#extrapyramidal

One of the difficulties of antipsychotic prescription is the event of Extrapyramidal Symptoms. These won't be quickly disposed of considering the pathophysiology of schizophrenia and the laid out component of activity of old style antipsychotics. The antipsychotics assist with further developing side effects of schizophrenia by restricting to dopamine receptors in the focal sensory system and impeding dopamine. This forestalls the basal ganglia from getting sufficient dopamine. Many medications utilized in the treatment of mental issues, for example, the neuroleptics and antidepressants antagonistically influence extrapyramidal framework capability, bringing about side effects, for example, quakes and muscle unbending nature by and large known as extrapyramidal side effects. Treatment by and large includes bringing down the portion or attempting an alternate antipsychotic yet medications may likewise be utilized explicitly to treat side effects. This survey analyzes the endeavor to wipe out extrapyramidal side effects by ages of antipsychotic drugs and their similar viability in the treatment of schizophrenia. A wide web search was completed utilizing watchwords and expressions that incorporate; Antipsychotics, Typical Antipsychotics, Atypical Antipsychotics, Dopaminergic, Extrapyramidal side effects, similar viability of Antipsychotics and Adverse Effect of Antipsychotics. This will additionally build up information and solution designs for antipsychotic drugs.

Abstract

Metoclopramide is antiemetic, antinauseant and gastric prokynetic. European medicines agency (EMA) in July 2013 has officially recommended a very restricted use of metoclopramide in children, because of serious and common neurological side effects. A 3 years old boy was admitted to our pediatric department due to altered consciousness, nausea, vomiting and dehydration. Day before he recived a one oral and one intravenous dose of Reglan (metoclopramide). Immidiately after admission he developed dramatic neurological symtoms with face and extremity muscles spasms, trismus, ophistotonus and extreme agitation. Neurological symptoms were present for about 3 hours, with periodically withdrawal and worsening. He received only symptomatic therapy and after 6 hours child was fully recovered and without complaints. Despite repeated warnings about the possible neurological side effects, metoclopramide continues to be used in children for the treatment of nausea and vomiting. If the physician is not familiar with these side effects of metoclopramide physician can easily incorrectly interpret these symptoms and diagnose it as tetany, convulsions, encephalitis, food poisoning, intoxication etc. Physicians need to follow the recommendations about indications, dosage, drug forms and way of administration of metoclopramide in children. Detailed previous medical history and drug use history is necessary for avoiding misdiagnosis, and for timely recognition and adequate treatment of metoclopramide side effects in children.

Keywords: Metoclopramide; Extrapyramidal; Side Effects; Children

Introduction

Metoclopramide(chemicalname: 4-amino-5-chloro-N-2-diethylaminoethyl-2-methoxybenzamide hydrochloride monohydrate) is antiemetic, antinauseant and gastric prokynetic. By blocking dopamine (D2) receptors, and affecting 5HT-3 receptors as antagonist and 5HT-4 receptors as agonist, metoclopramide inhibits brain vomiting center, accelerates gastric emptying and increases the resting tone of the lower esophageal sphincter. Metoclopramid administred intravenously expresses its effects after 1-3 minutes. The effect occurs 10-15 minutes after intramuscular administration, and 15-20 minutes after oral dose. Metabolism takes place in the liver, and about 80% of the drug is excreted in the urine in the first 24 hours after intake. Half-life vary from 2,5 to 6 hours. Dose of metoclopramide in children, if it must be given, should not exceede 0,10-1,15 mg/kg/8h, or 0,5mg/kg,/day.

European medicines agency (EMA) in july 2013 has officially recommended a changes to the use of metoclopramide in children. The use of metoclopramide in children now is very resticted because of serious and common neurological side effects, especially extrapyramidal disorders (acute dystonia, rigidity, hypokinesia/akinesia, dyskinesia, akathisia, tremor and paraesthesias, neurloleptic malignant syndrome). Acute dystonia is most frequent side effect in children. It includes tonic muscular contractions (face and extremity muscles), trismus, oculogyric crisis, torticollis, opisthotonus, pharyngeal muscle spasm or laryngospasm. Rigidity is increased muscle tone and steady resistance to pasive movements of the limbs. Tardive dyskinesia is characterized by involuntary choreiform movements of the tongue, face, mouth and extremities. It is side effect that appears more often in the elderly and can be permanent.

