It's estimated that erectile dysfunction (ED) affects more than 18 million men in the United States alone.[1] The majority of those men are over 40 years old, but it can strike no matter what your age. Sometimes ED is an unfortunate side effect of a disease. For instance, men who have diabetes, decreased testosterone levels, high blood pressure, an enlarged prostate, or some other health conditions may get ED. Often times after prostate surgery men experience ED due to nerve damage or other trauma to the male body.[2] Sometimes smoking, alcohol use, or certain medications can all cause ED. It can even be the result of everyday pressures such as stress, anxiety, or just nervousness.[3]Fortunately, no matter what the cause, Erectile Dysfunction can be successfully treated.[4]
While some men respond well to oral ED treatments such as Viagra or Cialis, others do not respond to these treatments or have uncomfortable or even dangerous side effects to these medications.[5] In those cases custom compounded medications can often be used successfully to treat ED.[6]
The injectable medications Papaverine, Phentolamine, Alprostadil (Prostaglandin E1), Atropine, Chlorpromazine, and/or Forskolin are used individually or in combination. While an injectable ED medication may sound intimidating or even painful, the truth is, the treatment involves very little discomfort and is an easy and very effective way to treat ED.[7]
Viagra (Sildenafil) is available as an oral tablet ranging from 25 mg to 100 mg. A starting dose of 50 Mg taken about one hour prior to sexual intercourse has been recommended[8]. Viagra has been reported as a safe and efficacious treatment for ED, however, it is ineffective in approximately 27 to 35% of the population and has been associated with a variety of adverse effects including headache, flushing, dyspepsia, and adverse interaction with nitrates and inhibitors of cytochrome P450 enzymes.[9] Viagra should not be taken in conjunction with nitrate therapy.[10]
Cialis (Tadalafil) is available as an oral tablet ranging from 5 to 20 mg. The recommended tadalafil starting dose for most men is 10 mg, taken as needed before sexual activity (but not more than once daily). The dose may be increased to 20 mg or decreased to 5 mg, per its efficacy and the man's personal tolerance of the drug[11]. Cialis's 36-hour effectiveness earned it the nickname, "The Weekend Pill"; like sildenafil, tadalafil is recommended as an 'as needed' medication. Cialis is the only one of the three that is also offered as a once-daily medication.
Compounded Tadalafil Troches or Sublingual Drops are Available as an option
They are available in various strengths and are typically a less expensive option
Papaverine is particularly known as a smooth muscle relaxant and vasodilator. Its principle pharmacological action is as a non-specific vasdilator of the arterioles and capillaries[12]. Major side-effects include priapism and corporal fibrosis. These side-effects are greatly reduced when papaverine is used in very low dosages and combined with phentolamine and alprostadil.
Phentolamine may provoke a reflex, increasing sympathetic outflow and the release of norepinephrine. [13]When phentolamine is used for the treatment of ED, it is often used in combination with other agents (e.g. papaverine) to enhance its efficacy. The combination of phentolamine and papaverine for the treatment of ED has been studied extensively[14][15]. This combination can be efficacious and may induce erections sufficient for sexual intercourse in over 90% of cases.[16]
Alprostadil (Prostaglandin E1) binds with PGE receptors, and the resultant relaxation response in the smooth muscle is mediated by cAMP[17]. Little is known about the pharmacokinetics of PGE1 but it is believed that as much as 80% may be metabolized in one pass through the lungs.[18] In all probability, this rapid degradation by the lungs accounts for its lack of any significant cardiovascular system side-effects when administered intracavernosally.[19] It can also be metabolized in the penis.[20] Alprostadil has also been used in combination with other agents, such as papaverine, and the combination was superior to only alprostadil.[21][22] Alprostadil is available as an intraurethral pellet (MUSE),[23] intraurethral gel with penetration enhancers [24], or intracavernosal injection. Numerous studies show that the injection is more efficacious.[25]
Chlorpromazine is an aliphatic phenothiazine that is used in the treatment of a variety of conditions, from anxiety and nausea to schizophrenia and the hiccups. Discovered in 1951, Chlorpromazine was rapidly implemented across the mental health community due to its powerful effects on several neurotransmitter channels[26] and has been called the greatest advancement in psychiatric care of the 20th century.[27] An element of its psychoactive profile, as an alpha 1-adrenoceptor-blocking agent, made chlorpromazine a natural candidate in the investigations of medications that could be used off-label in the treatment of erectile dysfunction[28] and considerable data have shown it to be analogous in efficacy and adverse effects to phentolamine, capable of bolstering combinations via its inclusion.[29]
Atropine is a non-selective muscarine agonist that functions by competitively binding to muscarine receptors, a class of acetylcholine receptor involved in the contraction and relaxation of smooth muscle and epithelial tissue throughout various parts of the body.[30] These receptors, when activated locally in the penis by acetylcholine molecules, cause the corpus cavernosum to contract[31]--by inhibiting the absorption of acetylcholine by these receptors into cells in the vasculature of the penis, Atropine effectively relaxes the vessels in the penis and helps in achieving erection.[32] While atropine's efficacy when used alone is relatively insignificant and it's use in combination with other injectables does not improve the success rates of a mixture without atropine, it can help reduce the pain[33] PGE1 can cause. [34]
Forskolin is an adenylate cyclase activator that directly stimulates the enzymes responsible for starting and maintaining erections. Adenylate cyclase activators trigger an increase in cyclic adenosine monophosphate (cAMP) which causes smooth muscle relaxation in the penis. This pharmacologic action enhances penile veno-occlusion and increases the quality of an induced erection.
Forskolin has demonstrated safety and efficacy in patients with vasculogenic impotence resistant to standard 3-agent (phentolamine/papaverine/prostaglandin E1) pharmacotherapy. As reported in the Journal of Urology, 1997 Nov;158(5):1752-8; discussion 1758-9.[35] Forskolin acts synergistically with prostaglandin E1 to produce improvement in rigidity and/or erection duration with no adverse events.[36][37]
Vasoactive Intestinal Polypeptide (VIP) is a potent vasodialator and smooth muscle relaxant[38]. It colocalizes with no synthase in penile nerve fibers and has an inhibitory and relaxation-producing effect on strips of human corpus cavernosum tissue and cavernosal vessels.[39] VIP may be the principal neurotransmitter involved in penile erection,[40] and also suggests that depletion of this powerful vasodilatory peptide may play a key role in the development of penile impotence.[41] Of the 171 patients in a placebo-controlled study treated, 75% responded to VIP/Pentolamine and only 12% to placebo (P<0.001)showing that it was a safe and effective means of treating male ED of primarily nonpsychogenic aetiology.[42]
