LEVELS IN ALCOHOL WITHDRAWAL SYNDROME

(1)

A CROSS SECTIONAL

LEVELS IN ALCOHOL WITHDRAWAL SYNDROME

Submitted in partial fulfilment of requirements for

M.D. DEGREE

THE TAMILNADU

INSTITUTE OF INTERNAL MEDICINE MADRAS MEDICAL COLLEGE

A dissertation on

CROSS SECTIONAL STUDY ON SERUM MAGNESIUM LEVELS IN ALCOHOL WITHDRAWAL SYNDROME

Submitted in partial fulfilment of requirements for

M.D. DEGREE IN GENERAL MEDICINE BRANCH-I

OF

THE TAMILNADU Dr. M.G.R. MEDICAL UNIVERSITY CHENNAI, INDIA.

INSTITUTE OF INTERNAL MEDICINE MADRAS MEDICAL COLLEGE

CHENNAI – 600 003

MAY 2020

STUDY ON SERUM MAGNESIUM LEVELS IN ALCOHOL WITHDRAWAL SYNDROME

Submitted in partial fulfilment of requirements for

IN GENERAL MEDICINE

MEDICAL UNIVERSITY

INSTITUTE OF INTERNAL MEDICINE

(2)

CERTIFICATE

This is to certify that this dissertation entitled “A CROSS SECTIONAL STUDY ON SERUM MAGNESIUM LEVELS IN ALCOHOL WITHDRAWAL SYNDROME” submitted by Dr. R.ANITHA with Registration Number 201711001, appearing for M.D Branch-I – General Medicine Degree examination in MAY 2020 is a bonafide record of work done by her under my direct guidance and supervision in partial fulfilment of regulations of The TamilNadu Dr. M.G.R. Medical University, Chennai. I forward this to The TamilNadu Dr. M.G.R. Medical University, Chennai, Tamil Nadu, India.

Prof. Dr. T.S. SANTHI M.D., Guide & Research Supervisor, Institute of Internal Medicine, Madras Medical College &

Rajiv Gandhi Govt. General Hospital, Chennai - 3.

Prof. Dr. S. RAGUNANTHANAN, M.D., Director (I/c) and Professor,

Institute of Internal Medicine, Madras Medical College &

Rajiv Gandhi Govt. General Hospital, Chennai - 3.

Prof.Dr. R. JAYANTHI M.D.,FRCP (Glasg) The Dean

MMC & RGGGH, Chennai – 03

(3)

DECLARATION

I, Dr. R. ANITHA, REGISTRATION NO: 201711001 solemnly declare that this dissertation entitled “A CROSS SECTIONAL STUDY ON SERUM MAGNESIUM LEVELS IN ALCOHOL WITHDRAWAL SYNDROME” is done by me at Institute of Internal Medicine, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai between April 2018 to March 2019 under the guidance and supervision of my Chief Prof. Dr. T.S. SANTHI M.D. This dissertation is submitted to the Tamil Nadu Dr.M.G.R. Medical University towards the partial fulfilment of requirements for the award of M.D. Degree in General Medicine (Branch-I).

Place: Chennai-3 Date:

Dr. R. ANITHA Post graduate student, M.D., General medicine Institute of Internal Medicine MMC & RGGGH

Chennai - 03

(4)

ACKNOWLEDGEMENT

At the outset, I sincerely thank Prof. Dr. R. JAYANTHI, M.D., FRCP (Glas) Dean, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai-3 for having permitted me to use hospital data for the study.

I am grateful to Prof. Dr. S. RAGUNANTHANAN, M.D., Director (I/C) and Professor, Institute of Internal Medicine, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai-3.

I am indebted to Prof. Dr. T. S. SANTHI M.D., Professor of Medicine, Institute of Internal Medicine, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai-3 for her valuable guidance.

I would like to thank my former chief Professor Dr. G.S. SUNDARAMURTHY M.D., Assistant professors Dr. T.S. KARTHIKEYAN M.D, and Dr. B. RAMESH M.D., Internal Medicine, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai-3 for their scrutiny and support.

I would also like to thank all the professors and assistant professors of the department of Psychiatry and Biochemistry for their continuous support and expert guidance.

I express my sincere gratitude to all the patients who participated in the study.

Lastly, I thank all my professional colleagues for their support and valuable criticism.

(5)

LIST OF ABBREVIATIONS

ACTH – Adrenocorticotrophic hormone ADH – Antidiuretic hormone

AMPA – Alpha amino 3 hydroxy 5 methyl 4 isoxazolepropionic acid ANP – Atrial natriuretic peptide

ARDS – Acute respiratory distress syndrome AUD – Alcohol use disorder

CIWA-Ar – Clinical institute withdrawal assessment of alcohol scale, revised ECF – Extracellular fluid

GABA – Gamma amino butyric acid HDL – High density lipoprotein LV – Left Ventricle

NAD – Nicotinamide adenine dinucleotide NMDA – N methyl D aspartate

PTH – Parathyroid hormone RBC – Red blood cell

ROMK – Renal outer medullary potassium

TRPM – Transient receptor potential ion channels melastatin

(6)

INTRODUCTION

(8)

1

INTRODUCTION

Alcohol is the 3^rd largest risk factor for disease burden all over the world causing nearly 3.5 million deaths each year. There is a 38 percent increase in the overall alcohol consumption in the last 7 years in India. It is one of the greatest causes of poverty in India.

The threshold for development of alcohol related liver diseases in males is around 14 drinks per week while it is 7 drinks per week for females. Repetitive serious alcohol problems occur in about 20 % of men and 10 % of women in their entire lifetime.¹³

Alcohol use disorders includes an entire spectrum of diseases ranging from a cluster of behavioral and physical symptoms that includes withdrawal, tolerance and craving.

Craving refers to a strong desire to drink that makes it difficult for them to think of anything else. The individual may incur socioeconomic losses apart from the harmful side effects of alcohol on every system of the human body. Alcohol affects gastro intestinal system including hepatobiliary system, hematopoietic system, cardiovascular system and most importantly central nervous system.

The central nervous system manifestations of alcohol related illness mainly manifests because of its central depressant action.^19,20 The conditions associated with alcohol abuse includes nutritional deficiency related illness like Wernicke’s

(9)

2

encephalopathy, Korsakoff syndrome and pellagra.²¹ Direct effects of alcohol include acute intoxication and fetal alcohol syndrome. Certain diseases occur due to poorly understood pathogenesis like alcoholic neuropathy, myopathy, cerebellar degeneration, amblyopia and marchiafa - Bignami disease.

The two major issues of alcohol related illnesses are abnormalities in serum electrolytes and osmolality and alcohol withdrawal syndromes. Among alcoholics the continued urinary excretion of magnesium despite very low levels has been noted.^52,53

Apart from magnesium, characteristic electrolyte imbalances noted among these patients are hyponatremia and hypokalemia especially among cirrhotic patients with a generalized volume overload state.

Overall causes for magnesium deficiency among alcoholics include inadequate intake, malnourishment, loss during vomiting, ethanol metabolism related urinary losses. Though the mechanism is uncertain, inability of kidney to retain magnesium appears to be a major contributing factor.

