Muscarinic symptoms

According to Grob et al., atropine given by any route has a marked inhibiting effect on the muscarinic symptoms due to... 

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. 

The mnemonic, SLUDGE, helps describe the prominent muscarinic symptoms ... 

At the St. Luke s International Hospital, after 9 00 am but before sarin poisoning was clearly suspected, atropine sulfate was administered pal-liatively to treat muscarinic symptoms such as miosis and increased secretion. A total of 515 mg was administered to 640 victims, and while this dose was sufficient, it was considerably lower than the recommended dose in war zones (Okumura et al, 1996,1998b,2005) and may have been related to the fact that the concentration of sarin used in the attack was 35%. The administration of 2-PAM by the St. Luke s hospital at approximately 11 00, appeared to control fasciculation, but the effects associated with sarin poisoning could have been alleviated by time and it is difficult to say whether 2-PAM was therapeutically effective. None of the patients were saved by the use of 2-PAM. In addition to atropine sulfate and 2-PAM, diazepam was used in patients with convulsions. 

The muscarinic symptoms are miosis (constriction of the pupil of the eye), vomiting, diarrhea, bradychardia (slow heartbeat frequency), and cardiovascular collapse. Muscarinic symptoms are attributable to peripheral parasympathetic stimulation. 

C. Reversal of central (by atropine) and peripheral (by atropine and glycopyrrolate) muscarinic symptoms in patients with intoxication by Clitocybe or In-ocybe mushroom species. 

Atropine. For adults, begin with 1-5 mg IV for children, give 0.02 mg/kg IV. (The drug may also be given via the intratracheal route dilute the dose in normal saline to a total volume of 1-2 mL.) Repeat this dose every 5-10 minutes until satisfactory atropinization is achieved. Note that severely poisoned patients may require exceedingly higher doses (eg, up to 100 mg over a few hours) of atropine determined by clinical titration and control of muscarinic symptoms. 

Several cholinergic strategies, other than cholinesterase inhibition, have been employed with the intention of ameliora ting the symptoms of AD. These include precursor loading acetylcholine release enhancement, and direct activation of both muscarinic and nicotinic receptors. 

Clinical signs and symptoms of toxicity are related to the overstimulation of muscarinic, nicotinic, and central nervous system receptors in the nervous system. Muscarinic receptors are those activated by the alkaloid drug muscarine. These receptors are under the control of the parasympathetic nervous system, and their hyperactivity results in respiratory and gastrointestinal dysfunction, incontinence, salivation, bradycardia, miosis, and sweating. Nicotinic receptors are those activated by nicotine. Hyperactivity of these receptors results in muscle fasciculations even greater stimulation results in blockade and muscle paralysis (Lefkowitz et al. 1996 Tafliri and Roberts 1987). Hyperactivity of central nervous system receptors results in the frank neurological signs of confusion, ataxia, dizziness, incoordination, and slurred speech, which are manifestations of acute intoxication. Muscarine and nicotine are not... 

In contrast to the nicotinic antagonists and indeed both nicotinic and muscarinic agonists, there are a number of muscarinic antagonists, like atropine, hyoscine (scopolamine) and benztropine, that readily cross the blood-brain barrier to produce central effects. Somewhat surprisingly, atropine is a central stimulant while hyoscine is sedative, as least in reasonable doses. This would be the expected effect of a drug that is blocking the excitatory effects of ACh on neurons but since the stimulant action of atropine can be reversed by an anticholinesterase it is still presumed to involve ACh in some way. Generally these compounds are effective in the control of motion but not other forms of sickness (especially hyoscine), tend to impair memory (Chapter 18) and reduce some of the symptoms of Parkinsonism (Chapter 15). 

The answer is g. (Hardman, p 870. Katzung, pp 230-231) Quini-dine causes prolongation of the QT interval at therapeutic doses, possibly because of its anti muscarinic actions In some patients, this is associated with recurrent lightheaded ness and fainting (known as qmmdine syncope). The symptoms result from torsades de pointes. They typically terminate but may become fatal by degeneration into ventricular fibrillation. 

Agents that increase acetylcholine activity can decrease manic symptoms (e.g, use of cholinesterase inhibitors or augmentation of muscarinic cholinergic activity). 

The symptoms that followed the daily intramuscular administration of D.F.P. for 5 days mimicked most of the muscarine-like and nicotine-like effects (see p. 37) of cholinergic drugs. There were also effects on the central nervous system. 

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