Causes
Delirium tremens is mainly caused after a long period of drinking, being stopped abruptly and experiencing withdrawal, leading to the biochemical regulation cascade. It may also be triggered by head injury, infection, or illness in people with a history of heavy use of alcohol. Yet another cause of delirium tremens is abrupt cessation of tranquilizer drugs of the barbiturate or benzodiazepine classes in a patient with a relatively strong addiction to them.
Because these tranquilizers' primary pharmacological and physiological effects stem from their manipulation of the GABA chemical and transmitter somatic system, the same endogenous neurotransmitter system affected by alcohol, delirium tremens can occur upon abrupt cessation of dosage in heavily dependent patients. These DTs are much the same as those caused by alcohol and so is the attendant withdrawal syndrome of which they are a manifestation. That is the primary reason benzodiazepines are such an effective treatment for DTs, despite also being the cause of them in many cases. Because ethanol and tranquilizers such as barbiturates and benzodiazepines function as positive allosteric modulators at GABA receptors, the brain, in its desire to equalize an unbalanced chemical system, triggers the abrupt cessation of the production of endogenous GABA. This cessation becomes more and more marked as the addiction becomes stronger and as higher doses are needed to cause intoxication. In addition to having sedative properties, GABA is an immensely important regulatory neurotransmitter that controls the heart rate, blood pressure, and seizure threshold among myriad other important autonomic nervous subsystems.
Delirium tremens is most common in people who have a history of alcohol withdrawal, especially in those who drink the equivalent of 7 to 8 US pints (3310–3790 ml or 5.83–6.66 imp pt) of beer or 1 US pint (473 ml or 16.65 imp fl oz) of distilled beverage daily. Delirium tremens also commonly affects those with a history of habitual alcohol use or alcoholism that has existed for more than 10 years.
The exact pharmacology of ethanol is not fully understood; however, it is theorized that delirium tremens is caused by the effect of alcohol on GABA receptors. Constant consumption of alcoholic beverages (and the consequent chronic sedation) causes a counterregulatory response in the brain in attempt to regain homeostasis.
This causes downregulation of these receptors, as well as an up-regulation in the production of excitatory neurotransmitters, primarily glutamate, and also such as norepinephrine, dopamine, epinephrine, and serotonin, all of which further the drinker's tolerance to alcohol. 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"; the effects of which 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 up-regulation, 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 up-regulated, contributing to the delirium and neurotoxicity (by excitotoxicity) of withdrawal. Direct measurements of central norepinephrine and its metabolites are in direct correlation to the severity of the alcohol withdrawal syndrome. It is possible that psychological (i.e., non-physical) factors also play a role, especially those of infections, malnutrition, or other underlying medical disorders, often related to alcoholism.
Read more about this topic: Delirium Tremens