(10)

AIMS AND OBJECTIVES

(11)

3

AIMS AND OBJECTIVES

1. To measure the serum magnesium levels in chronic alcoholic patients who had abstained from alcohol for a minimum period of 6 hours

2. To estimate its relation with the severity of alcohol withdrawal symptoms

(12)

REVIEW OF LITERATURE

(13)

4

REVIEW OF LITERATURE

ALCOHOL AND ITS EFFECTS

There are widespread effects on the body by direct or indirect impacts on neurochemical systems in the brain due to various toxins including alcohol. There are 20% and 10% chances of repetitive alcohol related problems for men and women respectively.^1,2 There is a reduction in lifespan by 10 years due to the alcohol use disorders.

ETHANOL

Ethanol is a two carbon alcohol which has rewarding and addictive properties because of its effects on various neurochemical systems and signaling cascades.

METABOLISM:

It is absorbed from mouth and esophagus in small amounts, from stomach and large bowel in modest amounts while the proximal part of small intestine remains the major site of absorption.¹ The blood levels of alcohol after 30 minutes of ingestion is highest i.e. when stomach is empty. The oral ingestion of ethanol results in slightly lower blood alcohol levels due to first pass metabolism by liver and gastric ADH. Factors that increase absorption are rapid gastric emptying, absence of proteins, fats and carbohydrates that might interfere with the absorption. Ethanol is excreted directly through lungs, urine or sweat but majority of it is metabolized in the liver. The enzymes primarily involved in ethanol

(14)

metabolism are aldehyde dehydrogenase, alco

P450.³ Alcohol consumption and its dependence is influenced by variations in the genes for these enzymes.

and the extent of first pass metabolism through stomach and liver rate of rise of blood alcohol concentration.

to acutely affect the cell function by interacting with the proteins and cell membranes. Acetaldehyde that is generated during its metabolism which is hig toxic and contributes to the tissue damage, formation of reactive oxygen species and a change in the redox state of liver cells.

and non-oxidative pathways. In organs like brain that do not have alcohol dehydrogenase, it is metabolized by enzymes like cytochrome P450 and catalase.

OXIDATIVE PATHWAY

The conversion of ethanol to acetaldehyde also involves an intermediate carrier of electrons NAD+ which is reduced to form NADH. Aldehyde dehydrogenase 2 enzyme metabolizes acetaldehyde to acetate and NADH. The

5

metabolism are aldehyde dehydrogenase, alcohol dehydrogenase and cytochrome Alcohol consumption and its dependence is influenced by variations in the genes for these enzymes.⁴ The speed at which alcohol is emptied from stomach and the extent of first pass metabolism through stomach and liver

rate of rise of blood alcohol concentration.^5,17 It can diffuse across cell membranes to acutely affect the cell function by interacting with the proteins and cell membranes. Acetaldehyde that is generated during its metabolism which is hig toxic and contributes to the tissue damage, formation of reactive oxygen species and a change in the redox state of liver cells.⁶ Alcohol is metabolized by oxidative oxidative pathways. In organs like brain that do not have alcohol

e, it is metabolized by enzymes like cytochrome P450 and catalase.

OXIDATIVE PATHWAY:

The conversion of ethanol to acetaldehyde also involves an intermediate carrier of electrons NAD+ which is reduced to form NADH. Aldehyde dehydrogenase 2 enzyme metabolizes acetaldehyde to acetate and NADH. The hol dehydrogenase and cytochrome Alcohol consumption and its dependence is influenced by variations in the The speed at which alcohol is emptied from stomach and the extent of first pass metabolism through stomach and liver determines the It can diffuse across cell membranes to acutely affect the cell function by interacting with the proteins and cell membranes. Acetaldehyde that is generated during its metabolism which is highly toxic and contributes to the tissue damage, formation of reactive oxygen species Alcohol is metabolized by oxidative oxidative pathways. In organs like brain that do not have alcohol e, it is metabolized by enzymes like cytochrome P450 and catalase.

The conversion of ethanol to acetaldehyde also involves an intermediate carrier of electrons NAD+ which is reduced to form NADH. Aldehyde dehydrogenase 2 enzyme metabolizes acetaldehyde to acetate and NADH. The

(15)

acetate thus formed is further oxidized to CO

liver and also depresses the central nervous system. In chronic alcoholic conditions brain starts using acetate as a source of energy.

NON OXIDATIVE PATHWAYS:

The two main non

(fatty acid ethyl esters) from reaction with fatty acid and formation of phosphatidyl ethanol from reaction with phospholipid. The latter requires the enzyme phospholipase D and is important for cellular communication.

There are different

which are implicated in the tissue damage. The consequences of which includes hypoxia to liver, formation of adducts due to interaction between byproducts of alcohol metabolism and cell components, free radi

oxygen species formation.

malondialdehyde, 4-hydroxynonal, malondialdehyde hydroxyethyl radical.

6

acetate thus formed is further oxidized to CO2. Acetate increase blood flow to liver and also depresses the central nervous system. In chronic alcoholic conditions brain starts using acetate as a source of energy.

NON OXIDATIVE PATHWAYS:

The two main non-oxidative pathways result in the formation o

(fatty acid ethyl esters) from reaction with fatty acid and formation of phosphatidyl ethanol from reaction with phospholipid. The latter requires the enzyme phospholipase D and is important for cellular communication.

There are different products that are formed from ethanol metabolism which are implicated in the tissue damage. The consequences of which includes hypoxia to liver, formation of adducts due to interaction between byproducts of alcohol metabolism and cell components, free radicle injury due to reactive oxygen species formation.⁷ The adducts that are implicated include acetaldehyde, hydroxynonal, malondialdehyde- acetaldehyde adducts, 2. Acetate increase blood flow to liver and also depresses the central nervous system. In chronic alcoholic

oxidative pathways result in the formation of FAEE (fatty acid ethyl esters) from reaction with fatty acid and formation of phosphatidyl ethanol from reaction with phospholipid. The latter requires the enzyme phospholipase D and is important for cellular communication.

products that are formed from ethanol metabolism which are implicated in the tissue damage. The consequences of which includes hypoxia to liver, formation of adducts due to interaction between byproducts of cle injury due to reactive The adducts that are implicated include acetaldehyde, acetaldehyde adducts,

(16)

EFFECTS OF ETHANOL ON PHYSIOLOGICAL SYSTEMS CARDIOVASCULAR SYSTEM

7

EFFECTS OF ETHANOL ON PHYSIOLOGICAL SYSTEMS VASCULAR SYSTEM

EFFECTS OF ETHANOL ON PHYSIOLOGICAL SYSTEMS

(17)

The relationship between alcohol consumption and cardiovascular diseases is J shaped which implies that mild amount of intake has a protective role while moderate to severe intake has adverse cardiovascular outcomes.

diseases risk is decreased in people who consume less than 30 gm of alcohol per day without episodes of heavy drinking while it is increased in people with alcohol use disorders. The mechanism by which alcohol confers a beneficial role is by its effects on blood lipids. Ethanol binds to HDL thereby decreasing the cholesterol accumulation on the arterial walls. Both systolic and diastolic blood pressure rise is seen with chronic alcohol intake. Prolongation of QT interval that is noted with alcohol consumption leads to cardiac arrhythmias. Consumption of more than 80 gm of alcohol per day for more than 5 years can predispose an individual to alcoholic cardiomyopathy which is seen at lesser dose among

