Antidotes anticholinergic

A number of drugs in addition to atropine and scopolamine have antimuscarinic properties. Tbese include tricyclic antidepressants, phenothiazines, and antihistamines. Physostigmine has been used in the treatment of acute toxicity produced by these compounds. However, physostigmine can produce cardiac arrhythmias and other serious toxic effects of its own, and therefore, it should be considered as an antidote only in life-threatening cases of anticholinergic drug overdose. 

For the treatment of poisoning, a selective antidote (which antagonises the action) may be given e.g., nalorphine and naloxone in case of morphine poisoning, atropine in case of anticholinergic drugs, dimercaprol in mercury and penicillamine in lead poisoning, etc. 

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... 

Today, physostigmine is used only rarely in medicine, as a miotic, which helps to reduce intra-ocular pressure in the glaucomic eye, and as an antidote following the intake of anticholinergic drugs (e.g., atropine and scopolamine). 

Salicylates and anticholinergics are contraindicated in the management of DNOC-poisoned individuals because they may also potentiate the action of DNOC (Haddad and Winchester 1990). Because of the limited animal studies and understanding regarding the interaction between DNOC and proposed antidotes such as 4-methyl-2-thiouracil, chlorpromazine, and vitamins further animal testing would be useful before these dosages are used in cases of human DNOC toxicosis. 

Ct9nACh-R (mixed n-m properties R) ACh-competitive blocker (mACh-R antagonist) [anticholinergic, anti-spasmodic, antidote to organophosphorous insecticide poisoning, mydriatic, toxic, vasodilatorv]... 

TABLE 10.1. Structural formulae of some anticholinergic psychotomimetics and their antidotes... 

The antidotal effect of 7-MEOTA on the anticholinergic syndrome was potentiated by nootropics, by diazepam, and especially by opioid peptides (Fusek, 1977). 

Fusek, J. (1977). Tacrin and its analogues, antidotes against psychotomimetics with anticholinergic effects. Voj. Zdrav. Listy 46 21-7. (In Czech). 

Kassa, J., Fusek, J. (1998). The positive influence of a cholinergic-anticholinergic pretreatment and antidotal treatment on rats poisoned with supralethal doses of soman. Toxicology 128 1-7. 

Kassa, J., Fusek, J. (2000). The influence of anticholinergic drug selection on the efficacy of antidotal treatment of soman poisoned rats. Toxicology 154 ... 

Oximes bind to AChE as reversible inhibitors and form complexes with AChE either at the acylation (catalytic) site, at the allosteric site, or at both sites of the enzyme and protect AChE from phosphorylation. When the reversible inhibitor binds to the catalytic site, the protection is due to direct competition between OP and reversible inhibitor. Binding of a reversible inhibitor to the allosteric site induces indirect protection of the active site. Differences in the mechanisms of enzyme reactivation and protection demonstrate how stereochemical arrangements of oximes can play a role in the potency of their therapeutic efficacy. Direct pharmacological effects, such as direct reaction with OPs (Van Helden et al., 1996), anticholinergic and sympathomimetic effects may also be relevant for the interpretation of antidotal potency of oximes. 

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