phosphodiesterase-5 inhibitor

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Indications

* may reduce risk of Alzheimer's disease (RR=0.56-0.82) depending on dose[11]

* not effective in preventing Alzheimer's disease & related dementias[12]

Contraindications

Adverse effects

* downregulation of PDE5 is thought to increase invasiveness of melanoma; however, risk > for stages 0 & 1 but not stages 2-4 & no dose-response effect

* no plausible mechanism for increased risk of BCC

Drug interactions

Mechanism of action

Notes

  • some OTC supplements contain compounds that appear to inhibit phosphodiesterase 5
    • these include: Zimmaxx, Libidus, Neophase, Nasutra, Vigor-25, Actra-25, Actra-Rx, 4Everon
    • however, the amount & identity of the substances is neither standardized or well characterized

More general terms

More specific terms

References

  1. 1.0 1.1 Prescriber's Letter 13(9): 2006 FDA Warns Consumers About Dangerous Ingredients in 'Dietary Supplements' Promoted for Sexual Enhancement Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220906&pb=PRL (subscription needed) http://www.prescribersletter.com
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Medical Knowledge Self Assessment Program (MKSAP) 15, American College of Physicians, Philadelphia 2009
  3. Prescriber's Letter 19(9): 2012 Comparison of PDE5 Inhibitors Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=280912&pb=PRL (subscription needed) http://www.prescribersletter.com
    Prescriber's Letter 21(4): 2014 Comparison of PDE5 Inhibitors Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=300408&pb=PRL (subscription needed) http://www.prescribersletter.com
  4. Schwenk TL Association Between Erectile Dysfunction Drugs and Malignant Melanoma NEJM Journal Watch. June 23, 2015 Massachusetts Medical Society (subscription needed) http://www.jwatch.org
    Loeb S et al. Use of phosphodiesterase type 5 inhibitors for erectile dysfunction and risk of malignant melanoma. JAMA 2015 Jun 23; 313:2449 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26103029
  5. 5.0 5.1 <Internet> http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#ED
  6. 6.0 6.1 Cordell WH et al, Retinal Effects of 6 Months of Daily Use of Tadalafil or Sildenafil Archives of Ophthalmology 2009;127(4):367-373 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19365010
  7. 7.0 7.1 7.2 Etminan M, Sodhi M, Mikelberg FS et al Risk of Ocular Adverse Events Associated With Use of Phosphodiesterase 5 Inhibitors in Men in the US. JAMA Ophthalmol. Published online April 7, 2022. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35389459 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2790661
  8. 8.0 8.1 8.2 Holt A et al. Adverse events associated with coprescription of phosphodiesterase type 5 inhibitors and oral organic nitrates in male patients with ischemic heart disease: A case-crossover study. Ann Intern Med 2022 Apr 19; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35436155 https://www.acpjournals.org/doi/10.7326/M21-3445
  9. 9.0 9.1 Crist C Could Viagra Help Prevent Alzheimer's? Medscape. Dec 8, 2021 https://www.medscape.com/viewarticle/964389
    Fang J, Zhang P, Zhou Y et al Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer's disease. Nature Aging. 2021. Dec;1(12):1175-1188. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35572351 PMCID: PMC9097949 Free PMC article https://www.nature.com/articles/s43587-021-00138-z.epdf
    Desai RJ, Mahesri M, Lee SB et al No association between initiation of phosphodiesterase-5 inhibitors and risk of incident Alzheimer's disease and related dementia: results from the Drug Repurposing for Effective Alzheimer's Medicines (DREAM) study. Brain Communications. 2022. Oct 4 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36330433 https://academic.oup.com/braincomms/advance-article/doi/10.1093/braincomms/fcac247/6731685
  10. 10.0 10.1 Trolle Lagerros Y et al. Risk of death in patients with coronary artery disease taking nitrates and phosphodiesterase-5 inhibitors. J Am Coll Cardiol 2024 Jan 23; 83:417. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38233015 Free article https://www.sciencedirect.com/science/article/pii/S0735109723080749
  11. 11.0 11.1 George J Erectile Dysfunction Drugs Tied to Less Alzheimer's Risk. Large U.K. study tracked health records of 270,000 men. MedPage Today February 7, 2024 https://www.medpagetoday.com/neurology/dementia/108626
  12. 12.0 12.1 Desai RJ, Mahesri M, Lee SB et al No association between initiation of phosphodiesterase-5 inhibitors and risk of incident Alzheimer's disease and related dementia: results from the Drug Repurposing for Effective Alzheimer's Medicines (DREAM) study. Brain Communications. 2022. Oct 4 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36330433 https://academic.oup.com/braincomms/advance-article/doi/10.1093/braincomms/fcac247/6731685