Recreational Use and Misuse of Phosphodiesterase 5 Inhibitors

doi:10.1331/1544345052843165

Journal of the American Pharmacists Association

Volume 45, Issue 1, January–February 2005, Pages 63-75

https://doi.org/10.1331/1544345052843165 Get rights and content

ABSTRACT

Objective

To characterize the rationale for and extent of phosphodiesterase (PDE) 5 inhibitor use in recreational settings, describe risks from such misuse, and discuss postexposure clinical management strategies.

Data Sources

Published articles identified by searches through Medline, EMBASE, International Pharmaceutical Abstracts, and Toxline, from 1990 to March 2004, using the search terms sildenafil, tadalafil, vardenafil, phosphodiesterase inhibitor, abuse, overdose, adverse effects, recreational, and street drugs. Additional references identified within articles and information from the Internet were included.

Study Selection

Clinical trials, epidemiologic reviews, case reports, and news releases concerning the misuse of sildenafil.

Data Extraction

By the authors.

Data Synthesis

PDE5 inhibitors, indicated for treatment of erectile dysfunction, can produce several adverse effects, including potentially fatal cardiovascular events. Reports of recreational use and misuse of sildenafil appear in the medical literature and the media. The potential for abuse also exists for the two more recently approved drugs in this class, vardenafil and tadalafil. Increasing access to these drugs via the Internet may facilitate such misuse. Use in social settings has gained popularity, both in young, healthy patients, as well as those with chronic medical conditions, including human immunodeficiency virus infections. In these settings, the PDE5 inhibitors are sometimes used concomitantly with “club drugs” such as ketamine and amyl nitrite, leading to potentially harmful or fatal drug interactions.

Conclusion

Pharmacists should be cognizant of the potential for PDE5 inhibitors to be misused, particularly in patients who are at greater risk of cardiovascular complications, and should advise patients and other health care professionals accordingly.

Section snippets

Pharmacology

Nitric oxide is released in the corpus cavernosum of the penis during sexual stimulation, which subsequently activates guanylate cyclase. This enzymatic activation results in increased concentrations of cyclic guanosine monophosphate (cGMP), the trigger for smooth muscle relaxation, which facilitates increased blood flow and thereby produces an erection (tumescence). Sildenafil, tadalafil, and vardenafil potentiate this process by inhibiting PDE5, the substance responsible for degrading cGMP in

Adverse Effects

The most common adverse effects of sildenafil therapy are headache (16%), flushing (10%), and dyspepsia (7%). Abnormal vision, including light sensitivity and color impairment (e.g., blue tints of vision), may be experienced by up to 3% of patients, particularly those receiving doses in excess of 100 mg.⁷ Such experiences are more characteristic of sildenafil's weak inhibitory effect on PDE6. Prolonged erections, sometimes to the extent of at least 6 hours (i.e., priapism), have also been

Clinical Applications

In the United States, sildenafil, tadalafil, and vardenafil are approved for the treatment of erectile dysfunction.⁶^,⁸^,⁹ In addition to facilitating tumescence, these drugs shorten the refractory period associated with subsequent ejaculation. They are also effective in both iatrogenic and disease-related ED, including that resulting from diabetes or prostatectomy.³ Most men (35%–91%) respond to a single 50 mg dose of sildenafil; however, as little as 25 mg may be effective in some patients

Product Availability

Sildenafil citrate is marketed in the United States as 25, 50, and 100 mg tablets.¹¹ The drug is sometimes referred to as “vitamin V,” and slang terms pertaining to its recreational use include “hammerheading” and “sextasy” (use in conjunction with methylenedioxymethamphetamine [MDMA], ecstasy); and “tina,” (use in conjunction with methamphetamine).¹⁶ Also known as a “thrill pill,” sildenafil has been sold on school and college campuses and at parks, with subsequent consumption at clubs and

Epidemiology of Recreational Use

Soon after sildenafil was marketed in the United States, inappropriate use in several patients in the Iowa Medicaid system was noted.²⁶ Use of the drug in conjunction with nitrates, as well as prescriptions for large quantities that might have indicated abuse or diversion, was reported in 1999. In December 2000, ethnographers from a nationwide drug abuse epidemiology network reported the sometimes fatal practice of using sildenafil with methamphetamine or other drugs.²⁷ Use of sildenafil in

Safety Issues

Sildenafil data from the American Association of Poison Control Centers' Toxic Exposure Surveillance System (TESS) were described in 2000.¹ U.S. poison information centers received inquiries regarding sildenafil ingestion within days following the drug's approval, with the peak occurring within 3 months. During the 10 months that sildenafil was available in 1998, poison centers assisted in the management of 173 sildenafil exposures, 75% of which involved sildenafil as a single agent. Of these,

