Alcohol related disorders- by Swapnil Agrawal

2,436 views

Published on

Published in: Health & Medicine
0 Comments
5 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
2,436
On SlideShare
0
From Embeds
0
Number of Embeds
3
Actions
Shares
0
Downloads
200
Comments
0
Likes
5
Embeds 0
No embeds

No notes for slide
  • 22 unit= 4 pint of extra strong beer.. 2/3 bottle of spirits
  • Alcohol enhances the effect of GABA on GABA-A neuroreceptors, resulting in decreased overall brain excitability. Chronic exposure to alcohol results in a compensatory decrease of GABA-A neuroreceptor response to GABA, evidenced by increasing tolerance of the effects of alcohol. Alcohol inhibits NMDA neuroreceptors, and chronic alcohol exposure results in up-regulation of these receptors. Abrupt cessation of alcohol exposure results in brain hyperexcitability, because receptors previously inhibited by alcohol are no longer inhibited. An important concept in both alcohol craving and alcohol withdrawal is the "kindling" phenomenon; the term refers to long-term changes that occur in neurons after repeated detoxifications. Recurrent detoxifications are postulated to increase obsessive thoughts or alcohol craving.
  • Alcohol enhances the effect of GABA on GABA-A neuroreceptors, resulting in decreased overall brain excitability. Chronic exposure to alcohol results in a compensatory decrease of GABA-A neuroreceptor response to GABA, evidenced by increasing tolerance of the effects of alcohol
  • Alcohol inhibits NMDA neuroreceptors, and chronic alcohol exposure results in up-regulation of these receptors.
  • ?????
  • Abrupt cessation of alcohol exposure results in brain hyperexcitability, because receptors previously inhibited by alcohol are no longer inhibited.
  • Marchiafava-Bignami disease (MBD) is a rare condition characterized by demyelination of the corpus callosum. It is seen most often in patients with chronic alcoholism. In 1903, Italian pathologists Marchiafava and Bignami described 3 alcoholic men who died after having seizures and coma.Subtypes of MBDIn 2004, Heinrich et al described 2 clinical subtypes of MBD as follows, based on a review of 50 radiologic cases diagnosed in vivo[4] :Type A - Has predominant features of coma and stupor; this subtype is associated with a high prevalence of pyramidal-tract symptoms; radiologic features include involvement of the entire corpus callosumType B - Characterized by normal or mildly impaired mental status; radiologic features are partial or focal callosal lesions (see the image below).The prognosis for MBD is correlated with the subtype, as follows:Type A - Has a long-term disability rate of 86% and a mortality rate of 21%Type B - Has a long-term disability rate of 19% and a mortality rate of 0%TREATMENT-No specific, proven treatment is available for Marchiafava-Bignami disease (MBD).The most common treatments are thiamine, folate, and other B vitamins (especially vitamin B-12) a case report by Staszewski et al described amantadine given together with thiamine, vitamin B-12, and folate; the patient improved
  • Under certain circumstances, one to two drinks per day can have some beneficial effects. Low doses of ethanol appear to decrease the risk for myocardial infarction and thrombotic stroke, probably through decreasing platelet aggregation and enhancing the beneficial impact of high-density lipoprotein cholesterol. Additional cardioprotective action may occur through antioxidant flavinoids or the inhibition of the vasoconstrictor, endothelin-1, in the components of red wine. Low doses of alcohol have also been reported to decrease the risks for some old-age dementias, peripheral arterial disease, and gallstones.
  • Differences between icd-10 and dsm-iv?
  • Dsm-iv emphasises more on negative social consequences of subs abuse; while icd-10 on physical and psychological consequences.Term misuse also carries the same meaning.
  • Alcohol enhances the effect of GABA on GABA-A neuroreceptors, resulting in decreased overall brain excitability. Chronic exposure to alcohol results in a compensatory decrease of GABA-A neuroreceptor response to GABA, evidenced by increasing tolerance of the effects of alcohol. Alcohol inhibits NMDA neuroreceptors, and chronic alcohol exposure results in up-regulation of these receptors. Abrupt cessation of alcohol exposure results in brain hyperexcitability, because receptors previously inhibited by alcohol are no longer inhibited. An important concept in both alcohol craving and alcohol withdrawal is the "kindling" phenomenon; the term refers to long-term changes that occur in neurons after repeated detoxifications. Recurrent detoxifications are postulated to increase obsessive thoughts or alcohol craving
  • KINDLINGAn important concept in both alcohol craving and alcohol withdrawal is the "kindling" phenomenon; the term refers to long-term changes that occur in neurons after repeated detoxifications. Recurrent detoxifications are postulated to increase obsessive thoughts or alcohol cravingIn many alcoholics, the severity of withdrawal symptoms increases after repeated withdrawalepi sodes . Thi s exacerbat ion may be at t r ibutable to a kindl ing proces s . Kindl ing i s aphenomenon in which a weak electrical or chemical stimulus, which initially causes no overtbehavioral responses, results in the appearance of behavioral effects, such as seizures, whenit is administered repeatedly. Both clinical and experimental evidence support the existenceof a kindling mechanism during alcohol withdrawal. Withdrawal symptoms, such as seizures,result from neurochemical imbalances in the brain of alcoholics who suddenly reduce orcease alcohol consumption. These imbalances may be exacerbated after repeated withdrawalexperiences. The existence of kindling during withdrawal suggests that even patientsexperiencing mild withdrawal should be treated aggressively to prevent the increase inseverity of subsequent withdrawal episodes. Kindling also may contribute to a patient’srelapse risk and to alcohol-related brain damage and cognitive impairment
  • Autonomic dis include sweating,fever, tachycardia, high bp, dilated pupils.CASE-A 73-year-old professor emeritus at a university was believed to be in good health when he entered the hospital for an elective hernia repair. Perhaps reflecting his status in the community, the relatively brief history contained no detailed notes of his drinking pattern and made no mention of his γ-glutamyltransferase value of 55 U/L along with the MCV of 93.5 µm3. Eight hours postsurgery, the nursing staff noted a sharp increase in the pulse rate to 110, an increase in blood pressure to 150/100, prominent diaphoresis, and a tremor to both hands, after which the patient demonstrated a brief but intense grand mal convulsion. He awoke extremely agitated and disoriented to time, place, and person. A reevaluation of the history and an interview with the wife documented alcohol dependence with a consumption of approximately six standard drinks per night. Over the following 4 days, the patient's autonomic nervous system dysfunction decreased as his cognitive impairment disappeared. His condition is classified as alcohol withdrawal delirium in DSM-IV-TR.