Akathisia is a subjective feeling of objective sign of muscle unrest, particulary in the lower extremities. Patient has difficulty to remaine lying and stay calm, and it can be misdiagnosed as psychiatric disorder or encephalitis. Neuroleptic malignant syndrome is rare but fatal complication. It is presented with hypertermia, skeletal muscles hypertonicity, mental changes and autonomic instability. The incidence of some of these side effects in children is 6 times higher than in adults, and it can be up to 25%. Extrapyramidal disorders can occur even at minimal dosage level, usually within 24-72 hours after taking this medicine. Typical medical history and clinical signs are sufficient for diagnosis. Other less frequent side affects of metoclopramide are elevated prolactine levels, transient hypertension, cardiac conduction disturbances, altered hepatic function test results, methaemoglobinaemia,agranulocytosis etc. Dispite recomendations for restriction of use of metoclopramide in pediatric population, we often admitt child with the information about prescribed or applied metocopramide in emergency department. While pediatricians generally comply with these recommendations, very often metoclopramide is prescribed to the children by general practitioners and physicians in emergency services [1-5].

Official recomendations of European medicines agency about use of metoclopramide in children are:

Metoclopramide is officially contrainidcated in children under 1 year of age. In children and young over 1 year of age (and under 20 years) metoclopramide is restricted to following conditions and only as second line therapy:

Vomiting associated with radiation therapy, chemotherapy or postoperative nausea and vomiting.

Assist in small bowel intubation.

Oral formulations of metoclopramide are associated with overdose, and they are not recommended in children and adolescents. If they are administred, patients should use appropriately designed graduated oral syringe to ensure accuracy.

Intravenous administration should be as slow bolus over at least 3 minutes. Metoclopramide should only be prescribed for short-term use (up to 5 days) and maximum dose in 24 hours is 0,5 mg per kg body weight. Metoclopramide should not be used in pregnancy if not clearly needed, and it is not recommended during the first three months of pregnancy unless there are compelling reasons to do so. Metoclopramide is excreted in human breast milk and its use is not recommended in nursing mothers unless the expected benefit outweighs the potential risk.

The use of metoclopramide is strictly contraindicated in patients in whom increased gastrointestinal motility might be dangerous, in patients with phaeochromocytoma, hypersensitivity to metoclopramide, procaine, procainamide, patients with porphyria or epilepsy.

Case Report

A 3 years old boy was admitted to our pediatric department due to altered consciousness, nausea, vomiting and dehydration. One day before admision started diarrhea and vomiting. A morning before he recived a single adequate therapeutic oral dose of Reglan (metoclopramide), and night before in the emergency service with intravenous crystalloids he recived one adequate therapeutic intravenous dose of Reglan. At the admission child was exhaused, somnolent, and had signs of mild to moderate dehydration. His vital signs were as following: arterial blood pressure 90/60 mmHg, pulse 100/min, respiratory rate 20/min, axillary temperature 37,5oC, capillary refilling 2-3 sec. Immidiately after admission he developed dramatic neurological symtoms with face and extremity muscles spasms, trismus, ophistotonus and extreme agitation. Child periodically complained of pain in the arms and stomach. Laboratory testing was done and intravenous rehydration with crystalloids was administred. In laboratory results we found mild metabolic acidosis and mild hypokalaemia which were not present in control laboratory testing after one hour of rehydration and potassium substitution. Stool testing has shown a positive result for Rota virus. Neurological symptoms were present for about 3 hours, with periodically withdrawal and worsening. Intravenous rehydration and electrolyte substitution were continued and after 6 hours child was fully recovered and without complaints. Control examination was performed after two days, and finding was completely normal.

Discussion

Despite repeated warnings about the possible neurological and other side effects, metoclopramide continues to be used in children for the treatment of nausea and vomiting. Metoclopramide is prescribed to the children most often by the general practitioners and doctors in the emergency services. It is the duty of pediatricians to inform these colleagues with whom they cooperate about possible side effects of metoclopramide in children. Neurological adverse effects of metoclopramide are idiosyncratic and do not depend on dosage. They can appear even at standard treatment dose, but they are more likely to appear in overdoses and have cumulative effect with repeated use. Possible explanation is that metoclopramide by blocking a specific postsynaptic dopamine receptors in basal ganglia can produce acute extrapyramidale reactions. Children, particulary females are more susceptible. Fortunately, acute reactions are usually self limited, respond well to the treatment and do not need any further evaluation and follow-up . In children most frequent neurological reactions are face and extremity muscle contractions, torticolis, opisthotonus, oculogyric crises.

