Editing Evaluation and Management of Erectile Dysfunction (section)

=== Intracavernosal injections (ICI) ===

* First pharmacologic treatment available for ED
* Involves the delivery of vasoactive agents directly into the corpus cavernosum prior to intercourse
* Effective in all subtypes of ED.
* '''Drugs commonly used in clinical practice (4) PAPA: Papaverine, Alprostadil, Phentolamine, and Atropine'''
** '''Only alprostadil is FDA and Health Canada approved for ICI injection and is the only medication typically used as a single agent.'''
** '''Combination therapy''' '''(trimix is alprostadil + papaverine + phentolamine''') offers a synergistic mechanism of the vasoactive agents to elicit maximal erectile responses, particularly among patients who have failed monotherapy
*** Shown to be even more efficacious than alprostadil monotherapy while maintaining an acceptable side effect profile and less penile pain
** '''Alprostadil'''
*** '''MOA: synthetic form of prostaglandin E1 and induces tissue relaxation via increased cAMP'''
*** '''Advantages: lower incidences of prolonged erection''', '''systemic side effects, penile fibrosis'''
*** '''Disadvantages: higher incidence of painful erection''', '''higher cost, has a shortened half-life if not refrigerated after reconstitution into liquid from powder.'''
*** Rare systemic side effects that include vasodilation, inhibition of platelet aggregation and stimulation of intestinal activity.
** '''Papaverine'''
*** '''MOA: non-specific PDE inhibitor''' that prevents the degradation of cAMP and cGMP thereby promoting tissue relaxation; decreases venous outflow
*** Advantages: inexpensive and stable at room temperature
*** '''Disadvantages: commonly observed liver enzyme elevations, priapism risk (up to 35%), and penile fibrosis risk (1-33'''%) have led to its abandonment as monotherapy
** '''Phentolamine'''
*** '''MOA: non-selective, reversible, competitive, α1-blocker''' (stimulation of α1-adrenergic receptor inhibits erection), no effect on venous outflow
*** Advantages: limited success when administered intracavernosally as a sole agent, short half-life
*** Disadvantages: systemic hypotension, reflex tachycardia, nasal congestion, and gastrointestinal upset.
** VIP in combination with phentolamine is currently being sought for regulatory approval in the US

* '''Treatment option for men who have contraindications to the use of PDE5i, prefer not to take an oral medication, or find that PDE5i are inadequate or ineffective'''
** '''Effective in the general ED population as well as in men with diabetes, cardiovascular risk factors, men post-prostatectomy, and men with spinal cord injuries'''
* '''Adverse events'''
** '''Most serious adverse event is priapism. Other adverse events include prolonged erection (does not require treatment, unlike priapism), pain, ecchymosis, penile fibrosis, plaque, or curvature and other deformities''' (injection site nodules)
*** '''Patients should be thoroughly educated about priapism''' and instructed in actions to take in a prolonged erection situation.
**** Commonly-used strategies (but for which there is no evidence) include attempting ejaculation and, if unsuccessful, then oral pseudephedrine followed by the application of an ice pack to the penis for 30 minutes to an hour. If a painful, non-bendable erection persists after these strategies, then the man should proceed to the emergency room within 2-4 hours of medication administration.
**** ICI with PGE1 alone appears to have lower rates of priapism but is associated with more pain and higher risk of complications.
*** Repeated penile trauma from ICI inevitably causes penile fibrosis
**** ICI should be limited to 10 injections monthly to reduce risk of penile fibrosis
**** ICI induced fibrosis appears to be partially reversible, is often unnoticed by patients and does not contribute significantly to the development of meaningful penile curvature.
** '''AUA: in-office injection test should be performed for men with ED considering ICI therapy'''
*** Men should first have an in-office injection test to determine the appropriate dose and medication(s) to produce sufficient duration of response and to minimize adverse events. Start with a small dose of medication
* '''Contraindications (5):My Direct Pinches Cause Instant Priapism'''
*# '''Use of Monoamine oxidase inhibitors''' (risk of precipitating a life-threatening hypertensive crisis if an intracavernosal α-adrenergic agonist is used to reverse a priapic episode)
*# '''Reduced manual Dexterity''' (although the partner can be trained in the injection technique)
*# '''Psychological instability'''
*# '''Severe Coagulopathy or unstable Cardiovascular disease'''
*#* Anti-coagulation therapy is not a contraindication
*# '''Infection''' (systemic, cutaneous, or urinary tract infection)
*# '''History or risk for Priapism'''
*# Obesity (relative, from 2019 AUA Update on ICI)
* Application
** Injections should be conducted at 3 and 9 o’clock positions to avoid neurovascular structures on the dorsum of the penis and the urethra ventrally
*** Injections should be at 90° to the penile surface
* Outcomes
** Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) scores were not significantly different between ICI and oral therapy. However, EDITS scores were significantly higher with implants than with ICI or oral therapy
*** Patient satisfaction is often measured using EDITS (Erectile Dysfunction Inventory of Treatment Satisfaction) with higher EDITS scores correlating to greater satisfaction.
**** EDITS scores must be distinguished from the IIEF questionnaire, as EDITS scores tend to vary depending on comfort of the patient towards therapy.
** Patient attrition from ICI has been reported as 30-60% by 6 months and up to 80% beyond that time.
*** A majority of men who discontinued use were younger.
*** Attrition has been attributed to modifiable issues, such as inadequate penile rigidity and anxiety, and unmodifiable issues, such as lack of spontaneity, unnaturalness, lack of interest and health concerns.
**** Such high attrition rates in the modifiable category could be due to inadequate medication titration, injection technique or perhaps high expectations and anxiety that may be alleviated by psychological intervention.