Clinical presentation of chronic alcohol use
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1. Chronic alcohol use can lead to alcohol use disorder, characterized by increased tolerance, withdrawal symptoms, and impaired control over drinking. Prolonged heavy drinking causes adaptive changes in the brain that can result in addiction. 2. Alcohol is broken down in the liver by enzymes, producing toxic compounds like acetaldehyde that can damage cells. Intoxication from high alcohol levels causes impaired behavior and thinking, while withdrawal can cause tremors, anxiety, and occasionally seizures. 3. Heavy long-term drinking is associated with increased risks of liver diseases like fatty liver, hepatitis, and cirrhosis as well as cancers, heart and digestive problems, immune system weaknesses, birth defects, and bone damage.
Clinical presentation of chronic alcohol use
- 2. OVERVIEW • Alcohol-use disorder results from a variety of genetic, psychological, and environmental factors. It is characterized by increased tolerance to the effects of alcohol, the presence of characteristic withdrawal signs and symptoms, and impaired control over the quantity and frequency of drinking. Prolonged exposure causes adaptive changes in brain receptors and neurotransmitters, leading to effects such as addiction, tolerance, and withdrawal. Alcohol-use disorder, particularly when chronic and severe, can be associated with a variety of medical and psychiatric sequelae.
- 3. THE CHEMICAL BREAKDOWN OF ALCOHOL IN THE BODY • The chemical name for alcohol is ethanol (CH3CH2OH). • The body processes and eliminates ethanol in separate steps. Chemicals called enzymes help to break apart the ethanol molecule into other compounds (or metabolites), which can be processed more easily by the body. Some of these intermediate metabolites can have harmful effects on the body. • Most of the ethanol in the body is broken down in the liver by an enzyme called alcohol dehydrogenase (ADH), which transforms ethanol into a toxic compound called acetaldehyde (CH3CHO), a known carcinogen. However, acetaldehyde is generally short-lived; it is quickly broken down to a less toxic compound called acetate (CH3COO-) by another enzyme called aldehyde dehydrogenase (ALDH). Acetate then is broken down to carbon dioxide and water, mainly in tissues other than the liver.
- 4. ALCOHOL USE DISORDER CAN INCLUDE PERIODS OF ALCOHOL INTOXICATION AND SYMPTOMS OF WITHDRAWAL. • Alcohol intoxication results as the amount of alcohol in your bloodstream increases. The higher the blood alcohol concentration is, the more impaired you become. Alcohol intoxication causes behavior problems and mental changes. These may include inappropriate behavior, unstable moods, impaired judgment, slurred speech, impaired attention or memory, and poor coordination. You can also have periods called "blackouts," where you don't remember events. Very high blood alcohol levels can lead to coma or even death. • Alcohol withdrawal can occur when alcohol use has been heavy and prolonged and is then stopped or greatly reduced. It can occur within several hours to four or five days later. Signs and symptoms include sweating, rapid heartbeat, hand tremors, problems sleeping, nausea and vomiting, hallucinations, restlessness and agitation, anxiety, and occasionally seizures. Symptoms can be severe enough to impair your ability to function at work or in social situations.
- 5. WHAT ALCOHOL REALLY DOES TO YOUR BRAIN When a person consumes alcohol above and beyond moderate levels, it can have damaging effects on the body and on the brain. Alcohol reduces glutamate excitotoxicity (VTA); enhances GABA inhibitory activity (VTA) and enhances dopamine release from the VTA to NA by disinhibiting GABA via endogenous opioids. The release of dopamine mediates alcohol’s pleasurable and reinforcing actions. 1-“For starters, alcohol slows down the neurotransmitter GABA, and that’s what drives the sluggish movement, slurred speech, and slower reaction time in someone who’s intoxicated,”. 2-At the same time, alcohol speeds up a neurotransmitter called glutamate, which is responsible for regulating dopamine in the brain’s reward center. “It’s generating feelings of pleasure and well-being,”. “That’s why you might get that warm, fuzzy feeling when you’re drinking.” 3-alcohol also increases the release of dopamine in your brain's "reward center“. The effect is that you keep drinking to get more dopamine release, but at the same time you're altering other brain chemicals that are enhancing feelings of depression.
