TriMix Injection
Overview of TriMix Injection
Dosage Strength
TriMiX Injection:Papaverine HCl 150 mg, Phentolamine Mesylate 5 mg, Prostaglandin E1 50 mcg. Lyophilized.
Once reconstituted with 5 mL of Bacteriostatic Water: Papaverine HCl 30 mg/mL, Phentolamine Mesylate 1 mg/mL, Prostaglandin E1 10 mcg/mL.
Super TriMiX Injection:
Papaverine HCl 150 mg, Phentolamine Mesylate 10 mg, Prostaglandin E1 100 mcg. Lyophilized.
Once reconstituted with 5 mL of Bacteriostatic Water: Papaverine HCl 30 mg/mL, Phentolamine Mesylate 2 mg/mL, Prostaglandin E1 20 mcg/mL.
General Information
TriMix is given as a penile self-injection, which is generally regarded as the most effective type of anti-erectile dysfunction medications. 1 While each of the TriMix ingredients—Papaverine, Phentolamine, and Prostaglandin E1—can be used to treat a wide range of conditions on their own, combining them to treat erectile dysfunction has become a common practice in sexual medicine and is now the preferred option when conventional PDE5 inhibitors are contraindicated or ineffective. 21 and is currently the recommended medication when a patient does not respond to more traditional PDE5 inhibitors like Viagra or Cialis. 1 TriMix is recommended for the treatment of male erectile dysfunction. TriMix is a sterile injection that combines three medications from complementary classes that are intended to work together synergistically. As follows:
Papaverine HCl
An erection is brought on by a medicine called a vasodilator, which allows for increased blood flow to the penis. Papaverine interacts with adenylate cyclase to promote the generation of cyclic adenosine monophosphate (cAMP), which in turn causes the smooth muscle of the penile to relax, increasing erectile function. 3 One of the first effective medications for erectile dysfunction to be injected into the penile was this one. 4 Papaverine improves erectile function via indirectly suppressing PDE, in addition to working in a variety of other ways. 5 Papaverine’s main mode of action has not been determined by the body of recent medical literature. The multiple mechanisms by which this medicine works might vary depending on concentration. Papaverine acts to relax the penile arteries, cavernosal sinusoids, and penile veins, according to in-vitro experimental evidence. 6 Papaverine has been shown in canine experiments to have the potential to both increase and decrease the resistance to venous and arterial inflow and outflow. 7 In clinical trials, papaverine’s capacity to lessen venous outflow resistance has been confirmed. 8 The above findings could be caused by a veno-occlusive mechanism.
Phentolamine Mesylate
It relaxes and dilates the penis’ blood vessels while also increasing cardiac output when injected into the penis to cause an erection.
Phentolamine is categorized as an antagonist of the alpha-adrenoceptor. Noradrenaline causes the corpora cavernosa to remain tight, which affects the smooth muscle tone of the penile tissues. An erectile response can be obtained by inhibiting the Alpha-Adrenoceptor, which are the functioning noradrenaline receptors. Endogenous norepinephrine and phentolamine compete for the Alpha1- and Alpha2-Adrenoceptors. Similar amounts of phentolamine can bind to both receptors. According to recent research, this is how phentolamine mostly exerts its physiological effects. Additionally, phentolamine inhibits 5-HT receptors, which causes mast cells to release histamine. Studies have also suggested that NOS activation may have a role in a different process that results in enhanced vasodilation. 1314
It is thought that phentolamine’s alpha-adrenoceptor antagonist is complicated. Adrenergic nerves are complicatedly impacted by the non-selective receptor blocking effect. The effects of phentolamine on adrenergic neurons are still being studied. Pre- and post-junctional nerves may be subject to opposing control, according to theory. The effectiveness of phentolamine for the treatment of erectile dysfunction may be impacted by the counteracting regulation, however this is unknown.
Penile arterial inflow resistance was reduced in animal experiments. This demonstrates in vivo that phentolamine’s physiological reaction behaves in a way that results in erectile response. 7 Phentolamine hasn’t shown any discernible impact on human venous outflow from penile tissues, though. 15 Pharmacokinetics for phentolamine have not been demonstrated in the present corpus of literature.
