What is the role of apomorphine in treating erectile dysfunction and Parkinson's disease?

Role of Apomorphine in Erectile Dysfunction and Parkinson's Disease

Apomorphine has limited clinical utility in erectile dysfunction but can be beneficial for managing motor symptoms in Parkinson's disease while potentially improving sexual function in some PD patients.

Apomorphine for Erectile Dysfunction

Mechanism of Action

• Apomorphine is a dopamine D1 and D2 receptor agonist that acts centrally as an initiator of erection by stimulating dopamine receptors in the brain 1, 2
• It works through selective activation of the nucleus paraventricularis, leading to erectogenic signals 3

Efficacy in Erectile Dysfunction

• Sublingual apomorphine (2-3 mg) has shown modest efficacy with 49.4% of attempts resulting in erections firm enough for intercourse compared to baseline value of 24.3% 3
• Clinical trials show apomorphine provides 6-27% more successful intercourse attempts than placebo, but with lower efficacy than PDE5 inhibitors 4
• Erections typically occur between 18-19 minutes after taking sublingual apomorphine 3

Limitations and Patient Selection

• Apomorphine shows poor overall response in older patients with multiple vascular risk factors and systemic vascular damage 2
• Not effective in patients previously treated with radical prostatectomy 4
• Current guidelines do not recommend apomorphine as a first-line treatment for erectile dysfunction 5

Safety Profile

• Most common side effect is nausea, which tends to decline with continued use 3
• Vasovagal syncope reported in <0.2% of men, typically preceded by prodromal symptoms 3
• Sublingual apomorphine is the only licensed oral drug for erectile dysfunction not absolutely contraindicated with nitrates 4

Apomorphine for Parkinson's Disease

Therapeutic Benefits in Parkinson's Disease

• Subcutaneous apomorphine is used for managing motor fluctuations in Parkinson's disease 6
• Penile erections have been regularly induced by intermittent subcutaneous injections of apomorphine in PD patients 6

Impact on Sexual Function in PD

• Two out of four PD patients with pre-existing erectile dysfunction reported significant improvement in sexual function with apomorphine treatment 6
• The erectile effect is likely mediated through central D2-type dopamine receptor stimulation and oxytocin release from the paraventricular nucleus of the hypothalamus 6

Current Treatment Guidelines and Recommendations

First-Line Treatments for Erectile Dysfunction

• PDE5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil) are the recommended first-line pharmacological treatment for erectile dysfunction 7
• These medications have demonstrated superior efficacy compared to non-PDE5 inhibitor treatments, including apomorphine 5

Alternative Options When PDE5 Inhibitors Are Contraindicated

• For patients who cannot take PDE5 inhibitors (e.g., those using nitrates), sublingual apomorphine could be considered as an alternative option 4
• Other alternatives include topical anesthetics, intracavernosal injections, vacuum devices, and penile prostheses 5, 8

Treatment Algorithm for Erectile Dysfunction

1. First-line: PDE5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil) 7
2. Second-line: Intracavernosal injections or intraurethral suppositories 8
3. Third-line: Vacuum erection devices 8
4. Fourth-line: Penile prosthesis implantation 8
5. Consider apomorphine only when PDE5 inhibitors are contraindicated and patient has no history of prostatectomy 4

Conclusion

While apomorphine has demonstrated some efficacy in treating erectile dysfunction, its clinical utility is limited compared to PDE5 inhibitors. However, it may serve as an alternative for patients who cannot take PDE5 inhibitors due to contraindications. In Parkinson's disease, apomorphine's primary role is managing motor fluctuations, with improvement in sexual function being a potential additional benefit in some patients.