  • Research over the past 30 years has identified several mechanisms through which alcoholism may contribute to thiamine deficiency. The most important of these mechanisms (as discussed in Hoyumpa 1980) include:-Inadequate nutritional intake-Decreased absorption of thiamine from the gastrointestinal tract and reduced uptake into cells-Impaired utilization of thiamine in the cells.Inadequate Nutritional IntakeAlthough most people require a minimum of 0.33 mg thiamine for each 1,000 kcal of energy they consume, alcoholics tend to consume less than 0.29 mg/1,000 kcal (Woodhill and Nobile 1972). In fact, in an early study of 3,000 alcoholics admitted to hospitals because of alcohol withdrawal symptoms or other alcohol–related illnesses, 40 percent exhibited periodic thiamine deficiency during drinking binges, 25 percent exhibited prolonged thiamine deficiency with some periods of normal intake, and 35 percent exhibited continuous thiamine deficiency (Leevy and Baker 1968). A later study found that alcoholic patients had significantly lower average levels of a thiamine compound containing one phosphate group (i.e., thiamine monophosphate), but the average levels of free thiamine and ThDP were similar in alcoholics and control subjects (Tallaksen et al. 1992). However, some of the alcoholics in that study had extremely high levels of free thiamine, suggesting that they may have had a problem in the steps that lead to the conversion of thiamine into its active, phosphate–containing form.Decreased Uptake of Thiamine From the Gastrointestinal TractAnimal studies have helped elucidate the mechanisms of normal and alcohol–impaired thiamine uptake from the gastrointestinal tract into the blood and cells. To be used by the body, thiamine must cross a number of barriers, first transferring across the membranes of the cells lining the gut (i.e., enterocytes), then entering those cells, and then crossing the membranes at the other end of the cells to enter the bloodstream. At low thiamine concentrations, such as those normally found in the human body, this transfer is achieved by a specific thiamine transporter molecule that requires energy. This is called an active transport process and seems to be associated with the rapid addition of two phosphate groups by the enzyme thiamine diphosphokinase (TPK) once the thiamine is inside the cell. At high thiamine concentrations, however, such as can be achieved after additional thiamine is administered, thiamine transport occurs through a passive process—that is, a mechanism that requires no energy.Acute alcohol exposure interferes with the absorption of thiamine from the gastrointestinal tract at low, but not at high, thiamine concentrations (Hoyumpa 1980). Furthermore, in studies using rats, the activity of the TPK enzyme from various tissues decreased with acute alcohol exposure to about 70 percent of the activity level in control animals, and with chronic alcohol exposure to about 50 percent (Laforenza et al. 1990). Although no studies have addressed whether alcohol directly affects TPK in humans, indirect analyses have found that the ratio of phosphorylated thiamine (primarily ThDP) to thiamine is significantly lower in alcoholics than in nonalcoholics (Poupon et al. 1990; Tallaksen et al. 1992)—that is, that less thiamine is converted to ThDP. This finding suggests that TPK is less active in the alcoholics.Thiamine malabsorption could become clinically significant if combined with the reduced dietary thiamine intake that is typically found in alcoholics, when other aspects of thiamine utilization are compromised by alcohol, or when a person requires increased thiamine amounts because of his or her specific metabolism or condition (e.g., in pregnant or lactating women).Impaired Thiamine UtilizationThe cells’ utilization of thiamine can be affected in different ways by chronic alcohol use. As mentioned earlier, once thiamine is imported into the cells, it is first converted into ThDP by the addition of two phosphate groups. ThDP then binds to the thiamine–using enzymes, a reaction that requires the presence of magnesium. Chronic alcohol consumption frequently leads to magnesium deficiency, however (Morgan 1982; Rindi et al. 1992), which also may contribute to an inadequate functioning of the thiamine–using enzymes and may cause symptoms resembling those of thiamine deficiency. In this case, any thiamine that reaches the cells cannot be used effectively, exacerbating any concurrently existing thiamine deficiency.Abstinence from alcohol and improved nutrition have been shown to reverse some of the impairments associated with thiamine deficiency, including improving brain functioning (Martin et al. 1986). Researchers also administered thiamine to alcoholic patients and laboratory animals and found that this treatment reversed some of the behavioral and metabolic consequences of thiamine deficiency (Victor et al. 1989; Lee et al. 1995). Most recently, researchers administered different thiamine doses for two days to a group of alcoholics undergoing detoxification, none of whom were diagnosed with WKS, and then tested the participant’s working memory. These studies found that participants who received the highest thiamine dose performed best on tests of working memory (Ambrose et al. 2001).DIFFERENTIAL SENSITIVITY TO THIAMINE DEFICIENCYDifferences in Sensitivity Among PeopleSeveral findings suggest that not all people are equally sensitive to thiamine deficiency and its consequences. For example, although thiamine deficiency may occur in up to 80 percent of alcoholics (Tallaksen et al. 1992; Hoyumpa 1980; Morgan 1982), only about 13 percent of alcoholics develop WKS (Harper et al. 1988). This means that the severest consequences of thiamine deficiency develop only in a subset of people who consume alcohol and have poor nutrition on a chronic basis. A possible explanation for this differential sensitivity is that some people are genetically predisposed to develop brain damage after experiencing repeated episodes of alcohol–related thiamine deficiency. To investigate this hypothesis, researchers have studied the activities of thiamine–using enzymes in patients with and without Korsakoff’s psychosis, arguing that variants of these enzymes may exist that could differ in their susceptibility to thiamine deficiency. The results of these investigations, however, have been inconsistent.2 (2 The studies cited in this section mostly used enzymes isolated from skin or blood cells of the participants. Although it is not known whether the effects of thiamine deficiency on these cells are identical to those on brain cells, the thiamine–using enzymes in these cells should be similar to the enzymes in brain cells, which are not accessible to the researchers. Using such model systems to investigate mechanisms of cell function has a long tradition in research.)One study (Blass and Gibson 1977) compared the activity of transketolase, PDH, and α–KGDH derived from skin cells of people with and without Korsakoff’s psychosis. These investigators found that transketolase from the Korsakoff’s patients bound ThDP less avidly than did the enzyme from the control subjects. Transketolase from the Korsakoff’s patients could function normally when sufficient thiamine or ThDP was present; under conditions of thiamine deficiency, however, the transketolase molecules would not be able to bind enough ThDP to maintain normal enzyme activity. As a result, the Korsakoff’s patients would be more susceptible to developing complications of thiamine deficiency than would people with a transketolase variant that more readily binds ThDP. The investigators found no differences, however, between Korsakoff’s patients and control subjects in the ability of the PDH and α–KGDH enzymes to bind ThDP.In another study (Mukherjee et al. 1987), researchers studied transketolase activity in alcoholic men without Korsakoff’s psychosis and their sons who had not yet been exposed to alcohol (i.e., who were alcohol naive) and compared it with transketolase activity in nonalcoholic volunteers and their sons. This analysis found that the enzyme from the alcoholic men and their sons also bound ThDP less strongly than did the enzyme from the healthy volunteers and their sons (fathers and sons were similar to each other in both groups). This finding suggests that the genetic makeup of alcoholics or those who are at risk of becoming alcoholic (e.g., sons of alcoholics who are still alcohol naive) might cause them to be more affected by thiamine deficiency