Kindling because the substance of withdrawal refers to the neurological conditions resulting from the recurrent episodes of hypnotic sedative drugs such as alcohol and benzodiazepines. Each withdrawal resulted in more severe withdrawal symptoms than in the previous episode. Individuals with more episodes of withdrawal are at an increased risk of severe withdrawal symptoms, up to and including seizures and death. The long-term use of GABAergic-hypnotic tranquilizers causes chronic GABA receptor downregulation as well as glutamate overactivity, which can lead to drug sensitization and neurotransmitters, central nervous system hyperexitability, and excitotoxicity.
Video Kindling (sedative-hypnotic withdrawal)
Definisi
Kindling refers to the phenomenon of increasingly severe withdrawal symptoms, including an increased risk of seizures, occurring as a result of repeated withdrawal from alcohol or other hypnotic tranquilizers with associated action mode. Ethanol (alcohol) has a tolerance and withdrawal mechanism very similar to benzodiazepines, involving GABA receptors , NMDA receptors and AMPA receptors, but most studies on firewood are mainly focused on alcohol. Intensification of anxiety and other psychological symptoms of alcohol withdrawal also occur. Maps Kindling (sedative-hypnotic withdrawal)
Symptoms
Alcohol drinking parties are believed to increase impulsivity due to changes in the function of prefrontal-subcortical and orbitofrontal circuits. Binge drinking alcoholic who has undergone repeated detoxification is associated with an inability to interpret facial expressions correctly; This is believed to ignite the amygdala with distortions resulting from neurotransmission. Teenagers, women and young adults are most sensitive to the neuropsychological effects of binge drinking. Adolescence, especially early adolescence, is a developmental stage that is particularly vulnerable to neurotoxic and neurocognitive side effects of binge drinking because it becomes a significant time of brain development.
About 3 percent of people who have alcohol dependence experience psychosis during acute intoxication or withdrawal. Alcohol-related psychosis may manifest itself through the mechanism of kindling. Alcohol-related psychotic mechanisms are due to distortions to neuronal membranes, gene expression, and thiamin deficiency. It is possible in some cases that alcohol abuse through the mechanism of kindling can lead to the development of psychotic disorders induced by chronic substances, namely schizophrenia. The effects of alcohol-related psychosis include an increased risk of depression and suicide as well as psychosocial disorders.
Recurrent acute intoxication followed by acute withdrawal is associated with profound behavioral changes and neurobiological changes in some brain regions. Much documented evidence of firewood caused by repeated detoxification is associated with an increase in seizure frequency. Increased fear and anxiety and cognitive impairment are also associated with alcohol withdrawal caused by alcoholic or alcoholic binge with a recurring alcoholic withdrawal experience. Distractions caused by alcoholic binge or alcoholic detoxification lead to loss of inhibition of prefrontal cortical behavior; the prefrontal cortex is mediated by a subcortical system such as the amygdala. Loss of behavior control due to brain disorders affects individuals for alcoholism and increases the risk of alcohol abstain recurrence. This damage can also result in long-term adverse effects on emotional behavior. Impaired associative learning may make behavioral therapy that involves a conditioning approach to alcoholics less effective.
Cause
Alcohol drinking regime is associated with causing an imbalance between amino acid inhibition and excitability and changes in monoamine release in the central nervous system, which increases neurotoxicity; this can cause cognitive impairment, psychological problems, and can cause irreversible brain damage in both adult and adult teenage drinkers. Similar to party drinkers, individuals suffering from alcohol dependence develop changes to the neurotransmitter system, which occurs as a result of kindling and sensitization during withdrawal. This progressively lowers the threshold needed to cause brain damage and alcohol-related cognitive impairment, leading to changes in neurological function. The alterations in the activity of excitatory and inhibitory neurotransmitter systems are similar to those occurring in individuals suffering from limbic or temporal lobe epilepsy.
