Therapy influencing the autonomic nervous system (1952)

functional demands for example its activity quickens or slows the heart constricts or dilates the blood vessels control certain internal secretory processes initiates intestinal paris's two opposing subdivisions make possible with accommodation to changing demands they are known as the parasympathetic and the sympathetic each consists essentially of a separate neural network thus providing a double innervation to smooth muscle and many secret or eat issues through the functioning of these two subdivisions the normal healthy individual maintains a balance between organ or system function and the demand placed upon it and imbalance between these two subdivisions however may result in the development of one or more well recognised clinical conditions among the diseases in which autonomic imbalance is considered to be a prominent etiologic factor are such very diseases as essential hypertension gastritis peptic ulcer talara spasm intestinal hyper motility mucus [ __ ] and ulcerative colitis hyperhidrosis and other conditions not easily classified but which are characterized by vague subjective symptoms and few if any objective findings for great many years these conditions were associated with what was called nervousness a term which has given way to the more descriptive term situational stress situational stress is the term now used to describe the sum total of life situations which consciously or subconsciously result in tension in a particular individual it is now thought that in susceptible individuals with tension of this type there develops an imbalance between the two sub divisions of the autonomic nervous system with the resulting more or less constant barrage of neural stimuli over the parasympathetic division this parasympathetic imbalance has been called vagal tone heeya or parasympathetic in order to have a better understanding of diseases resulting from this imbalance and in order that therapeutic approaches maybe more logically applied it is desirable to review the functioning of the autonomic nervous system the cells of origin of the sympathetic subdivision are situated in the lateral horns of the gray matter of the spinal cord from the first thoracic segment to the third lumbar the axons of these cells travel through the anterior nerve roots and synapse at one of two ganglion sites with a single exception of adrenal innervation one of the ganglion sites to which sympathetic fibers travel is the sympathetic chain this structure consists of some 22 ganglia which lie near the spinal column and extend from the base of the skull to the coccyx some preganglionic sympathetic fibers pass through this chain to the second site which consists of the so-called pre vertebral group of ganglia included in this group are the celiac who superior mesenteric and the inferior mesenteric ganglia since neural impulses travel over these fibers prior to ganglionic synapse they are known as preganglionic fibers but regardless of the actual site of the ganglion the preganglionic fiber synapses with a ganglion cell and its fibers in turn carry the impulse from the ganglion to the innervated organ and are known as postganglionic fibers further each preganglionic fiber is thought to synapse with several ganglion cells thus accounting for the diffuse nature of the sympathetic discharge the second sub division of the autonomic nervous system is known as the parasympathetic system preganglionic fibers of this subdivision leave the central nervous system from the hypothalamus the midbrain the medulla or the second third and four what sacral segments of the spinal cord those from the hypothalamus innervate the secretory glands of the posterior lobe of the pituitary those leaving the midbrain traveled to the ciliary ganglion where they synapse with post ganglion fibers providing parasympathetic innervation to the eye some of those from the medulla become a part of the seventh cranial nerve traveled to the sea no palatine or to the submaxillary ganglion from which postganglionic fibers innervate the lacrimal and salivary glands in a similar way other fibers reach the otic ganglion by way of the ninth cranial nerve and postganglionic fibers innervate the parotid gland this parasympathetic innervation to the eye and to the salivary glands explains some of the side actions commonly seen in the use of drugs acting on the parasympathetic division however most of the parasympathetic preganglionic fibers which leave the medulla are contained in the vagus nerve and are distributed to the thoracic and abdominal viscera unlike the fibers included in the third seventh and ninth nerves the preganglionic fibers of the Vegas do not synapse in well-defined ganglia but connect with ganglion cells situated within the substance of the innervated organ thus the preganglionic fibers of this group may be very long and the postganglionic fibers very short the parasympathetic outflow from the sacral section of the spinal cord originates in the lateral horns of the second third and fourth segments emerge in the anterior roots of these spinal nerves form the pelvic nerve and terminate around ganglion cells lying in close proximity to the pelvic organs these postganglionic fibers innervate the descending colon and the pelvic organs to summarize the anatomy of the autonomic nervous system the fibers of the sympathetic subdivision arise from the first thoracic to the third lumbar segments of the spinal cord the preganglionic fibers proceed usually too well the fine ganglia where synapse is made with postganglionic fibers which in turn travel to the innervated structure the preganglionic fibers of the parasympathetic subdivision arise variously from the hypothalamus the midbrain the medulla or from sacral segments of the spinal cord these fibers travel to well-defined ganglia for structures of the head and neck but the ganglion cells associated with thoracic abdominal and pelvic viscera are within the viscera themselves the physiology of the autonomic nervous system should also be reviewed since its understanding is necessary to the clinical application of the so-called autonomic blocking agents it is generally accepted that neural stimuli are transmitted to effectors by means of chemical mediators such mediators also serve in the transmission of the neural stimulus across the ganglion synapse the chemical which mediates such transmission at the ganglionic synapse of both subdivisions is acetylcholine acetylcholine also acts as a mediator at the postganglionic effectors of the parasympathetic subdivision however at the effector site of the sympathetic subdivision the chemical mediator is a substance which has been called sympathy the exact chemical nature of which is still under dispute there is considerable evidence to support the view that there are two sympathies and that one is epinephrine or adrenaline and the other is norepinephrine or arter on all it is probable that it is this difference between the two subdivisions which permits the application of therapeutic agents to clinical conditions characterized by an imbalance of the autonomic nervous system there is considerable confusion in the terminology of drugs which act on the autonomic nervous system or which provide effects simulating its activity properly