Exposure Management

Should individuals develop signs and symptoms of excessive PDE5 inhibitor exposure, the primary management approach is to stabilize the patient, as well as anticipate and minimize any adverse effects (e.g., hypotension).¹^,⁵⁶ If the ingestion was recent, gastrointestinal decontamination may be of value; however, rapid absorption of the drug may preclude any benefits of this maneuver. If pursued, activated charcoal slurry may be administered in a dose of 25–100 grams. Adverse effects are unlikely

Role of the Pharmacist

In addition to dispensing PDE5 inhibitors, pharmacists may be requested to assist in the management of patients with adverse symptoms of PDE5 inhibitor exposure. However, perhaps more important is the role of pharmacists in counseling both health care professionals and patients regarding the risks of improper drug use. Possible prescription drug interactions, relevant dosage adjustments, and proper dosage frequencies may be topics pharmacists should routinely discuss with patients being treated

Conclusion

PDE5 inhibitors may be misused for their perceived effects on sexual performance, as well as for the drugs' proven effects in erectile dysfunction. Such use may also occur in conjunction with other compounds used in a recreational fashion, including a number of club drugs. Concomitant administration may place patients at greater risk for cardiovascular complications, yet extensive information in this area is currently lacking. Several epidemiologic studies have demonstrated the extent of this

References (56)

E.G. Boyce et al.
Sildenafil citrate: a therapeutic update
Clin Ther.
(2001)
D.K. Wysowski et al.
Comparison of reported and expected deaths in sildenafil (Viagra) users
Am J Cardiol.
(2002)
J.R. Berman et al.
Safety and efficacy of sildenafil citrate for the treatment of female sexual arousal disorder: a doubleblind, placebo controlled study
J Urol.
(2003)
S. Caruso et al.
Premenopausal women affected by sexual arousal disorder treated with sildenafil: a double-blind, crossover, placebo-controlled study
Br J Obstet Gynecol.
(2001)
A.R. Winstock et al.
Drugs and the dance music scene: a survey of current drug use patterns among a sample of dance music enthusiasts in the UK
Drug Alcohol Depend.
(2001)
R. Nandwani et al.
Possible interaction between sildenafil and HIV combination therapy
Lancet.
(1999)
G. Famularo et al.
Acute aortic dissection after cocaine and sildenafil abuse [letter]
J Emerg Med.
(2001)
E.P. Krenzelok
Sildenafil: clinical toxicology profile
Clin Toxicol.
(2000)
E. Padma-Nathan et al.
A 4-year update on the safety of sildenafil citrate (Viagra)
Urology.
(2002)
K. Breslau
The ‘sextasy’ craze. Clubland’s dangerous party mix: Viagra and ecstasy
Newsweek
(2002)

D.A. Hussar

The phosphodiesterase type 5 (PDE5) inhibitors for erectile dysfunction

Drug Advisor

(2003)

Anonymous

Tadalafil (Cialis) for erectile dysfunction

Med Letter Drugs Ther.

(2003)

M.D. Cheitlin et al.

Use of sildenafil (Viagra) in patients with cardiovascular disease

ACC/AHA Expert Consensus Document. Circulation.

(1999)

Levitra (vardenafil) [prescribing information]

(2003)

R.A. Kloner et al.

Cardiovascular effects of sildenafil citrate and recommendations for its use

Am J Cardiol.

(1999)

Viagra (sildenafil) [prescribing information]

(2002)

R. Basson et al.

Efficacy and safety of sildenafil citrate in women with sexual dysfunction associated with female sexual arousal disorder

J Womens Health Gend Based Med.

(2002)

B. Cremers et al.

Non-erectile dysfunction application of sildenafil

Herz.

(2003)

Anonymous. Street terms: drugs and the drug trade. Office of National Drug Control Policy. Accessed at...

Peterson KS. Young men add Viagra to their drug arsenal. Accessed at...

T. Tong et al.

Club drugs, smart drugs, raves, and circuit parties: an overview of the club scene

Pediatr Emerg Care.

(2002)

J. Burke

Prescription drugs on the Internet

Pharm Times

(2003)

B.S. Bloom et al.

Internet availability of prescription pharmaceuticals to the public

Ann Intern Med.

(1999)

G. Eysenbach

Online prescribing of sildanefil (Viagra) on the World Wide Web

J Med Internet Res.

(1999)

www.whitehousedrugpolicy.gov/publications/drugfact/pulsechk/nov02/other_drugs.html, November 11,...

