This drug, therefore, has a cumula tive and prolonged action. It would :seem that sulphonal chiefly, if not wholly, affects the cerebral centres, and a large number of the symptoms pro duced—such as somnolence, stupor, dis inclination to mental or physical effort, muscular weakness, inco-ordination and paresis, diplopia, aphasia, and slow and weak respiration and pulse—may be ex plained by the theory that the irritability of the central nervous system is ob by its action (M. L. Foster).
Poisoning by Sulphonal. — Disagree after-effects have followed the use of sulphonal in ordinary therapeutic doses. In the report of the Therapeutic Com mittee appointed by the British Medical Association to investigate the utility of various hypnotics these untoward effects -are summarized as follows:— "In (3 out of 10 cases in which 20 grains had been given disagreeable after effects were noted: drowsiness next day was noted 6 times, giddiness 4 times, and headache and inco-ordination of gait each twice. In 4 cases where 10 grains has been given drowsiness was noticed once; in 5 cases with 15 grains drowsi ness was noticed twice and giddiness twice; with 25 grains (4 cases) drowsi ness was noticed twice, giddiness once, headache once. In 7 cases with 30 to GO grains drowsiness was noticed 4 times, giddiness twice, inco-ordination of gait and vomiting each once." Although sulphonal is claimed by many to be an absolutely safe hypnotic, there are numerous cases of death on record, some as the result of moderate doses. The most striking of these, per haps, is reported by Pettit (Med. News, Aug. 10, 'S9). A woman, 2S years old, suffering from melancholia and hyster ical manifestations, but not known to have any organic disease, took 30 grains of sulphonal in two equal doses, an hour and a quarter apart. She slept for 12 hours and then could be roused and could swallow, but somnolence increased for the next 12 hours. The pupils be gan to contract 1S hours after the last close. At the end of 40 hours the tem perature began to rise, and the patient died in spite of active treatment.
Rehm (Berl. klin. Woch., No. 16, '89) reports a case in which a patient nar rowly escaped death as the result of tak ing 18 grains for three successive days. Reinfuss (Wiener med. Blatt., Jan. 7, '92), Stern (Wiener med. Woch., No. 10, '94), Herting (Allg. Zeit. f. Psych., B. 51, H. 1, '9-1), and others report fatal cases. The cases of Stern and Herting were instances of chronic poisoning; they had been under treatment for some time, and has been apparently benefited by the drug up to the time of the ap pearance of the toxic symptoms.
The recorded cases of sulphonal poison ing have been in women for the most part. Among twenty-one cases, Schulz found that twenty were in women, and all observers have found that the victims of sulphonal poisoning were to a certain degree. The inference seems reasonable that certain conditions of the blood, such as chlorosis, have a direct connection with the supervention of toxic phenomena under the use of sulphonal. Pollitz (Wiener klin. Woch., June 9, '98).
Since the drug was introduced by Rust in 1888, 30 fatal cases and about 50 non fatal severe cases have been described, all chronic in character, and mostly in lunatic asylums. The amount necessary to cause poisoning varies extremely 1500 grammes in 6 years, 224 grammes in 205 days, 393 grammes in 971 days, 12S grammes in 91 days, and similar amounts have frequently been taken without any ill effects. On the other hand, death has occurred after 19 grammes in one month and 90 grammes in three months, and severe poisoning after 1S0 grammes in 270 days, 132 grammes in 120 days, and so on. Poison ing, therefore, does not depend directly on the amount taken, but probably to a large extent on the circumstances of the individual. Women are more commonly affected than men, and poor diet, age, and debility all increase the tendency. Constipation specially favors poisoning. Sulphonal should never be given continu ously, and its administration should be interrupted every five to seven days or thereabouts. Dietrich (Ther. Monats., Apr., 1900).
The various symptoms of sulphonal poisoning, though all are not usually present in any one case, are: drowsiness, stupor, muscular incoordination, inca pacity for physical or mental exertion, tinnitus aurium, headache, vertigo, par tial loss of the reflexes, nausea, vomiting, constipation, sometimes diarrhoea, ataxic nervous troubles, diplopia, muscular tremor or paresis, ptosis, oedema of the eyelids, slow and weak (possibly ster torous) respiration, slow pulse, elevation of temperature, general anaesthesia, red dish-brown urine, urine diminished or suppressed, aphasia, and cyanosis. Death results from failure of respiration pre ceded by deep unconsciousness. In sev eral fatal cases motor paralysis appeared to be the most prominent symptom (Foster).