than nonalcoholics.Other investigators, however, have found no differences in the ability of transketolase from Korsakoff’s patients and healthy subjects to bind ThDP (Nixon et al. 1984). Several reasons may explain these differences in findings. For example, if a study includes active alcoholics, toxic substances formed during alcohol degradation in the body (e.g., acetaldehyde or oxygen radicals) could conceivably damage the transketolase, leading to impaired transketolase activity even if the person does not have a genetic predisposition. Moreover, processing of the samples being studied could have modified and deactivated the transketolase. Overall, researchers to date have found no consistent correlation between genetically determined transketolase variants and a person’s sensitivity to thiamine deficiency (McCool et al. 1993). To determine whether a genetic predisposition to thiamine deficiency and resulting brain damage does indeed exist, more detailed molecular genetic studies are required.Another possible explanation for the differences among people in their sensitivity to thiamine deficiency has focused on the assembly of functional transketolase. To yield a functional enzyme, two transketolase molecules—each of which is bound to ThDP and to magnesium—must come together. This assembly step is aided by an as yet unidentified “assembly factor,” which is probably also involved in the assembly of other thiamine–using enzymes. If this factor were defective, the final enzyme complex would be formed at a lower rate and would be unstable (Wang et al. 1997). Researchers have identified at least one person with WKS whose cells showed enhanced sensitivity to thiamine deficiency and in whom the assembly factor was defective (Wang et al. 1997). Other mechanisms that could contribute to individual differences in the sensitivity to alcoholism could involve variability in the capacity for thiamine uptake into the cells or in the overall sensitivity to cell damage induced by oxidative stress.Differential Sensitivity of Various Brain RegionsVarious brain regions and even different cell types within one brain region may differ in their sensitivity to alcohol–induced damage as well as in their susceptibility to associated problems, including alcohol–related malnutrition (e.g., thiamine deficiency). For example, as mentioned earlier, the cerebellum appears to be particularly sensitive to thiamine deficiency, as indicated by the high frequency of cerebellar degeneration in alcoholics. Autopsy studies have found that a region of the cerebellum known as the anterior superior cerebellar vermis most frequently exhibits alcohol–induced damage (Baker et al. 1999). Additional studies have found that the cerebellar vermis is particularly sensitive to the deleterious effects of thiamine deficiency (Baker et al. 1999; Lavoie and Butterworth 1995; Victor et al. 1989). For example, thiamine deficiency contributes to a reduction in the number and size of a certain cerebellar cell type called Purkinje cells in parts of the cerebellar vermis (Philips et al. 1987).The sensitivity of the cerebellum to alcohol–related damage was confirmed in a recent study in which investigators used an imaging technique called proton magnetic resonance spectroscopy (proton MRS) to determine the levels of certain molecules (i.e., metabolites) that reflect the functionality of the cells in various brain regions of alcoholics and nonalcoholics. For example, one metabolite reflects nerve cell activity, another metabolite reflects the degradation and formation (i.e., turnover) of cell membrane components, and a third metabolite reflects cellular energy levels. The results of the analyses indicated that these metabolites are significantly reduced in the cerebellum of alcoholics, more so than in another brain region commonly affected by alcohol, the frontal white–matter cortex (Parks et al. 2002). Moreover, only some of these reductions in metabolite levels were reversed when the subjects were tested again after 3 weeks and then 3 months of abstinence. These findings suggest that the cerebellum, in particular the cerebellar vermis, is uniquely sensitive to alcohol’s effects, including alcohol–related thiamine deficiency, and therefore may be the initial target of alcohol–related damage.This hypothesis is consistent with the clinical course of the neurocognitive deficits observed in alcoholics. Networks of nerve cells (i.e., neural pathways) extend from the cerebellum through brain regions called the basal ganglia and thalamus to the frontal lobe. These pathways mediate not only traditional cerebellar functions, such as motor control, but also perceptual– motor tasks, executive functions, and learning and memory, all of which are impaired in alcoholics (see Parks et al. 2002). Accordingly, alcohol–induced damage to the cerebellar vermis could indirectly affect neurocognitive functions attributed to the frontal lobe, even early in the disease process when no cortical damage is detectable, by disrupting the neural pathways connecting the two brain regions. As the alcoholism progresses and alcohol exposure persists, damage to the frontal lobe is also likely to occur, further interfering with the functions of that brain region.In addition to the cerebellum, numerous other brain regions and structures are damaged in people with WKS. Although animal studies have suggested that thiamine deficiency may contribute to damage to these structures, the exact role of thiamine deficiency and the level of sensitivity of these structures to thiamine deficiency have not yet been determined. Further studies are certainly needed in this area.SUMMARYThiamine deficiency, which is found in a large number of alcoholics, is an important contributor to alcohol–related brain damage of all kinds, not only WKS, as was commonly thought in the past. Thiamine is an essential cofactor for several enzymes involved in brain cell metabolism that are required for the production of precursors for several important cell components as well as for the generation of the energy–supplying molecule ATP. Thiamine deficiency leads to significant reductions in the activities of these enzymes, and to deleterious effects on the viability of brain cells.Chronic alcohol consumption can cause thiamine deficiency and thus reduced enzyme activity through several mechanisms, including inadequate dietary intake, malabsorption of thiamine from the gastrointestinal tract, and impaired utilization of thiamine in the cells. Accordingly, thiamine deficiency can potentiate a number of processes associated with chronic alcohol consumption that are toxic to brain cells, as discussed in other articles in this journal issue. It is important to note that these adverse effects of alcohol–induced thiamine deficiency, particularly the reduction of transketolase activity, can occur even in alcoholics who do not show evidence of WE or WKS.The extent to which alcohol exerts its detrimental effects on the brain and various other tissues may be genetically determined via individual differences in predisposition to thiamine deficiency disorders. For example, some studies have suggested that there may be different variants of the genes encoding transketolase, which differ in their ability to bind the active form of thiamine, particularly at low thiamine concentrations. Such a genetic variation could be one explanation for why only a subset of alcoholics who experience thiamine deficiency develop the pathological consequences of that condition, such as WKS. Additional genetic studies are necessary, however, to clarify the roles of different genetic variants and determine whether a genetically determined susceptibility does indeed exist.Various brain regions also differ in their sensitivity to alcohol’s effects, including alcohol–induced thiamine deficiency. The cerebellum appears to be particularly sensitive to the effects of thiamine deficiency and is the region most frequently damaged in association with chronic alcohol consumption. This heightened susceptibility is consistent with the cognitive deficits typically associated with alcoholism. These deficits are indicative either of cerebellar damage or of damage to the frontal lobes, which are connected to the cerebellum through neural pathways. Accordingly, reversal of thiamine deficiency—for example, by administering thiamine at pharmacological levels—may not only ameliorate the consequences of cerebellar damage but improve some brain functions typically associated with the frontal lobe.