Patient and parents experience these sudden and rapidly accelerated symptoms very dramaticly and should be, in case of prescribing metoclopramide, warned in advance about the possibility of developing these symptoms. If he is not familiar with these side effects of metoclopramide physician can easily incorrectly interpret these symptoms and diagnose it as tetany, convulsions, encephalitis, food poisoning, intoxication etc. Phyisicians in the first place need to take good previous medical history, and history about drug use, and than recognise these side effects and treat them properly. Recommended treatment in acute phase is to secure airway in case of upper airway obstruction because of pharyngeal muscle spasm or laryngospasm, then apply oral, intravenously or intramuscular: Diphenhydramine hydrochloride (1,25 mg/kg/dose, maximum 300 mg/day with 6 hour intervals), or benztropine mesylate (0,02-0,05 mg/kg/ dose, maximum 2 mg/kg/day and once or twice per day), or biperiden lactate (0,04 mg/kg, maximum four doses with 30 minute intervals). Midazolam can be administred in patients with convulsions, in common anticonvulsive doses.

Conclusion

Use of metoclopramide in the pediatric population should be restricted to some specific conditions such as small bowel intubation procedures, radiotherapy, chemotherapy and postoperative period associated nausea and vomiting, and only as a second line medication. Metoclopramide is contraindicated in children under one year of age. Physicians need to follow the recommendations about dosage, drug forms and way od administration of metoclopramide in children. Detail previous medical history and drug use history is necessary for avoiding misdiagnosis, and for timely recognition and adequate treatment of metoclopramide side effects in children.

For more Open Access Journals in Juniper Publishers please click on: https://juniperpublishers.com

For more articles in Academic Journal of Pediatrics & Neonatology please click on: https://juniperpublishers.com/ajpn/index.php

Extrapyramidal symptoms, also called drug-induced movement disorders, describe side effects caused by certain antipsychotics and certain drugs. These side effects include: • Involuntary or uncontrolled movements • Shivering • Muscle contractions Symptoms; it may be severe enough to affect daily life, making it difficult to walk around, communicate with others, or perform the usual tasks at work, school or home. Treatment usually helps, but some symptoms can be permanent and the sooner the treatment is, the better. What are extrapyramidal symptoms? All these symptoms can occur both in adults and children and may be severe. Early symptoms may start shortly after starting the drug. They can usually occur a few hours after the first dose and may also occur within the first few weeks. The timing may be due to a particular side effect. Delayed symptoms occur after using the drug for a while. The symptoms are as follows: Akathisia: With  akathisia, the person may feel himself / herself tense and very restless; In children this may occur as physical discomfort, agitation, anxiety or general irritability. It can be seen that continuous stepping, ie pacing, shaking legs or feet, rubbing the face, helping to alleviate restlessness. Research shows that akathisia risk increases with higher doses of medication. Symptoms are also associated with another condition called tardive dyskinesia. 5 to 36 percent of individuals using antipsychotics may develop akathisia in any way. Some drugs, including beta-blocker drugs, can help relieve symptoms. Decreasing the antipsychotic drug dose may also lead to recovery. Acute dystoniaDystonic reactions are involuntary muscle contractions. These movements are often repetitive and, inter alia, may include eye spasms or continuous blinking, dizziness, tongue sagging and contraction neck. The movements can be very short, but they can affect posture or harden the muscles for a while. Although they appear in other parts of the body, they usually affect the head and neck. Dystonia can cause painful muscular stiffness and other disorders. In addition, if the reaction affects the muscles in the throat, it can be suffocated or breathing problems may occur. Statistics indicate that 25 to 40 percent of people using antipsychotics live in acute dystonia anywhere, but they are more common in children and young adults. It usually starts within 48 hours of using an antipsychotic and usually requires treatment. Antipsychotic drug may help in the treatment of lowering the dose. Dystonic reactions can also be treated with antihistamines and drugs that treat symptoms of Parkinson's disease. parkinsonism: Parkinsonism describes symptoms similar to Parkinson's disease. The most common symptom is the hard muscles in the limbs. There may also be tremors, increased salivation, slow motion, posture, or changes in walking. Usually they start slowly a few days after the antipsychotic has been used. The dose may affect whether this side effect is improved. The severity of symptoms varies, but may affect movement and function. In 

