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phosphodiesterase-5 inhibitor

Indications: - used for treatment of erectile dysfunction (ED) * 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: 1) intermediate-high risk of coronary artery disease 2) use of nitrates - increased all-cause mortality when also prescribed nitrate (RR=1.4) [10] - nitrates might be less harmful than previously thought [8] - not taking the two medications in close temporal proximity may minimize interaction [8] 3) retinitis pigmentosa 4) history of non-arteric ischemic optic neuropathy 5) prevention of Alzheimer's disease [9] Adverse effects: 1) adverse ocular effects a) blurred vision b) cataracts c) changes in color perception d) conjunctivitis e) dry eyes f) eye hemorrhage g) eye pain h) mydriasis i) small number of post-marketing reports of sudden vision loss, attributed to NAION (non arteritic ischemic optic neuropathy) Viagra, Cialis & Levitra specifically implicated. [5] Viagra, Cialis & Levitra specifically implicated. [1] j) risk for serous retinal detachment & retinal vascular occlusion [7] - no adverse visual or retinal effects associated with daily administration of tadalafil or sildenafil for 6 months [6] - absolute risk is low [7] 2) reports of sudden hearing loss [2], generally unilateral, sometimes persistent, tinnitus may be associated 3) headache [2] 4) flushing [2] 5) dyspepsia [2] 6) rhinitis [2] 7) back pain/myalgias (tadalafil, others ?) [2] 8) increased risk of cutaneous melanoma [2] (RR=1.21)* 9) increased risk of basal cell carcinoma (BCC) [2] (RR=1.19)* * 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: - nitrates Mechanism of action: - inhibits phosphodiesterase-5 Notes: - some OTC supplements contain compounds that appear to inhibit phosphodiesterase 5 a) these include: Zimmaxx, Libidus, Neophase, Nasutra, Vigor-25, Actra-25, Actra-Rx, 4Everon b) however, the amount & identity of the substances is neither standardized or well characterized

Interactions

drug interactions drug adverse effects (more general classes)

Specific

avanafil (Stendra) sildenafil (Viagra, Revatio, Caverta) tadalafil (Cialis, Adcirca, 'weekend Viagra') vardenafil (Levitra, Staxyn)

General

phosphodiesterase inhibitor vasodilator agent

Properties

INHIBITS: phosphodiesterase-5

References

  1. Prescriber's Letter 13(9): 2006 FDA Warns Consumers About Dangerous Ingredients in 'Dietary Supplements' Promoted for Sexual Enhancement Detail-Document#: 220906 (subscription needed) http://www.prescribersletter.com
  2. 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#: 280912 (subscription needed) http://www.prescribersletter.com - Prescriber's Letter 21(4): 2014 Comparison of PDE5 Inhibitors Detail-Document#: 300408 (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 PMID: 26103029
  5. http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#ED
  6. 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: 19365010
  7. 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: 35389459 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2790661
  8. 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: 35436155 https://www.acpjournals.org/doi/10.7326/M21-3445
  9. 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: 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: 36330433 https://academic.oup.com/braincomms/advance-article/doi/10.1093/braincomms/fcac247/6731685
  10. 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: 38233015 Free article https://www.sciencedirect.com/science/article/pii/S0735109723080749
  11. 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. 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: 36330433 https://academic.oup.com/braincomms/advance-article/doi/10.1093/braincomms/fcac247/6731685