Parasympathetic nervous system systemic effects

Moreover organophosphoric acid esters have found application as insecticides (e.g. Parathion). Some derivatives are highly toxic to man (e.g. Sarin, Soman). The organophosphonates act as inhibitors of the enzyme cholinesterase by phosphorylating it. This enzyme is involved in the proper function of the parasympathetic nervous system. A concentration of 5 x 10 g/L in the air can already cause strong toxic effects to man. 

The simplification of the local anesthetic phaimacophore of cocaine to an aryl substituted ester of ethanolamine has been described previously. Atropine (S2) is a structurally closely related natural product whose main biologic action depends on inhibition of the parasympathetic nervous system. Among its many other actions, the compound exerts useful spasmolytic effects. 

Ocular Effects. One study reported that seven children exposed to methyl parathion by inhalation, oral, and possibly dermal routes exhibited pinpoint pupils (miosis) (Dean et al. 1984). This effect is a consequence of the effects on the parasympathetic nervous system. No other studies were located regarding ocular effects in humans after oral exposure to methyl parathion. 

Figure 15.4 Effects of the autonomic nervous system on mean arterial pressure. The baroreceptors, chemoreceptors, and low-pressure receptors provide neural input to the vasomotor center in the brainstem. The vasomotor center integrates this input and determines the degree of discharge by the sympathetic and parasympathetic nervous systems to the cardiovascular system. Cardiac output and total peripheral resistance are adjusted so as to maintain mean arterial pressure within the normal range.

Figure 15.5 Effects of sympathetic and parasympathetic nervous activity on mean arterial pressure. The parasympathetic nervous system innervates the heart and therefore influences heart rate and cardiac output. The sympathetic nervous system innervates the heart and veins and thus influences cardiac output. This system also innervates the arterioles and therefore influences total peripheral resistance. The resulting changes in cardiac output and total peripheral resistance regulate mean arterial pressure.

Of the following effects, which is not elicited by activation of the parasympathetic nervous system ... 

Another clinically important effect I would like to mention is the inhibition of salivary secretion by clonidine. Both the sympathetic nervous system and the parasympathetic nervous system are involved in the physiological regulation of salivation. HOEFKE (53) as well as RAND and coworkers (54) found that parasympathetic salivary secretion stimulated by electrical impulses on the chorda tympani and by carbachol could not be blocked by clonidine in anaesthetised animals. In our own experiments in rats with clonidine and the 2,6-diethyl derivative St 91 which does not penetrate to the CNS, secretion of saliva was blocked only after clonidine, (HOEFKE (55)) indicating a central mode of action. 

Perhaps the most prominent and well-studied class of synthetic poisons are so-called cholinesterase inhibitors. Cholinesterases are important enzymes that act on compounds involved in nerve impulse transmission - the neurotransmitters (see the later section on neurotoxicity for more details). A compound called acetylcholine is one such neurotransmitter, and its concentration at certain junctions in the nervous system, and between the nervous system and the muscles, is controlled by the enzyme acetylcholinesterase the enzyme causes its conversion, by hydrolysis, to inactive products. Any chemical that can interact with acetylcholinesterase and inhibit its enzymatic activity can cause the level of acetylcholine at these critical junctions to increase, and lead to excessive neurological stimulation at these cholinergic junctions. Typical early symptoms of cholinergic poisoning are bradycardia (slowing of heart rate), diarrhea, excessive urination, lacrimation, and salivation (all symptoms of an effect on the parasympathetic nervous system). When overstimulation occurs at the so-called neuromuscular junctions the results are tremors and, at sufficiently high doses, paralysis and death. 

E. The effect of ganglionic blockade depends upon the predominant autonomic tone exerted within various organ systems. Since the activity of the parasympathetic nervous system predominates in the eye, the effect of ganglionic blockade is mydriasis, not miosis. Similarly, stimulation of the genital tract and urinary retention would be decreased. Since sympathetic nervous system activity predominates in blood vessels and the ventricles, vasodilation and a decreased cardiac output would follow ganglionic blockade. 

Autonomic and hormonal control of cardiovascular function. Note that two feedback loops are present the autonomic nervous system loop and the hormonal loop. The sympathetic nervous system directly influences four major variables peripheral vascular resistance, heart rate, force, and venous tone. It also directly modulates renin production (not shown). The parasympathetic nervous system directly influences heart rate. In addition to its role in stimulating aldosterone secretion, angiotensin II directly increases peripheral vascular resistance and facilitates sympathetic effects (not shown). The net feedback effect of each loop is to compensate for changes in arterial blood pressure. Thus, decreased blood pressure due to blood loss would evoke increased sympathetic outflow and renin release. Conversely, elevated pressure due to the administration of a vasoconstrictor drug would cause reduced sympathetic outflow, reduced renin release, and increased parasympathetic (vagal) outflow. 

Early studies of the parasympathetic nervous system showed that the alkaloid muscarine mimicked the effects of parasympathetic nerve discharge that is, the effects were parasympathomimetic. Application of muscarine to ganglia and to autonomic effector tissues (smooth muscle, heart, exocrine glands) showed that the parasympathomimetic action... 

The effects of the cholinesterase inhibitors on these organ systems, all of which are well innervated by the parasympathetic nervous system, are qualitatively quite similar to the effects of the direct-acting cholinomimetics (Table... 

Muscarinic antagonists are sometimes called parasympatholytic because they block the effects of parasympathetic autonomic discharge. However, they do not "lyse" parasympathetic nerves, and they have some effects that are not predictable from block of the parasympathetic nervous system. For these reasons, the term "antimuscarinic" is preferable. 

The ganglion-blocking drugs cause a predictable cycloplegia with loss of accommodation because the ciliary muscle receives innervation primarily from the parasympathetic nervous system. The effect on the pupil is not so easily predicted, since the iris receives both sympathetic innervation (mediating pupillary dilation) and parasympathetic innervation (mediating pupillary constriction). Ganglionic blockade often causes moderate dilation of the pupil because parasympathetic tone usually dominates this tissue. 

Cardiac effects include diminished contractility and, because the sinoatrial node is usually dominated by the parasympathetic nervous system, a moderate tachycardia. 

NPY produces a variety of central nervous system effects, including increased feeding (it is one of the most potent orexigenic molecules in the brain), hypotension, hypothermia, respiratory depression, and activation of the hypothalamic-pituitary-adrenal axis. Other effects include vasoconstriction of cerebral blood vessels, positive chronotropic and inotropic actions on the heart, and hypertension. The peptide is a potent renal vasoconstrictor and suppresses renin secretion, but can cause diuresis and natriuresis. Prejunctional neuronal actions include inhibition of transmitter release from sympathetic and parasympathetic nerves. Vascular actions include direct vasoconstriction, potentiation of the action of vasoconstrictors, and inhibition of the action of vasodilators. 

Lowenfeld12 identified the components of the fight reflex that were controlled by parasympathetic and sympathetic innervation of the smooth muscles controlling pupil diameter. They concluded that the parasympathetic nervous system must be intact to observe the light reflex the sympathetic nervous system influences the shape of the reflex. For example, in the absence of sympathetic innervation, the constriction velocity is increased and the dilation velocity is decreased. Conversely, in situations of increased sympathetic tone, the constriction is sluggish and incomplete, and the pupil slowly returns to its baseline size. The effects of abused drugs on these and other components of the light reflex were studied in the experiment described below. 

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