8

The relationship between alcohol consumption and cardiovascular diseases is J shaped which implies that mild amount of intake has a protective role while moderate to severe intake has adverse cardiovascular outcomes.

diseases risk is decreased in people who consume less than 30 gm of alcohol per day without episodes of heavy drinking while it is increased in people with alcohol use disorders. The mechanism by which alcohol confers a beneficial role by its effects on blood lipids. Ethanol binds to HDL thereby decreasing the cholesterol accumulation on the arterial walls. Both systolic and diastolic blood pressure rise is seen with chronic alcohol intake. Prolongation of QT interval that alcohol consumption leads to cardiac arrhythmias. Consumption of more than 80 gm of alcohol per day for more than 5 years can predispose an individual to alcoholic cardiomyopathy which is seen at lesser dose among The relationship between alcohol consumption and cardiovascular diseases is J shaped which implies that mild amount of intake has a protective role while moderate to severe intake has adverse cardiovascular outcomes.⁸ Ischemic heart diseases risk is decreased in people who consume less than 30 gm of alcohol per day without episodes of heavy drinking while it is increased in people with alcohol use disorders. The mechanism by which alcohol confers a beneficial role by its effects on blood lipids. Ethanol binds to HDL thereby decreasing the cholesterol accumulation on the arterial walls. Both systolic and diastolic blood pressure rise is seen with chronic alcohol intake. Prolongation of QT interval that alcohol consumption leads to cardiac arrhythmias. Consumption of more than 80 gm of alcohol per day for more than 5 years can predispose an individual to alcoholic cardiomyopathy which is seen at lesser dose among

(18)

women.^9,10 A syndrome known as ‘holiday he

evidence of heart disease manifesting as atrial or ventricular tachyarrythmias after heavy drinking.

The interstitial fibrosis if myocardium is the cause for the diastolic dysfunction seen among patients with alcohol

asymptomatic patients with a preserved LV systolic function have ECF demonstrable evidence of LV hypertrophy.

9

ndrome known as ‘holiday heart’ occurs in individuals with no evidence of heart disease manifesting as atrial or ventricular tachyarrythmias after

The interstitial fibrosis if myocardium is the cause for the diastolic dysfunction seen among patients with alcoholic cardiomyopathy. 50 % of asymptomatic patients with a preserved LV systolic function have ECF demonstrable evidence of LV hypertrophy.

occurs in individuals with no evidence of heart disease manifesting as atrial or ventricular tachyarrythmias after

The interstitial fibrosis if myocardium is the cause for the diastolic ic cardiomyopathy. 50 % of asymptomatic patients with a preserved LV systolic function have ECF

(19)

GASTROINTESTINAL SYSTEM

The gut liver axis system emphasizes the role of intestinal flora and gut derived toxins in the development of alcoholic liver disease.

intestinal barrier dysfunction along with the overgrowth of gram negative bacteria in the intestine of chronic alcoholic patients are one of the prime factors in the development of alcoholic liver diseases.

Liver being the major organ that is involved in ethanol metabolism, is the prime target organ for the pathological effects of ethanol.

spectrum of liver injury begins with fatty infiltration which then progresses to stage of alcoholic hepatitis and then to cirrhosis and hepatocellular carcinoma.

Hepatocellular carcinoma occurs in the setting of macro nodular cirrhosis.

10 GASTROINTESTINAL SYSTEM

The gut liver axis system emphasizes the role of intestinal flora and gut in the development of alcoholic liver disease.^11,12

intestinal barrier dysfunction along with the overgrowth of gram negative bacteria in the intestine of chronic alcoholic patients are one of the prime factors in the

lic liver diseases.

Liver being the major organ that is involved in ethanol metabolism, is the prime target organ for the pathological effects of ethanol.¹³

spectrum of liver injury begins with fatty infiltration which then progresses to stage of alcoholic hepatitis and then to cirrhosis and hepatocellular carcinoma.

Hepatocellular carcinoma occurs in the setting of macro nodular cirrhosis.

The gut liver axis system emphasizes the role of intestinal flora and gut

11,12

Alcohol induced intestinal barrier dysfunction along with the overgrowth of gram negative bacteria in the intestine of chronic alcoholic patients are one of the prime factors in the

Liver being the major organ that is involved in ethanol metabolism, is the The histological spectrum of liver injury begins with fatty infiltration which then progresses to a stage of alcoholic hepatitis and then to cirrhosis and hepatocellular carcinoma.^14,15 Hepatocellular carcinoma occurs in the setting of macro nodular cirrhosis.

(20)

The main clinical features of patients in alcoholic hepatitis phase includes hepatic encephalopathy, increased prothrombin time, a rise in serum bilirubin, and also the development of renal failure in few cases. The stage of alcoholic hepatitis can be reversed with strict abstinence of alcohol. The patients with alcoholic hepatitis are treated with steroids if the maddrey’s discriminant factor is above 32.

11

The main clinical features of patients in alcoholic hepatitis phase includes hepatic encephalopathy, increased prothrombin time, a rise in serum bilirubin, and also the development of renal failure in few cases. The stage of alcoholic hepatitis rsed with strict abstinence of alcohol. The patients with alcoholic hepatitis are treated with steroids if the maddrey’s discriminant factor is above 32.

(21)

The degree of pathological injury determines the prognosis of the patient with alcoholic liver disease. The presence of co morbidities has a major effect on the adverse outcomes of these patients. Best outcome is observed among patients with fatty liver, the alcoholic hepatitis patients have intermediate outcome. The outcome is worst among patients

help in determining the need for drug therapy as indicated by the maddrey’s score in patients with alcoholic hepatitis and liver transplant for patients with alcoholic cirrhosis.

12

The degree of pathological injury determines the prognosis of the patient isease. The presence of co morbidities has a major effect on the adverse outcomes of these patients. Best outcome is observed among patients with fatty liver, the alcoholic hepatitis patients have intermediate outcome. The outcome is worst among patients with cirrhosis. These estimations of prognosis in determining the need for drug therapy as indicated by the maddrey’s score in patients with alcoholic hepatitis and liver transplant for patients with alcoholic The degree of pathological injury determines the prognosis of the patient isease. The presence of co morbidities has a major effect on the adverse outcomes of these patients. Best outcome is observed among patients with fatty liver, the alcoholic hepatitis patients have intermediate outcome. The e estimations of prognosis in determining the need for drug therapy as indicated by the maddrey’s score in patients with alcoholic hepatitis and liver transplant for patients with alcoholic

(22)

Other parts of the GIT including esophagus, stomach, intestines and pancreas are also affected by alcohol intake. It is one of the major risk factors for esophageal reflux disorders, Mallory Weiss tears and esophageal carcinoma. It can cause acute on chron

are up to 5 % gastric acid secretion is stimulated while above 5 % have no effect on the gastric acid secretion. Gastric motility is inhibited at concentrations above 15%. Heavy drinking can lead to

functional changes in the small intestine and this chronic diarrhea can result in rectal fissures or pruritis ani. These can be reversed if there is abstinence of alcohol. Pancreatitis both acute and chronic are

intake but the incidence of acute pancreatitis is 3 times higher among the alcohol use disorder patients.

