Treatment of Acute Primidone Poisoning with Bemegride and Amiphenazole

Abstract

inflamed than the mucosa, and the cell reaction was largely polymorphonuclear. The outer surface showed peritonitis of apparently some days' duration. An occasional Grampositive coccus was seen. Special staining revealed amyloid deposits in small vessels and in the basement membrane. DiscussionThe diagnosis of peritonitis was based on the sudden onset of upper abdominal pain radiating to the right iliac fossa and acute abdominal tenderness, followed later by rigidity and absence of bowel sounds. In retrospect, the episode three days-previously was one of perforation with local peritonitis, and this was supported by histological examination. Before operation the gall-bladder was not suspected as the seat of disease, and it is probable that a reflex pylorospasm was responsible for the symptom-complex.The significance of the relationship of onset of dyspepsia to the starting of treatment with prednisone is difficult to assess. It is known that peptic ulceration occurs more frequently with prednisone than with cortisone, but cholecystitis has not yet been described as a complication of either of these drugs. Because of deterioration in the general condition associated with persistent vomiting, prednisone was replaced by intramuscular cortisone. The stress associated with surgical trauma was covered by intravenous hydrocortisone.Corticotrophin has been found to bring the temperature and pulse rate to normal levels within 12-36 hours after its administration (Beck et al., 1950). lt also causes a decrease of the leucocytes during the first few hours, with lymphopenia and eosinopenia. In the reported cases of patients undergoing treatment with corticotrophin and cortisone we found that the physical signs of all underlying diseases were obscured and there was a delay in diagnosis due to the reduction of inflammatory response caused by these drugs.When an operation is contemplated on a patient undergoing treatment with corticotrophin and cortisone, care must be taken to ensure that large doses of cortisone are given immediately before and after the operation, because there is a possibility that, without taking this precaution, the patient may develop post-operative adrenal cortical insufficiency due to stress (Salassa et al., 1953). As cortisone was withdrawn, adrenal stimulation with intramuscular corticotrophin was maintained. Adequate dosage of corticosteroids must be ensured, otherwise clinical features of adrenal cortical insufficiency develop quickly, the most important being restlessness, nausea, vomiting, weakness, hypotension, and coma. In treating the adrenal cortical deficiency state, intravenous hydrocortisone-the quickest therapeutic agent-gives an almost immediate response; oral cortisone acts in four to six hours, and intramuscular cortisone more slowly.Because the severity of the post-operative renal failure was more marked than could be accounted for by the transient oliguria, the possibility of amyloidosis was considered and a special staining technique confirmed this in the specimen removed. Two months ...

Bemegride Analepsis

“…Clinical antagonism has been reported to such drugs as pentobarbitone, thiopentone, glutethimide, methyprylone, persedon, primidone, carbromal, and bromvaletone, either alone or occasionally combined with structurally unrelated hypnotics (Shulman, Shaw, Cass, and Whyte, 1955;Harris, 1955;Holten, 1956;Palmer, 1956;von Planta and Klingler, 1956;Dotevall and Herner, 1957).…”

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The article by Dotevall and Herner (1957) has prompted us to summarize some recent pharmacological observations concerning the safe and widespread analeptic activity of bemegride to hypnotics both structurally related and unrelated to it.Bemegride (f8-methyl-fi-ethylglutarimide) will wake mice from moderately deep acute hypnosis (ready response to pain, moderate depression of corneal reflex, sleeping time 60-80 minutes) due to such structurally related hypnotics as barbiturates (pentobarbitone), thiobarbiturates (thiopentone), glutarimides (glutethimide; " doriden " and others), diketopiperidines (methyprylone; "noludar "), diketotetrahydropyridines (" persedon"), diketothiazanes (" dolitrone "), diketothiazolidines (5: 5-diethyl-2: 4-diketothiazolidine), monoureides (carbromal and bromvaletone), and succinimides (5-

…”

“…The article by Dotevall and Herner (1957) has prompted us to summarize some recent pharmacological observations concerning the safe and widespread analeptic activity of bemegride to hypnotics both structurally related and unrelated to it.…”

Primidone intoxication in a child.

“…Serious acute intoxication with primidone has been reported in 7 adults attempting suicide (Arnold and Ceranke-Hofermayer, 1953;Bogan, Rentoul, and Smith, 1965;Del Greco and Arieff, 1962;Dotevall and Herner, 1957;Fazekas and Renger, 1960; Morley and Wynne, 1957;Sciarra et al, 1954), 3 of whom succeeded (Bogan et al, 1965;Fazekas and Renger, 1960;Morley and Wynne, 1957). The lethal dose in each case was 20-30 g.; but 2 of the 4 survivors had also ingested 25-30 g. Accidental intoxication with primidone has been reported once in adults (Ajax, 1966), and twice in children (Gellman, 1965;Morley and Wynne, 1957).…”

Clinical Studies on the Action of Bemegride in Barbiturate Overdosage

“…Sundberg, R. D. (1955 Since bemegride (l/3-methylethylglutarimide) was introduced by Shaw et al in 1954, there has been much discussion on whether this drug is a specific antagonist to the barbiturates or a non-specific central analeptic. Many papers have described the stimulating effect of bemegride in barbiturate coma (Shulman et al, 1955;Clemmesen, 1956), but more recent reports have suggested that it appears to have a restorative action in coma due to non-barbiturate sedatives, such as primidone (Dotevall and Herner, 1957) and glutethimide (Rowell, 1957). The factors which influence the outcome in patients suffering from sedative poisoning are so varied that it is impossible to assess the specificity of action of bemegride in such circumstances.…”