to impotence Urinalysis: urine is analyzed for albumin, glucose, & testosterone levels that may indicate DM, kidney dysfunction, & testosterone deficiency Blood hormone studies: measure testosterone and/or prolactin levels to look for any abnormalities with these sex hormones. Blood LH and FSH levels evaluate the pituitary's role in regulating these hormones. Nocturnal Penile test: used to differentiate organic & psychogenic impotence. Frequency & rigidity of erections are recorded by a simple device attached to the penis before sleep. Patients w/psychogenic impotence will have nocturnal erections of adequate frequency & adequacy. Prostrate Examination: an enlarged prostrate can interfere w/blood flow & nerve impulse in the penis

Treatment Pharmacological Management 1.Phosphodiesterase-5 Inhibitor MOA:

Pharmacological Management PDE-5 Inhibitor OnsetDurationHalf-lifeSide effectsDrug interaction Sildenafil (Viagra) 25, 50, 100 mg tab min4-6 hr4-5 hrHeadaches, flushing, indigestion CYP3A4 inhibitors (eg. Erythromycin, ketoconazozle, cimetidine, indinavir) Potentiates hypotensive effects of nitrates or α- blockers Vardenafil (Levitra) 2.5, 5, 10, 20 mg tab min4.8-6 hr Tadalafil (Cialis) 5, 10, 20 mg tab min36 hr hr

Pharmacological Management KineticsMOAS/E Apomorphine (Uprima) Onset: 10 min Duration: 30min Prep: 2-6mg SL Dopaminergic agonist. Agent has been shown to specifically activate c-fos gene expression in the paraventricular & supraoptic nuclei of hypothalamus. These areas are known to be involved w/penile erections Nausea Vomiting Dizziness Somnolence Hypotension YohimbineΑ-2-adrenergic receptor agonistNervousness Headache Dizziness nausea Testosterone Supplementation It works by correcting a hormonal deficiency Decreased lbido or testosterone level

Pharmacological Management KineticsMOAS/E AlprostadilIntracorporal injection (Caverject) – the basal & lateral aspect of the penis is used as the injection site Uretthral suppository (MUSE) – pellet must be inserted directly into penis through urethral opening Corporal smooth muscle relaxation when injected into the penile shaft, it relaxes trabecular smooth muscle, dilating cavernosal arteries, which then promotes blood flow & entrapment in the penis, causing penile erection Lightheadedness Burning sensation of the penis Prolonged priapism PhentolamineAlfa-adrenoceptor antagonist PapaverineVasodilator Combination of phentolamine & papaverine, when injected directly into penis, may cause erection in men w/sexual dysfunction Fibrotic reaction (long- term administration Orthostatic hypotension

Treatment Non-pharmacological Management 1.Vacuum constriction device: causes an erection by creating vacuum around the penis, which draws blood into the corpora cavernosa 2.Surgery a.Penile prosthesis: when erectile dysfunction does not respond to other treatments, a device that stimulates an erection (prothesis) can be surgically implanted in the penis b.Penile revascularization: patients with disorders of the arterial system are candidates 3.Psychological Therapy

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