Death, atropine causing

Therapeutic doses of scopolamine produce CNS depression, characterized by drowsiness, amnesia, and dreamless sleep (Brown and Taylor 1996). It reduces arousal and increases the effort required to awaken (Parrott 1987). Higher therapeutic doses of atropine cause central excitation, characterized by restlessness, irritability, confusion, disorientation, hallucinations, and delirium. Larger doses produce central depression, paralysis, coma, and death by respiratory failure and cardiovascular collapse. 

Atropine is an alkaloid isolated from Atropa bellactonna, the deadly nightshade plant. In the Renaissance, women used the juice of the berries of the nightshade to enlarge the pupils of their eyes for cosmetic reasons. Atropine causes an increase in heart rate, relaxes smooth muscles, and interferes with nerve impulses transmitted by acetylcholine In higher doses atropine is poisonous, leading to convulsions, coma, and death. 

When administered to animals, muscarin causes increased se- cretion of saliva and tears vomiting evacuation of fseces, at first solid, later liquid contraction of the pupils, almost to the extent of closure diminution of the rapidity of the pulse interference with respiration and locomotion gradual sinking of the heart s action and respiration and death. Atropin prevents the action of muscarin, and dijninishes its intensity when already established. 

Impens (121) also stated that the rate and depth of respiration of the rabbit is significantly increased by moderate doses of atropine. On the contrary, large doses decrease the depth and death is caused in the animal by a failure of the respiratory center. Impens refused to classify atropine among the respiratory analeptics because he considered that the stimulation of the respiration is only due to the agitated state of the animal. If the rabbit receives a sedative before the atropine the latter (40 mg./kg.) does not modify the depth of respiration. 

Of course, none of these data precisely establish the LD50, which is needed to estimate the therapeutic ratio (LD50/ID50). Nevertheless, extrapolation of the approximate therapeutic ratio for atropine (while also taking into account that lethality among the glycolates is proportional to their peripheral potency) provides the most feasible way to estimate the LD50 for the other belladonnoids (none of which have been known to have caused death in humans). 

Delayed neuropathy characterized by distal axonal degeneration is a systemic health effect caused by some organophosphate pesticides and is not due to anticholinesterase inhibition. EPN is neurotoxic to atropine-protected hens, producing polyneuropathy progressing to paralysis and some deaths after ingestion of 5-10mgA g/day. There are no reports, however, of neurotoxicity from EPN in humans. ... 

Rarely did the intramuscular or intravenous doses exceed 1.5 times the Incapacitating dose. Inhalation doses were higher, but potencies were lower by this route (usually about 60 percent of that by the Intravenous or intramuscular route). Compared with doses described in the scientific literature on atropine coma therapy 18-23 or scopolamine therapy, the BZ doses to which volunteers were exposed appear modest. As much as 20 times the ID50 of atropine and 30-40 times the ID50 of scopolamine have been administered in the past by clinicians—often to older and less robust patients. Many patients received multiple exposures of this magnitude over a period of days or weeks. These therapeutic procedures, reported several decades ago in refereed journals, actually stressed and advocated the benefits of such treatment, despite occasional deaths (most of which appear to have been caused by hyperthermia). 

Galantamine (Razadyne) [Cholinesterase Inhibitor] Uses Alzheimer Dz Action Acetylcholinesterase inhibitor Dose 4 mg PO bid, T to 8 mg bid after 4 wk may T to 12 mg bid in 4 wk Caution [B, ] T Effect w/ suc-cinylcholine, amiodarone, dildazem, verapamil, NSAIDs, digoxin X- effect w/ anticholinergics, T risk of death vs placebo Contra Severe renal/hepadc impair Disp Tabs, soln SE GI disturbances, wt loss, sleep disturbances, dizziness, HA Interactions T Effects W/ amitriptyline, cimeddine, erythromycin, fluoxetine, fluvoxamine, ketoconazole, paroxetine, quinidine EMS Use succinylcholine w/ caudon, may need a reduced dose monitor ECG for induced conduction abnormalities OD May cause cholinergic Sxs (SLUDGE), muscle weakness, resp depression, and Szs atropine may be used as antidote... 

Intoxications with higher concentrations will cause tachycardia, mydriasis, CNS excitations and hallucinations, coma and ultimately death [42], Incorporation of atropine (more correctly S-hyoscyamine) is the predominant reason for TA intoxication after ingestion of Datura plants. 

Most of the experimental chemicals were administered to too few volunteers to be examined separately for an influence on mortality. However, a few were considered of sufficient interest to justify being examined in that way (Table 4-4). The specific chemicals are grouped by type. The SMRs for these individual compounds range from a low of 0.80 (nine observed, 11.3 expected deaths) for the men rested with sarin only, to a high of 2.50 (five observed, two expected) for scopolamine only. Atropine, a therapeutic anticholinergic similar to scopolamine, had the next highest SMR, 1 76 (three observed, 1.7 expected). Of the eight deaths of men who received one or the other of these two therapeutically similar compounds, three were attributed to trauma (one accident, one suicide, and one other trauma), and one was due to cancer the causes of the other four will not be known until the death certificates are obtained. 

Disadvantage is that absorption can occur, especially when there is tissue destruction so that systemic effects result, e.g. adrenal steroids and neomycin to the skin, atropine to the eye. Ocular administration of a P-adrenoceptor blocker may cause systemic effects (any first-pass elimination is bypassed) and such eye drops are contraindicated for patients with asthma or chronic lung disease. There is extensive literature on this subject characterised by expressions of astonishment that serious effects, even death, can occur. 

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