Parasympathetic receptor blocking agents

Blockage of cholinergic receptors prevents the symptoms of intoxication by cholinesterase inhibitors, which result from the accumulation of endogenous acetylcholine. There are four major classes of cholinergic receptor  

Treatment of cholinergic symptoms by autonomic ganglionic blockade would be undesirable in that the effect of such treatment is to abolish sympathetic as well as parasympathetic tone. Removal of sympathetic tone adds to the existing bradycardia and hypotension which form part of the syndrome of intoxication by cholinesterase inhibitors. 

In spite of the continuing search for an improved muscarinic cholinergic blocking agent, atropine and its salts are still most widely used in the treatment of intoxication by organophosphate and carbamate inhibitors of cholinesterase. Therefore, the characteristics of this compound in the 

Intravenous infusions of atropine sulphate into cats at different rates result in the attainment of various levels of the compound in the plasma. These are accompanied by the appearance of atropine in the effluent collected from the perfused cerebral ventricles and the spinal subarachnoid space, demon-trating the penetration of the compound from the plasma to the CSF. The concentration in the latter fluid is not related to the plasma concentration 

Further evidence that atropine sulphate exerts an effect in the brain following systemic administration whereas methylatropine does not was obtained in rabbits [130]. The duration of the EEG after-discharge is increased four times following the intravenous injection of 3 mg/kg of atropine sulphate while methylatropine is without effect. The intraventricular injection of the latter compound, however, increases the duration of the after- 

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Neurotransmission in autonomic ganglia is more complex than depolarization mediated by a single transmitter 190 Muscarinic receptors are widely distributed at postsynaptic parasympathetic effector sites 190 Stimulation of the motoneuron releases acetylcholine onto the muscle endplate and results in contraction of the muscle fiber 191 Competitive blocking agents cause muscle paralysis by preventing access of acetylcholine to its binding site on the receptor 191... 

The answer is d. (Hardman, pp 192-193.) Nicotine is a depolarizing ganglionic blocking agent that initially stimulates and then blocks nicotinic muscular (NM) (skeletal muscle) and nicotinic neural (NN) (parasympathetic ganglia) cholinergic receptors. Blockade of the sympathetic division of the autonomic nervous system (ANS) results in arteriolar vasodilation, bradycardia, and hypotension. Blockade at the neuromuscu-... 

In contrast to the actions of ganglionic blocking agents, guanethidine suppresses equally the responses mediated by alpha- and beta-adrenergic receptors but does not produce parasympathetic blockade. It reduces both the systolic and diastolic pressures, and the effect is especially pronounced when the patient is standing. 

These agents inhibit the muscarinic actions of acetylcholine at postganglionic parasympathetic neuroeffector sites including smooth muscle, secretory glands, and CNS sites. Large doses may block nicotinic receptors at the autonomic ganglia and at the neuromuscular junction. 

Most blood vessels receive no direct innervation from the parasympathetic system. However, parasympathetic nerve stimulation dilates coronary arteries, and sympathetic cholinergic nerves cause vasodilation in the skeletal muscle vascular bed (see Chapter 6). Atropine can block this vasodilation. Furthermore, almost all vessels contain endothelial muscarinic receptors that mediate vasodilation (see Chapter 7). These receptors are readily blocked by antimuscarinic drugs. At toxic doses, and in some individuals at normal doses, antimuscarinic agents cause cutaneous vasodilation, especially in the upper portion of the body. The mechanism is unknown. 

ANS [Autonomic Nervous System] Part of die nervous system of vertebrates that controls involuntary actions of the smooth muscles, heart, and glands. The components of the peripheral and central nervous system concerned with the regulation of involuntary actions. It has two divisions the sympathetic and parasympathetic nervous systems. Anticholinergic Inhibiting or blocking the physiological action of acetylcholine at a receptor site. An agent that blocks the parasympathetic nerves. 

Ganglion blockers (Ng antagonists) block nicotinic receptors in both sympathetic and parasympathetic ganglia (Table 2.8). Because of the complex and unpredictable actions of these agents, they are seldom used clinically. Triethephan is, however, occasionally used to treat hypertensive crisis. 

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