some cases, treatment may be needed when they eventually go on their own . Treatment usually involves lowering the dose or using a different antipsychotic. Drugs used to treat symptoms of Parkinson's disease may also be used to treat symptoms of this disease. Neuroleptic Malignant Syndrome (NMS) This reaction is rare but very serious. In general, the first signs are stiff muscles, fever, then numbness or confusion. It may also experience seizures and affect the function of the nervous system. Symptoms usually occur several hours after they start using antipsychotics. Research shows that this disorder is not more than 0.02 percent. This condition can cause coma, kidney failure and death. It is most often associated with starting with an antipsychotic drug, but it is also linked to stopping or replacing drugs at the same time. The treatment includes stopping the antipsychotic agent immediately and providing supportive medical care. Emergency medical care may take two weeks or more, but complete recovery is usually possible. Tardive Dyskinesia Tardive dyskinesia is a late onset extrapyramidal symptom. It includes repetitive, involuntary facial movements, such as tongue twisting, chewing movements and lip smacking, cheek swelling. In addition, changes in walking, jerky, limb movements or shrug may also occur. Usually it does not develop until the drug is used for six months or longer and symptoms may persist despite treatment. Women are more likely to have this side effect. Conditions such as age, diabetes, symptoms of negative schizophrenia, or symptoms affecting the typical function may increase the risk. Among those using first-generation antipsychotics, this side effect can be seen up to about 30 percent. Treatment includes stopping the drug, lowering the dose, or switching to another drug. For example clozapine, Subtypes of Tardive Dyskinesia • If dystonia has occurred in the past: This subtype is more severe than acute dystonia and usually involves slower twist movements in the body, such as withdrawing on one side of the neck or body. Permanent or chronic akathisia: This refers to symptoms of akathisia, such as leg movements, arm movements, or swinging, which take one month or longer while taking the same dose of the drug. Both of these can be started later and persist despite treatment, but the types of movement associated with these symptoms may be different. Children who stop taking drugs suddenly may have withdrawal dyskinesia. These jerky and repetitive movements are usually seen in the body, neck and limbs. They usually go on their own in a few weeks, but restarting the drug and gradually decreasing the dose may reduce the symptoms.

The Molecular Mechanisms That Causes Parkinson’s Disease

What Causes Extrapyramidal Symptoms? The extrapyramidal system is a neural network that helps regulate motor control and coordination in the brain. It contains basal ganglia with a number of important structures for motor function. Basal ganglia need dopamine for proper functioning.

Antipsychotics help to improve symptoms by binding to dopamine receptors in the central nervous system and blocking dopamine. This may prevent the basal ganglia from receiving enough dopamine. As a result, extrapyramidal symptoms may develop. While the first generation antipsychotics usually cause extrapyramidal symptoms, the second-generation antipsychotics tend to occur at lower rates. These drugs have less affinity for dopamine receptors, bind loosely and block some serotonin receptors. First generation antipsychotics include: • Chlorpromazine • Haloperidol • Levomepromazine • Thioridazine • Trifluoromethylbenzamide • Perfenazine • Flupentixol • Flufenazine • Second generation antipsychotics include: • Clozapine • Risperidone • Olanzapine • Quetiapine • Paliperidone • Aripiprazole • Ziprasidone How is extrapyramidal symptoms diagnosed? It is important to pay attention to these symptoms if the person and the person they know are using antipsychotics. The drug side effects are sometimes similar to the symptoms of the condition used in the treatment of a drug, but the doctor can help in the diagnosis of symptoms. The doctor may ask for symptoms and observe the difficulties experienced by the person during his / her movement or coordination during an appointment. They may also use an assessment scale such as the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) or the Extrapyramidal Symptoms Rating Scale (ESRS). These scales can provide more information about symptoms and severity. https://www.orak11.com/index.php/what-is-the-difference-between-ketosis-and-ketoacidosis/ How is extrapyramidal symptoms treated? Treatment of extrapyramidal symptoms may be difficult. Medications can have different side effects can affect different ways and there is no way to predict the response. Usually the only treatment is to try different drugs or lower doses to see the most relief with minimal side effects. Depending on the symptoms, another type of drug may be given with antipsychotics to help treat them. Without the doctor, the drug should never adjust or change the dose. Changing the dose or drug may cause other symptoms, so the doctor should be informed about the undesirable side effects. If there is a lower dose of antipsychotic prescription, the doctor should be told to the doctor or therapist when the symptoms or other symptoms of psychosis should be treated. If hallucinations, delusions or other disturbing symptoms occur, help should be obtained immediately. These symptoms may increase the risk of harm to oneself or someone else, so the doctor may want to try a different treatment approach. Talking to the therapist can help if you experience difficulties as a result of extrapyramidal symptoms. Therapy cannot directly address side effects, but can support ways to cope when symptoms affect daily life or cause distress. In some cases, extrapyramidal symptoms may not affect the individual too much, and in some cases they may be painful or irritating.