Effectively decreasing the effectiveness of erectile dysfunction medication is first pass metabolism. As a result, this medication must be injected. Phentolamine has a half-life of 30 minutes, and its effects last for 2.5 to 4 hours. 16 Within 20 to 30 minutes following penile injection, the concentration of phentolamine in serum reaches its peak. The medication is quickly metabolized after this period of time. 17
Phenttolamine rarely has negative side effects. However, it has been documented that penile injection can result in orthostatic hypotension, tachycardia, arrhythmias, and myocardial infarction. This group of side effects’ mechanism has not been rationally deduced by scientific research. To improve erectile response, phentolamine is frequently combined with papaverine or vasoactive intestinal peptide. 18 19
Prostaglandin E1
A strong hormone-like substance that can cause erections by relaxing the blood vessels in the penis and widening the cavernosal arteries. This widening of the cavernosal arteries is accompanied by increased arterial inflow velocity and increased venous outflow resistance, which allows for more blood to enter and less blood to exit the penis.
Intracavernosally injected prostaglandin E1 is used. After oral PDE5 inhibitors have failed to treat erectile dysfunction, this medication is administered as a last resort. 20 Previous reviews have covered a variety of its effects and clinical applications. 2122 A growing corpus of research in medicine shows that 40 to 70 percent of erectile dysfunction patients benefit from prostaglandin E1 therapy. It has not been proven that prostaglandin E1 did not cause a response. The finding that prostaglandin E1 and S-nitrosoglutathione work better together than they do separately may explain why some people don’t experience any benefit. 23
Patients who do not respond to prostaglandin E1 may require medications that activate additional relaxant pathways in addition to this one. The ability to erection is critically dependent on smooth muscular relaxation. Prostaglandin E1 might be combined with other substances to function more effectively therapeutically. Male erectile dysfunction may benefit from the combination of prostaglandin E1 and S-nitrosoglutathione or other erectile dysfunction drugs. In order to create treatments that benefit from the combination of multiple compounds, Empower Pharmacy works hard. Prostaglandin E1 is easily converted into other erectile-promoting chemicals after being administered into penile tissue. The effectiveness of prostaglandin E1 is enhanced by these substances. There is now evidence that prostaglandin E1 can change noradrenaline levels, providing a second mechanism of action. Prostaglandin E1 is still thought to mostly function directly by boosting cAMP production via EP receptor contact, resulting in increased muscle relaxation. 25
Prostaglandin E1 controls numerous processes in tissues throughout the body. Systemic vasodilation, the reduction of platelet aggregation, and the stimulation of intestinal function are all known actions of prostaglandin E1. So, systemic prostaglandin E1 administration has only very infrequently been used. Prostaglandin E1 pharmacokinetics data are currently insufficient, although the available information points to a short action duration and a high rate of metabolic breakdown. 70% of the substance is digested following the first passage through the lungs. 26 Since prostaglandin E1 is easily digested by all body parts, penile injection primarily affects penile tissues. This also explains the unusual circulatory side effects.
References
1.Montague DK, Jarow JP, Broderick GA, et al. Chapter 1: The management of erectile dysfunction: an AUA update. J Urol 2005;174:230-9.
2.Leungwattanakij S, Flynn V, Hellstrom WJG. Intracavernosal injection and intraurethral therapy for erectile dysfunction. Urol Clin North Am 2001;28:343-354.
3.Andersson, K.E., Pharmacology of penile erection. Pharmacol Rev, 2001. 53(3): p. 417-50.
4.Virag, R., et al., Vasoactive intestinal polypeptide release during penile erection in man. Lancet, 1982. 2(8308): p. 1166.
5.K.E., A., Pharmacology of erection: agents which initiate and terminate erection. Sex Disabil 1994. 12: p. 53–79.
6.Kirkeby, H.J., et al., [Infusion cavernosography and erectile dysfunction]. Ugeskr Laeger, 1990. 152(24): p. 1724-6.