  • Carbohydrate def transferrin is a variant of serum protein that transports iron, and inreased in heavy drinking…more specific than GGT.
  • KINDLINGAn important concept in both alcohol craving and alcohol withdrawal is the "kindling" phenomenon; the term refers to long-term changes that occur in neurons after repeated detoxifications. Recurrent detoxifications are postulated to increase obsessive thoughts or alcohol cravingIn many alcoholics, the severity of withdrawal symptoms increases after repeated withdrawalepi sodes . Thi s exacerbat ion may be at t r ibutable to a kindl ing proces s . Kindl ing i s aphenomenon in which a weak electrical or chemical stimulus, which initially causes no overtbehavioral responses, results in the appearance of behavioral effects, such as seizures, whenit is administered repeatedly. Both clinical and experimental evidence support the existenceof a kindling mechanism during alcohol withdrawal. Withdrawal symptoms, such as seizures,result from neurochemical imbalances in the brain of alcoholics who suddenly reduce orcease alcohol consumption. These imbalances may be exacerbated after repeated withdrawalexperiences. The existence of kindling during withdrawal suggests that even patientsexperiencing mild withdrawal should be treated aggressively to prevent the increase inseverity of subsequent withdrawal episodes. Kindling also may contribute to a patient’srelapse risk and to alcohol-related brain damage and cognitive impairment
  • Rx of severe disulfiram reac– iv fluids, dopamine infusion if severe hypotension, antihistaminics, 4-methylpyrazole(fomepizole)??- To block formation of acetaldehyde by inhibiting alc dehydrogenase.
  • Alcohol related disorders- by Swapnil Agrawal

    1. 1. "... alcohol has existed longer than all human memory. It has outlived generations, nations and ages. It is a part of us, and that is fortunate indeed. For although alcohol will always be the master of some, for most of us it will continue to be the servant of man" Director of the National Institute on Alcohol Abuse and Alcoholism(Chafetz, 1965, p. 223).
    2. 2. Historical Aspects One of the most commonly used chemical substances for intoxication by humans in history. Word alcohol originates from the Arabian term al-kuhul, meaning "the kohl" a powder for the eyes, which later came to mean "finely divided spirit".
    3. 3. ..history No one knows when beverage alcohol was first used The discovery of late Stone Age beer jugs has established the fact that intentionally fermented beverages existed at least as early as 10,000 B.C.(Patrick, 1952, pp. 12-13). In INDIA alcoholic beverages appeared in between 3000 BC - 2000 BC.
    4. 4. EPIDEMIOLOGY According to a study conducted by the NIMHANS for the WHO, published in 2006, nearly 30% of adult men and <5% of women consume alcohol. Male to female ratio of 6:1 Age- Men in their late teens or early 20s are heaviest drinkers. Occupation- more in chefs, barmen, executives, actors, Doctors etc( as they have easy access to alcohol) Average age of initiation has reduced from 28 years during the 80s to 20 years in recent years. Alcohol-dependent person decreases his life span by 10 to 15 years.
    5. 5. allOverall prevalence~ 30%
    6. 6. Overall prevalence<5%
    7. 7. Alcohol content of different beverages Expressed as `UNIT‟. 1unit=8grams of alcohol. BEVERAGE ALCOHOL UNITS OF CONTENT(%) ALCOHOL Ordinary Beer 3% 2 per pint Strong Beer 5.5% 4 per pint Extra strong Beer 7% 5 per pint Table wine 8-10% 7 per bottle Fortified wines 13-16% 15 per bottle (sherry, pot, vermouth) Spirits(whisky, gin, 32% 30 per bottle brandy, vodka)
    8. 8. Risk of social and healthproblems ALCOHOL INTAKE RISK OF PROBLEMS (units/week) MEN 0-21 LOW WOMEN 0-14 MEN 22-50 INCREASING, particularly in WOMEN 15-35 smokers MEN > 50 HIGH, particularly in smokers WOMEN > 35
    9. 9. ETIOLOGY Various theories to explain alcoholism-1. Psychological theories2. Psychodyanamic theories3. Behavioral theories4. Sociocultural theories5. Genetic theories6. Childhood history
    10. 10. ETIOLOGY Psychological Theories Alcohol reduces tension, increase feelings of power, decrease the effect of psychological pain Alcohol decreases nervousness, increased feeling of well being, help them to cope with day to day stresses of life. Psychodynamic Theories Due to anxiety lowering effects of alcohol, people may use this to help them deal with self-punitive harsh superegoes and to decrease unconscious stress levels. Fixation at oral stage of development may also explain use of alcohol to relieve frustations by taking the substance by mouth.
