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ing diabetic gastroparesis over the short term, but its effectiveness seems to diminish over time It is a dopamine antagonist that has central antiemetic effects as well as a cholinergic action to facilitate gastric emptying It is given in a dose of 10 mg orally three or four times a day, 30 minutes before meals and at bedtime Drowsiness, restlessness, fatigue, and lassitude are common adverse effects Tardive dyskinesia and extrapyramidal effects also occur Erythromycin appears to bind to motilin receptors in the stomach and has been found to improve gastric emptying in doses of 250 mg three times daily Tegaserod (Zelnorm), the partial 5-HT4 agonist, has been withdrawn from the US market by the FDA, so it is no longer used for this indication In selected patients, injections of botulinum toxin into the pylorus can reduce pylorus sphincter resistance and enhance gastric emptying Gastric electrical stimulation has been reported to improve symptoms and quality of life indices in patients with gastroparesis refractory to pharmacologic therapy Diarrhea associated with autonomic neuropathy has occasionally responded to broadspectrum antibiotic therapy, although it often undergoes spontaneous remission Refractory diabetic diarrhea is often associated with impaired sphincter control and fecal incontinence Therapy with loperamide, 4 8 mg daily, or diphenoxylate with atropine, two tablets up to four times a day, may provide relief In more severe cases, tincture of paregoric or codeine (60-mg tablets) may be required to reduce the frequency of diarrhea and improve the consistency of the stools Clonidine has been reported to lessen diabetic diarrhea; however, its usefulness is limited by its tendency to lower blood pressure in these patients who already have autonomic neuropathy, resulting in orthostatic hypotension Constipation usually responds to stimulant laxatives such as senna Bethanechol in doses of 10 50 mg three times a day has occasionally improved emptying of the atonic urinary bladder Catheter decompression of the distended bladder has been reported to improve its function, and considerable benefit has been reported after surgical severing of the internal vesicle sphincter Mineralocorticoid therapy with fludrocortisone, 02 03 mg/d, and elastic stockings or pressure suits have reportedly been of some help in patients with orthostatic hypotension occurring as a result of loss of postural reflexes b Management of erectile dysfunction There are medical, mechanical, and surgical treatments available for treatment of erectile dysfunction Penile erection depends on relaxation of the smooth muscle in the arteries of the corpus cavernosum, and this is mediated by nitric oxide-induced cyclic 3 ,5 -guanosine monophosphate (cGMP) formation cGMP-specific phosphodiesterase type 5 (PDE5) inhibitors impair the breakdown of cGMP and improve the ability to attain and maintain an erection Sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis) have been shown in placebocontrolled clinical trials to improve erections in response to sexual stimulation The recommended dose of sildenafil for most patients is one 50-mg tablet taken approximately 1 hour before sexual activity The peak effect is at 15 2 hours, with some effect persisting for 4 hours Patients with diabetes mellitus using sildenafil reported 50 60% improvement in erectile function The maximum recommended dose is 100 mg The recommended doses of both vardenafil and tadalafil
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is 10 mg The doses may be increased to 20 mg or decreased to 5 mg based on efficacy and side effects Tadalafil has been shown to improve erectile function for up to 36 hours after dosing In clinical trials, only a few adverse effects have been reported transient mild headache, flushing, dyspepsia, and some altered color vision Priapism can occur with these drugs and patients should be advised to seek immediate medical attention if an erection persists for longer than 4 hours The PDE5 inhibitors potentiate the hypotensive effects of nitrates and their use is contraindicated in patients who are concurrently using organic nitrates in any form Caution is advised for men who have suffered a heart attack, stroke, or life-threatening arrhythmia within the previous 6 months; men who have resting hypotension or hypertension; and men who have a history of cardiac failure or have unstable angina Rarely, a decrease in vision or permanent visual loss has been reported after PDE5 inhibitor use Intracorporeal injection of vasoactive drugs causes penile engorgement and erection Drugs most commonly used include papaverine alone, papaverine with phentolamine, and alprostadil (prostaglandin E1) Alprostadil injections are relatively painless, but careful instruction is essential to prevent local trauma, priapism, and fibrosis Intraurethral pellets of alprostadil avoid the problem of injection of the drug External vacuum therapy (Erec-Aid System) is a nonsurgical treatment consisting of a suction chamber operated by a hand pump that creates a vacuum around the penis This draws blood into the penis to produce an erection which is maintained by a specially designed tension ring inserted around the base of the penis and which can be kept in place for up to 20 30 minutes While this method is generally effective, its cumbersome nature limits its appeal In view of the recent development of nonsurgical approaches to therapy of erectile dysfunction, resort to surgical implants of penile prostheses is becoming less common
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