13

Other parts of the GIT including esophagus, stomach, intestines and pancreas are also affected by alcohol intake. It is one of the major risk factors for esophageal reflux disorders, Mallory Weiss tears and esophageal carcinoma. It can cause acute on chronic gastritis in the stomach. When ethanol concentrations are up to 5 % gastric acid secretion is stimulated while above 5 % have no effect on the gastric acid secretion. Gastric motility is inhibited at concentrations above 15%. Heavy drinking can lead to diarrhea which can be due to structural and functional changes in the small intestine and this chronic diarrhea can result in rectal fissures or pruritis ani. These can be reversed if there is abstinence of alcohol. Pancreatitis both acute and chronic are well known effects of alcohol intake but the incidence of acute pancreatitis is 3 times higher among the alcohol Other parts of the GIT including esophagus, stomach, intestines and pancreas are also affected by alcohol intake. It is one of the major risk factors for esophageal reflux disorders, Mallory Weiss tears and esophageal carcinoma. It ic gastritis in the stomach. When ethanol concentrations are up to 5 % gastric acid secretion is stimulated while above 5 % have no effect on the gastric acid secretion. Gastric motility is inhibited at concentrations above diarrhea which can be due to structural and functional changes in the small intestine and this chronic diarrhea can result in rectal fissures or pruritis ani. These can be reversed if there is abstinence of well known effects of alcohol intake but the incidence of acute pancreatitis is 3 times higher among the alcohol

(23)

HEMATOPOEITIC SYSTEM

Ethanol use is one of the causes of macrocytic anemia. If there is associated folate deficiency, hyper segmented neutrophils are also present.

Anemia in chronic alcohol use can occur due to chronic infection, blood loss due to bleeding from varices, hyper spleenism secondary to portal hypertension, zieve syndrome presenting as hemolytic an

on the bone marrow stem cells and causing a decreased production of RBCs.

Chronic alcohol intake can cause leukopenia, decreased neutrophilic mobility and adherence. In the presence of associated immune defic

prone to infections. Thrombocytopenia is a common finding among patients with alcoholic cirrhosis or congestive splenomegaly.

14 HEMATOPOEITIC SYSTEM

Ethanol use is one of the causes of macrocytic anemia. If there is deficiency, hyper segmented neutrophils are also present.

Anemia in chronic alcohol use can occur due to chronic infection, blood loss due to bleeding from varices, hyper spleenism secondary to portal hypertension, zieve syndrome presenting as hemolytic anemia. Alcohol also exerts a direct toxic effect on the bone marrow stem cells and causing a decreased production of RBCs.

Chronic alcohol intake can cause leukopenia, decreased neutrophilic mobility and adherence. In the presence of associated immune deficiencies, it makes the patient prone to infections. Thrombocytopenia is a common finding among patients with alcoholic cirrhosis or congestive splenomegaly.¹⁶

Ethanol use is one of the causes of macrocytic anemia. If there is deficiency, hyper segmented neutrophils are also present.

Anemia in chronic alcohol use can occur due to chronic infection, blood loss due to bleeding from varices, hyper spleenism secondary to portal hypertension, zieve emia. Alcohol also exerts a direct toxic effect on the bone marrow stem cells and causing a decreased production of RBCs.

Chronic alcohol intake can cause leukopenia, decreased neutrophilic mobility and iencies, it makes the patient prone to infections. Thrombocytopenia is a common finding among patients with

(24)

CANCERS

Chronic alcohol intake is associated with a 3

cancers. Alcohol consumption is associated with cancers of oral cavity, esophagus, colorectal, pharynx, larynx and liver.

increased risk of breast cancer among chronic alcoholics. Patients with deficient ALDH2 activity are more prone to e

identified as a carcinogen among animal models. There is an important role of aberrant DNA methylation patterns among alcohol induced cancer development and progression.

CENTRAL NERVOUS SYSTEM

In the central nervous system, ethanol primarily acts as a CNS depressant.

The level of depression correlates directly with the amount ingested and absorbed, where ultimately it results in general anesthesia. Extreme toxic doses of ethanol

15

Chronic alcohol intake is associated with a 3-fold increase in the risk of Alcohol consumption is associated with cancers of oral cavity, esophagus, colorectal, pharynx, larynx and liver.¹⁸ Among women there is an increased risk of breast cancer among chronic alcoholics. Patients with deficient ALDH2 activity are more prone to esophageal cancers. Acetaldehyde has been identified as a carcinogen among animal models. There is an important role of aberrant DNA methylation patterns among alcohol induced cancer development

CENTRAL NERVOUS SYSTEM

The level of depression correlates directly with the amount ingested and absorbed, where ultimately it results in general anesthesia. Extreme toxic doses of ethanol fold increase in the risk of Alcohol consumption is associated with cancers of oral cavity, Among women there is an increased risk of breast cancer among chronic alcoholics. Patients with deficient sophageal cancers. Acetaldehyde has been identified as a carcinogen among animal models. There is an important role of aberrant DNA methylation patterns among alcohol induced cancer development

The level of depression correlates directly with the amount ingested and absorbed, where ultimately it results in general anesthesia. Extreme toxic doses of ethanol

(25)

can result in severe respiratory depression causing death. The neuro adaptive responses depend on whether the ethanol exposure was acute or chronic. Ethanol disturbs the homeostasis between excitatory and inhibitory stimuli by antagonizing excitatory NMDA or facilitating

GABA. Ethanol exerts its action via ligand gated NMDA, voltage activated K channel, large conductance calcium channels and GABA receptor operated channels. By receptor phosphorylation and trafficking mechanisms it alte

channel functions indirectly.

Alcohol use disorder is like a vicious cycle comprising of binge drinking followed by withdrawal affect and craving (preoccupation

Sustained consumption of alcohol will result in dependency and

tolerance which occurs along with the reduced sensitivity to GABA and increased sensitivity to NMDA receptors. Anti convulsant, sleep inducing, muscle

16

vere respiratory depression causing death. The neuro adaptive responses depend on whether the ethanol exposure was acute or chronic. Ethanol disturbs the homeostasis between excitatory and inhibitory stimuli by antagonizing excitatory NMDA or facilitating the inhibitory neurotransmitters like GABA. Ethanol exerts its action via ligand gated NMDA, voltage activated K channel, large conductance calcium channels and GABA receptor operated channels. By receptor phosphorylation and trafficking mechanisms it alte

channel functions indirectly.

Alcohol use disorder is like a vicious cycle comprising of binge drinking followed by withdrawal affect and craving (preoccupation

Sustained consumption of alcohol will result in dependency and

tolerance which occurs along with the reduced sensitivity to GABA and increased sensitivity to NMDA receptors. Anti convulsant, sleep inducing, muscle vere respiratory depression causing death. The neuro adaptive responses depend on whether the ethanol exposure was acute or chronic. Ethanol disturbs the homeostasis between excitatory and inhibitory stimuli by the inhibitory neurotransmitters like GABA. Ethanol exerts its action via ligand gated NMDA, voltage activated K channel, large conductance calcium channels and GABA receptor operated channels. By receptor phosphorylation and trafficking mechanisms it alters the ion

Alcohol use disorder is like a vicious cycle comprising of binge drinking followed by withdrawal affect and craving (preoccupation -anticipation).