D. Berry

Thousands of British men buying fake ED drug

Pharm Today

(2004)

Anonymous

FDA raid blocks counterfeit Viagra

US Pharm.

(2004)

A.J. Sabucedo et al.

Sex, lies and Niagra

JAMA

(2004)

Cited by (75)

Construction of a novel sensor based on activated nanodiamonds, zinc oxide, and silver nanoparticles for the determination of a selective inhibitor of cyclic guanosine monophosphate in real biological and food samples
2023, Diamond and Related Materials
In the present work, we developed a highly sensitive and selective method for the determination of sildenafil (SIL) using a modified glassy carbon electrode (GCE) with activated nanodiamonds, zinc oxide, and silver nanoparticles nanocomposite (AND@ZnO-Ag/GCE). Various voltammetric techniques, including CV, DPV, and EIS, were employed to investigate the electrochemical process of SIL on the modified electrode. The resulting AND@ZnO-Ag/GCE electrode exhibited enhanced electron transfer between the electrode and the analyte, resulting in an excellent electrocatalytic performance for SIL oxidation under optimized conditions. The analytical performance of the AND@ZnO-Ag/GCE sensor demonstrated two linear responses within the concentration range of 0.01–0.08 μM and 0.08–14.6 μM, with a remarkably low detection limit of 7.08 nM. Moreover, the modified sensor (AND@ZnO-Ag/GCE) exhibited high selectivity and anti-interference capacity. It successfully detected trace amounts of SIL in biological and food samples, yielding satisfactory results. Furthermore, this work provides insights into the potential adulteration of energy drinks with sildenafil, addressing an area that has received limited attention in previous research.
Sildenafil citrate ameliorates the adverse effects of cryopreservation on sperm quality in asthenozoospermic men
2023, Cryobiology
In this study, the effects of Sildenafil Citrate on the sperm quality during cryopreservation in the asthenozoospermic patients were investigated for the first time. Thirty semen samples were collected from asthenozoospermic patients and each sample was divided into 3 groups: Control (fresh), Freeze and Freeze + Sildenafil. In each groups the sperm parameters, DNA fragmentation, acrosome integrity, protamine deficiency, mitochondrial membrane potential, plasma membrane integrity, the expression of Bcl-2 and HSP70 genes, as well as the level of Tumor necrosis factor-alpha, Malondialdehyde and antioxidants (Catalase, Glutathione, and Superoxide dismutase) in sperm were assessed. Data were analyzed statistically using Repeated Measure Analysis. The level of Malondialdehyde and Tumor necrosis factor-alpha, morphological abnormalities, DNA fragmentation, protamine deficiency and the expression of Bcl-2 and HSP70 genes increased significantly in the Freeze group compared to the Control, while the level of sperm parameters and antioxidants, plasma membrane integrity, mitochondrial membrane potential and acrosomal integrity significantly decreased. In the Freeze + Sildenafil group, compared to the Freeze group, all the mentioned parameters were significantly reversed except for the acrosomal integrity (decreased even more) and the expression of Bcl-2 (increased even more) and HSP70 genes (with no change). Although adding Sildenafil to the freezing medium decreased the adverse effects of freezing on the sperm of asthenozoospermic patients and improved sperm quality, but it also caused premature acrosome reaction. Therefore, we suggest the consumption of Sildenafil along with another antioxidant, to benefit from the favorable effects of Sildenafil as well as to maintain the integrity of the sperm acrosome.
Recreational Use of Oral PDE5 Inhibitors: The Other Side of Midnight
2022, Sexual Medicine Reviews
Nowadays, Oral phosphodiesterase type 5 inhibitors (PDE5Is) are widely used for the treatment of erectile dysfunction (ED). However, these drugs have become abused among some men for recreational use to enhance their sexual performance.
To shed a light on the recreational use of oral PDE5Is.
A literature review was performed in the PubMed, Medline Medical Subject Heading, Science Direct, Scopus, Cochrane Library, EMBASE, CINAHL, Academic Search Complete, Google scholar, Egyptian Knowledge Bank (EKB) databases, Medline, Embase, and Chem ID using the keywords; sexual health, erectile dysfunction, recreational use/abuse, phosphodiesterase type 5 inhibitors, sildenafil, tadalafil, vardenafil, avanafil, and adverse effects.
Overall, 52 studies were retained for review out of 166 papers. Twenty-two studies that assessed the prevalence of the problem were investigated including 25,279 men from different countries. Most of these studies were cross-sectional studies that depend on multiple questionnaires representing the extent as well as the attitude of the recreational use of PDE5Is.
Oral PDE5Is have become used among some men for recreational use to enhance their sexual performance. To counteract the possible side effects of such abuse, the media, as well as health authorities, should be aware of the potential adverse effects of such abuse and strengthen the regulatory activity to protect the customers from such risks.
Mostafa T, Alghobary MF. Recreational Use of Oral PDE5 Inhibitors: The Other Side of Midnight. Sex Med Rev 2022;10:385–395.
Influence of Alcohol on Phosphodiesterase 5 inhibitors Use in Middle- to Old-Aged Men: A Comparative Study of Adverse Events
2019, Sexual Medicine
Some previous studies reported recreational use of phosphodiesterase type 5 (PDE-5) inhibitors by ingesting the medicine with alcohol in patients with erectile dysfunction, but the rate of misuse in general population has never been researched.
To investigate the frequency of concomitant alcohol consumption with PDE-5 inhibitors in the general male population. We secondarily analyzed the influence of alcohol on PDE-5 inhibitor.
