Delirium tremens pathophysiology: Difference between revisions
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Delirium tremens appears after a rapid reduction in the amount of [[alcohol]] being consumed by heavy drinkers, or a [[benzodiazepine withdrawal syndrome|rapid reduction of intake of benzodiazepines]] or [[barbiturates]]. If caused by alcohol, it only occurs in individuals with a history of constant, long-term alcohol consumption. Occurrence due to [[benzodiazepine withdrawal syndrome|benzodiazepine]] or barbiturate withdrawal does not require as long a period of consistent intake of such drugs. Prior use of both tranquilizers and alcohol can compound the symptoms, and while extremely rare, is the most dangerous especially if untreated. Barbiturates are generally accepted as being extremely dangerous, both due to overdose potential and addiction potential including the extreme withdrawal syndrome that usually is marked by delirium tremens upon discontinuation. | Delirium tremens appears after a rapid reduction in the amount of [[alcohol]] being consumed by heavy drinkers, or a [[benzodiazepine withdrawal syndrome|rapid reduction of intake of benzodiazepines]] or [[barbiturates]]. If caused by alcohol, it only occurs in individuals with a history of constant, long-term alcohol consumption. Occurrence due to [[benzodiazepine withdrawal syndrome|benzodiazepine]] or barbiturate withdrawal does not require as long a period of consistent intake of such drugs. Prior use of both tranquilizers and alcohol can compound the symptoms, and while extremely rare, is the most dangerous especially if untreated. Barbiturates are generally accepted as being extremely dangerous, both due to overdose potential and addiction potential including the extreme withdrawal syndrome that usually is marked by delirium tremens upon discontinuation. | ||
The exact pharmacology of ethanol is not fully understood: however, it is theorized that delirium tremens is caused by the effect of alcohol on the benzodiazepine-GABA<sub>A</sub>-chloride receptor complex for the inhibitory neurotransmitter [[Gamma-aminobutyric acid|GABA]]. Constant consumption of [[alcoholic beverage]]s (and the consequent chronic sedation) causes a counterregulatory response in the brain in attempt to re-achieve [[homeostasis]]. This causes [[downregulation]] of these [[Receptor (biochemistry)|receptor]]s, as well as an up-regulation in the production of excitatory [[neurotransmitters]] such as norepinephrine, dopamine, epinephrine, and serotonin - all of which further the drinker's tolerance to alcohol and may intensify tonic-clonic seizures. When alcohol is no longer consumed, these down-regulated GABA<sub>A</sub> receptor complexes are so insensitive to GABA that the typical amount of GABA produced has little effect; compounded with the fact that GABA normally inhibits [[action potential]] formation, there are not as many receptors for GABA to bind to - meaning that [[sympathetic nervous system|sympathetic]] activation is unopposed. This is also known as an "[[adrenergic]] storm". | The exact pharmacology of ethanol is not fully understood: however, it is theorized that delirium tremens is caused by the effect of alcohol on the benzodiazepine-GABA<sub>A</sub>-chloride receptor complex for the inhibitory neurotransmitter [[Gamma-aminobutyric acid|GABA]]. Constant consumption of [[alcoholic beverage]]s (and the consequent chronic sedation) causes a counterregulatory response in the brain in attempt to re-achieve [[homeostasis]]. This causes [[downregulation]] of these [[Receptor (biochemistry)|receptor]]s, as well as an up-regulation in the production of excitatory [[neurotransmitters]] such as norepinephrine, dopamine, epinephrine, and serotonin - all of which further the drinker's tolerance to alcohol and may intensify tonic-clonic seizures. When alcohol is no longer consumed, these down-regulated GABA<sub>A</sub> receptor complexes are so insensitive to GABA that the typical amount of GABA produced has little effect; compounded with the fact that GABA normally inhibits [[action potential]] formation, there are not as many receptors for GABA to bind to - meaning that [[sympathetic nervous system|sympathetic]] activation is unopposed. This is also known as an "[[adrenergic]] storm". Effects of this "[[adrenergic]] storm" can include (but are not limited to) [[tachycardia]], [[hypertension]], [[hyperthermia]], [[hyperreflexia]], [[diaphoresis]], [[myocardial infarction|heart attack]], [[cardiac arrhythmia]], [[stroke]], [[anxiety]], [[panic attacks]], [[paranoia]], and [[agitation]]. | ||