Sustained consumption of alcohol will result in dependency and increased tolerance which occurs along with the reduced sensitivity to GABA and increased sensitivity to NMDA receptors. Anti convulsant, sleep inducing, muscle

(26)

relaxation and anti-anxiety effects of ethanol are due to the enhancement of GABA chloride channel. There is release of GABA when ethanol is consumed acutely while the same when done on a chronic basis reflects as an increase in the density of GABA A receptors. Withdrawal state of alcohol is characterized by an decreased activity of GABA. Acute into

equally important action of inhibiting the excitatory glutamate receptor NMDA.

Hence the acute effects of alcohol intoxication are characterized by enhanced GABA and diminished NMDA receptor activity while the opposite

during alcohol withdrawal state.

Apart from these two neurotransmitters, alcohol also increases serotonin levels in the synapses during acute alcohol intoxication. There is enhanced dopamine and nicotinic acetylcholine levels in the ventr

it also impacts the cannabinoid receptors which in turn leads to the release of dopamine, GABA and glutamate.

17

anxiety effects of ethanol are due to the enhancement of nel. There is release of GABA when ethanol is consumed acutely while the same when done on a chronic basis reflects as an increase in the density of GABA A receptors. Withdrawal state of alcohol is characterized by an decreased activity of GABA. Acute intoxication of alcohol has an additional equally important action of inhibiting the excitatory glutamate receptor NMDA.

Hence the acute effects of alcohol intoxication are characterized by enhanced GABA and diminished NMDA receptor activity while the opposite

during alcohol withdrawal state.

Apart from these two neurotransmitters, alcohol also increases serotonin levels in the synapses during acute alcohol intoxication. There is enhanced dopamine and nicotinic acetylcholine levels in the ventral tegmental region where it also impacts the cannabinoid receptors which in turn leads to the release of dopamine, GABA and glutamate.

anxiety effects of ethanol are due to the enhancement of nel. There is release of GABA when ethanol is consumed acutely while the same when done on a chronic basis reflects as an increase in the density of GABA A receptors. Withdrawal state of alcohol is characterized by an xication of alcohol has an additional equally important action of inhibiting the excitatory glutamate receptor NMDA.

Hence the acute effects of alcohol intoxication are characterized by enhanced GABA and diminished NMDA receptor activity while the opposite is observed

Apart from these two neurotransmitters, alcohol also increases serotonin levels in the synapses during acute alcohol intoxication. There is enhanced al tegmental region where it also impacts the cannabinoid receptors which in turn leads to the release of

(27)

There is an increase in cortisol and ACTH levels during intoxication which is linked to the rise in dopamine levels

reward during intoxication and depression during the stage when blood alcohol levels fall. Alcohol induced change in opioid receptors occurs in nucleus accumbens with the release of beta endorphins during acute

Blood alcohol levels determine the behavioral, cognitive and psychomotor changes. Death occurs at levels between 0.30 and 0.40 gm/dl. There is also a significant difference among men and women owing to the body size, body water percentages and hence the volume of distribution.

18

There is an increase in cortisol and ACTH levels during intoxication which is linked to the rise in dopamine levels and in their contribution to the feelings of reward during intoxication and depression during the stage when blood alcohol levels fall. Alcohol induced change in opioid receptors occurs in nucleus accumbens with the release of beta endorphins during acute alcohol ingestion.

Blood alcohol levels determine the behavioral, cognitive and psychomotor changes. Death occurs at levels between 0.30 and 0.40 gm/dl. There is also a significant difference among men and women owing to the body size, body water

es and hence the volume of distribution.

There is an increase in cortisol and ACTH levels during intoxication which and in their contribution to the feelings of reward during intoxication and depression during the stage when blood alcohol levels fall. Alcohol induced change in opioid receptors occurs in nucleus alcohol ingestion.

Blood alcohol levels determine the behavioral, cognitive and psychomotor changes. Death occurs at levels between 0.30 and 0.40 gm/dl. There is also a significant difference among men and women owing to the body size, body water

(28)

EFFECTS OF BLOOD ALCOHOL LEVELS IN THE ABSENCE OF TOLERANCE:

Alcohol imparts motivational properties to previously neutral stimuli. The compulsive drug seeking behavior which is frequently associated with the addiction has a 3 stage addiction cycle of intoxication, withdrawal and anticipation which reflect the incentive salience, reward deficits and executive function deficits. The activation of ventral striatum will recruit basal ganglia globus pallidus - thalamic

formation center.¹⁹ With further continued intake of alcohol tolerance occurs to the rewarding effects of alcohol. Tolerance is defined by the requirement of a higher dose of the drug to p

much lesser dosages. Tolerance is divided into acute and chronic tolerance. Acute alcohol intolerance which is otherwise known as Mellanby effect means that behavioral impairment and intoxication effects a

alcohol concentration on the ascending limb than on the descending limb. Chronic tolerance of alcohol includes both the pharmacokinetic and pharmacodynamics elements the former due to induction of alcohol metabolizing enzymes wh attained with a doubling of normal metabolic rate. Pharmacokinetic tolerance is

19

EFFECTS OF BLOOD ALCOHOL LEVELS IN THE ABSENCE OF

Alcohol imparts motivational properties to previously neutral stimuli. The compulsive drug seeking behavior which is frequently associated with the addiction has a 3 stage addiction cycle of intoxication, withdrawal and anticipation which reflect the incentive salience, reward deficits and executive function deficits. The activation of ventral striatum will recruit basal ganglia

thalamic – cortical loops which then engages the striatal habit With further continued intake of alcohol tolerance occurs to the rewarding effects of alcohol. Tolerance is defined by the requirement of a higher dose of the drug to produce the same effect which was earlier seen with much lesser dosages. Tolerance is divided into acute and chronic tolerance. Acute alcohol intolerance which is otherwise known as Mellanby effect means that behavioral impairment and intoxication effects are greater at a given blood alcohol concentration on the ascending limb than on the descending limb. Chronic tolerance of alcohol includes both the pharmacokinetic and pharmacodynamics elements the former due to induction of alcohol metabolizing enzymes wh attained with a doubling of normal metabolic rate. Pharmacokinetic tolerance is EFFECTS OF BLOOD ALCOHOL LEVELS IN THE ABSENCE OF

Alcohol imparts motivational properties to previously neutral stimuli. The compulsive drug seeking behavior which is frequently associated with the drug addiction has a 3 stage addiction cycle of intoxication, withdrawal and anticipation which reflect the incentive salience, reward deficits and executive function deficits. The activation of ventral striatum will recruit basal ganglia – cortical loops which then engages the striatal habit With further continued intake of alcohol tolerance occurs to the rewarding effects of alcohol. Tolerance is defined by the requirement of a roduce the same effect which was earlier seen with much lesser dosages. Tolerance is divided into acute and chronic tolerance. Acute alcohol intolerance which is otherwise known as Mellanby effect means that re greater at a given blood alcohol concentration on the ascending limb than on the descending limb. Chronic tolerance of alcohol includes both the pharmacokinetic and pharmacodynamics elements the former due to induction of alcohol metabolizing enzymes which is attained with a doubling of normal metabolic rate. Pharmacokinetic tolerance is

(29)

20

also known as metabolic tolerance while pharmacodynamics tolerance is called as cellular tolerance.²⁰ Behavioral tolerance is when individuals learnt to change their behavior even under the influence of alcohol to function better. Other central nervous system effects of alcohol include cognitive impairment and insomnia.