- 6. ALCOHOL LIVER DISEASE 1-Alcoholic Fatty Liver:- • Alcohol exposure may induce fatty liver by increasing NADH/NAD+ ratio, increasing sterol regulatory element‐binding protein‐1 (SREBP‐1) activity, decreasing peroxisome proliferator‐activated receptor‐α (PPAR‐α) activity, and increasing complement C3 hepatic levels. Alcohol may increase SREBP‐1 activity by decreasing the activities of AMP‐activated protein kinase and sirtuin‐1. • (TNF‐α) produced in response to alcohol exposure may cause fatty liver by up‐regulating SREBP‐1 activity, whereas betaine and pioglitazone may attenuate fatty liver by down‐regulating SREBP‐1 activity. PPAR‐α agonists have potentials to attenuate alcoholic liver. Adiponectin and interleukin‐6 may attenuate alcoholic fatty liver by up‐regulating PPAR‐α and insulin signaling pathways while down‐regulating SREBP‐1 activity and suppressing TNF‐α production. • Furthermore, oxidative modifications and inactivation of the enzymes involved in the mitochondrial and/or peroxisomal β‐oxidation of fatty acids could contribute to fat accumulation in the liver.
- 7. ALCOHOL LIVER DISEASE 2-Alcoholic hepatitis:- (inflammation of the liver) due to excessive intake of alcohol. - Alcoholic hepatitis is characterized by the inflammation of hepatocytes. - Inflammatory cytokines (TNF-alpha, IL6 and IL8) are thought to be essential in the initiation and perpetuation of liver injury by inducing apoptosis and necrosis. One possible mechanism for the increased activity of TNF-α is the increased intestinal permeability due to liver disease. - This facilitates the absorption of the gut-produced endotoxin into the portal circulation. The Kupffer cells of the liver then phagocytose endotoxin, stimulating the release of TNF-α. TNF- then triggers apoptotic pathways through the activation of caspases, resulting in cell death.
- 8. ALCOHOL LIVER DISEASE 3-Cirrhosis:- -Cirrhosis is a late stage of serious liver disease marked by inflammation (swelling), fibrosis (cellular hardening) and damaged membranes preventing detoxification of chemicals in the body, ending in scarring and necrosis (cell death). -Acetaldehyde may be responsible for alcohol-induced fibrosis by stimulating collagen deposition by hepatic stellate cells. -The production of oxidants derived from NADPH oxi- dase and/or cytochrome P-450 2E1 and the formation of acetaldehyde-protein adducts damage the cell membrane.
- 9. DIGESTIVE PROBLEMS 1- Gastritis:- Heavy drinking can result in inflammation of the stomach lining (gastritis), as well as stomach and esophageal ulcers. - Drinking – even a little – makes your stomach produce more acid than usual, which can in cause gastritis (the inflammation of the stomach lining). This triggers stomach pain, vomiting, diarrhoea and, in heavy drinkers, even bleeding. 2-pancreatitis:- - Scientists aren’t sure exactly how alcohol causes the condition. One theory is that the molecules in alcohol interfere with the cells of the pancreas, stopping them working properly. Whatever the cause, there is a clear link between drinking alcohol and acute pancreatitis – and the more alcohol you drink, the higher your risk of developing the condition.
- 10. HEART PROBLEMS - Drinking too much alcohol can raise the levels of some fats in the blood (triglycerides). - It can also lead to high blood pressure, heart failure and an increased calorie intake. (Consuming too many calories can lead to obesity and a higher risk of developing diabetes.) - Excessive drinking and binge drinking can lead to stroke. Other serious problems include fetal alcohol syndrome, cardiomyopathy, cardiac arrhythmia and sudden cardiac death. Weakened Immune System - Excessive drinking reduces the number and function of three important kinds of cells in your immune system–macrophages, T and C cells. - Alcohol affects the way health gut microbes interact with the immune system. Alcohol also disrupts the gut barrier, allowing more bacteria to pass into the blood. These rogue bacteria can cause inflammation in the liver and may lead to liver damage. - Excessive drinking may impair the function of immune cells in the lungs and upper respiratory system, leading to increased risk for pneumonia, tuberculosis, and acute respiratory distress syndrome, or ARDS.
- 11. ALCOHOL INCREASED RISK OF CANCER • Multiple ways that alcohol may increase the risk of cancer, including: 1) metabolizing (breaking down) ethanol in alcoholic drinks to acetaldehyde, which is a toxic chemical and a probable human carcinogen; acetaldehyde can damage both DNA (the genetic material that makes up genes) and proteins 2) generating reactive oxygen species (chemically reactive molecules that contain oxygen), which can damage DNA, proteins, and lipids (fats) in the body through a process called oxidation 3) impairing the body’s ability to break down and absorb a variety of nutrients that may be associated with cancer risk, including vitamin A; nutrients in the vitamin B complex, such as folate; vitamin C; vitamin D; vitamin E; and carotenoids 4) increasing blood levels of estrogen, a sex hormone linked to the risk of breast cancer.
