Treatment of Ulcerative Colitis with Local Hydrocortisone Hemisuccinate Sodium

Abstract

TOXIC EFFECTS OF IPRONIAZID BRrrsHMEDICAL JOURNAL within 36 hours. He continued on the same dose of iproniazid for a further five months, during which time he showed signs of increasing restlessness, euphoria, insomnia, and other mild toxic effects. He died in coma after an acute illness characterized by fever, coarse tremor, hallucinations, and " auditory delusions." At necropsy the brain showed that death was due to haemorrhagic encephalitis; since no other cause was apparent this was believed to be due to the toxic effect of iproniazid. The toxic manifestations of the central nervous system caused by pethidine and iproniazid are similar: cerebral excitation, confusion, restlessness, and muscle twitchings are common to both. It is difficult to decide whether in our own and Mitchell's case cerebral symptoms were caused by the simple additive effect of the two drugs or by a more complex inhibition of the enzyme-detoxicating system in the liver. The problem, however, is of theoretical interest. It is of practical importance that the two drugs become incompatible once a certain level of iproniazid is reached in the tissues. This may take up to four weeks.The response to chlorpromazine was remarkable and perhaps a life-saving measure in our patient. Barbituirates commonly invoked in the treatment of cerebral excitation did not help, and in larger doses could have done actual harm if, as we have suggested, the liver detoxicating system was affected by iproniazid.Although the pharmacological action on the heart is not yet clearly established, the improvement in this case and in others still under observation suggests that iproniazid is a promising drug in the treatment of angina. Patients with decubital angina, however, need heavy sedation with morphine analogues and barbiturates; potentiation with iproniazid may give rise to toxic cerebral reactions as in our patient. It is because of such therapeutic implications that this case is reported. Summary A case of decubital angina treated with iproniazid is reported. Although the frequency of the attacks diminished, occasional pethidine injections were still needed for the relief of pain. During the fifth week of iproniazid treatment these injections were followed by signs of severe cerebral irritation and excitement which responded dramatically to chlorpromazine. Either the simple additive effect of the two drugs or more complex interference with the normal detoxication of pethidine in the liver by iproniazid is believed to have caused toxic cerebral damage. It is suggested that pethidine should be used with caution in patients on iproniazid treatment.ADDENDUM.-Since this paper was submitted a different complication of iproniazid treatment has been encountered in a 63-year-old man suffering from incapacitating angina of effort. On a dose of 50 mg. twice daily, much improvement resulted. One month later, while still on the same dose, he complained of difficulty of micturition and giddiness, and his blood pressure had fallen from 140/80 to 110/ 75. Iproniazid was disconti...

The course and prognosis of ulcerative colitis: Part I Short-term prognosis

“…Local corticosteroid treatment began to be used in 1955 but was at first confined to selected mild or moderate cases (Truelove, 1956(Truelove, , 1957. When subsequent controlled trials had shown it to be beneficial in such cases (Truelove, 1958;Watkinson, 1958) it began to be used more extensively but its use in severe attacks of the disease did not begin until 1957. Subsequently the combined use of systemic and local corticosteroid treatment was found to.…”

A budesonide prodrug accelerates treatment of colitis in rats.

“…Pancolitis was induced with 40/o acetic acid. Animals were then randomised to receive oral therapy for 72 hours with (1) budesonide-3-D-glucuronide, (2) free budesonide, or (3) vehicle. Drug efficacy and colitic healing was determined by measuring gross colonic ulceration, myeloperoxidase activity, and in vivo colonic fluid absorption.…”

The medical treatment of ulcerative colitis

“…Topical treatment of colitis with corticosteroids Steroids were first used topically in colitis by Truelove in 1956 and their value in distal disease confirmed by a series of controlled trials (Truelove, 1958;Watkinson, 1958Watkinson, , 1961aMatts, 1960Matts, , 1962Matts & Gaskell, 1961;Patterson et al 1965). The major attractions of this method of treatment are that minimal or no side-effects develop, and it is possible to obtain much higher concentrations of steroid locally than could be achieved by systemic therapy.…”

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