Alcoholic dementia also occurs due to shrinkage of brain due to loss of gray and white matter due to chronic heavy alcohol drinking. Overall it reduces the metabolism of brain and this hypo metabolic state is determined by the patient’s age and number of years of alcohol consumption. Chronic alcohol use is also associated with peripheral neuropathy, cerebellar degeneration or atrophy which manifests in the form of progressive unsteady stance and gait. There is atrophy of cerebellar vermis noted on neuroimaging. Two very important neuropsychiatric manifestations of alcohol use disorder are Wernicke encephalopathy and korsakoff psychosis. Wernicke encephalopathy is reversible while korsakoff is irreversible.²¹ They are not two different diseases but different stages of the same disease process. Carl Wernicke described it as a triad of mental confusion with ophthalmoplegia and gait ataxia. Among these three confusion is the most common symptom. Ataxia seen in these patients is limited to truncal ataxia and not limb ataxia. Korsakoff psychosis generally follows repeated episodes of encephalopathy or inadequately treated acute encephalopathy.²² Confabulation is a prominent feature of korsakoff psychosis especially in the early stages of the disease process. Serum thiamine and erythrocyte transketolase activity are decreased along with an elevation in the levels of serum pyruvate.

(30)

Neurological complications of alcohol abuse include the following:

Marchiafava-Bignami disease

It is a syndrome of selective demyelination of

chronic alcoholic patients. The patients frequently present with a

confusional state or dementing syndrome. Seizures, coma and hemiparesis can occur among these patients. Treatment is mainly supportive care, nutritio support and rehabilitation

Alcoholic cerebellar degeneration This is the most common form of most prominent findings among

ataxia.

21

Neurological complications of alcohol abuse include the following:

Bignami disease:

It is a syndrome of selective demyelination of the corpus callosum in alcoholic patients. The patients frequently present with a

confusional state or dementing syndrome. Seizures, coma and hemiparesis can occur among these patients. Treatment is mainly supportive care, nutritio support and rehabilitation

Alcoholic cerebellar degeneration:

This is the most common form of acquired cerebellar degeneration with the most prominent findings among these patients being broad based gait and truncal Neurological complications of alcohol abuse include the following:

the corpus callosum in alcoholic patients. The patients frequently present with an acute confusional state or dementing syndrome. Seizures, coma and hemiparesis can occur among these patients. Treatment is mainly supportive care, nutritional

acquired cerebellar degeneration with the these patients being broad based gait and truncal

(31)

NEUROENDOCRINE SYSTEM

Ethanol regulates the endocrine system by affecting the Hypothalamo pituitary-gonadal, hypothalamo

thyroid axes. Ethanol can cause impotence in males. It will also cause decreased sexual arousal, increased ejaculation. In patients with alcohol use disorder, 70%

develop sexual dysfunction. A reversible decrease

also noted among the alcoholics which disappear after a month of abstinence.

BONE

Parathyroid hormones levels decrease after acute exposure to ethanol, which in turn leads to increased loss of calcium. There is decrease in serum calcium levels due to disruption of vitamin D metabolism among chronic alcoholics. Apart from these two effec

22 NEUROENDOCRINE SYSTEM

Ethanol regulates the endocrine system by affecting the Hypothalamo gonadal, hypothalamo-pituitary-adrenal and hypothalamo

thyroid axes. Ethanol can cause impotence in males. It will also cause decreased sexual arousal, increased ejaculation. In patients with alcohol use disorder, 70%

develop sexual dysfunction. A reversible decrease in T4 levels and T3 levels are also noted among the alcoholics which disappear after a month of abstinence.

Parathyroid hormones levels decrease after acute exposure to ethanol, which in turn leads to increased loss of calcium. There is decrease in serum calcium levels due to disruption of vitamin D metabolism among chronic alcoholics. Apart from these two effects, ethanol is directly toxic to bone forming Ethanol regulates the endocrine system by affecting the Hypothalamo-

adrenal and hypothalamo-pituitary- thyroid axes. Ethanol can cause impotence in males. It will also cause decreased sexual arousal, increased ejaculation. In patients with alcohol use disorder, 70%

in T4 levels and T3 levels are also noted among the alcoholics which disappear after a month of abstinence.

Parathyroid hormones levels decrease after acute exposure to ethanol, which in turn leads to increased loss of calcium. There is decrease in serum calcium levels due to disruption of vitamin D metabolism among chronic ts, ethanol is directly toxic to bone forming

(32)

23

cells. Increased incidence of osteoporosis among patients with alcohol use disorders predispose them to increased risk of fractures

OTHER SYSTEMS

In lungs, alcohol use disorder increases the risk for ARDS and pneumonia as it interferes the pulmonary response to injury and inflammation. Chronic ethanol ingestion causes decreased muscle mass and strength resulting in skeletal muscle myopathy.

(33)

Following potassium, magnesium is the second most ab

intracellular fluid. It is the fourth abundant cation in the body. It is used as a catalyst in many reactions involved in the carbohydrate metabolism. The extracellular fluid concentration of magnesium is 1.7 to 2.3 mEq/L. Magnesium plays a major role in the regulation of mitochondrial function, immune defense, cardiac excitability, neuronal control, vasomotor tone and blood pressure.

Movement of magnesium inside and outside the cell are dependent on the carbohydrate metabolism. Beta ad

ions to move out of the cell while insulin, vitamin D and vitamin B6 will cause the entry of magnesium ions into the cells.

Magnesium ions from the diet are mainly reabsorbed from the distal small intestine and colon.²³ The absorption occurs both via passive transport process and

24

MAGNESIUM

Following potassium, magnesium is the second most abundant cation in the intracellular fluid. It is the fourth abundant cation in the body. It is used as a catalyst in many reactions involved in the carbohydrate metabolism. The extracellular fluid concentration of magnesium is 1.7 to 2.3 mEq/L. Magnesium ays a major role in the regulation of mitochondrial function, immune defense, cardiac excitability, neuronal control, vasomotor tone and blood pressure.

Movement of magnesium inside and outside the cell are dependent on the carbohydrate metabolism. Beta adrenoreceptor stimulation will cause magnesium ions to move out of the cell while insulin, vitamin D and vitamin B6 will cause the entry of magnesium ions into the cells.

