Extrapyramidal tract

The nigrostriatal pathway participates in the production of smooth physical motion. It is not the brain area that works to initiate movement, which is in the cerebral cortex (pyramidal tract) it is the region that helps one to have fluid motion (extrapyramidal tract). Although many neurotransmitters are found in this latter system, two neurotransmitters—dopamine and acetylcholine—are predominantly involved in this pathway. The brain normally maintains a relatively stable ratio of dopamine and acetylcholine in the pathway. However, when something happens to upset this ratio, problems arise. 

Certain drugs with anticholinergic effects are used for the symptomatic treatment of Parkinson s disease (paralysis agitans) and related syndromes of the extrapyramidal tracts. (Of the presently available drugs, none is useful in all cases of Parkinsonism.) Despite claims of superiority for newly introduced synthetic agents, none possesses outstanding efficacy and freedom from adverse side effects when compared clinically with atropine and scopolamine (241). 

Parkinsonism occurs as a metabolic disorder of the extrapyramidal tract involving dopamine. Namely, to keep the extrapyramidal tract functioning, a balance of the amount of acetylcholine (ACh) and dopamine is needed in Parkinsonism, dopamine is lacking. Thus, for the treatment of Parkinsonism, medication with anti-acetylcholine agents or with l-DOPA, the precursor of dopamine, in order to increase the amount of dopamine, is effective. 

AMANTADINE The nurse administers this drug for the prevention or treatment of respiratory tract illness caused by influenza A virus. Some patients are prescribed this drug to manage extrapyramidal effects caused by drugp used to treat Parkinsonism (See Chaps. 29 and 32). The nurse should protect the capsules from moisture to prevent deterioration. When the drug is administered for symptoms of influenza, it is important to start therapy within 24 to 48 hours after symptoms begin. 

The extrapyramidal motor system controls muscle movement through a system of pathways and nerve tracts that connect the cerebral cortex, basal ganglia, thalamus, cerebellum, reticular formation, and spinal neurons. Patients with PD lose dopamine neurons in the substantia nigra, which is located in the midbrain within the brain stem. The substantia... 

Figure 7.4 Summary of some of the wide array of afferent and efferent connections of midbrain dopaminergic neurons (SN/A9, RRF/A8, and VTA/A10 in center of figure). This emphasizes their potential involvement in coordination of seemingly disparate behaviors inclusive of the sleep-wake state of the organism. Abbreviations BP, blood pressure BST, bed nucleus of the stria terminalis CEA, central nucleus of the amygdala MEA, midbrain extrapyramidal area NTS, nucleus of the solitary tract O2, oxygen tension PPN, pedunculopontine tegmental nucleus RRF, retrorubral field SN, substantia nigra VTA, ventral tegmental area.

Because clozapine may block specific DA receptors, its antipsychotic activity could be consistent with an antidopaminergic mechanism of action. Conversely, clozapine does not typically induce extrapyramidal symptoms, which are presumably subserved by the A-9 system. Thus, while clozapine is known to block striatal DA receptors, in positron emission tomography (PET) studies, resolution is not sufficient to clarify effects on other tracts. Furthermore, low doses of metoclopramide, which significantly decrease the number of DA neurons spontaneously active in A-9, do not have antipsychotic effects (except at high doses) but can induce tardive dyskinesia (TD), as well as acute extrapyramidal side effects (EPS). 

The working assumption that the striatal system is only involved with extrapyramidal function (e.g., parkinsonian side effects, dystonias, and TD) and that the mesolimbic or mesocortical systems are only involved with psychosis may be an oversimplification. Many of the neuroanatomical studies on the identified dopaminergic tracts are done with rats. In the monkey, by contrast, there are many more DA tracts that are either absent in the rat or at least markedly different human systems could be different from the rat s or monkey s. Understanding the neuropharmacology of the antipsychotics is further complicated, given that neither the mesolimbic-mesocortical nor the striatal systems are homogeneous but may also include various subsystems. 

Qll Other neuroleptic agents include phenothiazines, such as chlorpromazine, promazin and thioridazine, and thioxanthines, such as flupenthixol. The non-specific blockade of dopaminergic receptors afforded by these drugs leads to development of side effects, such as endocrine dysfunction and extrapyramidal motor symptoms. The unwanted antagonism of motor tracts results in extrapyramidal side effects, such as Parkinsonism and tardive dyskinesia. The latter is associated with involuntary movements of the face, limbs and trunk. Chronic neuroleptic therapy can inhibit the release of GABA. This in turn leads to changes in mobility. 

Paradoxical behaviour effects (see above) and perceptual disorders, e.g. hallucinations, occur occasionally. Headache, giddiness, alimentary tract upset, skin rashes and reduced libido can occur. Extrapyramidal reactions, reversible by flumazenil, are rare. 

Extrapyramidal Outside the pyramidal tracts, with origin in the basal ganglia. These cell bodies are involved with starting, stopping, and smoothing out movements (Chapter 13). 

Parkinsonism (Parkinson s disease) is a chronic neurologic disorder affecting balance and motion at the extrapyramidal motor tract. Five major symptoms of Parkinsonism are ... 

Cell bodies in the substantia nigra project to the striatum, where they release DA, which inhibits GABA-ergic neurons. In Parkinson disease, the loss of DA neurons in this tract leads to excessive ACh activity — extrapyramidal dysfunction. 

Domperidone (100 mg p.o.) is an antiemetic agent that blocks selectively peripheral dopamine receptors in the chemoreceptor trigger zone for emesis, as well as those in the GI tract. Unlike metoclopramide, domperidone does not pass across the blood-brain barrier, and hence it is thought to be devoid of any extrapyramidal side effects. Clinical evidence indicates that domperidone, by blocking dopamine receptors in the wall of the Gl tract, enhances normal synchronized Gl peristalsis and motility in the proximal portion of the Gl tract (see also Figure 73). 

Extrapyramidal side-effects y-Aminobutyric acid receptor, type A Gastrointestinal tract Genitourinary... 

Parkinsonian adverse effects occur more commonly with haloperidol than with thioridazine. One possible explanation is that thioridazine exerts more pronounced blocking actions at brain muscarinic receptors. This action partly compensates for dopamine receptor blockade in the ni-grostriatal tract, so that extrapyramidal function is more effectively maintained. A second possibility (not listed) is that haloperidol has a higher affinity for dopamine D2 receptors than does thioridazine. The answer is (D). 

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