Atropine cholinesterase inhibitor

Atropine Cholinesterase inhibitors (e.g., organophosphorus insecticides, fi-blocker poisoning)... 

Carbon dioxide Sulfur dioxide Aliphatic hydrocarbons Aromatic hydrocarbons Cholinesterase inhibitors Paraquat Lead Arsenic Mercury Removal from exposure and administer oxygen Removal from exposure Removal from exposure Removal from exposure Atropine, pralidoxime Gastric lavage and dialysis Dimercaprol, penicillamine Dimercaprol, penicillamine Dimercaprol (elemental), penicillamine, dimercaprol (inorganic salts)... 

Journal reports by Bell and Gershon indicated that tetrahydroaminoacridine (THA), a cholinesterase inhibitor, was effective in reversing delirium induced by Ditran (JB-329) as a form of psychiatric treatment It is interesting that their use of Ditran for this purpose was similar to the atropine coma treatment method reported more than a decade earlier by Forrer, Miller et al. In our study, five subjects were given 5.0 mcg/kg of oral BZ on two occasions, 8-14 days apart 60 mcg/kg of THA was administered iv four hours after the time of the second BZ dose. We observed definite partial reversal of impairment soon after injection, but it was brief. An unexpected observation was the general tendency by the subjects to become impaired more rapidly and intensely by BZ on the second occasion - a finding that was later confirmed in a more careful study. 

Atropine is used as an antidote in poisoning by an overdose of a cholinesterase inhibitor (see Chapter 14). It also is used in cases of poisoning from species of mushroom that contain high concentrations of muscarine and related alkaloids (e.g., Clitocybe dealbata). 

Cholinesterase inhibitors have minimal effects by direct action on vascular smooth muscle because most vascular beds lack cholinergic innervation (coronary vasculature is an exception). At moderate doses, cholinesterase inhibitors cause an increase in systemic vascular resistance and blood pressure that is initiated at sympathetic ganglia in the case of quaternary nitrogen compounds and also at central sympathetic centers in the case of lipid-soluble agents. Atropine, acting in the central and peripheral nervous systems, can prevent the increase of blood pressure and the increased plasma norepinephrine. 

The major therapeutic uses of the cholinomimetics are for diseases of the eye (glaucoma, accommodative esotropia), the gastrointestinal and urinary tracts (postoperative atony, neurogenic bladder), the neuromuscular junction (myasthenia gravis, curare-induced neuromuscular paralysis), and very rarely, the heart (certain atrial arrhythmias). Cholinesterase inhibitors are occasionally used in the treatment of atropine overdosage. Several newer cholinesterase inhibitors are being used to treat patients with Alzheimer s disease. 

If muscarinic effects of such therapy are prominent, they can be controlled by the administration of antimuscarinic drugs such as atropine. Frequently, tolerance to the muscarinic effects of the cholinesterase inhibitors develops, so atropine treatment is not required. 

Contraindications to the use of antimuscarinic drugs are relative, not absolute. Obvious muscarinic excess, especially that caused by cholinesterase inhibitors, can always be treated with atropine. 

Atropine Nonselective competitive antagonist at all muscarinic receptors in CNS and periphery Blocks muscarinic excess at exocrine glands, heart, smooth muscle Mandatory antidote for severe cholinesterase inhibitor poisoning Intravenous infusion until antimuscarinic signs appear continue as long as necessary Toxicity Insignificant as long as AChE inhibition continues... 

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... 

Atropine Generic Peptic ulcer, irritable bowel syndrome, neurogenic bladder, bronchospasm, preoperative antisecretory agent, cardiac arrhythmias (e.g., sinus bradycardia, postmyocardial infarction, asystole], reversal of neuromuscular blockade, antidote to cholinesterase inhibitor poisoning... 

Muscarinic cholinomimetics mediate contraction of the circular pupillary constrictor muscle and of the ciliary muscle. Contraction of the pupillary constrictor muscle causes miosis, a reduction in pupil size. Miosis is usually present in patients exposed to large systemic or small topical doses of cholinomimetics, especially organophosphate cholinesterase inhibitors. Ciliary muscle contraction causes accommodation of focus for near vision. Marked contraction of the ciliary muscle, which often occurs with cholinesterase inhibitor intoxication, is called cyclospasm. Ciliary muscle contraction also puts tension on the trabecular meshwork, opening its pores and facilitating outflow of the aqueous humor into the canal of Schlemm. Increased outflow reduces intraocular pressure, a very useful result in patients with glaucoma. All of these effects are prevented or reversed by muscarinic blocking drugs such as atropine. 

---