Cholinergic effects

Propranolol may increase procainamide plasma levels. Additive cholinergic effects may occur when procainamide is administered with other drugp with anticholinergic effects. There is the potential of additive cardiodepressant effects when procainamide is administered with lidocaine. When a beta blocker, such as Inderal, is administered with lidocaine, there is an increased risk of lidocaine toxicity. 

The antidiarrheal drugs cause an additive CNS depression when administered with alcohol, antihistamines, narcotics, and sedatives or hypnotics. There are additive cholinergic effects when administered with other drugp having anticholinergic activity, such as antidepressants or antihistamines. Concurrent use of the antidiarrheals witii a monoamine oxidase inhibitor increases the risk of a hypertensive crisis. 

Compounds that affect activities of hepatic microsomal enzymes can antagonize the effects of methyl parathion, presumably by decreasing metabolism of methyl parathion to methyl paraoxon or enhancing degradation to relatively nontoxic metabolites. For example, pretreatment with phenobarbital protected rats from methyl parathion s cholinergic effects (Murphy 1980) and reduced inhibition of acetylcholinesterase activity in the rat brain (Tvede et al. 1989). Phenobarbital pretreatment prevented lethality from methyl parathion in mice compared to saline-pretreated controls (Sultatos 1987). Pretreatment of rats with two other pesticides, chlordecone or mirex, also reduced inhibition of brain acetylcholinesterase activity in rats dosed with methyl parathion (2.5 mg/kg intraperitoneally), while pretreatment with the herbicide linuron decreased acetylcholine brain levels below those found with methyl parathion treatment alone (Tvede et al. 1989). 

A crude alkaloidal fraction from the stem of Tabernaemontana pandacaqui decreased the motor activity, respiratory rate, induced ataxia, antinociception, and loss of screen grip in rats, suggesting a CNS depression. The extract brought about the prolongation of pentobarbital sleeping time and the oxotremorine-induced salivation, hence possible cholinergic effects (13). 

Antidotic agents presently used in poisoning with organophosphorus substances are aimed at blocking the cholinergic effects resulted from a rise in ACh level as well as lowering its concentration in synapses. 

Cross-tolerance between disulfoton and another organophosphate, chlorpyrifos, was observed in mice (Costa and Murphy 1983b). Because of this cross-tolerance, a benefit is derived as a result of this interaction. In the same study, propoxur-tolerant mice were tolerant to disulfoton but not vice versa. Propoxur (a carbamate) is metabolized by carboxylesterases, and these enzymes are inhibited in disulfoton-tolerant animals disulfoton-tolerant animals are more susceptible to propoxur and/or carbamate insecticides than are nonpretreated animals. In another study, disulfoton-tolerant rats were tolerant to the cholinergic effects of octamethyl pyrophosphoramide (OMPA) but not parathion (McPhillips 1969a, 1969b). The authors were unable to explain why the insecticides OMPA and parathion caused different effects. 

The test substance is administered orally in a single dose to domestic hens, which have been protected from acute cholinergic effects, when appropriate. The animals are observed for 21 days for behavioral abnormahties, ataxia, and paralysis. Biochemical measurements, in particular NTE (Neuropathy Target Esterase), are undertaken on hens randomly selected from each group (normally 24 and 48 h after dosing). Twenty-one days after exposure, the remainder of the hens is sacrificed and histopathological examination of selected neural tissues is undertaken. 

E) The cholinergic effects of procainamide would aggravate the diabetes. 

Metrifonate is an organophosphorous compound that is effective only in the treatment of S. haematobium The active metabolite, dichlorvos, inactivates acetylcholinesterase and potentiates inhibitory cholinergic effects. The schistosomes are swept away from the bladder to the lungs and are trapped. Therapeutic doses produce no untoward side effects except for mild cholinergic symptoms. It is contraindicated in pregnancy, previous insecticide exposure, or with depolarizing neuromuscular blockers. Metrifonate is not available in the United States. 

The inhibition of MAO enzymes increases the concentrations of these neurotransmit-ters at storage sites throughout the CNS. Side effects of MAOIs include hypotensive effects from the inhibition of central vasomotor centers and cholinergic effects. 

Peripherally, all organs are innervated sympathetically (as well as parasympatheti-cally), and in most cases the adrenergic action of this system is opposite to the cholinergic effects. The neurotransmitter secreted by the nerve endings is norepinephrine and, to a lesser extent, epinephrine. 

Because of their peripheral vasodilator effect, these drugs are used in the treatment of hypertension. They act beneficially in shock and frostbite by increasing peripheral circulation. Some, like phenoxybenzamine, also have cholinergic effects, indicating that these antagonists cross-react with the AChR. 

Side effects include drowsiness, dry mouth, skin rash, insomnia and other cholinergic effects. 

Central anticholinergic syndrome due to the potent muscarinic-cholinergic effects of many psychotropics... 

Sulser F, Bickel MH, Brodie BB. The action of desmethylimipramine in counteracting sedation and cholinergic effects of reserpine-like drugs. J Pharmacoi Exp Ther 1964 144 321-330. 

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