J R Army Med Corps 2002; 149: 388-391 J R Army Med Corps: first published as 10.1136/jramc-148-04-09 on 1 December 2002. Downloaded from

Centrally Acting Incapacitants

GENERAL CNS Stimulants CNS stimulants cause excessive neuronal Introduction activity by facilitating neurotransmission. An incapacitant is a chemical agent which The effect is to overload the cortex and produces a disabling condition that persists other higher regulatory centres making for hours to days after exposure to the agent concentration difficult, causing indecisive- (unlike that produced by riot control agents). ness and inability to act in a sustained Medical treatment will facilitate more rapid purposeful manner. A well known drug recovery, but may not be essential in some which acts in this way is D-lysergic acid cases. Specifically, the term has come to diethylamide (LSD); similar effects are mean those agents that are: sometimes produced by large doses of amphetamines. - highly potent (an extremely low dose is effective) and logistically feasible. Detection - able to produce their effects by altering the In general, no automated stand-off point higher regulatory activity of the CNS. detector systems exist for agents in this - of a duration of action lasting hours or category and only limited field laboratory days, rather than of a momentary or methods exist for the identification of such fleeting action. agents in environmental samples. Initial - not seriously dangerous to life except at diagnosis rests almost entirely upon clinical doses many times the effective dose. acumen, combined with whatever field - not likely to produce permanent injury in intelligence may be available. concentrations which are militarily effective. Protection It is likely that such agents will be dispersed These criteria eliminate many drugs that as solid aerosols by either pyrotechnic or might otherwise be considered as incapa- explosive munitions, using the respiratory http://militaryhealth.bmj.com/ citants. Opiates and strong sedatives are too tract as a portal of entry; the use of the dangerous on account of their low margin of respirator is essential. Some agents may be safety and tranquillisers cause little actual absorbed percutaneously and therefore full loss of performance capability. Many individual protective equipment may be compounds have been considered as required. incapacitants and medical staff must be alert to detect and report any unusual clinical Decontamination appearances. Removal of contaminated clothing and Two categories will be discussed: CNS complete cleansing of the skin with soap depressants (e.g. BZ) and CNS stimulants and water should be accomplished at the

(e.g. LSD). Although cannabinols and earliest opportunity. Symptoms may appear on September 25, 2021 by guest. Protected copyright. psylocibin, for instance, have been as late as 36 h after percutaneous exposure, considered in the past, their effective dose is even if the skin is washed within an hour. In too high for these to be regarded as likely fact, a delay in onset of several hours is agents for use in the field. typical.This time should be used to prepare for the possibility of an outbreak of effects 6 CNS Depressants - 24 h after the attack. CNS depressants produce their effects by interfering with neurotransmission. An General Management example of this type of agent is 3- Following the occurrence of a suspected quinuclidinyl benzilate (BZ), which blocks chemical attack with incapacitating agents, the muscarinic action of acetylcholine both the medical officer should be prepared to peripherally and centrally. In the CNS, take the following steps: anticholinergic compounds disrupt the - resistant or disoriented casualties will cognitive functions such as memory, need to be disarmed and may have to be problem solving, attention and comp- restrained during evacuation and whilst in rehension. Relatively high doses produce the medical treatment facility. toxic delirium which destroys the ability to - once the diagnosis of a nerve agent or perform any military task. other lethal substance has been ruled out, the principal signs and symptoms to consider are those shown in Table 9. 389 J R Army Med Corps: first published as 10.1136/jramc-148-04-09 on 1 December 2002. Downloaded from

Table 9.Signs and Symptoms Produced by Incapacitating Agents. Signs and Symptoms Possible Restlessness, dizziness or giddiness; failure Anticholinergics (eg. BZ), indoles (eg. to obey orders, confusion, erratic behaviour; LSD), cannabinols (eg. Marihuana), stumbling or staggering; vomiting. anxiety reaction, other intoxications (eg. alcohol, bromides, barbiturates, lead).

Dryness of mouth, tachycardia at rest, Anticholinergics. elevated temperature, flushing of face; blurred vision, pupillary dilation; slurred or nonsensical speech, hallucinatory behaviour, disrobing, mumbling and picking behaviour, stupor and coma.

Inappropriate smiling or laughter, irrational Indoles. (Schizophrenic psychosis may fear, distractability, difficulty expressing self, mimic in some respects). perceptual distortions; labile increase in pupil size, heart rate, blood pressure. Stomach cramps and vomiting may occur.

Euphoric relaxed, unconcerned day- Cannabinols. dreaming attitude, easy laughter; hypotension and dizziness on sudden standing.

