Intracavernosal injection

Other routes of delivery are sometimes simpler, there being a more intimate contact between the formulation and the absorbing surface -as in the skin and the rectal routes - so the formulation and the thermodynamic activity of the dmg in the vehicle is important. 

Lipinski, F. Lombardo, B. W. Dominy and P. J. Feeney. Experimental and computational approaches to estimate solubility and permeability in dmg discovery and development settings. Adv. Drug Deliv. Rev., 46, 3-26 (2001) 

Ochsenfahrt and D. Winne. Contribution of solvent drag to the intestinal absorption of the basic dmgs amidopyrine and antipyrine from the jejunum of the rat. Arch. Pharmacol. (NS), 281, 195-6(1974) 

Florence. The oral absorption of micro- and nanoparticulates neither exceptional nor unusual. Pharm. Res., 14, 259-66 (1997) 

Florence and P. U. Jani. Particulate delivery The challenge of the oral route. In Pharmaceutical Particulate Carriers (ed. A. RoUand), Marcel Dekker, New York 1993, pp. 65-107 

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Vacuum erection devices and intracavernosal injections are highly effective for many patients, but side effects, lack of spontaneity, and fear of needles limit their widespread use as first-line therapy. 

Satisfaction and effectiveness are evaluated after a 4-week trial unless the patient initiates follow-up sooner. Some therapies such as intracavernosal injections will require multiple visits over the long term to detect adverse effects. If the initial therapy is not effective, the patient must be further evaluated to determine if the initial assessment of comorbid disease states, type of dysfunction, and patient goals were correct. After ensuring that patient goals are realistic and providing further counseling, providers will then increase the dose of drug if not at maximum, switch to another therapy, or add a therapy if indicated. 

Intracavernosal injection therapy should be used cautiously in patients at risk of priapism (e.g., sickle cell disease or lymphoproliferative disorders) and bleeding complications secondary to injections. 

Examples of other agents include trazodone (50 to 200 mg/day), yohimbine (5.4 mg three times daily), papaverine (7.5 to 60 mg [single agent therapy] or 0.5 to 20 mg [combination therapy] intracavernosal injection), and phentolamine (1 mg [combination therapy] intracavernosal injection). 

Adjunct to the diagnosis of erectile dysfunction (Caverject only) - Patients are monitored for the occurrence of an erection after an intracavernosal injection of alprostadil. Use a single dose of alprostadil that induces a rigid erection. 

Intracavernosal Following intracavernosal injection of 20 meg, mean peripheral plasma concentrations at 30 to 60 minutes after injection (89 to 102 peg/mL, respectively) were not significantly greater than baseline levels of endogenous alprostadil (96 peg/mL). 

Kaplan SA et al Combination therapy using oral B-blockers and intracavernosal injection in men with erectile dysfunction. Urology 1998 52 739. [PMID 9801091]... 

Intracavernosal injection or urethral suppository therapy with alprostadil (PGE1) is a second-line treatment for erectile dysfunction. Doses of 2.5-25 meg are used. Penile pain is a frequent side effect, which may be related to the algesic effects of PGE derivatives however, only a few patients discontinue the use because of pain. Prolonged erection and priapism are side effects that occur in less than 4% of patients and are minimized by careful titration to the minimal effective dose. When given by injection, alprostadil may be used as monotherapy or in combination with either papaverine or phentolamine. 

Priapism associated with intracavernosal injection of cocaine has also been reported. 

A 43-year-old man developed persistent painful erection after intracavernosal injection of cocaine (215). He had previously administered cocaine in this way to prolong erections. Cavernosal aspiration resulted in partial detumescence, but the condition recurred. Urine screen was positive for cocaine. Aspiration and irrigation fully alleviated the condition. 

Mirekn-Boateng AO, Tasie B. Priapism associated with intracavernosal injection of cocaine. Urol Int 2001 67(1) 109-10. 

Moxisylyte is an alpha-adrenoceptor antagonist with vasodilatory activity (1). It is used orally in the treatment of peripheral vascular disease and by intracavernosal injection in erectile dysfunction. 

Intracavernosal alprostadil is still the most effective treatment, although its use is limited by the side effects and the inconvenience of self-injection and rapid onset of action, which results in an unnatural erection. More than 90% of alprostadil intracavernosal injections result in successful sexual intercourse (126). Transurethral alprostadil is a micro-suppository that is inserted into the stem of the urethra using an applicator. Although it is a more convenient route of administration, its overall efficacy is about 50% (126,127). 

Alprostadil is commercially available as an intracavernosal injection (Caverject and Edex) and as an intraurethral insert (medicated urethral system for erection MUSE). 

