Alcohol withdrawal pathophysiology: Difference between revisions
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'''For patient information click [[Alcohol withdrawal (patient information)|here]].''' | '''For patient information click [[Alcohol withdrawal (patient information)|here]].''' | ||
{{CMG}}; {{AE}} {{ADI}} | {{CMG}}; {{AE}} {{SHA}} {{ADI}} | ||
== Pathophysiology == | == Pathophysiology == | ||
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* Elevated [[norepinephrine]] has been found in the [[CSF]] patients in acute alcohol withdrawal. It is postulated that there is a decreased amount of alpha 2-receptors, resulting in less inhibition of [[presynaptic]] [[norepinephrine]] release. | * Elevated [[norepinephrine]] has been found in the [[CSF]] patients in acute alcohol withdrawal. It is postulated that there is a decreased amount of alpha 2-receptors, resulting in less inhibition of [[presynaptic]] [[norepinephrine]] release. | ||
==Overview== | |||
Under normal conditions in the brain, there is a balance between [[excitatory neurotransmitters]] such as [[glutamate]] and [[inhibitory neurotransmitters]] such as [[GABBA| gamma-aminobutyric acid (GABA)]]. Chronic [[alcohol]] intake and acute discontinuation of [[alcohol]] intake affect the balance of the [[neurotransmitters]] and cause many of the [[symptoms]] observed in [[alcohol]] withdrawal. | |||
==Pathophysiology== | |||
Under normal conditions in the brain, there is a balance between [[excitatory neurotransmitters]] such as [[glutamate]] and [[inhibitory neurotransmitters]] such as [[GABBA| gamma-aminobutyric acid (GABA)]].<ref name="pmid15706727">{{cite journal| author=Saitz R| title=Introduction to alcohol withdrawal. | journal=Alcohol Health Res World | year= 1998 | volume= 22 | issue= 1 | pages= 5-12 | pmid=15706727 | doi= | pmc=6761824 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15706727 }} </ref> | |||
Chronic [[alcohol]] intake and acute discontinuation of [[alcohol]] intake affect the balance of the [[neurotransmitters]] and cause many of the [[symptoms]] observed in [[alcohol]] withdrawal.<ref name="pmid25666543">{{cite journal| author=Mirijello A, D'Angelo C, Ferrulli A, Vassallo G, Antonelli M, Caputo F | display-authors=etal| title=Identification and management of alcohol withdrawal syndrome. | journal=Drugs | year= 2015 | volume= 75 | issue= 4 | pages= 353-65 | pmid=25666543 | doi=10.1007/s40265-015-0358-1 | pmc=4978420 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25666543 }} </ref> <ref name="pmid26861990">{{cite journal| author=Schmidt KJ, Doshi MR, Holzhausen JM, Natavio A, Cadiz M, Winegardner JE| title=Treatment of Severe Alcohol Withdrawal. | journal=Ann Pharmacother | year= 2016 | volume= 50 | issue= 5 | pages= 389-401 | pmid=26861990 | doi=10.1177/1060028016629161 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26861990 }} </ref><ref name="pmid32256131">{{cite journal| author=Wolf C, Curry A, Nacht J, Simpson SA| title=Management of Alcohol Withdrawal in the Emergency Department: Current Perspectives. | journal=Open Access Emerg Med | year= 2020 | volume= 12 | issue= | pages= 53-65 | pmid=32256131 | doi=10.2147/OAEM.S235288 | pmc=7093658 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32256131 }} </ref><ref name="pmid15706727">{{cite journal| author=Saitz R| title=Introduction to alcohol withdrawal. | journal=Alcohol Health Res World | year= 1998 | volume= 22 | issue= 1 | pages= 5-12 | pmid=15706727 | doi= | pmc=6761824 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15706727 }} </ref> | |||
'''Acute Alcohol Consumption''' | |||
* Increases the [[GABA neurotransmitter]] and sensitivity of [[GABA-A receptor]] subtypes, which in turn, increases [[inhibitory neurotransmission]]. | |||
* Prevents the effects of [[glutamate]] (an [[excitatory neurotransmitter]]) on the [[NMDA receptors|N-methyl-d-aspartate (NMDA) receptors]] by inhibiting the binding of [[glycine]] to the [[NMDA receptors]].<ref name="Goodman 2011 p. ">{{cite book | last=Goodman | first=Louis | title=Goodman & Gilman's pharmacological basis of therapeutics | publisher=McGraw-Hill | publication-place=New York | year=2011 | isbn=978-0-07-162442-8 | oclc=498979404 | page=}}</ref><ref name="Nelson 2011 p. ">{{cite book | last=Nelson | first=Lewis | title=Goldfrank's toxicologic emergencies | publisher=McGraw-Hill Medical | publication-place=New York | year=2011 | isbn=978-0-07-160594-6 | oclc=470694511 | page=}}</ref> | |||