Tremor, clinging or pleading, crying; clear Anxiety reaction. answers, decrease in disturbance with reassurance; history of nervousness or immaturity, phobias.

In a large-scale attack, the diagnosis will detector systems exist for these agents. be simplified by the epidemiological However, field laboratory methods are distribution of the casualties. It is better to available to isolate and identifiy BZ, e.g. in look for characteristics common to all or the DraegerTM Tube System. most casualties, than to be overly impressed

with atypical features. For example, some Protection http://militaryhealth.bmj.com/ anticholinergics are capable of causing Protection is given by the respirator, NBC marked disorientation, incoherence, hall- suit, foot protection and gloves. ucinations and confusion (the patho- gnomonic features of delirium) with very Properties little, if any, evidence of peripheral BZ and its analogues are glycollic acid esters. autonomic effect (such as tachycardia and Some members of the group are liquid at dilated pupils).This should not dissuade the ambient temperatures but BZ is a stable medical officer from considering the white crystalline powder that is only slightly likelihood of a centrally predominant soluble in water. These agents are metabolised primarily in the liver and

anticholinergic being the causative agent, on September 25, 2021 by guest. Protected copyright. since very few other pharmaceutical classes excreted by the kidneys. can produce delirium in militarily effective doses. The disturbance produced in indoles Mechanism of Action (such as LSD) or the cannabinols (such as BZ (3-quinuclidinyl benzilate) is an anti- marihuana extracts) is not really delirium, cholinergic agent that at single doses of less because the casualties remain receptive to than 1 mg produces delirium lasting several their environment and can comprehend days. In this respect, it resembles the well quite well, even though they may have great known belladonna alkaloids atropine and difficulty reacting appropriately. Differential scopolamine, except that it is more potent diagnosis should consider atropine and its effects last longer. The safety margin overdose, malingering, heat or battle stress. (ratio of lethal to incapacitating dose) in man is estimated to be at least 30. CNS DEPRESSANTS - BZ BZ is effective by all routes of administration, but its effectiveness (3-QUINOCLINIDINYL percutaneously (when mixed with a suitable BENZILATE) AND SIMILAR solvent) is limited, so that route is not likely COMPOUNDS to be used. However there are other related compounds which are effective percu- Detection taneously. BZ and other glycollates produce In general, no automated stand off point their effects within the nervous system in the 390 J R Army Med Corps: first published as 10.1136/jramc-148-04-09 on 1 December 2002. Downloaded from same way as atropine and scopolamine, that of 2-4 mg every 1 or 2 h may be required. is by interfering with cholinergic trans- The dose should be titrated against mission at muscarinic sites, both in the symptoms with gradual tapering of the dose peripheral autonomic nervous system and in as the effect of the poisoning runs its course. the brain and spinal cord. Because of the This may vary from a few hours to several wide distribution of these sites, measurable days. The temptation to substitute a slow IV effects upon almost every phase of neural infusion for intramuscular injections should regulation may be observed. It readily crosses be tempered by the awareness that IV the blood-brain barrier and is distributed to infusion may lead to nerve-agent-like all areas of the brain and spinal cord. bradycardia and too rapid infusion might After exposure to an effective dose, mild lead to arrhythmias, excessive secretions (to peripheral effects of BZ occur within 1 h and the point of compromising air exchange), central effects occur after about 4 h. The and convulsions. Oral dosing should replace central effects peak at 8 - 10 h and last 24 - intravenous therapy as soon as possible (2 to 48 h. Some other compounds in this group 5 mg every 1 to 2 h). may take longer for their effects to develop 7-methoxytocrine (7-MEOTA) can also be and to disappear. Doubling the dose used as an antidote for BZ.To eliminate BZ- prolongs the duration of severe central effects induced signs and symptoms, one tablet (100 by about 40 h and shortens the onset time of mg) 7-MEOTA should be used. In the case severe effects to about 1 h. of severe poisoning, intramuscular admin- istration (50 mg 7-MEOTA lactate in 5 ml) Signs and Symptoms is preferred; the dose is required every 8 h to Small doses of BZ cause sleepiness and reach a stable therapeutic level of this diminished alertness. Diagnosis can be made antidote. During this dose regimen, no side by noting increased heart rate, dry skin and effects are expected. lips, drowsiness and progressive signs of Peripherally acting drugs which do not intoxication in the untreated individual as cross the blood-brain barrier - such as follows: pyridostigmine, neostigmine and pilocarpine - 1-4 h: tachycardia, dizziness, ataxia, - are ineffective antagonists of the central vomiting, dry mouth, blurred vision, effects of BZ and should not be used in place confusion, sedation progressing to stupor. of physostigmine. - 4-12 h: inability to respond to the environment effectively or to move about. CNS STIMULANTS-LSD - 12-96 h: increasing activity, random (D-LYSERGIC ACID unpredictable behaviour with delusions and hallucination; gradual return to DIETHYLAMIDE)