7.Juenemann, K.P., et al., Hemodynamics of papaverine- and phentolamine-induced penile erection. J Urol, 1986. 136(1): p. 158-61.
8.Delcour, C., et al., The effect of papaverine on arterial and venous hemodynamics of erection. J Urol, 1987. 138(1): p. 187-9.
9.Mooradian, A.D., et al., Biweekly intracavernous administration of papaverine for erectile dysfunction. West J Med, 1989. 151(5): p. 515-7.
10.Dinsmore, W.W., Medical treatment of impotence with papaverine and phentolamine intracavernosal injection. Ulster Med J, 1990. 59(2): p. 174-6.
11.Keogh, E.J., et al., Treatment of impotence by intrapenile injections of papaverine and phenoxybenzamine: a double blind, controlled trial. Aust N Z J Med, 1989. 19(2): p. 108-12.
12.Viswaroop, B., A. B, and G. Gopalakrishnan, Evaluating erectile dysfunction: oral sildenafil versus intracavernosal injection of papaverine. Natl Med J India, 2005. 18(6): p. 299-301.
13.Traish, A.M., et al., Expression of functional alpha2-adrenergic receptor subtypes in human corpus cavernosum and in cultured trabecular smooth muscle cells. Recept Signal Transduct, 1997. 7(1): p. 55-67.
14.Traish, A., et al., Phentolamine mesylate relaxes penile corpus cavernosum tissue by adrenergic and non-adrenergic mechanisms. Int J Impot Res, 1998. 10(4): p. 215-23.
15.Wespes, E., C. Rondeux, and C.C. Schulman, Effect of phentolamine on venous return in human erection. Br J Urol, 1989. 63(1): p. 95-7.
16.P.R., I., G. B., and B.L. . Human pharmacology of orally administered phentolamine, in Phentolamine in Heart Failure and Other Cardiac Disorders., in Proceedings of an International Workshop London, November 1975 T. S.H. and G. L.A., Editors. 1975, Hans Huber Publishers: Bern, Switzerland.
17.O, H., W. U, and K. U, Systemic pharmacokinetics of papaverine and phentolamine: comparison of intravenous and intracavernous application. Int J Impot Res, 1990. 2 (Suppl 2): p. 247–248.
18.Eardley, I., et al., Pharmacotherapy for erectile dysfunction. J Sex Med, 2010. 7(1 Pt 2): p. 524-40.
19.Dinsmore, W.W. and M.G. Wyllie, Vasoactive intestinal polypeptide/phentolamine for intracavernosal injection in erectile dysfunction. BJU Int, 2008. 102(8): p. 933-7.
20.Albersen, M., et al., Evaluation and treatment of erectile dysfunction. Med Clin North Am, 2011. 95(1): p. 201-12.
21.Linet, O.I. and F.G. Ogrinc, Efficacy and safety of intracavernosal alprostadil in men with erectile dysfunction. The Alprostadil Study Group. N Engl J Med, 1996. 334(14): p. 873-7.
22.Porst, H., The rationale for prostaglandin E1 in erectile failure: a survey of worldwide experience. J Urol, 1996. 155(3): p. 802-15.
23.Angulo, J., et al., Rationale for the combination of PGE(1) and S-nitroso-glutathione to induce relaxation of human penile smooth muscle. J Pharmacol Exp Ther, 2000. 295(2): p. 586-93.
24.Molderings, G.J., et al., Inhibition of noradrenaline release from the sympathetic nerves of the human saphenous vein by presynaptic histamine H3 receptors. Naunyn Schmiedebergs Arch Pharmacol, 1992. 346(1): p. 46-50.
25.Palmer, L.S., et al., Characterization of cyclic AMP accumulation in cultured human corpus cavernosum smooth muscle cells. J Urol, 1994. 152(4): p. 1308-14.
26.Golub, M., et al., Metabolism of prostaglandins A1 and E1 in man. J Clin Invest, 1975. 56(6): p. 1404-10.
Legal Disclaimer: All information presented in this website is intended for informational purposes only and not for the purpose of rendering medical advice.