The adaptation of changes to the benzodiazepine receptor gABA A complex does not fully explain tolerance, dependence, and withdrawal from benzodiazepines. Other receptor complexes may be involved; in particular, excitatory glutamate systems are involved. Glutamate involvement in benzodiazepine dependence explains long-term potentiation as well as neuro-typeling phenomena. The use of short-acting benzodiazepines at night due to sleeping pills causes recurrent acute dependence followed by acute withdrawal. There is some evidence that a history of depression of CNS depressants (eg alcohol) increases the risk of dependence on benzodiazepines. Tolerance to drugs is generally believed to be caused by regulation of decreased receptors; However, there is very limited evidence to support this, and this hypothesis comes from studies in animals that use very high doses. In contrast, other mechanisms, such as uncoupling receptors, may play a more important role in the development of benzodiazepine dependence; this may lead to prolonged changes in the reformation of the receptor or the composition of the altered receptor subunit.
Pathophysiology
Benzodiazepines
Recurrent episodes of withdrawal benzodiazepines may produce the same neuronal binding as seen after recurrent episodes of withdrawal from alcohol, with improved neuro-stimulatory results. The glutamate system is believed to play an important role in this kindling phenomenon with the AMPA receptor which is a subtype of glutamate receptor modified by recurrent withdrawal from benzodiazepines. Changes that occur after withdrawal at AMPA receptors in animals have been found in areas of the brain that regulate the threshold of anxiety and seizures; thus firewood can cause an increase in the severity of anxiety and the seizure threshold that is lowered during repeated withdrawals. Changes in the glutamate system and GABA system can play an important role at different time points during the benzodiazepine withdrawal syndrome.
Alcohol
Bingeing can cause brain damage due to recurrent cycle of acute intoxication followed by acute drug withdrawal. Based on animal studies, regular party drinking over the long term is considered more likely to cause brain damage than chronic alcoholism (daily). This is due to a 4-5 fold increase in glutamate release in the nucleus accumbens during acute withdrawal between binges but only in doses of 3 g/kg, in 2 g/kg there is no increase in glutamate release. Conversely, during withdrawal from chronic alcoholism only an increase of 2 to 3 fold in the release of glutamate occurs. High levels of glutamate release cause chain reactions in other neurotransmitter systems. The reason that chronic alcoholism is constantly perceived by some researchers as less brain damaging than binge drinking is because tolerance develops into the effects of alcohol and irregular parties drinking periods of recurrent acute withdrawal does not occur, but there are also many alcoholics who usually drink alcohol. in binges followed by period not drinking. Excessive release of glutamate is a major cause of neuronal cell death. Glutamate causes neurotoxicity due to excitotoxicity and oxidative glutamate toxicity. Evidence from animal studies suggests that some people may be more genetically sensitive to neurotoxic and brain damage associated with binge drinking. Binge drink activates microglial cells that lead to the release of inflammatory cytokines and mediators such as tumor necrosis factor, and nitric oxide that causes neuroinflammation that causes nerve damage.
Recurrent acute withdrawal from alcohols occurring in heavy party drinkers has been shown in several studies to be associated with cognitive deficits as a result of neural firewood; twigs due to repeated withdrawal are believed to be cognitive impairment mechanisms in party drinkers and alcoholics. Neural kindling may explain the pathogenesis that advances and progressively worsens the direction of alcoholism and explains the continued alcohol abuse as a result of avoiding acute drug withdrawal symptoms that worsen with each withdrawal. Some withdrawal from alcohol is associated with long-term nonverbal memory disorders in adolescents and poor memory in adult alcoholics. Adult alcoholics who have two or more withdrawals show more frontal lobe damage than alcoholics who have a history of one or no previous alcohol withdrawal. The findings of kindling in alcoholism are consistent with the mechanism of brain damage due to binge drinking and subsequent withdrawal.
Treatment
Failure to properly manage alcohol withdrawal syndrome can lead to permanent brain damage or death.
Acamprosate, a drug used to promote abstinence from alcohol, the NMDA antagonist drug, reduces excessive glutamate activity in the central nervous system and thereby reduces the excitotoxicity and withdrawal of associated brain damage.
See also
- Alcohol withdrawal syndrome
- Binge drinking
- Kindling Model
References
Source of the article : Wikipedia
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