ED IDM1 Winter 2024 1SPP.pdf

Erectile Dysfunction Integrated Disease Management I Winter 2024 FRANCES M. COLÓN-PRATTS; PHARM D. CDCES CLINICAL ASSISTANT PROFESSOR PHARMACY PRACTICE DEPARTMENT NOVA SOUTHEASTERN UNIVERSITY COLLEGE OF PHARMACY- PUERTO RICO [email protected] Lecture Objectives  After completing the lecture, students...

Erectile Dysfunction Integrated Disease Management I Winter 2024 FRANCES M. COLÓN-PRATTS; PHARM D. CDCES CLINICAL ASSISTANT PROFESSOR PHARMACY PRACTICE DEPARTMENT NOVA SOUTHEASTERN UNIVERSITY COLLEGE OF PHARMACY- PUERTO RICO [email protected] Lecture Objectives  After completing the lecture, students should be able to:  Define erectile dysfunction (ED) and risk factors associated with the development of ED.  List drugs that can contribute to the development of ED.  Design an appropriate pharmacotherapy plan based on patient-specific characteristics, ensuring indication, efficacy, safety, and convenience, thus preventing or managing drug-related problems.  Give appropriate counseling information for a patient regarding pharmacological and non-pharmacological therapies for the management of ED. Introduction/ Incidence Anger Embarrassment  Erectile Dysfunction (ED):  Definition:  Failure to achieve and/or maintain a penile erection appropriate for sexual intercourse.  Other Name:  Impotence  Incidence  Low in men < 40y/o  Increase as men age Low self confidence Anxiousness Loss of interest in Performance sexual activity anxiety Depression Etiology Organic ED: Vascular, nervous, or hormonal systems are compromise Accounts for approximately 80% of ED cases Psychogenic ED: Psychological factors, do not respond to psychic stimulus or arousal Mixed ED: Combination of both: Organic and Psychogenic ED Others: Social habits: smoking, excessive ethanol intake, etc. Organic ED Arteriosclerosis Peripheral vascular disease (PVD) Hypertension (HTN) Diabetes mellitus (DM) Spinal cord injury Stroke DM Hypogonadism Vascular Nervous Hormonal Penile vasculature and smooth muscle relaxation →Erection -Acetylcholine (Ach) -Dopamine -Nitric Oxide (NO) -Prostaglandins E1 (PGE1) Penile vasculature and smooth muscle contraction → Detumescence -Noradrenaline (NE) -Serotonin -Phosphodiesterase 5 (PDE5) Detumescence Medications are estimated to be responsible for approximately 10% to 25% of cases of ED.  Some of the mechanism of actions for causing ED are not know, but many of them have sympatholytic, anticholinergic, sedative or, antiandrogenic effects.  Erection Medication Induced ED Medication Induced ED Selected Medications that cause Erectile Dysfunction Propose MOA Management/Alternatives Antihypertensives: clonidine, methyldopa, beta blockers (except for nebivolol), diuretics, etc. Decrease penile blood flow Alternative less likely associated with ED included: nebivolol, ACEI, ARBs, CCBs, and α1-adrenergic antagonists (terazosin, doxazosin) CNS Depressants (e.g., benzodiazepines, anticonvulsants such as: phenytoin, carbamazepine, phenobarbital, primidone, narcotics) Suppress perception of psychogenic stimulus Anticonvulsant less likely associated with ED included: valproic acid or gabapentin Decrease ACh activity Alternative less likely associated with ED included: bupropion, venlafaxine, trazodone, 2nd generation antihistamines, etc. Medication Induce ED Anticholinergics (TCAs, 1st generation antihistamines, etc.) Abbreviations: MOA: mechanism of action, ED: erectile dysfunction, ACEI: angiotensin converting enzyme inhibitors, ARBs: angiotensin receptor blockers; CCBs: calcium channel blockers, ACh: acetylcholine, and TCAs: tricyclic antidepressant Medication Induced ED Selected Medications that cause Erectile Dysfunction Propose MOA Management/Alternatives Dopamine antagonist (e.g., metoclopramide) Antagonizes dopamine activity PPIs, erythromycin SSRIs/SNRIs Spironolactone Cimetidine Finasteride, Dutasteride Lithium Serotonin involved in detumescence Suppress testosteronemediated stimulation of libido/ Antiandrogenic effects Unknown Mechanism Trazodone SSRI cause less ED than TCAs. Of the SSRIs, paroxetine, sertraline, fluvoxamine, and fluoxetine cause ED more commonly than venlafaxine, nefazodone, trazodone, bupropion, duloxetine, mirtazapine, escitalopram, or vilazodone Alternative less likely associated with ED included: nebivolol, ACEI, ARBs, CCBs, and α1-adrenergic antagonists (terazosin, doxazosin) Others H2RAs Inhibitors, PPIs, etc. Terazosin, alfuzosin, etc. Valproic Acid Abbreviations: PPIs: proton pump inhibitors; H2RAs: histamine 2 receptor antagonist, SSRIs: serotonin selective reuptake inhibitors, SNRIs: serotonin norepinephrine reuptake inhibitors Adapted from Pharmacotherapy: Lee M, Sharifi R. Erectile Dysfunction. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach Table 83-2, 10e New York, NY: McGraw-Hill;.and Lee M, Sharifi R. Erectile Dysfunction. In: DiPiro JT, Yee GC, Posey L, Haines ST, Nolin TD, Ellingrod V. eds. Pharmacotherapy: A Pathophysiologic Approach Table 99-2, 11e New York, NY: McGraw-Hill. Cardiovascular Disease (CVD) and ED  CV evaluation should be conducted; in all patients with ED:  ED might be an early symptom of an unidentified comorbid CVD (even in patients with ED and no other apparent health conditions)  E.g., atherosclerosis  Sexual activity can be demanding; sympathetic activation during sexual activity may increase blood pressure (BP) and heart rate (HR) → increasing the risk of myocardial infarction (MI)  Those with CVD wishing to initiate or resume sexual activity should be evaluated prior sexual intercourse and/or pharmacotherapy for ED. Cardiovascular Disease (CVD) and ED The following males should be referred for cardiovascular assessment and management and should avoid sexual activity until their CVD is controlled or stabilized:  Unstable, symptomatic, or refractory angina  Uncontrolled HTN (e.g., >170/100mmHg)  Congestive Heart Failure (CHF) – New York Heart Association(NYHA) Class IV  Recent MI or stroke (4hrs or have a painful erection, seek medical attention right away. If you experience ringing in the ears or hearing loss in one or both ears, seek immediate attention and stop taking the medication. May cause reversible problems with color discrimination (difficulty discriminating blue from green), due to their affinity to PDE6 found on the retina Sudden vision loss in one or both eyes can occur , seek immediate attention and stop taking the medication. Counseling Points:  Nonarteritic Anterior Ischemic Optic Neuropathy (NAION)      Blood flow to the optic nerve is blocked S/S: sudden, one-sided, painless decrease or loss of sight May be irreversible Risk factors associated with NAION: DM, smoking, HTN, CVD, dyslipidemia, and age >50y/o. PDE5 Inhibitors Labeling:  States the possibility of NAION and instructs the patient with sudden decreased vision or vision loss to stop the use of all PDE5 inhibitors and look for immediate medical attention. Questions Which of the following is NOT a counseling point for PDE5 inhibitors? a. Be aware for signs of low blood pressure b. This is contraindicated in patients with diabetes c. Can cause a prolonged painful erection d. Do not used, if you are using a nitrate Test your knowledge!  a. b. c. d. A 59-year-old male calls your clinic because he is using avanafil and has an erection that has persisted for 2 hours. At what point should the patient seek medical emergency? 50 minutes 25 minutes 4 hours 24 hours Case JH is a 56-year-old male who brings a prescription for sildenafil 50mg 1 tab 1 hr. prior sexual activity every day, as needed.  His medical conditions include: HTN (BP Today: 122/78mmHg), depression, obesity and, prostate enlargement.  Medications:  Tamsulosin 0.4mg daily  Vitamin D 400 IU daily  Propranolol LA 80mg daily  ASA 325mg daily  APAP 500mg 1-2 tabs prn for headaches  Fosinopril 10mg bid   Sertraline 100mg daily Case  a) b) c) d) Is sildenafil CI in this patient? (Select ALL that apply) Yes, the combination of tamsulosin and sildenafil is CI. No, but he must be caution about dizziness. No, but he must begin sildenafil at lower dose. Yes, tamsulosin should be changed to doxazosin. Test your knowledge!  a) b) c) d) e) Which of JH medications could be contributing to his ED? (Select ALL that apply) Propranolol LA Sertraline Vitamin D ASA APAP Alprostadil  Alprostadil  Effective for every etiology of ED (organic, psychogenic, mixed ED)  A prostaglandin E1 synthetic analog  Usually, prescribed after failure PDE5 Inhibitors and for patients who cannot use these therapies.  