    11. 11. Behavioral Theories Expectations about the rewarding effects of alcohol, and subsequent reinforcement after alcohol intake all contribute to decision to drink again after first drink.. Sociocultural Theories Cultural attitudes toward drinking, and personal responsibilities for consequences are important contributors to alcohol use.. Childhood history Childhood history of ADHD, conduct disorder, antisocial personality disorder increases a child‟s risk for an alcohol related disorder as an adult..
    12. 12. Genetic Theories Close family members have a fourfold increased risk. The identical twin of an alcoholic person is at higher risk than is a fraternal twin. Adopted-away children of alcoholic people have a fourfold increased risk.
    13. 13. EFFECTS OF ALCOHOL ON BODY1) Absorption- 10% from stomach, 90%-small intestine(proximal).2) Peak blood conc.- In 30-90 minutes.3) Metabolism- 90% in liver (by ADH and ALDH enzymes) -10% ex unchanged by kidney and lungs Body can metabolises ¾ ounce(1 ounce=28.35 gms) of 40%spirits in 1 hour.
    14. 14. Causes Histamine Toxic release ACETALDEHYDE Disulfiram reaction.ALCOHOL ALDH Non- toxic ACETIC ACID
    15. 15. …EFFECT OF ALCOHOL ON BODYEFFECT ON BRAIN(Pathophysiology)- Dopamine increase in limbic system- pleasure(alcohol acutely increase dopamine levels in brain) Serotonin- related to amount of intake GABAA receptors NMDA receptors
    16. 16. …EFFECT OF ALCOHOL ON BODY1) EFFECT ON SLEEP- - decreased sleep latency, but - decrease in REM and NREM stage 4 - more sleep fragmentation, and longer episodes of awakening (thus overall harmful effect on sleep)2) TOLERANCE- With repeated administration of alcohol, larger and larger doses are required to produce the desired effect.3) CRAVING- The state of motivation to seek out alcohol.
    17. 17. 4) BLACKOUTS- Blackout indicates a memory impairment (anterograde amnesia) for the period when the person was drinking heavily and was awake5)PERIPHERAL NEUROPATHY - tingling and numbness in hands & feet - develops in about 10% alcoholics6) CEREBELLAR DEGENERATION7) CENTRAL PONTINE MYELINOSIS(present as quadriplegia, lethargy, and cognitive impairment )8) MARCHIAFAVA- BIGNAMI SYNDROME(thinning of the corpus callosum along with a change in consciousness, ataxia, and possible dementia)
    18. 18. 9) Pathological intoxication (mania a potu)- - An extraordinary severe response to small amounts of alcohol - marked by apparently senseless violent behaviour, usually followed by sleep, exhaustion & „amnesia‟ for the episode.
    19. 19. GIT- - Gatritis, fatty liver, alcoholic cirrhosis, pancreatitis.CVS- - Hypertension and increased risk of Stroke. (Paradoxically, moderate drinkers i.e. about 7-10 units/week have lower risk of coronary artery disease than non-drinkers!!)FETAL ALCOHOL SYNDROME- - seen in about 5% children born to heavy-drinker mothers. -severe mental retardation, microcephaly, facial defects, asd etc. -even fetal death, and spontaneous abortion.
    20. 20. ICD-10- F10--F19 Mental and behavioural disorders due to psychoactive substance use F10. -Alcohol F11.-Opioids F12.-Cannabinoids F13.- Sedatives or hypnotics F14.-Cocaine F15.-Other stimulants, including caffeine F16.-Hallucinogens F17. -Tobacco F18.-Volatile solvents F19.-Multiple drug use and use of other psychoactive substances
    21. 21. CLASSIFICATION OF ALCOHOL-RELATEDDISORDERS ICD-10 DSM-IV1. F10.0 Intoxication 1. Intoxication2. F10.1 Harmful use 2. Abuse3. F10.2 Dependence syndrome 3. Dependence4. F10.3 Withdrawal state 4. Withdrawal5. F10.4 Withdrawal state with 5. Withdrawal delirium delirium 6. Psychotic disorders6. F10.5 Psychotic disorders 7. Mood disorders7. F10.6 Amnestic syndrome 8. Anxiety disorders8. F10.7 Residual and late 9. Amnestic disorders onset psychotic disorder 10. Dementia9. F10.8 Other mental and 11. Sexual dysfunction behavioral disorders 12. Sleep disorders
    22. 22. F10.0 ACUTE INTOXICATION A transient syndrome-due to recent substance ingestion-that produces clinically significant psychological and physical impairment. Changes are reversible upon elimination of substance from the body. Legal definition of intoxication in USA is alcohol conc. > 80-100 mg/dl of blood.
    23. 23. LEVEL LIKELY IMPAIRMENT 20-30 mg/dl  Slowed motor performance, decreased thinking ability. 30-80 mg/dl  Increase in motor & cognitive problems. 80-200 mg/dl  Increase in incoordination and judgement errors. Lability of mood, Cognitive deterioration 200-300 mg/dl  Marked slurring of speech, Nystagmus, Blackouts. >300 mg/dl  Impirement in vital signs, possibly Death!.
    24. 24. F10.1 ALCOHOL HARMFUL USE A pattern of psychoactive substance use -that is causing damage to health, -the damage may be physical or mental.Diagnostic guidelines Actual damage to physical or mental health. Acute intoxication itself is not a sufficient evidence of the damage to health. Harmful use should NOT be diagnosed if dependence syndrome, a psychotic disorder (F10.5), or another specific form of alcohol-related disorder is present.
    25. 25. F10.2 DEPENDENCE SYNDROME A cluster of physiological, behavioural, and cognitive phenomena -in which the use of a substance takes on a much higher priority for an individual than other behaviours that once had greater value.
    26. 26. Diagnostic guidelines for dependence syndrome- Three or more of the following is necessary to diagnosis in previous year.a) Strong desire.b) Progressive neglect of alternative pleasures or interests.c) Evidence of tolerance.d) Signs of withdrawal on attempted abstinencee) Loss of control of consumption.f) Continued drug use despite negative consequences.