325 men with erectile dysfunction (age 34–78) who received PDE-5 inhibitors at a single medical institution from January 2016–February 2018 were included in the study. All patients fulfilled a survey questionnaire assessing (i) average alcohol consumption amount, (ii) previous use of PDE-5 inhibitors with alcohol and purpose of concomitant alcohol use, (iii) and background knowledge about PDE-5 inhibitors' side effects.
The main outcome measure was frequency of concomitant alcohol consumption with PDE-5 inhibitors in the general male population.
Overall 148 patients committed concomitant alcohol use (group 1), and 177 patients did not (group 2). No significant differences were observed between 2 groups regarding types of PDE-5 inhibitors used and underlying disease. Group 2 had significantly more patients with the correct knowledge concerning concomitant alcohol use than group 1 (24.9% vs 13.5%). Group 1 had more patients with average alcohol consumption >15 drinks/week (64.8% vs 14.1%). The reasons for concomitant alcohol use were curiosity (35.1%), enhancing sexual desire (27%) and recommendation from friends (16.9%). Group 1 showed significantly greater complications, including headache (23.6% vs 7.3%) and facial flushing (69.6% vs 12.4%), than group 2. 1 patient in group 1 experienced severe chest discomfort and underwent coronary artery angiography, but no severe obstructive lesion was observed.
45.5% of middle- to old-age men committed concomitant use of PDE-5 inhibitor with alcohol because of recreational purpose, and this alcohol abuse might lead to severe complications, including chest discomfort and dizziness.
Kim JN, Oh JJ, Park DS, et al. Influence of Alcohol on Phosphodiesterase 5 inhibitors Use in Middle- to Old-Aged Men: A Comparative Study of Adverse Events. Sex Med 2019;7:425–432.
Update on the Safety of Phosphodiesterase Type 5 Inhibitors for the Treatment of Erectile Dysfunction
2018, Sexual Medicine Reviews
Phosphodiesterase type 5 inhibitors (PDE5Is) have demonstrated efficacy in the treatment of erectile dysfunction (ED). Although historically found to have limited drug-related adverse events, emerging data have suggested that PDE5Is might be associated with melanoma or recurrence of prostate cancer after radical prostatectomy.
To summarize the literature on the safety of PDE5Is.
A literature review was performed through PubMed from 1990 through 2016 regarding ED. Keywords used for the search were erectile dysfunction, phosphodiesterase type 5 inhibitors, sildenafil, vardenafil, tadalafil, avanafil, safety, side effects, and adverse events, among others.
Visual, auditory, cardiovascular, renal, hepatic, priapic, and oncologic outcomes associated with the intake of PDE5Is for the treatment of ED, in addition to drug interactions, abuse, overdose, and the phenomenon of counterfeit medications.
PDE5Is are safe drugs for the management of ED. Although recent studies have shown an increased risk of non-arteritic ischemic optic neuropathy with PDE5Is, the magnitude of that risk is small. The possibility that PDE5Is cause sensorineural hearing loss remains uncertain. PDE5Is display a safe cardiovascular profile if used according to the Princeton III Consensus guidelines. There appears to be an association between PDE5I use and melanoma but the absence of a mechanism of causation raises doubt that the association is cause and effect. PDE5Is do not increase the risk of biochemical recurrence after prostate cancer management. PDE5I abuse and use of counterfeit medications present serious global health concerns.
Current data strongly support the efficacy, tolerability, and overall safety of PDE5Is for the treatment of ED. PDE5Is probably cause a small increase in the risk of non-arteritic ischemic optic neuropathy. Evidence on increased rates of melanoma and prostate cancer recurrence is weak and controversial. PDE5Is should still be considered first-line therapy for the treatment of most etiologies of ED.
Yafi FA, Sharlip ID, Becher EF. Update on the Safety of Phosphodiesterase Type 5 Inhibitors for the Treatment of Erectile Dysfunction. Sex Med Rev 2018;6:242–252.
Demographics and sexual characteristics of sex-enhancing medication users: Study of a web-based cross-sectional sample of sexually active men
2017, Arab Journal of Urology
Citation Excerpt :
With the discovery of oral phosphodiesterase type 5 inhibitors (PDE5i), the use of sex-enhancing medications (S-EM) became more appealing to a large majority of males with ED, irrespective of the nature of their problem. Moreover, the use of S-EM has become more recreational, especially amongst the young [8–11]. There have been a few research investigations [2,11,12] of different magnitudes exploring the prevalence and characteristics of ED, and patterns of S-EM use in the Middle East.
To evaluate the frequency of sex-enhancing medications (S-EM) use and to investigate the demographics and sexual characteristics of the S-EM users amongst a Saudi Arabian male population.
A cross-sectional sample of 1176 Saudi Arabian men was recruited using a web-based survey between 1 January and 1 April 2015. The survey included multiple open and closed questions to assess the frequency of S-EM use; and demographics, clinical, and sexual characteristics of S-EM users, as well as their perceptions of S-EM.
Amongst the participants, 1008 were sexually active and included in the data analysis. Of the sexually active participants, 402 (39.9%) reported S-EM use in the form of herbal or phosphodiesterase type 5 inhibitors at some time in their lives. Comparing S-EM users with S-EM non-users, the S-EM users had a number of demographic and sexual characteristics including: higher education level, higher income, smoking, more than one sexual partner, longer sexual activity duration, higher frequency of sexual intercourse, and lower sexual satisfaction level. Most of the S-EM users (82.1%) bought S-EM without a medical prescription and 62.5% had used them recreationally. In all, 52% of respondents used S-EM to treat ED and 69% of those who used it recreationally reported enhancement of erection with S-EM usage.
Demographic and sexual characteristics of S-EM users and the attitude of the users towards the S-EM were identified amongst a Saudi Arabian male population.

