The Central Control of Vomiting

In addition to agents that stimulate or irritate the stomach, many other factors may be responsible for inducing emesis centrally. The central control of vomiting is vested in two areas  

The vomiting center, which is located in the lateral reticular formation in the midst of a group of cells governing such activities as salivation and respiration 

The chemoreceptor trigger zone, which is a narrow strip along the floor of the fourth ventricle located close to the vomiting center 

The vomiting center is activated by impulses that originate from the gastrointestinal tract and other peripheral structures. In addition, there are unidentified tracts that extend from the cerebral cortex to the vomiting center, such that emotional trauma and unpleasant olfactory and visual stimuli may cause nausea and vomiting. 

FIGURE 18.4 Pharmacologist s view of emetic stimuli. Myriad signaling pathways lead from the periphery to the emetic center. Stimulants of these pathways are noted in italics. These pathways involve specific neurotransmitters and their receptors (bold text). Receptors are shown for dopamine, D acetylcholine (muscarinic), M histamine, H and 5-hydroxytryptamine, 5-HT. Some of these receptor types also may mediate signaling in the emetic center. This knowledge offers a rationale for current antiemetic therapy. 

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These include atropine, scopolamine (hyoscine), trihexyphenidyl (benzhexol) and benzatropine. They block central muscarinic receptors involved in various afferent pathways of the vomiting reflex (Fig. 1). They have been used to control motion sickness, emesis in Meniere s disease and postoperative vomiting. Currently, hyoscine is largely restricted to the treatment of motion sickness where it has a fast onset of action but a short duration (4-6 h). Administration of hyoscine by transdermal patch produces a prolonged, low-level release of the drug with minimal side effects. To control postoperative vomiting, it should be applied >8 h before emesis is anticipated. 

Nevertheless it must also be expected that anything which increases DA function not only controls extrapyramidal function but also reproduces the other central effects of DA i.e. vomiting, a reduction in prolactin secretion and some psychotic manifestations. In excess it may also cause dyskinesias. Despite these problems, the therapy of PD is one of the success stories of neurology. 

Another important side effect of all opiates on the central nervous system is respiratory depression. This is caused by an inhibitory effect on the brain stem, which is the part of the brain that controls breathing and other involuntary bodily systems such as heart beat, etc. Like nausea and vomiting, people who take methadone and other opiates normally develop a tolerance to this side effect. However, even people who have taken methadone for a long period of time can develop major respiratory depression. 

Selective 5-HT3 receptor antagonists have potent antiemetic properties that are mediated mainly through peripheral 5-HT3 receptor blockade on intestinal vagal afferents. In addition, central 5-HT3 receptor blockade in the vomiting center and chemoreceptor trigger zone probably plays an important role. The antiemetic action of these agents is restricted to emesis attributable to vagal stimulation other emetic stimuli such as motion sickness are poorly controlled. 

Following the ingestion of a large dose of pseudoephedrine, dogs and cats may exhibit hyperactivity, mydriasis, depression, vomiting, hyperthermia, disorientation, bradycardia, and tachycardia. Therapy is directed at prevention of absorption and control of tachyarrhythmias with lidocaine (dogs only) or procainamide (dogs only). Diazepam may be used for symptoms associated with central nervous system (CNS) stimulation. 

Buclizine (50 mg p.o. 30 minutes prior to travel) is a centrally acting antiemetic agent used for the control of the nausea, vomiting, and dizziness of motion sickness. Buclizine depresses conduction in vestibular-cerebellar pathways and hence reduces labyrinth excitability (antivertigo action), and it inhibits the chemotrigger zone for emesis (antiemetic action) (see also Figures 73 and 81). 

Carbidopa is often coadministered with L-dopa to reduce the amount of l-dopa converted to dopamine in the periphery. Carbidopa thereby increases l-dopa s effectiveness and reduces its associated side effects, including nausea, vomiting, and loss of appetite. This compound blocks the action of the enzyme dopa-decarboxylase, which converts L-dopa into dopamine. Controlled-release Sinemet is a combination of L-dopa and carbidopa, with an extended half-life of immediate-acting combination products, producing an increased duration of effect. A combination of immediate-acting and controlled-release L-dopa and carbidopa is often used. In a number of patients, administration of the controlled-release pill only results in an insufficient conversion of central dopamine (93). The most common side effects associated with the administration of l-... 

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