'''Chronic Alcohol Consumption''' | |||
* Causes [[tolerance]] and compensation by [[downregulation]] [[GABA-A receptor]]s and [[upregulating]] [[NMDA receptors]], and requires higher [[blood]] levels of [[alcohol]] to cause the same effect.<ref name="Goodman 2011 p. ">{{cite book | last=Goodman | first=Louis | title=Goodman & Gilman's pharmacological basis of therapeutics | publisher=McGraw-Hill | publication-place=New York | year=2011 | isbn=978-0-07-162442-8 | oclc=498979404 | page=}}</ref><ref name="Nelson 2011 p. ">{{cite book | last=Nelson | first=Lewis | title=Goldfrank's toxicologic emergencies | publisher=McGraw-Hill Medical | publication-place=New York | year=2011 | isbn=978-0-07-160594-6 | oclc=470694511 | page=}}</ref> | |||
'''Alcohol Withdrawal in Chronic Alcohol Consumption''' | |||
* Exposes the [[downregulation]] of [[GABA-A receptors]] and the [[upregulation]] of [[NMDA receptors]], resulting in [[hyperexcitability]] of the [[neurons]] that lower the threshold for [[seizures]].<ref name="pmid25666543">{{cite journal| author=Mirijello A, D'Angelo C, Ferrulli A, Vassallo G, Antonelli M, Caputo F | display-authors=etal| title=Identification and management of alcohol withdrawal syndrome. | journal=Drugs | year= 2015 | volume= 75 | issue= 4 | pages= 353-65 | pmid=25666543 | doi=10.1007/s40265-015-0358-1 | pmc=4978420 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25666543 }} </ref><ref name="pmid12724485">{{cite journal| author=Kosten TR, O'Connor PG| title=Management of drug and alcohol withdrawal. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 18 | pages= 1786-95 | pmid=12724485 | doi=10.1056/NEJMra020617 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12724485 }} </ref><ref name="pmid9217770">{{cite journal| author=Hall W, Zador D| title=The alcohol withdrawal syndrome. | journal=Lancet | year= 1997 | volume= 349 | issue= 9069 | pages= 1897-900 | pmid=9217770 | doi=10.1016/S0140-6736(97)04572-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9217770 }} </ref> | |||
* [[Upregulation]] of [[noradrenergic]] and [[dopaminergic]] receptors cause the [[autonomic]] hyperactivity and [[hallucinations]] that are seen in patients with [[alcohol withdrawal]].<ref name="pmid17986499">{{cite journal| author=McKeon A, Frye MA, Delanty N| title=The alcohol withdrawal syndrome. | journal=J Neurol Neurosurg Psychiatry | year= 2008 | volume= 79 | issue= 8 | pages= 854-62 | pmid=17986499 | doi=10.1136/jnnp.2007.128322 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17986499 }} </ref> | |||
* Kindling is increased [[excitability]] and sensitivity of the [[neurons]] after repeated events of [[alcohol]] withdrawal,<ref name="pmid9872344">{{cite journal| author=Lejoyeux M, Solomon J, Adès J| title=Benzodiazepine treatment for alcohol-dependent patients. | journal=Alcohol Alcohol | year= 1998 | volume= 33 | issue= 6 | pages= 563-75 | pmid=9872344 | doi=10.1093/alcalc/33.6.563 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9872344 }} </ref><ref name="pmid11584152">{{cite journal| author=Reoux JP, Saxon AJ, Malte CA, Baer JS, Sloan KL| title=Divalproex sodium in alcohol withdrawal: a randomized double-blind placebo-controlled clinical trial. | journal=Alcohol Clin Exp Res | year= 2001 | volume= 25 | issue= 9 | pages= 1324-9 | pmid=11584152 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11584152 }} </ref> and is suggested to be the reason for progressing from milder to more severe [[symptoms]] of [[alcohol]] withdrawal in some patients.<ref name="pmid25666543">{{cite journal| author=Mirijello A, D'Angelo C, Ferrulli A, Vassallo G, Antonelli M, Caputo F | display-authors=etal| title=Identification and management of alcohol withdrawal syndrome. | journal=Drugs | year= 2015 | volume= 75 | issue= 4 | pages= 353-65 | pmid=25666543 | doi=10.1007/s40265-015-0358-1 | pmc=4978420 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25666543 }} </ref> | |||
==References== | ==References== | ||
Revision as of 13:27, 13 November 2020
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[2] Aditya Govindavarjhulla, M.B.B.S. [3]
Pathophysiology
- Prolonged exposure to alcohol results in inhibition of the inhibitory GABA A-type and NMDA-type glutamate receptors located in the CNS. Without the alcohol, greater CNS excitability results, due to lack of inhibition on the CNS inhibitory receptors by alcohol.
