Intra-cavernosal Injection of Vasoactive Drugs --Practical Approach

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One of the most dramatic changes in urology has been the introduction of intracavernous injection of vasoactive drugs for the diagnosis and treatment of ED. At the 1983 annual meeting of the American Urological Association, Brindley personally demonstrated erection after injection of phenoxybenzamine(much to the surprise and shock to the audience). Subsequently, Zorgniotti and Lefleur (1985) reported their experience instructing patients in the technique of autoinjection of a mixture of papaverine and phentolamine for home use.
Intracavernosal injections provide an effective therapy for men with erectile purchase cialis who can not take oral agents or for whom oral agents are not effective.

Drugs and Pathophysiology:
Papaverine.
Papaverine, an alkaloid isolated from the opium poppy, exerts an inhibitory effect on PDE, leading to increased cyclic AMP and cyclic GMP in penile erectile tissue. Papaverine also blocks voltage-dependent calcium channels, thus impairing calcium influx, and it may also impair calcium-activated potassium and chloride currents.All these actions relax cavernous smooth muscle and penile vessels. Papaverine is metabolized in the liver, and the plasma half-life is 1 to 2 hours.
Alprostadil (Prostaglandin E1).
Alprostadil is the synthetic form of a naturally occurring fatty acid (i.e., alprostadil refers to the exogenous form, PGE1 to the endogenous compound). It causes smooth muscle relaxation, vasodilation, and inhibition of platelet aggregation through elevation of intracellular cyclic AMP. Alprostadil is metabolized by the enzyme prostaglandin-15-hydroxydehydrogenase, which has been shown to be active in human corpus cavernosum. After intracavernous injection, 96% of alprostadil is locally metabolized within 60 minutes and no change in peripheral blood levels has been observed.


How to give Injection:

The injection may be given anywhere from the base of the penis to two-thirds of the way down the penile shaft at the 10 o'clock and 2 o'clock locations on the upper side of the penis away from the urethra and the head of the penis. Injections are rotated within that area and the side of the injection is alternated with each injection.

Pathophysiology:
Preparation:


Methodology: :Start with 29-30 G Insulin syringe for the injection therapy.



Papavarine:It can be started with 15 and given till 60 mg. Inject in any corpus.
Bimix:Add chlorpromazine ( 4 ml papavarine to 0.1 ml chlorpromazine combination) start with 0.1 to 0.2 ml and then gradually increased .Again the injection can be given in any one of the corpus.
Trimix:add PGE-1 50 mcg( conventional vial contains 500 mcG so we will have to tae 0.1 ml ).



Procedure:

1)start in lying down position
2)Give complete privacy
3)Ask patient to fantasize and stroke his penis(patient allowed to read erotic materials)
4)If no response after 15 minutes ask him to stand erect and repeat the procedure.
5)Some men are known to have late response so minimum wait till 30-45 minutes advisable.
6)If no benefit call the pateint at next sitting and increase the dose.

Commonly encountered situations in andrology practice:
1)A 50 year old diabetic usinessman came to me .He had history of impotence.He was seen by Urologist outside and was given intra-cavernosal injection with no benefit.
When we enquired history ;he was given the injection without asking him to engage in sexual provokation.Poor man kept on waiting for the drug to act.The person was declared a failure case for the ICIVAD.We repeated the test after providing him erotic materials and he was able to get nice erection.He is now on self administered injections at home.
2)Many times patient is not at all comfortable at hospital setting.There is no privacy.There is no separate room only a curtain.The patient can hear every thing that goes around on that side of the curtain.Worst sometimes some hospital personnel mistakenly peeps inside.This makes the patient very nervous and his vasomotor tone prevents erection.
3)We have seen middle aged people not getting erection in lying position.So they prefer sex in standing position with female partner on the couch in lying position. Somehow they get reasonable erection in this position.Similar thing should be replicated if patient doesnot get erectiojn with the injection in the lying postion.