Magnesium ions from the diet are mainly reabsorbed from the distal small The absorption occurs both via passive transport process and undant cation in the intracellular fluid. It is the fourth abundant cation in the body. It is used as a catalyst in many reactions involved in the carbohydrate metabolism. The extracellular fluid concentration of magnesium is 1.7 to 2.3 mEq/L. Magnesium ays a major role in the regulation of mitochondrial function, immune defense, cardiac excitability, neuronal control, vasomotor tone and blood pressure.

Movement of magnesium inside and outside the cell are dependent on the renoreceptor stimulation will cause magnesium ions to move out of the cell while insulin, vitamin D and vitamin B6 will cause

Magnesium ions from the diet are mainly reabsorbed from the distal small The absorption occurs both via passive transport process and

(34)

saturable process among which the para cellular transport accounts for 80 to 90 % of the intestinal magnesium uptake. This para cellular transport does not occur in places that lack tightening claudins. Transcellular transport of magnesium ions occurs vis TRPM6 and TRPM7 channels.

Up to 60% of ingested magnesium is absorbed which can rise up to 80%

when the intake is low. Factors interfering with magnesium absorption are high phosphate and high phytate consumption. Among the hormonal influences, growth hormone increase while calcito

reabsorption.

The elimination of magnesium is via the kidney and also minor amounts via intestinal secretion and sweat. 80% of the extracellular magnesium is ultra filterable while only 5% of the filtered load is

25

saturable process among which the para cellular transport accounts for 80 to 90 % of the intestinal magnesium uptake. This para cellular transport does not occur in k tightening claudins. Transcellular transport of magnesium ions occurs vis TRPM6 and TRPM7 channels.^23,24

when the intake is low. Factors interfering with magnesium absorption are high phosphate and high phytate consumption. Among the hormonal influences, growth hormone increase while calcitonin and aldosterone decreases magnesium

The elimination of magnesium is via the kidney and also minor amounts via intestinal secretion and sweat. 80% of the extracellular magnesium is ultra filterable while only 5% of the filtered load is excreted in the urine. The saturable process among which the para cellular transport accounts for 80 to 90 % of the intestinal magnesium uptake. This para cellular transport does not occur in k tightening claudins. Transcellular transport of magnesium ions

when the intake is low. Factors interfering with magnesium absorption are high phosphate and high phytate consumption. Among the hormonal influences, nin and aldosterone decreases magnesium

The elimination of magnesium is via the kidney and also minor amounts via intestinal secretion and sweat. 80% of the extracellular magnesium is ultra-

excreted in the urine. The

(35)

reabsorption of magnesium ions occurs in renal tubules with proximal tubule contributing to 25 %, thick ascending limb up to 65 % and distal tubule 5 %.

Hence the major site of reabsorption is the thick ascending limb of loop of where it is primarily via the

magnesium reabsorption at thick ascending limb of loop of henle.

generation of an electrical lumen positive gradient which is induced by the sodium chloride reabsorption. This in turn will create a driving force for the reabsorption of divalent cations. The second is expression of claudins

selective tight junction to facilitate magnesium transport.

In the distal tubule transcel

magnesium reabsorption. It occurs against an uphill electrochemical gradient.

26

Hence the major site of reabsorption is the thick ascending limb of loop of where it is primarily via the Para cellular route. There are two prerequisites for magnesium reabsorption at thick ascending limb of loop of henle.

generation of an electrical lumen positive gradient which is induced by the sodium e reabsorption. This in turn will create a driving force for the reabsorption of divalent cations. The second is expression of claudins -16 and 19 which will for selective tight junction to facilitate magnesium transport.

In the distal tubule transcellular transport is the major pathway for magnesium reabsorption. It occurs against an uphill electrochemical gradient.

Hence the major site of reabsorption is the thick ascending limb of loop of henle route. There are two prerequisites for magnesium reabsorption at thick ascending limb of loop of henle.^25,26 One is generation of an electrical lumen positive gradient which is induced by the sodium e reabsorption. This in turn will create a driving force for the reabsorption 16 and 19 which will for

lular transport is the major pathway for magnesium reabsorption. It occurs against an uphill electrochemical gradient.

(36)

TRPM6 is the gate keeper channel that controls the entry of magnesium into the tubular epithelium across the apical membrane. TRPM6 is in

estrogen and epidermal growth factor.

Increase in serum magnesium or calcium impairs the magnesium transport.

ECF volume expansion decreases the proximal tubular reabsorption of sodium, calcium and magnesium. In the kidney,

vasopressin, calcitonin, glucagon and PTH via the paracellular pathway and urinary magnesium excretion is stimulated by acetylcholine, bradykinin and ANP.

Drugs causing hypomagnesemia are loop diuretics, thiazide diuret

diuretics which disrupts the electrochemical gradient for magnesium entry by increasing the distal sodium delivery.

is reduced by the thiazide diuretics. Among the extracellular magnesium, 30% i

27

TRPM6 is the gate keeper channel that controls the entry of magnesium into the tubular epithelium across the apical membrane. TRPM6 is in

estrogen and epidermal growth factor.²⁸

ECF volume expansion decreases the proximal tubular reabsorption of sodium, calcium and magnesium. In the kidney, tubular reabsorption is increased by vasopressin, calcitonin, glucagon and PTH via the paracellular pathway and urinary magnesium excretion is stimulated by acetylcholine, bradykinin and ANP.

Drugs causing hypomagnesemia are loop diuretics, thiazide diuret

diuretics which disrupts the electrochemical gradient for magnesium entry by increasing the distal sodium delivery.^27,29 In addition to this, TRPM6 is expression is reduced by the thiazide diuretics. Among the extracellular magnesium, 30% i TRPM6 is the gate keeper channel that controls the entry of magnesium into the

turn regulated by

ECF volume expansion decreases the proximal tubular reabsorption of sodium, tubular reabsorption is increased by vasopressin, calcitonin, glucagon and PTH via the paracellular pathway and urinary magnesium excretion is stimulated by acetylcholine, bradykinin and ANP.

Drugs causing hypomagnesemia are loop diuretics, thiazide diuretics and osmotic diuretics which disrupts the electrochemical gradient for magnesium entry by In addition to this, TRPM6 is expression is reduced by the thiazide diuretics. Among the extracellular magnesium, 30% is

(37)

protein bound, 15 % is loosely bound to phosphate and other anions. 50 % of the total body magnesium is present in the bone.

RELATIONSHIP BETWEEN POTASSIUM AND MAGNESIUM

A decrease in magnesium levels will exacerbate the hypokalemia, by increasing distal potassium secretion. The mechanism behind this is that ROMK channels are generally under magnesium mediated inhibition. Therefore, in magnesium deficiency this disinhibition results in loss of potassium. Another mechanism is that magnesium deficienc

gastrointestinal and urinary systems which would further lead to potassium wasting.

HYPOMAGNESEMIA

When the total body magnesium levels decrease, it is termed as hypomagnesemia. The incidence of hypomagnesemia is

critical care units. The etiology for hypomagnesemia are usually GI diseases in particular the malabsorption syndromes. PPIs are also implicated in the selective impairment in intestinal magnesium absorption.

28

protein bound, 15 % is loosely bound to phosphate and other anions. 50 % of the total body magnesium is present in the bone.