Intracavernosal route preferred over intraurethral route because of better efficacy. Use cautiously in those at risk of priapism and bleeding complications secondary to injections. Intraurethral Alprostadil  MUSE®- medicated urethral system for erection  Urethral pellet inside a prefilled urethral applicator  Onset of Action: ≈5 to 10 minutes  Duration: ≈ 30 to 60 minutes  SE: pain, warmth or burning sensation in the urethral, voiding difficulties, bleeding or spotting, priapism, partners may experience vaginal burning or itching.  Do not use more than twice in a 24 hrs. period. http://www.diabetesindia.com/diabetes/erectile_dysfunction/muse_d octor.htm Intracavernosal Alprostadil  Caverject® or Edex®  Injected into the corpus cavernosum  Onset of Action: 5 to 10 minutes  Duration of action : dose titrate (in provider’s office) until an erection lasting no more than one hour is obtain  Not to be used more than 3 times a week. Wait at least 24 hrs. between doses.  Efficacy: 70 to 90% of patients have reported improvement (more effective when contrast with urethral administration)  Disadvantages: fear of needles, invasiveness, lack of spontaneity, complicated administration technique, etc.  SE: pain, bleeding (careful with anticoagulants), hematoma, fibrosis, priapism, etc. Algorithm for selecting Treatment for Patients with ED Assess if the patient is a candidate for pharmacotherapy (e.g., assess cardiovascular risk) Treat underlying disease(s) Discontinue medication that could contribute to ED, if possible Remove modifiable risk factors If patient has hypogonadism, give testosterone replacement therapy PDE5 Inhibitors If effective continue If ineffective, ensure the treatment is optimized by, ensuring patient takes dose at correct time, patient has had 5 to 8 doses, dosage is titrated up If ineffective If contraindicated or patient prefers, use vacuum erection devices (VED) or if not willing to use VED Intracavernosal or intraurethral alprostadil If ineffective Penile Prosthesis Adapted from: Figure 103-2 Algorithm for selecting treatment for erectile dysfunction In: DiPiro JT, Yee GC, Posey L, Haines ST, Nolin TD, Ellingrod V. eds. Pharmacotherapy: A Pathophysiologic Approach, 12e New York, NY: McGraw-Hill. Take Away Points  ED is defined as failure to achieve and/or maintain an erection appropriate for sexual intercourse.  A patient with ED should be evaluate for CV risk.  PDE5 Inhibitors are consider as first line agents for ED.  Are CI in patients taking nitrates  Have similar efficacy profile, but have different onset and duration of action, and side effect profile.  Pain and priapism may occur with alprostadil. Selected References:        Lee M, Sharifi R. Erectile Dysfunction. In: DiPiro JT, Yee GC, Posey L, Haines ST, Nolin TD, Ellingrod V. eds. Pharmacotherapy: A Pathophysiologic Approach, 11e New York, NY: McGraw-Hill;. http://accesspharmacy.mhmedical.com.ezproxylocal.library.nova.edu/content.aspx?bookid=2577&sectionid=230460622. Accessed March 09, 2020. Erectile Dysfunction. In: Schwinghammer TL, DiPiro JT, Ellingrod VL, DiPiro CV. eds. Pharmacotherapy Handbook, 11e. McGraw Hill; Accessed August 13, 2021. https://accesspharmacy-mhmedical-com.ezproxylocal.library.nova.edu/content.aspx?bookid=3012& sectionid= 253437624 Linnebur SA, Wallace JI. Chapter 30. Erectile Dysfunction. In: Wofford MR, Posey LM, Linn WD, O'Keefe ME, eds. Pharmacotherapy in Primary Care. New York: McGraw-Hill; 2009. http://www.accesspharmacy.com/content.aspx?aID=3603552. Accessed August 15, 2016. Cantrell MA, Kelly M, Vouri SM. Chapter 63. Urology. In: Cantrell MA, Kelly M, Vouri SM, eds. McGraw-Hill's NAPLEX® Review Guide. New York: McGraw-Hill; 2011. http://www.accesspharmacy.com/content.aspx?aID=7256161. Accessed August 15, 2016. McVary KT. Chapter 48. Sexual Dysfunction. In: Fauci AS, Kasper DL, Jameson JL, Longo DL, Hauser SL, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012. http://www.accesspharmacy.com/content.aspx?aID=9093136. Accessed August 15, 2016. Brodeur M, Thompson J. Chapter 101. Geriatric Urologic Disorders. In: Koda- Kimble, M, Yee L, Alldredge B, eds. Applied Therapeutics: The Clinical use of Drugs. 9th ed. Maryland: Lippincott Williams & Willkins; 2009. Lidat C, Heyneman C. Chapter 48. Erectile Dysfunction. In Chismholm-Burns M, Wells B, Schwinghammer T, Mlone P, Kolesar J, Rotschafer, Dipiro J, eds. Pharmacotherapy: Principles and Practice. New York: McGraw-Hill; 2008.