    27. 27. Five-character codes for dependence F10.20 Currently abstinent F10.21 Currently abstinent, but in a protected environment F10.22 Currently on a clinically supervised maintenance or replacement regime [controlled dependence] F10.23 Currently abstinent, but receiving treatment with aversive or blocking drugs (e.g. naltrexone or disulfiram) F10.24 Currently using the substance [active dependence] F10.25 Continuous use F10.26 Episodic use [dipsomania]
    28. 28. Subtypes of Alcohol DependenceType A alcohol dependence Late onset Few childhood risk factors Mild dependence (with few alcohol related problems and little psychopathology)Type B alcohol dependence Early onset Many childhood risk factors Severe dependence( with a strong family history and much psychopathology)
    29. 29. Some more subtypes…. Gamma alcohol dependence Represents alc. Dep. In those who are active in Alcoholic Anonyms. These persons are unable to stop drinking once they start, but if drinking is terminated (due to ill health or lack of money), they can abstain quite well.. Delta alcohol dependence Include those who must drink a certain amount each day, but are unaware of a lack of control
    30. 30. Difference b/w harmful use anddependence- For a person meeting criteria of both harmful use and dependence, the diagnosis of DEPENDENCE should be made. Tolerance and Withdrawal state are features of DEPENDENCE. Harmful use should NOT be diagnosed if dependence syndrome, a psychotic disorder (F10.5), or another specific form of alcohol-related disorder is present.
    31. 31. F10.3 ALCOHOL WITHDRAWAL “A group of symptoms and signs which occur on cessation or reduction of use of a psychoactive substance, -that has been taken repeatedly, usually for a prolonged period and/ or in high doses.” It can be- Uncomplicated- ocurring in 6-48 hrs and abates after 2-5 days. Complicted- with seizures, delirum.
    32. 32. Diagnosis of alc. withdrawalA) Cessation of (or reduction in) alcohol use.B) Two (or more) of the following, developing within several hours to a few days after Criterion A: (1) Autonomic hyperactivity (2) Increased hand tremor (3) Insomnia (4) Nausea or vomiting (5) Transient hallucinations or illusions (6) Psychomotor agitation (7) Anxiety (8) Grand mal seizuresC) Social & occupational functioning impairment.D) Not due to a general medical condition or mental disorder.
    33. 33. S/S ALCOHOL WITHDRAWAL SYNDROME Time withdrawal symptoms6 to 12 hours Insomnia, tremulousness, mild anxiety, gastrointestinal upset, headache, diaphoresis, palpitations, anorexia12 to 24 hours Alcoholic hallucinosis: visual, auditory, or tactile hallucinations24 to 48 hours Withdrawal seizures: generalized tonic-clonic seizures48 to 72 hours Alcohol withdrawal delirium (delirium tremens): hallucinations (predominately visual), disorientation, tachycardia, hypertension, low-grade fever, agitation, diaphoresis
    34. 34. ALCOHOL WITHDRAWAL SEIZURES 5-15% cases of alcohol withdrawal Within 24-48hrs but may up to 7days Tonic-clonic in nature Usually one or two episodes 30% of pts develop delirium Give IV diazepam until seizure activity ceases 5-10mg IV initially, repeat if necessary every 15min up to a maximum dose of 100mg Call to neurologist Avoid anticonvulsant unless history of primary SD
    35. 35. F10.4 DELIRIUM TREMENS Medical Emergency < 5% of Alcohol Withdrawal syndrome Usually begins in 48-96hrs. Last for 1-5 days May be associated with seizure(F10.41) In untreated cases mortality is up to 20%. Triad of symptoms includes- - Clouding of consciousness, - Hallucinations and Illusions, - Marked tremors. Autonomic hyperactivity, dehydration, electrolyte imbalance. Delusions may be present May lead to circulatory collapse, coma & death
    36. 36. Management of Delirium tremens IV Fluid for hydration. Mainstay are BZDS- -Lorazepam 2mg or Diazepam 10mg IV/IM. -Repeated doses till symptoms clear -Doses should be tapered in 5-7days Thiamine 200-300mg IM daily for 3-5 days. Oral Thiamine three times a day. Monitor vitals 4hrly Closely observe for focal neurological deficit Pt should be on high calorie, high carbohydrate diet.
    37. 37. F10.5 PSYCHOTIC DISORDERS Occur during or immediately after alcohol use and are characterized by- .Vivid hallucinations (mainly auditory), .Delusions or ideas of reference(morbid jealosy), .Psychomotor disturbances (excitement or stupor), .Abnormal affect. Sensorium is usually clear but some clouding of consciousness may be present. The disorder typically resolves in 1-6 months.
    38. 38. Diagnostic guidelines.. A psychotic disorder occurring during or immediately after drug use (usually within 48 hours) - provided that it is not a manifestation of withdrawal state with delirium and - should NOT be of late onset. Late-onset psychotic disorders (with onset more than 2 weeks after substance use) should be coded as F10.75.
    39. 39.  The diagnosis of psychotic state may be further specified by the following five character codes:1. F10.50 Schizophrenia-like2. F10.51 Predominantly delusional3. F10.52 Predominantly hallucinatory (includes alcoholic hallucinosis)4. F10.53 Predominantly polymorphic5. F10.54 Predominantly depressive symptoms6. F10.55 Predominantly manic symptoms7. F10.56 Mixed
    40. 40. F10.6 AMNESTIC SYNDROMES A syndrome associated with chronic prominent impairment of RECENT memory; remote memory is sometimes impaired, while immediate recall is preserved. Diagnostic guidelines-1. Impairment of RECENT memory(learning of new material) ; Disturbance of time sense.2. Preserved immediate recall;3. Preserved consciousness; and absence of generalised cognitive impairment.4. Evidence of chronic (high-dose) use of alcohol. Includes:- Wernicke’s encephalopathy, & Korsakov’s syndrome.
    41. 41. WERNICKE ENCEPHALOPATHY Acute onset Completely reversible G.O.A. Global confusion Opthalmoplegia - Horizontal nystagmus, 6th n. palsy Ataxia, Vestibular dysfunction Rapidly reversible with large parenteral doses 200- 300mg of Thiamine. Then 100mg orally BD or TDS for 1-2 wk. In pts. receiving iv fluids, include 100mg of thiamine in each liter of iv glucose solution.
