Parasympathetic stimulants

Local adverse reactions associated with administration of tiie cycloplegic mydriatics include increased IOP, transient stinging or burning, and irritation with prolonged use (eg, conjunctivitis, edema, exudates). Systemic adverse reactions include dryness of the mouth and skin, blurred vision, photophobia, corneal staining, tachycardia, headache, parasympathetic stimulation, and somnolence. 

During phase I, each seizure causes a sharp increase in autonomic activity with increases in epinephrine, norepinephrine, and steroid plasma concentrations, resulting in hypertension, tachycardia, hyperglycemia, hyperthermia, sweating, and salivation. Cerebral blood flow is also increased to preserve the oxygen supply to the brain during this period of high metabolic demand. Increases in sympathetic and parasympathetic stimulation with muscle hypoxia can lead to ventricular arrhythmias, severe acidosis, and rhabdomyolysis. These, in turn, could lead to hypotension, shock, hyperkalemia, and acute tubular necrosis. 

Tissue Sympatheticreceptor Sympathetic stimulation Parasympathetic stimulation... 

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. 

The autonomic nervous system (ANS) modifies contractile activity of both types of smooth muscle. As discussed in Chapter 9, the ANS innervates the smooth muscle layer in a very diffuse manner, so neurotransmitter is released over a wide area of muscle. Typically, the effects of sympathetic and parasympathetic stimulation in a given tissue oppose each other one system enhances contractile activity while the other inhibits it. The specific effects (excitatory or inhibitory) that the two divisions of the ANS have on a given smooth muscle depend upon its location. 

Parasympathetic stimulation causes a decrease in heart rate. Acetylcholine, which stimulates muscarinic receptors, increases the permeability to potassium. Enhanced K+ ion efflux has a twofold effect. First, the cells become hyperpolarized and therefore the membrane potential is farther away from threshold. Second, the rate of pacemaker depolarization is decreased because the outward movement of K+ ions opposes the effect of the inward movement of Na+ and Ca++ ions. The result of these two effects of potassium efflux is that it takes longer for the SA node to reach threshold and generate an action potential. If the heart beat is generated more slowly, then fewer beats per minute are elicited. 

Parasympathetic stimulation decreases heart rate. Acetylcholine, the neurotransmitter released from the vagus nerve (the parasympathetic nerve to the heart), binds to muscarinic receptors and causes the following effects ... 

The effects of the autonomic nervous system on MAP are summarized in Figure 15.4. The parasympathetic system innervates the SA node and the AV node of the heart. The major cardiovascular effect of parasympathetic stimulation, by way of the vagus nerves, is to decrease HR, which decreases CO and MAP. 

Because baroreceptors respond to stretch or distension of the blood vessel walls, they are also referred to as stretch receptors. A change in blood pressure will elicit the baroreceptor reflex, which involves negative feedback responses that return blood pressure to normal (see Figure 15.6). For example, an increase in blood pressure causes distension of the aorta and carotid arteries, thus stimulating the baroreceptors. As a result, the number of afferent nerve impulses transmitted to the vasomotor center increases. The vasomotor center processes this information and adjusts the activity of the autonomic nervous system accordingly. Sympathetic stimulation of vascular smooth muscle and the heart is decreased and parasympathetic stimulation of the heart is increased. As a result, venous return, CO, and TPR decrease so that MAP is decreased back toward its normal value. 

Due to parasympathetic stimulation of the salivary glands, saliva is secreted continuously at a basal rate of approximately 0.5 ml/min. Secretion may be enhanced by two types of reflexes ... 

The return of the bile salts to the liver from the small intestine is the most potent stimulus of bile secretion. In fact, these bile salts may cycle two to five times during each meal. The intestinal hormone secretin, which is released in response to acid in the duodenum, enhances aqueous alkaline secretion by the liver. Secretin has no effect on the secretion of bile salts. During the cephalic phase of digestion, before food even reaches the stomach or intestine, parasympathetic stimulation, by way of the vagus nerve, promotes bile secretion from the liver. 

Alimentary canal sympathetic dilates, parasympathetic constricts, especially the rectum (see effect of D.F.P. in treatment of post-operative paralytic ileus, p. 196). Furthermore, parasympathetic stimulates glandular secretion. 

Gastro/ntest/na/Tobacco has gastrointestinal effects that result from parasympathetic stimulation, with a net effect of increased bowel activity (Taylor 1996). Initial exposure to nicotine typically causes nausea, vomiting, and occasionally diarrhea. 

Stimulation of saliva production is under sympathetic and parasympathetic control. Parasympathetic stimulation produces a serous watery secretion, whereas sympathetic stimulation produces much thicker saliva. Drug delivery systems, therefore, should not be placed over a duct or adjacent to a salivary duct, as this may dislodge the retentive system or may result in excessive wash-out of the drug or rapid dissolution/erosion of the delivery system making it difficult to achieve high local drug concentrations. If a retentive system is placed over salivary ducts, the reduced salivary flow rate may produce less or no mucus which is required for the proper attachment of a mucoadhesive delivery device. 

C. Glaucoma as a preexisting condition does not contraindicate an AChE inhibitor. The other preexisting conditions preclude the administration of AChE inhibitors. Potentiation of parasympathetic stimulation can constrict airway smooth muscle and aggravate asthma, further weaken A-V conduction, and risk perforation of the bowel if an obstruction is present. 