A decrease in magnesium levels will exacerbate the hypokalemia, by distal potassium secretion. The mechanism behind this is that ROMK channels are generally under magnesium mediated inhibition. Therefore, in magnesium deficiency this disinhibition results in loss of potassium. Another mechanism is that magnesium deficiency impairs the Na-K ATPase pump in both gastrointestinal and urinary systems which would further lead to potassium

HYPOMAGNESEMIA

When the total body magnesium levels decrease, it is termed as hypomagnesemia. The incidence of hypomagnesemia is relatively high in the critical care units. The etiology for hypomagnesemia are usually GI diseases in particular the malabsorption syndromes. PPIs are also implicated in the selective impairment in intestinal magnesium absorption.^24,25 Poorly controlled

protein bound, 15 % is loosely bound to phosphate and other anions. 50 % of the

A decrease in magnesium levels will exacerbate the hypokalemia, by distal potassium secretion. The mechanism behind this is that ROMK channels are generally under magnesium mediated inhibition. Therefore, in magnesium deficiency this disinhibition results in loss of potassium. Another K ATPase pump in both gastrointestinal and urinary systems which would further lead to potassium

When the total body magnesium levels decrease, it is termed as relatively high in the critical care units. The etiology for hypomagnesemia are usually GI diseases in particular the malabsorption syndromes. PPIs are also implicated in the selective Poorly controlled diabetes

(38)

mellitus, acute pancreatitis seen in chronic alcoholics are also causes of magnesium deficiency. CaSR gene mutation results in impaired paracellular transport of magnesium causing hypomagnesemia. Autosomal recessive pattern of diseases involving m

hypermagnesuria, hypomagnesemia, hypercalciuria and nephrocalcinosis.

Hypomagnesemia manifests clinically with generalized weakness, neuromuscular hyper excitability, seizures, tremor. ECG may reveal a long QT interval with ST segment depression. Magnesium deficiency in turn leads to hypocalcemia and hypokalemia. Patients are managed by IV magnesium sulfate or oral magnesium oxide or hydroxide tablets.

29

mellitus, acute pancreatitis seen in chronic alcoholics are also causes of magnesium deficiency. CaSR gene mutation results in impaired paracellular transport of magnesium causing hypomagnesemia. Autosomal recessive pattern of diseases involving mutations of CLDN 16 AND CLDN19 causes hypermagnesuria, hypomagnesemia, hypercalciuria and nephrocalcinosis.

Hypomagnesemia manifests clinically with generalized weakness, neuromuscular hyper excitability, seizures, tremor. ECG may reveal a long QT erval with ST segment depression. Magnesium deficiency in turn leads to hypocalcemia and hypokalemia. Patients are managed by IV magnesium sulfate or oral magnesium oxide or hydroxide tablets.

mellitus, acute pancreatitis seen in chronic alcoholics are also causes of magnesium deficiency. CaSR gene mutation results in impaired paracellular transport of magnesium causing hypomagnesemia. Autosomal recessive pattern of utations of CLDN 16 AND CLDN19 causes hypermagnesuria, hypomagnesemia, hypercalciuria and nephrocalcinosis.

Hypomagnesemia manifests clinically with generalized weakness, neuromuscular hyper excitability, seizures, tremor. ECG may reveal a long QT erval with ST segment depression. Magnesium deficiency in turn leads to hypocalcemia and hypokalemia. Patients are managed by IV magnesium sulfate

(39)

HYPERMAGNESEMIA

Increase in serum magnesium most commonly o

which includes both acute and chronic. It can also occur in patients taking magnesium containing rectal enemas. It is observed in adrenal insufficiency and acromegaly. Deep tendon reflexes are lost in hypermagnesemia and with val reaching up to 12 mg/ dl results in respiratory paralysis, hypotension and loss of consciousness. Hypermagnesemia is treated with IV calcium infusions

ALCOHOL RELATED DISORDERS

Under DSM 5 criteria, alcohol related disorders are classified as alco use disorder, alcohol intoxication, alcohol withdrawal, other alcohol induced disorders, unspecified alcohol related disorder.

symptoms that includes withdrawal, tolerance and craving characterizes alcohol use disorder.³⁰ The severity of the disorder is given by the number of criteria fulfilled.

30 HYPERMAGNESEMIA

Increase in serum magnesium most commonly occurs due to renal failure which includes both acute and chronic. It can also occur in patients taking magnesium containing rectal enemas. It is observed in adrenal insufficiency and acromegaly. Deep tendon reflexes are lost in hypermagnesemia and with val reaching up to 12 mg/ dl results in respiratory paralysis, hypotension and loss of consciousness. Hypermagnesemia is treated with IV calcium infusions

ALCOHOL RELATED DISORDERS

Under DSM 5 criteria, alcohol related disorders are classified as alco use disorder, alcohol intoxication, alcohol withdrawal, other alcohol induced disorders, unspecified alcohol related disorder.¹ A group of behavioral, physical symptoms that includes withdrawal, tolerance and craving characterizes alcohol The severity of the disorder is given by the number of criteria ccurs due to renal failure which includes both acute and chronic. It can also occur in patients taking magnesium containing rectal enemas. It is observed in adrenal insufficiency and acromegaly. Deep tendon reflexes are lost in hypermagnesemia and with values reaching up to 12 mg/ dl results in respiratory paralysis, hypotension and loss of consciousness. Hypermagnesemia is treated with IV calcium infusions

Under DSM 5 criteria, alcohol related disorders are classified as alcohol use disorder, alcohol intoxication, alcohol withdrawal, other alcohol induced A group of behavioral, physical symptoms that includes withdrawal, tolerance and craving characterizes alcohol The severity of the disorder is given by the number of criteria

(40)

The DSM 5 criteria for alcohol use disorder is as follows

Alcohol use disorders has 60% rate of heritability. These genetic variations along with the environmental

related disorders.^31,32 The genes that are primarily implicated in all substance use disorders operate through schizophrenia, impulsivity and bipolar disorder. The effect of low response per drink is mediate

levels of GABA, Calcium, Potassium, nicotine, dopamine and serotonin systems.

The rate of this disorder among close relatives of patients with alcohol use disorder is 3 to 4 times higher. It is also observed among th

31

The DSM 5 criteria for alcohol use disorder is as follows:

Alcohol use disorders has 60% rate of heritability. These genetic variations along with the environmental influences alters the risk for high risk alcohol The genes that are primarily implicated in all substance use disorders operate through schizophrenia, impulsivity and bipolar disorder. The effect of low response per drink is mediated through various genes influencing the levels of GABA, Calcium, Potassium, nicotine, dopamine and serotonin systems.

The rate of this disorder among close relatives of patients with alcohol use disorder is 3 to 4 times higher. It is also observed among the children of patients Alcohol use disorders has 60% rate of heritability. These genetic variations influences alters the risk for high risk alcohol The genes that are primarily implicated in all substance use disorders operate through schizophrenia, impulsivity and bipolar disorder. The d through various genes influencing the levels of GABA, Calcium, Potassium, nicotine, dopamine and serotonin systems.

The rate of this disorder among close relatives of patients with alcohol use e children of patients

LEVELS IN ALCOHOL WITHDRAWAL SYNDROME

A CROSS SECTIONAL