    42. 42. KORSAKOFF’S SYNDROME Chronic condition Reversible in only 20% of cases Impaired Recent memory and anterograde amnesia in an alert and responsive pt. Confabulation +/- In most cases, the level of recent memory loss is out of proportion to the global level of cognitive impairment. Thiamine100mg orally BD or TDS for 3 to 12 months.
    43. 43. F10.7 RESIDUAL & LATE ONSETPSYCHOTIC DISORDER A disorder in which alcohol-induced changes of cognition, affect, personality, or behaviour persist beyond the period during which a direct alcohol- related effect might be assumed to be operating. Further subdivided by the following five-character codes:- F10.70 Flashbacks F10.71 Personality or behaviour disorder F10.72 Residual affective disorder F10.73 Dementia F10.74 Other persisting cognitive impairment F10.75 Late-onset psychotic disorder
    44. 44. F10.8 Other mental and behaviouraldisorders Code here any other disorder in which the use of a substance can be identified as contributing directly to the condition, but which does not meet the criteria for inclusion in any of the above disorders.
    45. 45. ALCOHOL INDUCED PERSISTINGDEMENTIA Global decreases in intellectual functioning, cognitive abilities, and memory. But recent memory difficulties are consistent with the global cognitive impairment. (an observation that distinguishes the syndrome from alcohol-induced persisting amnestic disorder.) 50-70% show increased size of the brain ventricles and atrophy of frontal lobe. (these changes appear to be partially or completely reversible.) Brain functioning improves with abstinence, but 1/2 of all affected patients have long-term and even permanent memory and thinking disabilities.
    46. 46. ALCOHOL INDUCED ANXIETYDISORDERS Only two anxiety disorders may be more closely tied to alcoholism: panic disorder & social phobia. During the first 4 to 6 weeks of abstinence Disappear with time alone.
    47. 47. ALCOHOL INDUCED SEXUALDYSFUNCTION Alcohol in small doses appears to enhance sexual receptivity in women and increase arousal to erotic stimuli in men. Heavy continued drinking may cause significant sexual impairment:- - impaired desire - impaired arousal - impaired orgasm - sexual pain. Symptoms usually subside after 3-4 weeks of alcohol abstinence.
    48. 48. MANAGEMENTManagement of-1) Alcohol Intoxication2) Dependence & Withdrawal3) With specific co-morbid conditions.
    49. 49. Mx of Alcohol intoxication Check for vital signs- blood pressure - respiratory depression - arrhythmias Any signs of Hypoglycemia, Hepatic failure If very aggressive- low dose lorazepam (1mg orally) or -antipsychotic(5mg Haloperidol) Ensure hydration (iv fluids) Symptomatic and supportive treatment.
    50. 50. Mx of Dependence Step 1) Detection of alcohol dependence Step 2)Intervention Step 3) Detoxification (or withdrawal from alcohol) Step 4) Relapse prevention (or maitenence of abstinence) & Rehabilitation.
    51. 51. The Moral and Medical models Moral model- Public drunkenness should be punished. Little evidence that it influences the behavior of excessive drinkers! Medical model- Jellinek in 1960- “The disease concept of alcoholism”. Instead of blame and punishment, Medical treatment is provided to excessive drinkers.
    52. 52. (A) DETECTION OF ALCOHOL MISUSEBy-1- Screening2- History taking3- Laboratory diagnosisSCREENING-1. CAGE questionnaire2. AUDIT questionnaire
    53. 53. CAGE Questionnaire Consist of 4 questions-1) Have you ever felt to Cut down on your drinking?2) Have people Annoyed you by criticizing your drinking?3) Have you ever felt Guilty about your drinking?4) Have you ever had a morning drink (Eye opener) to get rid of hangover? -> 2 or more yes= alcohol misuse. -> Overall sensitivity is Good but modest specifity.
    54. 54. AUDIT questionnaire Ten questions. Designed at the request of WHO. Scores are given for each answer. Score Intervention 8-15 - brief intervention based on risk factors. 16-19 - brief intervention, regular monitoring. 20-40 - diagnostic assessment, detoxification, and other treatments.
    55. 55. DRINKING HISTORY Describe a typical day‟s drinking. What time you take first drink of the day? When did daily drinking start? Any withdrawal symptoms in morning or after abstinence? Previous attempts at treatment? Medical complications? Patient‟s attitude towards drinking?
    56. 56. LABORATORY DIAGNOSISParameter Normal value Value in chronic alcoholicsSerum level of γ- Men 4-25 U/L >30 U/Lglutamyl transferase Women 7-40 U/L(GGT)Mean corpuscular 80-98μm3 >100 µm3volume(MCV)Carbohydrate-deficient <60mg/l >1.3% of total transferrintransferrin concentrationAST & ALT <45 U/L AST:ALT, 2:1Blood Alcohol conc.- if a person is not intoxicated even when blood alc.Levels are high, he is likely to be unusually tolerant to alcohol.
    57. 57. (B) INTERVENTION Goal is “to increase motivation” for treatment & continued abstinenceMotivational interviewing-Aim is to persuade pt. to engage in treatment programme.-Express empathy-Avoid arguing, let the pt.sayand then “roll with” resistance-usually multiple sessions are required to persuade the pt. In the meantime- Family may benefit from counselling or referral to self help groups like- AL-Anon(for spouses of excessive drinkers) & AL-Ateen(for their teenage children) Also pt.can be encouraged to meet people recovering from alcohol, through AA(Alcohol Anonymous)
    58. 58. (C) DETOXIFICATION i.e Withdrawal of patient from alcohol. Step 1) Thorough Physical examination (e.g. liver failure, gi bleed, arrhythmia, glucose or electrolyte imbalance; any combined drug abuse) Step 2) Rest & Adequate nutrition (Vit-B complex specially Thiamine) Step 3) BZD & other symptomatic pharmacotherapy
    59. 59. Pharmacotherapy1) Benzodiazepines- -drug of choice -decreases s/s of withdrawal & prevents seizures & DT also -long acting(chlordiazepoxide,diazepam) are preferred -Dose:- 20-30mg Chlordiazepoxide 6 hourly on day1 or 5-10mg Diazepam. (dose up to 250mg on day1 can be given in severe withdrawal) - then decrease gradually and stop in 5-7 days. (dose can be adjusted depending on s/s) Oxazepam/Lorazepam/Temazepam for elderly or hepatic impairment pts.