Intracavernosal injection should be made into one corpus cavernosum only. From this injection site, the drug will reach the other corpus cavernosum through vascular communications between the two corpora. Alprostadil acts rapidly, with an onset in 5 to 15 minutes. The duration is directly related to the dose, and within the usual dosage range of 2.5 to 20 meg, the duration of the erection lasts no more than 1 hour. Local enzymes in the corpora cavernosum quickly metabolize alprostadil. Any alprostadil that escapes into the systemic circulation is deactivated on first passage through the lungs. Hence the plasma half-life of alprostadil is approximately 1 minute. Also, dose modification is not necessary in patients with renal or hepatic diseases. 

Intracavernosal injections should be performed using a 0.5-inch, 27- or 30-gauge needle. Also, a tuberculin syringe or a syringe prefilled with diluent as supplied by the manufacturer should be used to ensure precise measurement of doses. Patients with needle phobia, poor vision, or poor manual dexterity can use commercially available autoinjectors (e.g., Peninject) to facilitate the administration of intracavernosal alprostadil. 

Intracavernosal injections are associated with several local adverse effects. Cavernosal plaques or areas of fibrosis at injection sites form in approximately 2% to 12% of patients. When these occur, the patient should suspend further injections until the plaques resolve. These plaques may cause penile curvature, similar to Peyronie s disease, which make sexual intercourse difficult or impossible. The cause for corporal fibrosis and plaque formation is unknown. This adverse effect may be caused by poor injection technique or by... 

FIGURE 81-7. Technique for administration of intracavernosal injections. Reprinted with permission from Kirby R, Carson C, Goldstein I. Erectile Dysfunction, A Clinical Guide. Oxford, England, ISIS Medical Media, 1999 58.)... 

Intracavernosal injection therapy should be used cautiously in patients at risk of priapism, which includes patients with sickle cell disease or lymphoprohferative disorders. It should also be used cautiously in patients who may develop bleeding compheations secondary to injections, including patients with thrombocytopenia or those on anticoagulants. It should also be used cautiously in patients who may use poor-quahty injection technique, including patients with psychiatric disorders, obese patients (who may not be able to reach or see the penile injection site), patients who are blind, and patients with severe arthritis. 

The mechanism by which trazodone produces an erection is not clear. It likely acts peripherally to antagonize a-adrenergic receptors. As a result, a predominant cholinergic effect results, which causes peripheral arteriolar vasodilation and relaxation of cavernosal tissues, which enhances blood filling of the corpora. Intracavernosal injection of trazodone in experimental studies supports this likely mechanism. ... 

A portion of each papaverine dose is systemicaUy absorbed, and its prolonged plasma half-life of 1 hour contributes to adverse effects. The usual dose of papaverine is 7.5 to 60 mg when used as a siugle agent for intracavernosal injection. When used in combination, the dose decreases to 0.5 to 20 mg (see Table 81-6). 

Phentolamine has most often been administered as an intracavernosal injection. Monotherapy is avoided, as large doses are required for an erection, and at these doses systemic hypotensive adverse effects would be prevalent. Most often, phentolamine has been used in combination with other vasoactive agents for intracavernosal administration. A ratio of 30 mg papaverine to 0.5 to 1 mg phentolamine is typical, and the usual dose ranges from 0.1 mL to 1 mL of the mixture. Such a mixture promotes local effects of phentolamine and minimizes systemic hypotensive adverse effects (see Table 81-6). ... 

Israilov S, Niv E, Livine PM, et al. Intracavernosal injections for erectile dysfunction in patients with cardiovascular diseases and failure or contraindications for sildenafil citrate. Int J Impot Res 2002 14 38 3. 

Leungwattanakij S, Hynn V, Hellstrom WIG. Intracavernosal injection and intraurethral therapy for erectile dysfunction. Urol Clin North Am 2001 28 343-353. 

Intracavernosal injection—Injection into the corpus spongiosum. 

As additional information about the physiological role of NO is accumulated, new ideas and strategies for the use of NO donors are emerging. For example, several studies have demonstrated the importance of NO in penile erection (Rajfer et al., 1992 Burnett et al., 1992), and it is possible that selective delivery of NO, through the use of NO donors, may improve erectile function in impotent men. Stief etal. (1992) have shown that intracavernosal injections of 0.1-1 mg of linsidomine in patients with erectile dysfunction produced dose-dependent erectile responses with no systemic or local side effects. Porst (1993) has also shown linsidomine injection to be useful in producing penile erection, but not as effective as injected prostaglandin Ei. Further studies to optimize NO delivery for erectile responses appear to be warranted. 

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