Parasympathetic agents

Pupil size and function can be affected by peripheral autonomic action and by centrally initiated impulses.The iris is an excellent indicator of autonomic activity because of the delicate balance between adrenergic and cholinergic innervation to the iris dilator and iris sphincter muscles, respectively. By acting directly on these muscles, both sympathetic and parasympathetic agents can influence pupil size and activity. 

The sympathetic or adrenergic nervous system operates in juxtaposition to the parasympathetic nervous system to maintain homeostasis in response to physical activity and physical or psychological stress. Sympathomimetic neurotransmission is generally mediated by norepinephrine [51-41 -2] (1), CgH NO, released from presynaptic storage granules upon stimulation. A second endogenous sympathomimetic agent, epinephrine [51-43-4] (2),... 

Both the G- and V-agents have the same physiological action on humans. They are potent inhibitors of the enzyme acetylcholinesterase (AChE), which is required for the function of many nerves and muscles in nearly every multicellular animal. Normally, AChE prevents the accumulation of acetylcholine after its release in the nervous system. Acetylcholine plays a vital role in stimulating voluntary muscles and nerve endings of the autonomic nervous system and many structures within the CNS. Thus, nerve agents that are cholinesterase inhibitors permit acetylcholine to accumulate at those sites, mimicking the effects of a massive release of acetylcholine. The major effects will be on skeletal muscles, parasympathetic end organs, and the CNS. 

A great many quaternary amines are active anticholinergic agents. One such parasympathetic blocking... 

Inspection of the retina during an ophthalmoscopic examination is greatly facilitated by mydriasis, or the dilation of the pupil. Parasympathetic stimulation of the circular muscle layer in the iris causes contraction and a decrease in the diameter of the pupil. Administration of a muscarinic receptor antagonist such as atropine or scopolamine prevents this smooth muscle contraction. As a result, sympathetic stimulation of the radial muscle layer is unopposed, causing an increase in the diameter of the pupil. These agents are given in the form of eye drops that act locally and limit the possibility of systemic side effects. 

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... 

Similar considerations would apply at the synapse between the preganglionic fibre and the nerve cell of the postganglionic fibre of the sympathetic and parasympathetic systems and curare is the blocking agent (fig. 7 A). 

Historically, the first effective pharmacologic agents for lowering the blood pressure were the ganglionic blockers. At the level of the ganglia, these compounds block both sympathetic and parasympathetic transmission. The decrease in parasympathetic function is responsible for urinary retention, for the failure to develop an erection in the male patient and for the paralytic ileus. 

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. 

The actions of anticholinesterase agents on the cardiovascular system are complex. The primary effect produced by potentiation of vagal stimulation is bradycardia with a consequent decrease in cardiac output and blood pressure. However, potentiation of both parasympathetic and sympathetic ganglionic transmis-... 

Nicotine, lobeline, trimethylammonium, and DMPP stimulate all autonomic ganglia by simple combination with ganglionic nicotinic receptors on the postsynaptic membrane. This leads to membrane depolarization, an influx of sodium and calcium ions, and the generation of a fast EPSP. These agents produce general stimulation of autonomic ganglia and a complex pattern of mixed sympathetic and parasympathetic responses. 

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