This is all made worse by [[excitatory neurotransmitter]] upregulation, so not only is sympathetic nervous system over-activity unopposed by GABA, there is also more of the [[serotonin]], [[norepinephrine]], [[dopamine]], [[epinephrine]], and particularly [[glutamate]]. Excitory [[NMDA receptor]]s are also upregulated, contributing to the [[delirium]] and neurotoxicity (by [[excitotoxicity]]) of withdrawal. Direct measurements of central [[norepinephrine]] and its metabolites is in direct correlation to the severity of the [[alcohol withdrawal]] syndrome. | This is all made worse by [[excitatory neurotransmitter]] upregulation, so not only is sympathetic nervous system over-activity unopposed by GABA, there is also more of the [[serotonin]], [[norepinephrine]], [[dopamine]], [[epinephrine]], and particularly [[glutamate]]. Excitory [[NMDA receptor]]s are also upregulated, contributing to the [[delirium]] and neurotoxicity (by [[excitotoxicity]]) of withdrawal. Direct measurements of central [[norepinephrine]] and its metabolites is in direct correlation to the severity of the [[alcohol withdrawal]] syndrome. | ||
Revision as of 16:06, 28 February 2013
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Vishnu Vardhan Serla M.B.B.S. [2]
Pathophysiology
Delirium tremens appears after a rapid reduction in the amount of alcohol being consumed by heavy drinkers, or a rapid reduction of intake of benzodiazepines or barbiturates. If caused by alcohol, it only occurs in individuals with a history of constant, long-term alcohol consumption. Occurrence due to benzodiazepine or barbiturate withdrawal does not require as long a period of consistent intake of such drugs. Prior use of both tranquilizers and alcohol can compound the symptoms, and while extremely rare, is the most dangerous especially if untreated. Barbiturates are generally accepted as being extremely dangerous, both due to overdose potential and addiction potential including the extreme withdrawal syndrome that usually is marked by delirium tremens upon discontinuation.
The exact pharmacology of ethanol is not fully understood: however, it is theorized that delirium tremens is caused by the effect of alcohol on the benzodiazepine-GABAA-chloride receptor complex for the inhibitory neurotransmitter GABA. Constant consumption of alcoholic beverages (and the consequent chronic sedation) causes a counterregulatory response in the brain in attempt to re-achieve homeostasis. This causes downregulation of these receptors, as well as an up-regulation in the production of excitatory neurotransmitters such as norepinephrine, dopamine, epinephrine, and serotonin - all of which further the drinker's tolerance to alcohol and may intensify tonic-clonic seizures. When alcohol is no longer consumed, these down-regulated GABAA receptor complexes are so insensitive to GABA that the typical amount of GABA produced has little effect; compounded with the fact that GABA normally inhibits action potential formation, there are not as many receptors for GABA to bind to - meaning that sympathetic activation is unopposed. This is also known as an "adrenergic storm". Effects of this "adrenergic storm" can include (but are not limited to) tachycardia, hypertension, hyperthermia, hyperreflexia, diaphoresis, heart attack, cardiac arrhythmia, stroke, anxiety, panic attacks, paranoia, and agitation.
This is all made worse by excitatory neurotransmitter upregulation, so not only is sympathetic nervous system over-activity unopposed by GABA, there is also more of the serotonin, norepinephrine, dopamine, epinephrine, and particularly glutamate. Excitory NMDA receptors are also upregulated, contributing to the delirium and neurotoxicity (by excitotoxicity) of withdrawal. Direct measurements of central norepinephrine and its metabolites is in direct correlation to the severity of the alcohol withdrawal syndrome.