- 12. #OTHER COMPLICATIONS • Drinking too much alcohol on a single occasion or over time can cause health problems, including: 1) Diabetes complications. Alcohol interferes with the release of glucose from your liver and can increase the risk of low blood sugar (hypoglycemia). This is dangerous if you have diabetes and are already taking insulin to lower your blood sugar level. 2) Birth defects. Alcohol use during pregnancy may cause miscarriage. It may also cause fetal alcohol syndrome, resulting in giving birth to a child who has physical and developmental problems that last a lifetime. 3) Bone damage. Alcohol may interfere with the production of new bone. This bone loss can lead to thinning bones (osteoporosis) and an increased risk of fractures. Alcohol can also damage bone marrow, which makes blood cells. This can cause a low platelet count, which may result in bruising and bleeding. 4) Medication and alcohol interactions. Some medications interact with alcohol, increasing its toxic effects. Drinking while taking these medications can either increase or decrease their effectiveness, or make them dangerous. 5) Sexual function and menstruation issues. Excessive drinking can cause erectile dysfunction in men. In women, it can interrupt menstruation. 6) Eye problems. Over time, heavy drinking can cause involuntary rapid eye movement (nystagmus) as
- 13. TREATMENT• Treatment for alcohol use disorder may include: • Detox and withdrawal. Treatment may begin with a program of detoxification or detox — withdrawal that's medically managed — which generally takes two to seven days. You may need to take sedating medications to prevent withdrawal symptoms. Detox is usually done at an inpatient treatment center or a hospital. . Oral medications: 1- Disulfiram (Antabuse) may help prevent you from drinking, although it won't cure alcohol use disorder or remove the compulsion to drink. *Mechanism of action: Disulfiram works by inhibiting the enzyme acetaldehyde dehydrogenase, so the concentration of acetaldehyde in the blood may be five to 10 times higher than that found during metabolism of the same amount of alcohol alone. As acetaldehyde is one of the major causes of the symptoms of a "hangover,“ , Symptoms include flushing of the skin, accelerated heart rate, shortness of breath, nausea, vomiting, throbbing headache, visual disturbance, mental confusion, postural syncope, and circulatory collapse. *Side effects: drowsiness, tiredness, headache, metallic or garlic-like taste in the mouth, skin rash or acne, impotence, and swollen or sore tongue, vision changes, numbness or tingling of arms and legs, muscle weakness, mental/mood changes, seizures.
- 14. TREATMENT 2-Naltrexone: a drug that blocks the good feelings alcohol causes, may prevent heavy drinking and reduce the urge to drink. Naltrexone does not treat alcohol or drug withdrawal symptoms, but can help people who've already stopped using remain drug- or alcohol-free. *The mechanism of action of naltrexone in alcoholism is not understood, but some scientists believe it works by decreasing the reinforcing effects of alcohol in certain neural pathways in the brain. *Side effects: nausea ,vomiting, loss of appetite , Headache ,dizziness , anxiety , Irritability , , tearfulness, Drowsiness, muscle or joint pain , Rash ,increased or decreased energy ,confusion , Hallucinations ,blurred vision , severe vomiting and/or diarrhea.
- 15. TREATMENT 3-Acamprosate (Campral): * Mechanism of action: Acamprosate is thought to stabilize the chemical balance in the brain that would otherwise be disrupted by alcoholism, possibly by blocking glutaminergic N-methyl-D-aspartate while gamma-aminobutyric acid type A receptors are activated. *side effects: include allergic reactions, irregular heartbeats, and low or high blood pressure, headaches, insomnia, and impotence. *contraindicated: Acamprosate should not be taken by people with kidney problems or allergies to the drug.
- 16. TREATMENT • Injected medication. Vivitrol, a version of the drug naltrexone, is injected once a month by a health care professional. Although similar medication can be taken in pill form, the injectable version of the drug may be easier for people recovering from alcohol use disorder to use consistently. • Treatment for psychological problems. Alcohol use disorder commonly occurs along with other mental health disorders. If you have depression, anxiety or another mental health condition, you may need talk therapy (psychotherapy), medications or other treatment. • Medical treatment for health conditions. Many alcohol-related health Problems improve significantly once you stop drinking. But some health conditions may warrant continued treatment and follow-up.