drugs which mimic the activity of the parasympathetic subdivision are parasympathetic and those having an action mimicking the sympathetic subdivision our sympathy limit conversely the inhibitors are known as parasympathetic or sympathetic further since of sita choline is the mediator of the parasympathetic subdivision the terms cholinergic adrenergic are frequently used to indicate a drug action as are the terms anticholinergic an Adreno lytic although these terms were originally employed to describe nerves and not drugs the physiology of the autonomic nervous system limits the sites of action of pharmacologic agents to three and in each of these sites it is possible to affect either stimulation or inhibition these three sites are first all autonomic ganglia since the serial cooling is the mediator in the gangly of both subdivisions second the effectors of the sympathetic subdivision where sympathy niz the mediator and third the effectors of the parasympathetic subdivision where acetylcholine again is the mediator but where for reasons not understood drugs act differently than they do against acetylcholine in ganglionic mediation stimulation of the autonomic nervous system which is accomplished by the so-called excitatory drugs can be brought about by one of two types of action first a drug may act to inhibit the mediator destroying enzyme and thus permit the accumulation of the chemical mediator examples of this type are physostigmine and neostigmine acting within the parasympathetic subdivision ephedrine may act in a similar way at the sympathetic effectors second excitatory drugs may act by supporting the normally occurring mediator or by acting on the innervated structure as does the mediator itself small doses of nicotine provide this action at the ganglia urecholine or pilocarpine cause this effect at the parasympathetic effectors in a similar way excitation or stimulation may occur at sympathetic effectors and an example of this type of drug is epinephrine inhibiting agents or blocking agents also act at one or of three possible sites but their action is usually that of competitive combination so that the normally occurring mediator does not cause stimulation examples of drugs which block at the ganglia are tetraethylammonium Penta Muthoni 'um and hexamethonium examples of drugs which block or inhibit only at the parasympathetic effectors in usual dosage are atropine hyoscyamine and scopolamine a few act both at the ganglia and at the parasympathetic effectors such drugs are probe and fine been fine and die butylene drugs which block at the effectors of the sympathetic subdivision are a special case in that no drug known at the present time blocks all adrenergic functions ergotamine the hydrogenated argot alkaloids dive enamine Pippa Rock sane and press choline will block the blood pressure raising effect of epinephrine but not the tachycardia which epinephrine causes the newer drugs which act in therapeutic doses to inhibit neural transmission at the ganglia of both subdivisions as does tetraethylammonium and which also inhibit at the effectors of the parasympathetic subdivision as does atropine allow a considerable therapeutic advantage over previously available blocking agents one of these is propylene bromide more commonly known as probe and fine it has relatively little action on the normal cardiovascular system which advantage has increased its sphere of practical application atropine and its related alkaloids act at only one site the effectors in this subdivision and are well known for their prominent side actions and for their toxicity when given inadequate dosage tetraethylammonium a newer drug must be given parenteral ii and is insufficiently selective in that it has too great an activity on the vascular system so that orthostatic hypotension is commonly associated with its administration many clinical conditions which are characterized by disturbances of the autonomic nervous system are commonly thought to be due to an overstimulation of the parasympathetic subdivision this excess stimulation is considered to be a prominent sector in such diverse conditions as gastritis peptic ulcer and hyperhidrosis and in some types of kilora spasm biliary dyskinesia pancreatitis intestinal hyper motility [ __ ] constipation and mucus and ulcerative colitis this excess parasympathetic stimulation or parasympathetic is but the neural manifestation of a more basic factor or disturbance which is not as yet understood most authorities however are of the opinion that this basic factor lies in the psyche and is the result of environmental situations commonly spoken of as situational stress if this basic concept of parasympathetic is correct the proper treatment for permanent relief in this class of conditions is the elimination of existing stresses unfortunately this is often impractical or impossible and it is therefore necessary to rely on medical or surgical interruption of the resulting shower of parasympathetic stimuli surgery of the parasympathetic system has been resorted to in the treatment of colitis hyperhidrosis and of peptic ulcer the results obtained by surgical procedures are not always entirely satisfactory and in general they are now reserved for certain specific or limited indications at the basis of medical treatment of the Paris epatha tonic conditions lies a determination of the degree of stress to which the patient is subjected when an estimate of the stress has been made dosages the anticholinergic drug is prescribed accordingly and a lesser dosage will not adequately offset the imbalance needless to say the patient should have the benefit of other forms of treatment such as diet rest and relaxation which are usually a part of these treatment programs as regards specific therapy with probe and fine clinical evidence indicates that the average patient will be adequately treated by the administration of one 15 milligram tablet with meals and two tablets at bedtime those patients with severe evidence of Paris and potato nia will require an increased dosage and as much as eight tablets or more per day may be safely prescribed all patients should have the benefit of antacid medication diet rest and relaxation as needed another consideration in the clinical use of these drugs is that of maintenance dosage it is readily understood that in most of these patients their basic factor of stress is still present even after the disease manifestation is brought under control there for maintenance dosage of approximately one-half the therapeutic dose is commonly recommended after adequate evidence of control or healing is obtained from a practical standpoint this maintenance dosage maybe two or three tablets daily thus the therapeutic principles involved in medication with anticholinergic drugs such as probe and fine our first dosage to fit the degree of stress effects operative in the individual patient and second maintenance dosage if the original stress has not been eliminated or resolved these newer therapeutic agents represent a major advance in our ability to control disease conditions and their development has gone hand in hand with a better understanding of the etiologic factors operative in disease and health they are properly used possible and every for the medical profession to serve humanity better