Cholinesterase inhibitors, and

New Chapters—new chapters are included, such as Chapter 33, Cholinesterase Inhibitors, and Chapter 18, Nonsteroidal Anti-Inflammatory Dragp. Several of the chapters in previous editions have been divided. For example, the chapter on antiviral and antifungal drugs was divided into two chapters Chapter 14, Antiviral Drags, and Chapter 15, Antifungal Drugs. 

Azinphos-methyl is unstable in basic conditions and can degrade to benzazimide, hydroxymethyl-benzazimide, mercaptomethylbenzazimide or bis(benzazimide-A/-methyl) sulfide Azinphos-methyl is an organophosphorus insecticide used to control chewing and sucking mites and insects such as aphids and scale. Azinphos-methyl has both contact and stomach action. Azinphos-methyl is a cholinesterase inhibitor and interferes with the nervous system... 

The current gold standard of treatment for cognitive symptoms includes pharmacologic management with a cholinesterase inhibitor and/or an N-methyl-D-aspartate (NMDA) antagonist. 

Summarise the actions of cholinesterase inhibitors, and describe their efficacy for Alzheimer s disease in clinical trials. 

Carbachol, topical cholinesterase inhibitors, and oral CAIs (e.g., aceta-zolamide) are used as last-resort options after failure of less toxic options. 

Cholinesterase inhibitors and memantine are first-line therapy in early management of behavioral symptoms. Modest improvement may be achieved. 

The causes of death in these studies were not specifically mentioned, but disulfoton is a cholinesterase inhibitor, and animals exposed to disulfoton typically exhibit cholinergic signs of toxicity (see Section 2.2.2.4). 

AFO -Related Therapeutic Response to Cholinesterase Inhibitors and Multifactorial Treatments... 

The Committee examined five organophosphate pesticides (acephate, chlorpyrifos, dimethoate, disulfoton, and ethion), which are all cholinesterase inhibitors and may be present as residues in fruits and vegetables. Chlorpyrifos was used as the index compound. The TEF was defined as the ratio of the NOAEL or LOAEL for each pesticide to the NOAEL or LOAEL for chlorpyrifos. TEFs based on LOAELs were used when a NOAEL could mot be established for two of the compounds. 

Toxicology. Ronnel is a weak cholinesterase inhibitor and has low toxicity. 

Drugs that may be affected by tacrine include anticholinergics, cholinomimetics, cholinesterase inhibitors, and theophylline. 

Metabolites of the cholinesterase inhibitors and in some instances significant amounts of the parent compound are eliminated in the urine. Renal excretion is very important in the clearance of agents such as neostigmine, pyridostigmine, and edrophonium. This is demonstrated by a twofold to threefold increase in elimination half-lives for these drugs in anephric patients. Renal elimination is largely the result of glomerular filtration but probably also involves, at least in the case of quaternary amines, secretion via the renal cationic transport system. 

In this chapter, we use the term cognitive enhancers to refer to two classes of pharmacological agents used in the treatment of Alzheimer s disease the cholinesterase inhibitors and the A-methyl-D-aspartate (NMDA) receptor antagonists. 

The organophosphate inhibitors are sometimes referred to as "irreversible" cholinesterase inhibitors, and edrophonium and the carbamates are considered "reversible" inhibitors because of the marked differences in duration of action. However, the molecular mechanisms of action of the three groups do not support this simplistic description. 

An example of absolutely cumulative toxicity is afforded by tri-o-cresyl phosphate or TOCP (Fig. 2.13). This compound is a cholinesterase inhibitor and neurotoxin. In chickens, an acute dose of 30 mg /kg has a severe toxic effect, which is produced to the same extent by a dose of 1 (mg/kg)/day given for 30 days. This effect may of course be produced by accumulation of the compound in vivo to a threshold toxic level, or it may result from the accumulation of the effect, as it probably does in the case of TOCP. 

Hydrolytic reactions. There are numerous different esterases responsible for the hydrolysis of esters and amides, and they occur in most species. However, the activity may vary considerably between species. For example, the insecticide malathion owes its selective toxicity to this difference. In mammals, the major route of metabolism is hydrolysis to the dicarboxylic acid, whereas in insects it is oxidation to malaoxon (Fig. 5.12). Malaoxon is a very potent cholinesterase inhibitor, and its insecticidal action is probably due to this property. The hydrolysis product has a low mammalian toxicity (see chap. 7). 

Several glycoalkaloids present in food are of toxicological interest. Solaninc. found in potatoes, tomatoes, apples, eggplant, and sugar beets, has been responsible lor several cases uf moderate to severe poisoning. Solanine is a cholinesterase inhibitor and toxic doses are probably ca 200 mg. Market potatoes contain about 1-5 mg of solanine per 10(1 g fresh weight, The USDA establishes solanine levels of 20 mg/100 g as the limit for safe consumption. 

To discuss the new cholinesterase inhibitors and treatments for enhancing memory or slowing the pace of memory loss in Alzheimer s disease. 

Lamirault L, Guillou C, Thai C, Simon H. Combined treatment with galan-thaminium bromide, a new cholinesterase inhibitor, and RS 67333, a partial... 

Friedman J. Cholinergic targets for cognitive enhancement in schizophrenia focus on cholinesterase inhibitors and muscarinic agonists. Psychopharmacology 2004 174 45-53. 

Improvements in medication by use of acetyl cholinesterase inhibitors and general therapy significantly reduce symptoms at the onset of the disease [3, 4] but do not address the severe mortality in the final stages. A causal therapy is, therefore, still very much in demand, because no existing therapy effectively stops or even cures the disease. Identification of gene mutations linked to Alzheimer s disease-afflicted families in London and Sweden and additional polymorphisms that either cause or promote Alzheimer s disease have provided some insight into the biological pathways and the involvement of the amyloid precursor protein (APP) [5-8],... 

Thus either intravenous or intramuscular doses of atropine are indicated to antagonize the muscarinic symptoms. Physostigmine and edrophonium are cholinesterase inhibitors and would exacerbate the problem. Norepinephrine would not be effective in combatting the cholinergic stimulation. Trimethaphan being a ganglionic blocker would also worsen the condition. 

Alisky JM. Could cholinesterase inhibitors and memantine alleviate HIV dementia J Acquir Immune Defic Syndr 2004 38 1-3. 

Carbachol, topical cholinesterase inhibitors, and oral CAIs (e.g., aceta-zolamide) are used as last-resort options after failure of less toxic options. The optimal timing of laser or surgical trabeculectomy is controversial, ranging from initial therapy to after failure of third- or fourth-hue drug therapy. Antiproliferative agents such as fluorouracil and mitomydn C are used to modify the healing process and maintain patency. 

Perhaps only 50% of Alzheimer patients are diagnosed, and only 50% of those diagnosed are treated, and only 50% of those treated are given a cholinesterase inhibitor, and then only for 200 days in a disease that lasts 7-10 years... 

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