Home Administered Injection:
If the diagnostic testing helps then patient is started on home administerd injection.Prefilled Bimi Insulin syringes can be given.This can be stored at room temperature for 6 months.
Good sexual counselling and involvement of female partner is essential
Some times obese person cannot do it on his own so wife can give injection while husband stretches the penis.

The patient has to be warned about priapism .It is always good for patient to have access to the andrologist for any complications.
As priapism is rare the pateint needs reassurance and fisrt 2 -3 injections can be started in Clinic to gain confidence and allay fears about the injection.

Patient Acceptance and Dropout
In long-term studies, 13% to 60% of patients drop out for a number of reasons. These include loss of interest, loss of partner, poor erectile response, penile pain, concomitant illness(Many obese individuals are relunctant for injection because abdominal fat apron prevents them good vision of the penis.And the partner initially may help but later on gives up thinking this as more of mechanical process than romantic emotional encounter) , recovery of spontaneous erection, and ultimate choice of other therapy(Many people in the interim go for penile implant without having to resort to injection everytime they have sexual act).
Serious Adverse Effects
Priapism and fibrosis are the two more serious side effects associated with intracavernous injection therapy. Some people face pain on injection and this can be a reason for abandoning the injection therapy.

Medical Ethics and Medicare Politics

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Two stories earlier this month tell a David and Goliath story about the U.S. health care system. Unfortunately, Goliath is winning.

Atul Gawande’s superb and widely cited New Yorker article “The Checklist” presents the “David” story. Intensivist Peter Pronovost has created checklists for key intensive care unit functions like managing intravenous lines and maintaining ventilator function. Implementing the checklists has produced spectacular results in preventing infection and improving survival. But despite their effectiveness, the checklists have in large measure been ignored. Gawande comments:

“If someone found a new drug that could wipe out infections with anything remotely like the effectiveness of Pronovost’s lists, there would be television ads with Robert Jarvik extolling its virtues, detail men offering free lunches to get doctors to make it part of their practice, government programs to research it, and competitors jumping in to make a newer, better version. That’s what happened when manufacturers marketed central-line catheters coated with silver or other antimicrobials; they cost a third more, and reduced infections only slightly—and hospitals have spent tens of millions of dollars on them.”

In contrast to the humble checklist, nuclear particle accelerators that deliver proton therapy, as described in a recent New York Times article, are mega-Goliaths. They are housed in football field sized buildings, weigh more than 200 tons, and currently cost upward of $100 million. Prostate cancer has thus far been the main target for proton therapy. A support program, “Brotherhood of the Balloon” (named for the water-filled balloon inserted into the rectum at the time of treatment) maintains a well designed informational website. Sites that offer proton therapy – like Loma Linda in Southern California, advertise widely and effectively.

Proton therapy appears to be comparable in effectiveness to alternative treatments – surgery and radiation. Not surprisingly, given its complexity, it is substantially more expensive. Although a cost-effectiveness study published four months ago concluded that proton therapy is not cost effective for most men with prostate cancer, 16 treatment centers are under development.

The checklist project costs relatively little and achieves substantial results. Proton therapy costs a lot and achieves substantially less per dollar invested. But in a health system that worships technology and avoids using cost effectiveness considerations, Goliath wins hands down.

Proton therapy is not a bad thing. But its energetic dissemination, compared to the lackluster uptake of checklists, tells a lot about why our health system costs are out of control and outcomes are mediocre relative to expenditures. Our reward systems favor Goliath. Proton therapy is glamorous and pays well. Checklists are humdrum and pay poorly.

Wringing our hands about misguided values will accomplish nothing. Controlling health costs requires structural changes. Medicare, which calls the tune for health insurance, is currently not allowed to consider cost effectiveness. Allowing Medicare to use its purchasing power wisely will require political action. Until this occurs Goliath will continue to prevail.

(P.S. Readers may have noticed Gawande's Op Ed about the checklist project and a misguided requirement for informed consent in today's New York Times. I will write about that topic tomorrow.)