normal 48 to 96 h after exposure. http://militaryhealth.bmj.com/ Properties Treatment LSD is solid at normal temperatures and is For most casualties, symptomatic treatment soluble in water. It is a very difficult agent to is all that will be necessary. Firm restraint disseminate and consequently is likely to be (when necessary) and a friendly attitude are used by an enemy only in a clandestine called for especially in dealing with casualties manner. capable of walking. All dangerous objects must be removed and anything likely to be Detection swallowed should be kept away from the There is no device available for detecting this subject as bizarre delusions may occur. The agent in the field. most important single medical consideration on September 25, 2021 by guest. Protected copyright. is the possibility of heat stroke. Clothing Protection should be removed if the temperature is No personal protection is available against greater than 25°C. If the body temperature is clandestine attack, but it seems probable that greater than 39°C, vigorous cooling is only small quantities of food or water could indicated. The casualty should be placed in be contaminated. Good security of the food the shade and air allowed to circulate. Water and water supply are therefore required. may be sprayed on the casualty to aid cooling, ice should not be applied to the skin. Mechanism of Action Physostigmine is an antidote to BZ but Very small doses (for example 50 µg per should be reserved for casualties who appear person) are capable of inducing a psychotic to be in danger. Physostigmine is minimally state in man, but the precise mechanism of effective during the first 4 h after exposure, action is not yet known. LSD has been but is very effective after 4 h. An injection of shown to facilitate neural activity in the 2-3 mg will be required to alleviate the reticular activating system of the brain stem. symptoms. Repeated injections at intervals of It appears to interfere with the normal approximately 15 min to 1 h may be required filtering action of this system, permitting to build up a sufficient level. Once a desirable sensory input to reach higher integrative effect is achieved, it should be maintained by centres without regard to its importance or slow intravenous injection or infusion. Doses relevance. The result is a decrease in the 391 J R Army Med Corps: first published as 10.1136/jramc-148-04-09 on 1 December 2002. Downloaded from

ability of the brain to process information presence of non-intoxicated personnel selectively and in logical sequence. enables affected subjects to maintain contact with reality. Pathophysiology Subjects intoxicated with LSD show LSD is the most potent of the biologically evidence of sympathetic stimulation (rapid active indole compounds, as little as 50 µg heart rate, sweating palms, apillary being required to produce dramatic enlargement, cold extremities) and mental psychological changes. Doses of 2 to 5 mg excitation (nervousness, trembling or have been taken without permanent spasms, anxiety, euphoria and inability to sequelae, and animal studies suggest that relax or sleep). Hyperthermia has been much higher doses may be tolerated, reported. Subjectively, feelings of tension, however, convulsions may occur at doses heightened awareness, exhilaration, kaleido- above 2 mg. LSD may be inhaled or scopic imagery, emotions of every type, ingested. Initial effects appear within a few hilarity and exultation are character-istic. minutes of inhalation or within 30 to 60 min Paranoid ideas and more profound states of of ingestion. Maximum effects are reached terror and ecstasy may also occur, especially within 2 to 3 h and gradually subside over the in highly suggestible individuals. True next 4 to 8 h. The half-life in human plasma hallucinations are rare, as is homicidal or is about 3 h.Tolerance is acquired rapidly on suicidal behaviour. repeated exposures at daily intervals, but is short-lived. LSD appears to interact with endogenous neurotransmitters such as Treatment serotonin with which it shares the common No true antagonist to the indoles is known. feature of an indole nucleus. It is metabolised The best treatment at present for LSD by the liver and excreted through the intoxication is the administration of kidneys. diazepam 10-20 mg intravenously or intramuscularly. Chlorpromazine has also Signs and Symptoms been suggested but does not appear to have The clinical manifestations of LSD any advantage over diazepam. intoxication often include an early stage of nausea followed 45-60 min after dosage by a Course and Prognosis confused state, in which delusions and The question of long term effects is still hallucinations are common but not always unresolved, but single exposures to doses in experienced.There is some evidence that the the clinical range (0.1 to 1.0 mg total dose) effects may be held off, at least for a time, by appear unlikely to cause any permanent determination to continue duty and that the biological damage. http://militaryhealth.bmj.com/ on September 25, 2021 by guest. Protected copyright.