Antihypertensives that may cause erectile dysfunction

B-blockers

Thiazide diuretics

Centrally-acting agents (Clonidine, methyldopa)

Spironolactone

alpha-blockers

Lipid lowering agents that may cause ED

Gemfibrozil

Antidepressants that may cause ED

TCAs

MAOIs

SSRIs

Antipsychotics that may cause ED

Phenothiazines

Risperidone

Lithium

Anticonvulsants that may cause ED

Carbamazepine

Phenytoin

Anti-androgens & hormones that may cause ED

5-alpha-reductase inhibitors

Progesterone/Estrogen

Cimetidine (Tagamet ®)

Sprionolactone (Aldactone ®)

Recreational substances that may cause ED

Ethanol

Cocaine

Marijuana

Classes of Meds that can cause ED

Antihypertensives

Lipid lowering agents

Antidepressants

Antipsychotics

Anticonvulsants

Anti-androgens & hormones

Recreation substances

Physiology of a normal erection

↓ sympathetic tone & ↑ parasympathetic tone

Net ↑ of blood flow into erectile tissue

Acetylcholine-mediated parasympathetic activity

-Nitric oxide: ↑ cGMP

-PGE1 & PGE2: ↑ cAMP

cGMP & cAMP - lead to ↓ calcium concentration in smooth muscle cells of penile arteries & sinusoidal spaces, leading to smooth muscle relaxation

Nonpharmacologic treatment of ED

ID associated disease states & lifestyle factors that may adversely effect erectile function

     - Rx meds: discontinue if possible, consider dosage reduction or med change
     - Encourage healthy diet & physical activity, maintenance of healthy body weight
     - Smoking cessation, discontinue excessive EtOH & illicit drug use
Psychotherapy - for psychogenic or mixed ED
Vacuum Erection Devices (pumps)
Prosthesis - Surgical; invasive techniques used for refractory or if contraindications to pharmacologic therapy

MoA of Phosphodiesterase (PDE) Type 5 Inhibitors

• Selective inhibition of PDE-5, inducing smooth muscle relaxation
• PDE-5: enzyme that breaks down cGMP
• "Erection Facilitators" - only effective in the presence of sexual stimulation to drive the nitric oxide/cGMP system

Adverse effects of PDE Type 5 inhibitors

• Headache, facial flushing, nasal congestion, dyspepsia
• Rare -- priapism (seek medical care for erection over 4 hours)
• Changes in vision, difficulty in blue-green discrimination
• Label warning: non-arteritic ischemic neuropathy (NAION) - blood flow is blocked at the optic nerve (sudden ↓ in vision)

Use of PDE-5 inhibitors for patient with:

Asymptomatic CV disease

Well-controlled HTN

Mild, stable angina

• Low Risk 

• PDE-5 inhibitors used in most cases

Use of PDE-5 inhibitor in patient with:

> 3 risk factors for CAD

Moderate, stable angina

Recent MI or CVA

• Moderate Risk

• Must do complete CV workup (including stress test) to determine tolerance to increased myocardial oxygen demand associated with physical activity

Use of PDE-5 Inhibitors in patient with:

Unstable or symptomatic angina (despite treatment)

Poorly controlled HTN

Moderate to severe valvular heart disease

• High Risk
• PDE-5 Inhibitors are CONTRAINDICATED

Drug Contraindications with PDE Inhibitors

PRN dosing & scheduled dosing of nitrates

Drug Interactions with PDE Inhibitors

• Caution with alpha-blocker therapy: increased risk of hypotension & possible prolonged QT
• CYP 450 3A4 inhibitors/inducers
• Ethanol: increased risk of hypotension with excessive EtOH intake

Use of PDE-5 Inhibitor

Sildenafil (Viagra®)

Take 1 hour prior to sexual activity

Max frequency is once per day

Absorption may be reduced/delayed with high fat meal

Use of PDE-5 Inhibitors

Vardenafil (Levitra ®)

Take about 1 hour before sexual activity

Absorption may be reduced/delayed with high fat meal

Use of PDE-5 Inhibitors

Tadalafil (Cialis ®)

• Can be taken without regard to meals (extent & rate of absorption is not significantly affected)
• Take at least 30 min prior to anticipated sexual activity
• Maximum dosing frequency is once per day
• Erectile function may be improved for up to 36 hours following 1 dose
• Approved for daily use - 2.5 mg taken daily at the same time (without regard to timing of sexual activity)

MoA of ED Treatment: Alprostadil

Prostaglandin E1 Analog

Induces erection by stimulating cAMP & causing smooth muscle relaxation & rapid arterial inflow

Dosage forms: injection & urethral suppositories

Alprostadil Intracavernosal injection

Caverject®, Edex®

• More effective than suppository
• Dosage titration in office - achieve an erection for no longer than 1 hour
• Injected into one side of the penis directly into the corpus cavernosum then massaged to distribute the medication
• Effective in 90% of patients

Adverse effects of Caverject® & Edex®

Pain with injection

Bleeding or bruising at injection site

Fibrosis

Priapism

Caution in patients with sickle cell disease or on anticoagulant therapy

Use of Alprostadil Transurethral suppository

MUSE®

• Medicated urethral system for erection - urethral pellet of alprostadil with an applicator
• Onset 5-10 minutes
• Duration 30-60 minutes
• Titration of dosage of both forms in physician's office to ensure correct dose, but avoid excessive adverse effects

Adverse Effects of MUSE®

• Aching in the penis, testicles, legs, perineum, warmth or burning sensation of the urethra, minor urethral bleeding or spotting, priapism, lightheadedness
• Cannot be used during sexual intercourse with pregnant partner (unless condom is used)
• Partner may also experience burning or itching

Papaverine

• Vasodilator
• Labeled use for relief of peripheral ischemia associated with arterial spasm
• Off-label use for ED; lack of clinical data for safety & efficacy

Yohimbine (Yocon®)

Use & MoA

• Herbal product
• Unlabeled/investigational treatment of SSRI-induced sexual dysfunction; impotence.  May have activity as an aphrodisiac
• Produces a presynaptic alpha2-adrenergic blockade.  Peripheral autonomic effect is to increase cholinergic and decrease adrenergic activity

Adverse Effects of Yohimbine (Yocon®)

Nausea

Irritability

Headache

Anxiety

Tachycardia

Hypertension

Use of testosterone supplementation: Androgens

• Important for general sexual function & libido
• Testosterone supplementation is only effective for treatment of ED in patients with low serum testosterone levels
• Routes of administration: Oral, IM, Topical patches or gel, Buccal tablet

Adverse effects & Monitoring with Use of Androgen Testosterone Supplementation

Gynecomastia

Dyslipidemia

Acne

Weight gain

Hypertension

Edema

Monitoring: prior to treatment, evaluate for BPH & prostate cancer.  Yearly, PSA, DRE, LFTs, lipid panel