UWORLD Chapter 50: Sexual Dysfunction

What is erectile dysfunction?

inability to achieve and maintain an erection sufficient to permit satisfactory sexual intercourse

What are key drugs that cause erectile dysfunction?

Alcohol

Antidepressants

Antihypertensives

Antipsychotics

BPH medications

Chronic Opioid use (Methadone specifically)

What is an antidepressant that does not cause sexual side effects?

Bupropion

What are non drug causes of erectile dysfunction?

- Dips in testosterone as men age

- HTN and atherosclerosis

- Diabetes (neuropathy)

What is nonpharmacological therapy for erectile dysfunction?

Weight loss, smoking cessation, and alcohol cessation

What are natural products that claim to treat erectile dysfunction?

- yohimbe

- L-arginine

- panax ginseng

What is the first line drug class in erectile dysfunction?

PDE-5 Inhibitors (sildenafil, vardenafil, tadalafil, avanafil)

What PDE-5 inhibitor treats BPH?

Tadalafil (Cialis)

What PDE-5 inhibitors is used for pulmonary arterial hypertension?

Sildenafil and Tadalafil

What is the mechanism of action for PDE-5 inhibitors?

Following sexual stimulation, there is a local increase of nitric oxide, which increases cGMP and causes smooth muscle relaxation. This permits blood flow in, resulting in an erection. PDE-5 inhibitors block PDE-5 from degrading cGMP.

What are the starting doses for each of the PDE-5 inhibitors?

- Sildenafil: 50 mg

- Vardenafil & Tadalafil: 10 mg

- Avanafil: 100 mg

When is it indicated to reduce PDE-5 inhibitor starting dosages?

- >/= 65 years old

- using an alpha blocker

- Using a CYP3A4 inhibitor

- Severe renal or liver disease

How much should starting dosages of PDE-5 inhibitors be decreased if indicated?

decrease starting dose by 50%

What is the on demand dosage and timing for Viagra?

50 mg ~1 hour prior to sexual activity

What is the daily dosing of Cialis?

5 mg daily

What is the on demand dosage and timing for Cialis?

10 mg at least 30 minutes prior to sexual activity

What is the on demand dosage and timing of Vardenafil?

10 mg ~1 hour prior to sexual activity

What is the on demand dosage of Avanafil (Stendra)?

100 mg 15-30 minutes before sexual activity

What medications are contraindicated with PDE-5 inhibitors?

Nitrates and riociguat

What are rare but serious warnings with PDE-5 inhibitors?

- Impaired color discrimination

- Hearing and vision loss

- Hypotension

- Priapism

- Chest Pain

What are common side effects of PDE-5 inhibitors?

Headaches, flushing, indigestion, nausea, vomiting, back pain, vision disturbances, muscle pain.

What is an administration counseling point specifically with sildenafil and vardenafil?

Sildenafil and vardenafil have decreased efficacy if taken with high fat or large meal (common cause of treatment failure).

What are the major drug interactions with PDE-5 inhibitors?

Nitrates, riociguat, alcohol, alpha 1 blockers, moderate and strong CYP3A4 inhibitors (grapefruit juice, protease inhibitors, azole antifungals)

What is the mechanism of action of alprostadil?

Prostaglandin E1, a vasodilator that allows blood to flow into the cavernosal arteries, which then enlarges the penis

What are the routes of administration for alprostadil?

injection of the penis or urethral suppositories

What are the main side effects of alprostadil?

penile pain and priapism

What are the storage recommendations for urethral pellets?

must be refrigerated

What is hypoactive sexual desire disorder?

Absence or deficiency of sexual desire or fantasies (more common in women, occurs in 20% of population)

What is the mechanism of action for flibanserin?

5-HT1A agonist and 5-HT2A antagonist

What are the boxed warnings for flibanserin?

Contraindicated with alcohol due to severe hypotension. Has a REMS program for this.

Combination with strong CYP3A4 inhibitors

What are the main side effects of flibanserin?

Hypotension, syncope

What is the mechanism of action of bremelanotide?

non selective melanocyte in receptor agonist

When is bremelanotide contraindicated?

uncontrolled hypertension or known cardiovascular disease

Which are FDA-approved to treat HSDD (hypoactive sexual desire disorder) for premenopausal women only?

• Flibanserin

• Bremelanotide

Which classes of antidepressant can cause sexual dysfunction

SSRI and SNRIs (including decrease in libido)

Which anti-HTNs can cause ED?

• BB

• Clonidine

• Thaizides

Which antipsychotics can cause sexual dysfunction?

• First gen (ex. chlorpromazine)

• Prolactin-raising 2nd gen (ex. risperidone, paliperidone)

Which BPH medications can cause sexual dysfunction?

• Finasteride

• Dutasteride

• Silodosin (retrograde ejaculation)

Other drugs that can cause ED?

• Anticancer — Leuprolide, Flutamide

• Anticholinergics

• Atomoxetine

• Digoxin

• Cimetidine

• Nicotine

• Opioids (chronic use, especially methadone)

What does ginseng increase the risk of?

• Bleeding

What is next is PDE-5 inhibitors are not tolerated?

• Alprostadil

• Eroxon (topical gel)

How does Eroxon work?

• Applied to the head of the penis prior to intercourse

• It stimulates the nerve endings which result in vasodilation + erection

For Cialis, at what other conditions do you start 5 mgs?

• Crcl 30-50 → 5 mg PRN

• CrCl < 30 → 5 mg PRN Q72Hr

If someone with ED has taken PDE-5 inhibitor and develops angina — how long after to take nitrates?

• Avanafil → after 12 hrs

• Sildenafil / vardenafil → after 24 hours

• Tadalafil → after 48 hours

If planning to use PDE-5 inhibitor and alpha-1 blocker,…?

• Patient should be stable on the alpha-1 blocker before starting PDE-5 inhibitor

What is HSDD?

• low sexual desire that causes marked distress or interpersonal difficulty — not due to health condition or drugs

Who should avoid taking Flibanserin and Bremelanotide?

• Avoid in pregnancy

• Avoid breastfeeding (Flibanserin)

• Effective contraception should be used