- Elevated norepinephrine has been found in the CSF patients in acute alcohol withdrawal. It is postulated that there is a decreased amount of alpha 2-receptors, resulting in less inhibition of presynaptic norepinephrine release.
Overview
Under normal conditions in the brain, there is a balance between excitatory neurotransmitters such as glutamate and inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA). Chronic alcohol intake and acute discontinuation of alcohol intake affect the balance of the neurotransmitters and cause many of the symptoms observed in alcohol withdrawal.
Pathophysiology
Under normal conditions in the brain, there is a balance between excitatory neurotransmitters such as glutamate and inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA).[1] Chronic alcohol intake and acute discontinuation of alcohol intake affect the balance of the neurotransmitters and cause many of the symptoms observed in alcohol withdrawal.[2] [3][4][1]
Acute Alcohol Consumption
- Increases the GABA neurotransmitter and sensitivity of GABA-A receptor subtypes, which in turn, increases inhibitory neurotransmission.
- Prevents the effects of glutamate (an excitatory neurotransmitter) on the N-methyl-d-aspartate (NMDA) receptors by inhibiting the binding of glycine to the NMDA receptors.[5][6]
Chronic Alcohol Consumption
- Causes tolerance and compensation by downregulation GABA-A receptors and upregulating NMDA receptors, and requires higher blood levels of alcohol to cause the same effect.[5][6]
Alcohol Withdrawal in Chronic Alcohol Consumption
- Exposes the downregulation of GABA-A receptors and the upregulation of NMDA receptors, resulting in hyperexcitability of the neurons that lower the threshold for seizures.[2][7][8]
- Upregulation of noradrenergic and dopaminergic receptors cause the autonomic hyperactivity and hallucinations that are seen in patients with alcohol withdrawal.[9]
- Kindling is increased excitability and sensitivity of the neurons after repeated events of alcohol withdrawal,[10][11] and is suggested to be the reason for progressing from milder to more severe symptoms of alcohol withdrawal in some patients.[2]
References
- ↑ 1.0 1.1 Saitz R (1998). "Introduction to alcohol withdrawal". Alcohol Health Res World. 22 (1): 5–12. PMC 6761824 Check
|pmc=value (help). PMID 15706727. - ↑ 2.0 2.1 2.2 Mirijello A, D'Angelo C, Ferrulli A, Vassallo G, Antonelli M, Caputo F; et al. (2015). "Identification and management of alcohol withdrawal syndrome". Drugs. 75 (4): 353–65. doi:10.1007/s40265-015-0358-1. PMC 4978420. PMID 25666543.
- ↑ Schmidt KJ, Doshi MR, Holzhausen JM, Natavio A, Cadiz M, Winegardner JE (2016). "Treatment of Severe Alcohol Withdrawal". Ann Pharmacother. 50 (5): 389–401. doi:10.1177/1060028016629161. PMID 26861990.
- ↑ Wolf C, Curry A, Nacht J, Simpson SA (2020). "Management of Alcohol Withdrawal in the Emergency Department: Current Perspectives". Open Access Emerg Med. 12: 53–65. doi:10.2147/OAEM.S235288. PMC 7093658 Check
|pmc=value (help). PMID 32256131 Check|pmid=value (help). - ↑ 5.0 5.1 Goodman, Louis (2011). Goodman & Gilman's pharmacological basis of therapeutics. New York: McGraw-Hill. ISBN 978-0-07-162442-8. OCLC 498979404.
- ↑ 6.0 6.1 Nelson, Lewis (2011). Goldfrank's toxicologic emergencies. New York: McGraw-Hill Medical. ISBN 978-0-07-160594-6. OCLC 470694511.
- ↑ Kosten TR, O'Connor PG (2003). "Management of drug and alcohol withdrawal". N Engl J Med. 348 (18): 1786–95. doi:10.1056/NEJMra020617. PMID 12724485.
- ↑ Hall W, Zador D (1997). "The alcohol withdrawal syndrome". Lancet. 349 (9069): 1897–900. doi:10.1016/S0140-6736(97)04572-8. PMID 9217770.
- ↑ McKeon A, Frye MA, Delanty N (2008). "The alcohol withdrawal syndrome". J Neurol Neurosurg Psychiatry. 79 (8): 854–62. doi:10.1136/jnnp.2007.128322. PMID 17986499.
- ↑ Lejoyeux M, Solomon J, Adès J (1998). "Benzodiazepine treatment for alcohol-dependent patients". Alcohol Alcohol. 33 (6): 563–75. doi:10.1093/alcalc/33.6.563. PMID 9872344.
- ↑ Reoux JP, Saxon AJ, Malte CA, Baer JS, Sloan KL (2001). "Divalproex sodium in alcohol withdrawal: a randomized double-blind placebo-controlled clinical trial". Alcohol Clin Exp Res. 25 (9): 1324–9. PMID 11584152.