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Disclosure: The authors declare no conflicts of interest or financial interests in any product or service mentioned in this article, including grants, employment, gifts, stock holdings, or honoraria.

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ReviewRecreational Use and Misuse of Phosphodiesterase 5 Inhibitors

ABSTRACT

Objective

Data Sources

Study Selection

Data Extraction

Data Synthesis

Conclusion

Section snippets

Pharmacology

Adverse Effects

Clinical Applications

Product Availability

Epidemiology of Recreational Use

Safety Issues

Exposure Management

Role of the Pharmacist

Conclusion

Clin Ther.

Am J Cardiol.

J Urol.

Br J Obstet Gynecol.

Drug Alcohol Depend.

Lancet.

J Emerg Med.

Sildenafil: clinical toxicology profile

Clin Toxicol.

A 4-year update on the safety of sildenafil citrate (Viagra)

Urology.

The ‘sextasy’ craze. Clubland’s dangerous party mix: Viagra and ecstasy

Newsweek

The phosphodiesterase type 5 (PDE5) inhibitors for erectile dysfunction

Drug Advisor

Tadalafil (Cialis) for erectile dysfunction

Med Letter Drugs Ther.

Use of sildenafil (Viagra) in patients with cardiovascular disease

ACC/AHA Expert Consensus Document. Circulation.

Levitra (vardenafil) [prescribing information]

Cardiovascular effects of sildenafil citrate and recommendations for its use

Am J Cardiol.

Viagra (sildenafil) [prescribing information]

Efficacy and safety of sildenafil citrate in women with sexual dysfunction associated with female sexual arousal disorder

J Womens Health Gend Based Med.

Non-erectile dysfunction application of sildenafil

Herz.

Club drugs, smart drugs, raves, and circuit parties: an overview of the club scene

Pediatr Emerg Care.

Prescription drugs on the Internet

Pharm Times

Internet availability of prescription pharmaceuticals to the public

Ann Intern Med.

Online prescribing of sildanefil (Viagra) on the World Wide Web

J Med Internet Res.

Thousands of British men buying fake ED drug

Pharm Today

FDA raid blocks counterfeit Viagra

US Pharm.

Sex, lies and Niagra

JAMA

Review
Recreational Use and Misuse of Phosphodiesterase 5 Inhibitors