Physostigmine side effects

Philippens IHCHM, Busker RW, Wolthuis OL, Olivier B, Bruijnzeel PLB, Melchers BPC. Subchronic physostigmine pretreatment in guinea pigs effective against soman and without side effects. Pharmacol. Biochem. Behav. 59(4) 1061-1067, 1998. 

Philippens IHCHM, Groen B, Vanwersch RAP. Direct effects of physostigmine as a pretreatment in guinea pigs side effects and efficacy against soman. Proc.TG004 meeting, Medicine Hat, Canada, 2003. 

Physostigmine, given intravenously, counteracts both the peripheral and central side effects of atropine and other anticholinergic drugs such as thioridazine (neuroleptic), imipramine (antidepressant), and benztropine (antiparkinsonian medication). 

Contrary to the need for periphery-selective drugs that avoid the brain for the treatment of myasthenia gravis, AD treatment demands carbamates which easily penetrate the blood-brain barrier. Moreover, since any activity in the periphery will cause undesirable side effects , it is preferable to develop and use a CNS-selective drug. Since physostigmine had already been shown to be of value in AD patients, it is only natural that the new carbamates were modeled on its structure. 

Physostigmine has limited medicinal use since it has serious side-effects, and as a result it has only been used in the treatment of glaucoma. However, simpler analogues have been made and have been used in the treatment of myasthenia gravis and as an antidote to curare. These analogues retain the important features mentioned above. Miotine (Fig. 11.51) still has the necessary carbamate, aromatic, and tertiary... 

Overdose of M blockers Poisoning most commonly follows excessive ingestion of over-the-counter (OTC) antihistamines and cold medications, or attempts to induce hallucinations. Note that M-blocking side effects (and possible toxicity) occur with both tricyclic antidepressants and phenothiazines. Management is largely symptomatic, although physostigmine can be seful and may counter both peripheral and central effects. 

More recently, as mentioned above, effort has been focused on the development of an alternative pretreatment based upon the centrally acting carbamate physostigmine, which has continued to be of interest despite having previously been considered and discounted because of concerns about its potential side-effects and relatively narrow therapeutic window. These concerns have largely been addressed by the concept of coadministration of the potent muscarinic antagonist, hyoscine, which has been shown to reduce... 

Cholinomimetics that can increase central cholinergic activity have produced some improvements in Alzheimer s disease AChE inhibitors, particularly physostigmine, have been most studied. A study with an experimental potent, centrally acting anticholinesterase compound l,2,3,4-tetrahydro-9-aminoacridine (THA, Tacrine) involving Alzheimer s patients over a year-long period showed encouraging improvement without some side effects. 

ChE inhibitors are the only inhibitors with well-documented efficacy, albeit limited, in the treatment of dementia symptoms of Alzheimer s disease. Physostigmine, with its shorter duration of action, is useful in the treatment of intoxication by atropine and several drugs with antichohnergic side effects it also is indicated for the treattnent of Friedreich s or other inherited ataxias. Edrophonium has been used for terminating attacks of paroxysmal supraventricular tachycardia. 

Physostigmine (eserinc) and echothiophate (phospholine) arc the two AChE-inhibiting compounds indicated for glaucoma. Both compounds are known to exert ocular side effects. 

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