Diazepam Atropine

Philippens, I.H.C.H.M., Melchers, B.P.C., De Groot, D.M.G. and Wolthuis, O.L. 1992. Behavioral performance, brain histology and EEG sequelae after combined atropine/diazepam treatment of soman-intoxicated rats. Pharmacol. Biochem. Behav., 42 711-719. 

Noninterfering atropine, diazepam, neostigmine, pancuronium, succinylcholine, thiopental... 

Diazepam, an anticonvulsant of the benzodiazepine family, has been shown to control soman-induced convulsions in monkeys96 and convulsions induced by other ChE inhibitors in the rabbit.97,98 There have also been anecdotal reports of its effectiveness in controlling convulsions induced by organophosphate insecticides. In rats, diazepam has been reported to decrease the frequency of convulsions and brain lesions (although, when given without atropine, it did not decrease mortality).99 When given with 2-PAM Cl, with or without atropine, diazepam reduced the severity, but not the incidence, of brain lesions in soman-poisoned rats.100... 

There is an increased central nervous system (CNS) depressant effect when the skeletal muscle relaxants are administered with other CNS depressants, such as alcohol, antihistamines, opiates, and sedatives. There is an additive anticholinergic effect when cyclobenzaprine is administered with other drugs with anticholinergic effects (eg, antihistamines, antidepressants, atropine, haloperidol). See Chapter 30 for information on diazepam. 

Additional doses of atropine and 2-PAMC1 depending on severity. Diazepam or lorazepam to prevent seizures if >4 mg atropine given ventilatory support. 

Reference compounds. Diazepam Rf 75, chlorprothixene Rf 56, codeine Rf 33, atropine Rf 18. 

Ventilate the patient. There may be an increase in airway resistance due to constriction of the airway and the presence of secretions. If breathing is difficult, administer oxygen. As soon as possible administer of atropine alone or in combination with pralidoxime chloride (2-PAMC1) or other appropriate oxime. Diazepam may be required to prevent or control severe convulsions. If diazepam is not administered within 40-minutes postexposure, then its effectiveness at controlling seizures is minimal. 

A principle of the therapy for acute poisonings with OPC lies in the complex performance of cholinolytics (atropine, scopolamine, aprofene, amisile etc.) with reversible ChE inhibitors (pyridostigmine, proserine etc.) or cholinolytics with tranquillizers (diazepam, fenozepame etc)... 

Drug solutions and implantation of osmotic mini-pumps Physostigmine hemisulphate and procyclidine hydrochlorid were obtained from Sigma (St.Louis, U.S.A.), scopolamine hydrobromid from Merck (Darmstadt, Germany), atropine sulphate was obtained from ACF (Amsterdam, The Netherlands), and diazepam from Roche (The Netherlands). HI-6 was made available by the Defence Research Establishment, Suffield, Canada. Soman (O-pinacolyl methylphosphonofluoridate) was synthesised at TNO. Alzet Osmotic Mini-pumps with a constant delivery rate of 0.55 pl/hr (Model 2002, Alza Corp., Palo Alto, USA) were used to deliver PYR, PHY and SCO. The vehicle consisted of 20% propylene glycol, 10% ethanol and 70% water. The pumps were implanted subcutaneously under isoflurane/02 inhalation anesthesia. 

Fig. 4.3 CSF concentration/free (unbound) plasma concentration ratios for neutral and basic drugs 1, ritropirronium 2, atenolol 3, sulpiride 4, morphine 5, cimetidine 6, meto-prolol 7, atropine 8, tacrine 9, digoxin 10, propranolol 11, carbamazepine 12, ondansetron 13, diazepam 14, imipramine 15, digitonin 16, chlorpromazine and acidic drugs, a, salicylic acid b, ketoprofen c, oxyphenbutazone and d, indomethacin compared to log D.

Reference Compounds Diazepam Rf= 75 chlorprothixene, Rf=56 Codeine Rf= 33 atropine... 

Individuals on very small amounts of heroin are prescribed diazepam for anxiety, agitation or craving, zopiclone or zolpidem for insomnia, hyoscine butylbromide (Buscopan) for stomach cramps, and diphenoxylate/atropine (Lomotil) for diarrhoea, over a seven-day period. The medication schedule provided to the user explains which drug is for which symptoms, and the maximum doses of each that can be taken in a day, which for diazepam varies during the course. The basic medication regime is included in the Appendix. 

Treatment of acute nicotine poisoning is largely symptom-directed. Muscarinic excess resulting from parasympathetic ganglion stimulation can be controlled with atropine. Central stimulation is usually treated with parenteral anticonvulsants such as diazepam. Neuromuscular blockade is not responsive to pharmacologic treatment and may require mechanical respiration. 

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