Both the parasympathetic and sympathetic nervous systems provide extrinsic gastrointestinal innervation. Parasympathetic stimulation increases muscle contraction of the gut, while sympathetic stimulation inhibits contractions. Stimulation of either a- or 13-adrenoceptors will result in inhibition of contractions. The intramural nervous system consists of a myenteric (Auerbach s) plexus between the circular and longitudinal muscle areas and a submucosal (Meissner s) plexus between the muscularis mucosa and the circular muscle layers. These two plexuses contain stimulatory cholinergic neurons. 

Transient elevations in blood pressure and heart rate occur with seizures, probably as a result of increased sympathetic stimulation that leads to increases in norepinephrine levels. Hypertension or increased pretreatment heart rate are strongly predictive of peak postictal change in both heart rate and blood pressure ( 38). Increased parasympathetic stimulation decreases the heart rate as a result of inhibition of the sinoatrial node. Stimulation of the adrenal cortex leads to increased plasma corticosteroids and stimulation of the adrenal medulla, which may also contribute to increases in blood pressure and heart rate. 

The primary receptor subtypes mediating each response are listed in parentheses Ce.g., alpha-1, beta-2], +Note that all organ responses to parasympathetic stimulation are mediated via muscarinic [muse] receptors. Represents response due to sympathetic postganglionic cholinergic fibers. 

Erection occurs when adrenergic-induced sinusoid tone is antagonized by sacral parasympathetic stimulation that produces sinusoidal relaxation primarily by synthesis and release of the nonadrenergic-noncholinergic (NANC) neurotransmitter nitric oxide (NO). The contribution of acetylcholine-dependent release of NO from the vascular endothelium is uncertain. In vitro electrical stimulation of isolated corpus cavemosum strips (with or without endothelium) produces sinusoidal relaxation by release of neurotransmitters within nerve terminals that is resistant to adrenergic and cholinergic blockers. Inhibitors of the synthesis of NO or of guanosine monophosphate (GMP),... 

Correct answer = O. Bradycardia (rather than tachycardia) and decreased cardiac output result from increased parasympathetic stimulation. Since isoflurophate inhibits acetylcholinesterase and increases the concentration of acetylcholine at the synapse, it mimics (parasympathetic) stimulation. 

Seeds of Areca catechu (betel nut) (Palmae) contain the simple jV-methyltetrahydropyridine 3-carboxylic acid (jV-methyl-A -tetrahydronicotinic acid) arecaidine and arecoline (arecai-dine methyl ester) (Section 1, Appendix) that are mACh-R agonists and accordingly parasympathetic stimulants. Betel nut also yields guvacine (A -tetrahydronicotinic acid) that is an anti-epileptic GABA transport inhibitor. Conversely the jV-methyl dihydropyridone derivative ricinine from seeds of Ricinus communis (castor seed) (Euphorbiaceae) is a stimulatory agonist acting at the benzodiazepine site of the GABA(A) receptor. 

Q10 Other bronchodilator agents include nebulized ipratropium. Ipratropium is a muscarinic receptor antagonist that helps to relax bronchial smooth muscle which has contracted via parasympathetic stimulation. The xanthines theophylline and aminophylline (theophylline ethylenediamine) are alternative bronchodilator agents. These agents may act as phosphodiesterase inhibitors and, although they have been used as bronchodilators for many years, adverse CNS, GI and cardiovascular effects may limit their usefulness. 

Parasympathetic stimulation increases bronchoconstriction via muscarinic cholinoceptors. A muscarinic agonist will increase bronchoconstriction, so this drug is definitely not recommended. 

Q10 Normally, pancreatic secretion is stimulated by eating. The factors involved are both nervous and hormonal. Pancreatic secretion is increased by vagal (parasympathetic) stimulation and inhibited by sympathetic stimulation. Cholecystokinin (CCK), released from the wall of the duodenum, stimulates pancreatic juice, which is rich in enzymes. Secretin (the first hormone to be discovered, by Bayliss and Starling), which is also produced in the duodenum, stimulates a pancreatic fluid with a high bicarbonate content. 

The stimulation of sympathetic neurones contracts the radial muscles and so dilates the pupil, whilst parasympathetic stimulation causes contraction of the concentric sphincter muscle, so constricting the pupil. 

The ANS governs life-sustaining functions that are critical and too complicated for the CNS to spend time on. If we had to think about how fast our heart should beat minute to minute, how high our blood pressure should be, or when the sandwich we ate for lunch is ready to move from the stomach to the small intestine, we would be too busy to do anything else. So the ANS controls all of these activities. It is divided into two parts the sympathetic nervous system and the parasympathetic nervous system. Some effects of the sympathetic versus parasympathetic stimulation on various organs are listed in Table 1.2. 

TABLE 1.2. Some Effects of Sympathetic and Parasympathetic Stimulation on Various Bodiiy Organs... 

If the effect of P2 agonists in asthma proves insufficient, one additional therapeutic option is to add a dmg that will inhibit the cholinergic (parasympathetic) stimulation of the bronchial smooth muscle, such as ipratropium bromide . 

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