    60. 60. Common benzodiazepines used to treatpatients with alcohol withdrawal SyndromeDrug Half Life Initial Dose Average Maximum Dose/ Day Dose/DayChlordiaze- 24-48 hours 25mg 50-100mg 250mgpoxideDiazepam 20-90 hours 5mg 10-20mg 100mgLorazepam 10-20 hours 1mg 2-4mg 12mgOxazepam 4-14 hours 15mg 10-30mg 200mg
    61. 61. …pharmacotherapy2) Thiamine & Magnesium Prevention & treatment of Wernicke‟s enceph & Korsakoff‟s psychosis. No impact on s/s of withdrawal or seizures or DT. Thiamine- 100 to 300mg im or orally daily. for at least 7 days (..upto 1-2 wk in WE & upto 3-12 months in KP ) Thiamine should always precede glucose administration
    62. 62. …pharmacotherapy Magnesium- HypoMagnesemia occurs in withdrawal Mg is required for normal utilization of Thiamine also! In severe case deficiency is 1-2 meq/kg body wt. Correct half of deficit on day1, then remaining on following 4 days Dose- 30-45 meq(4 to 6 ampules) of mag.sulphate in 2 litre of iv fluid on day1 Half of above dose Daily for 4 days
    63. 63. …pharmacotherapy OTHER DRUGS& ADJUNCTIVE THERAPIESSympatholytics--decreases autonomic hyperactivity in withdrawal.-Clonidine(α2 agonist)- can cause postural hypotension-Propanolol(β-blocker)- increases incidence of deliriumBarbiturates(Phenobarbital)-for withdrawal in pregnant women-lack of sufficient evidence
    64. 64. …pharmacotherapyNeuroleptics--Reduces symptoms of withdrawal(agitation & hallucinations) -Haloperidol & Phenothiazines- but increases risk of seizures.Carbamazepine- -can reduce minor s/s of withdrawal -no special benefit
    65. 65. (D)MAINTAINING ABSTINENCE & REHABILITAION Pharmacological Psychosocial Rx interventions1. Disulfiram 1. Brief interventions2. Acamprosate 2. Extended3. Naltrexone interventions4. Others 3. Group therapy -SSRI 4. Family therapy -Topiramate 5. Self-Help -Ondansetron groups(Alcohol Anonymous) -Baclofen
    66. 66. Disulfiram Inhibits Aldehyde dehydogenase(ALDH), so acetaldehyde accumulates Flushing, weakness, nausea, tachycardia on taking alcohol Thus acts as aversive Rx discouraging impulsive alcohol use Before starting disulfiram pt. should be abstinent from alcohol for 12 hours Disulfiram reactions can occur upto 2 weeks after last dose No tolerance with continous Rx of disulfiram Dose-800mg on day1 then100-250mg daily C/I – heart failure, CAD, HTN, pregnancy, psychosis High risk of serious S/E so generally not preferred
    67. 67. Acamprosate Calcium acetyl homotaurinate Decreases the glutamenergic excitatory activity (NMDA) & Increases GABA activity. Supresses the urge to drink Abstinence rates appear to be Doubled S/E – diarrhoea, skin rashes, decreased libido, anxiety, depression C/I – severe renal impairment (eliminated completely by kidney) Dose- 333mg 2TDS before meal (as food interferes with absorption)
    68. 68. Naltexone Opioid antagonist – blocks the reinforcing and rewarding effects of alcohol. Reduced Craving(anti-craving) and reduced rate of relapse S/E- nausea, constipation, anxiety, fatigue C/I - in pt. taking opioids, hepatic failure Dose- 50mg daily
    69. 69. BACLOFEN GABA-B agonist Primarily used for the treatment of spastic movement disorders. In 2012, Baclofen was approved for use in the treatment of alcoholism Shown to enhance abstinence, reduce drinking quantity, reduce craving, and reduce anxiety in alcohol- dependent individuals. Dose- 30mg/day
    70. 70. Antidepressants Useful in pt. who experience persistent symptoms of major depression after detoxification. May reduce drinking even in non-depressed subjects. Only SSRIs are recommended SSRIs may improve drinking outcome in Type 1 but may worsen outcome in Type 2 dependence.
    71. 71. Alcohol Anonymous AA is an international self-help organisation founded in USA by two alcoholic men- Dr. Bob Smith(surgeon) & Bill Wilson(a stockbroker) in 1935. AA says “its primary purpose is to stay sober and help other alcoholics achieve sobriety” Members attend group meetings, usually twice weekly on long-term basis. In crisis, immediate relief can be obtained from other members by telephone.
    72. 72. Treatment of specific co-morbid conditions1) Alcoholism with depressive symptoms- - increased risk for relapse - psychosocial Rx like Group therapy2) Alcoholism with major depression- - SSRI(fluoxetine, tianeptine) may be started - TCA(due to sympathetic s/e) are not used3) Alcoholism with dysthymic disorder- - frequent relapses are common - cognitive behaviour therapy may be considered
    73. 73. 4) Alcoholism with Anxiety- - for mild anxiety symptoms, Rx is deferred till pt. is abstinent for 2 wks - In pt. who experience anxiety disorder separately from any problem related to alcohol– anxiolytics (long acting BZD) can be started. - Buspirone (bcoz of no evidence of its interaction with alcohol) can be used.
    74. 74. Take Home Message… For a person meeting criteria of both harmful use and dependence, the diagnosis of DEPENDENCE should be made. Repeated detoxifications can produce „Kindling effect‟, so even mild withdrawal should be treated aggressively to prevent the increased severity of subsequent withdrawal episodes.
    75. 75.  In alcohol withdrawal seizures, avoid anticonvulsants unless there is H/O primary seizure disorder. (mainstay of t/t here is iv diazepam) In untreated DT mortality is upto 20%, so must be diagnosed and promptly treated. In Amnestic syndrome- Recent memory is impaired with ABSENCE of generalised cognitive impairment (presence of generalised cognitive impairment suggest dementia)
    76. 76.  Mainstay of t/t for amnestic syndr is Thiamine. (but has no role in t/t of withdrawal symptoms) Magnesium should be included in t/t for alcohol dependence. DOC for alcohol withdrawal is BZD (chlordiazepoxide or diazepam). Disulfiram- should be prescribed in motivated pt. only after explaining its s/e.

    ×