Sympathetic nervous system blocking

Sympatholytic drugs are a group of drugs, which decrease the activity of the sympathetic nervous system, mainly by blocking the action of adrenaline and noradrenaline at adrenoceptors. 

We will conclude this chapter by referring to a term often used for those symptomatic drugs inhibiting the action of the autonomic nervous system by interfering with the effect of the chemical mediators involved. There are two groups. (1) Para-sympatholytic drugs block the action of acetylcholine. These are included within the wider class of spasmolytics which, as the name suggests, check or eliminate spasms. (2) Sympatholytics inhibit the action of adrenaline, noradrenaline and the sympathetic 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. 

Tachycardia/Angina Minoxidil increases heart rate this can be prevented by coadministration of a -adrenergic blocking drug or other sympathetic nervous system suppressants. In addition, angina may worsen or appear for the first time... 

The sympatholyfics of this type interfere with the /3i- and /S2-adrenoceptor subtypes. Via this mechanism the stimulating influence of the sympathetic nervous system on the heart and the metabolism and its inhibiting influence on smooth muscle is blocked. /3-Adrenoceptor blocking agents, or /3-blockers, mostly have a typical isoproterenol-like structure with an isopropylamine or a tertiary butylamine group and a substituted phenoxy moiety bound to the isopropanol backbone. The substituents determine the physicochemical properties of the particular drug and thereby its pharmacokinetic proflle. 

Patients with anxiety have a variety of psychic and somatic symptoms. The peripheral manifestations of anxiety may include a number of symptoms (e.g., palpitations) that are due in part to overactivity of the sympathetic nervous system. The 3-blocking agents may offer some benefit in the treatment of anxiety. 

Unlike isoflurane, desflurane may stimulate the sympathetic nervous system at concentrations above 1 MAC. Sudden and unexpected increases in arterial blood pressure and heart rate have been reported in some patients, accompanied by increases in plasma catecholamine and vasopressin concentrations and increased plasma renin activity. These pressor effects may increase morbidity or mortality in susceptible patients. The mechanism of sympathetic activation is unclear but does not appear to be baroreceptor-mediated. Clonidine, esmolol, fentanyl and propofol partially block the response but lignocaine (lignocaine) is ineffective. 

Blood vessels receive chiefly vasoconstrictor fibers from the sympathetic nervous system therefore, ganglionic blockade causes a marked decrease in arteriolar and venomotor tone. The blood pressure may fall precipitously because both peripheral vascular resistance and venous return are decreased (see Figure 6-7). Hypotension is especially marked in the upright position (orthostatic or postural hypotension), because postural reflexes that normally prevent venous pooling are blocked. 

Several drugs that interfere with the sympathetic nervous system inhibit the secretion of renin. Examples are clonidine and propranolol. Clonidine inhibits renin secretion by causing a centrally mediated reduction in renal sympathetic nerve activity, and it may also exert a direct intrarenal action. Propranolol and other 13-adrenoceptor-blocking drugs act by blocking the intrarenal and extrarenal 3 receptors involved in the neural control of renin secretion. 

Cocaine inhibits the presynaptic reuptake of the neurotransmitters norepinehrine, serotonin, and dopamine at synaptic junctions. This results in increased concentrations in the synaptic cleft. Since norepinephrine acts within the sympathetic nervous system, increased sympathetic stimulation is produced. Physiological effects of this stimulation include tachycardia, vasoconstriction, mydriasis, and hyperthermia.3 CNS stimulation results in increased alertness, diminished appetite, and increased energy. The euphoria or psychological stimulation produced by cocaine is thought to be related to the inhibition of serotonin and dopamine reuptake. Cocaine also acts as a local anesthetic due to its ability to block sodium channels in neuronal cells.3... 

Recall that scopolamine, an ingredient in henbane, blocks muscarinic acetylcholine receptors. This blockade essentially removes the influence of the parasympathetic nervous system on the body. In the absence of this influence, the balance of forces is upset and the sympathetic nervous system gains the upper hand thus, your heart rate increases, your pupils dilate, salivation stops, your ability to urinate is impaired, and you become constipated overall, things get very uncomfortable. But none of this is directly lethal (unless the constipation makes one commit suicide). If you do die from an overdose of henbane, it is believed to result from either a complex series of events in your brain that lead to the loss of control of your diaphragm, causing death from asphyxiation, or from cardiac arrest. This is why the deadly nightshade is so deadly and how Shakespeare chose to kill King Hamlet with henbane. 

Drugs that block beta-1 receptors on the myocardium are one of the mainstays in arrhythmia treatment. Beta blockers are effective because they decrease the excitatory effects of the sympathetic nervous system and related catecholamines (norepinephrine and epinephrine) on the heart.5,28 This effect typically decreases cardiac automaticity and prolongs the effective refractory period, thus slowing heart rate.5 Beta blockers also slow down conduction through the myocardium, and are especially useful in controlling function of the atrioventricular node.21 Hence, these drugs are most effective in treating atrial tachycardias such as atrial fibrillation.23 Some ventricular arrhythmias may also respond to treatment with beta blockers. 

Beta-blocking drugs (eg, propranolol) may be used as antianxiety agents in situations such as performance anxiety. The sympathetic nervous system overactivity associated with anxiety appears to be satisfactorily relieved by the fblockers, and a slight improvement in the nonsomatic components of anxiety may also occur. Adverse central nervous system effects of propranolol include lethargy, vivid dreams, and hallucinations. 

Multiple sites in the CNS are affected by LSD. The drug shows serotonin (5-HT) agonist activity at presynaptic receptors in the midbrain, binding to both 5-HT and 5-HT2 receptors. Activation of the sympathetic nervous system occurs, which causes pupillary dilation, increased blood pressure, piloerection, and increased body temperature. Taken orally, low doses of LSD can induce hallucinations with brilliant colors, and mood alteration occurs. Tolerance and physical dependence have occurred, but true dependence is rare. Adverse effects include hyperreflexia, nausea, and muscular weakness. Sometimes high doses produce long-lasting psychotic changes in susceptible individuals. Haloperidol (see p. 127) and other neuroleptics can block the hallucinatory action of LSD and quickly abort the syndrome. 

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