Week 11 Notes - Alcohol, tobacco, drugs PDF

Cigarette smoking Incidence of deaths from cigarette smoking and the diseases associated with it.  Tobacco was introduced to Europe in 1559, and by the late 17th century, it was used not only for smoking but also as an insecticide.  Two thirds of today’s smokers live in 10 coun...

Cigarette smoking Incidence of deaths from cigarette smoking and the diseases associated with it.  Tobacco was introduced to Europe in 1559, and by the late 17th century, it was used not only for smoking but also as an insecticide.  Two thirds of today’s smokers live in 10 countries: China (~30%), India (~ 10%), followed by Indonesia, Russia, US, Japan, Brazil, Bangladesh, Germany, and Turkey.  ~ 4 millions of death annually, world wide  in US responsible for > 440,000 deaths per year (out of 2.4 million annual deaths)  Bronchogenic carcinoma- 169,000 deaths/year. >80% of lung cancers  Increases risk of cancer of the larynx, oral cavity, and esophagus by sevenfold. Contributes to cancer of kidney, urinary bladder and pancreas.  COPD – 124,000 deaths annually  Atherosclerosis- 1 pack/day increases risk of CHD twofold, and sevenfold for  During pregnancy affects fetus. Increased risk of spontaneous abortions, decreased birth weight, and increased perinatal mortality.  Contributes to acute gastritis  Increases risk of those who are exposed to asbestos Factors that affect the magnitude of the risk  Cumulative exposure i.e. number of cigarettes smoked a day and the years of use. o The pack-year = the amount a person has smoked over a long period of time. = [the number of packs of cigarettes smoked per day] multiplied by [the number of years the person has smoked]. o 1 pack-year is equal to smoking 20 cigarettes (1 pack) per day for 1 year, = 365.24 packs of cigarettes or 7,305 cigarettes, in a year.  Age at onset  Depth of inhalation  Concomitant exposure e.g. asbestos, alcohol  Possibly genetic factors Components  Nicotine: o ~ 2 mg per smoked cigarette (~ 3% of the dried tobacco plant) o binds to nicotinic acetylcholine receptors in CNS have higher affinity than those in muscles o stimulates the release of catecholamines from sympathetic neurons, & from adrenal glands. o → acute effects of smoking, such as: ↗ heart rate, blood pressure, cardiac contractility and output o Highly addictive: stimulate the reward pathway by ↗ dopamine and endorphins o Mild analgesic o half-life of 1–2 hours. metabolized in the liver, mostly by cytochrome P450 enzymes Dr M Hossu Notes 179  o inhibited by menthol → longer effects o also present in potato, tomato, eggplants (microdoses)  toxins and carcinogens (more than 60, out of thousands) Substance Effect Tar Carcinogenesis Polycyclic aromatic hydrocarbons Carcinogenesis Phenol Tumor promotion; mucosal irritation Benzo[a]pyrene Carcinogenesis Carbon monoxide Impaired oxygen transport and utilization Formaldehyde Toxicity to cilia; mucosal irritation Nitrogen oxides Toxicity to cilia; mucosal irritation Nitrosamine Carcinogenesis Benefits of quitting  Risk of sudden death falls the most rapidly, within about 24 hours  Risk of myocardial infarction falls rapidly. After 12-23 months the risk falls from 3 fold to 2 fold and after longer periods to baseline  For first 9 years risk of COPD continues to rise and then starts to fall  Fall in mortality from bronchogenic cancer occurs after 5-9 years and approaches baseline levels after 14 years of abstinence  Reduced predisposition to other diseases Passive smoking  Passive smokers may inhale the equivalent of 3 cigarettes per day.  Inhale side stream smoke, which contains different substances than mainstream smoke  relative risk of lung cancer in nonsmokers exposed to environmental smoke is about 1.3 times higher than that of nonsmokers who are not exposed to smoke.  Also higher rates of CHD and fatal MIs Cigar and pipe smoking o are not as dangerous since the smoke is not usually inhaled as deeply, o are still associated with oral, laryngeal and gastric cancers Smokeless tobacco use o is an important cause of oral cancers e-cigarettes o vaporized nicotine and flavorings Dr M Hossu Notes 180  Ethyl alcohol abuse (Alcoholism) Incidence of alcoholism o Estimated 10% of all men and 5% of all women o About 50% of these suffer actual physical disease o Recreational use is an accepted social practice worldwide  Can cause socially unacceptable behavior and even criminal behavior  Implicated as contributing cause in 50% of fatal traffic accidents Mechanisms o CNS depressant  Negative modulator of NMDA glutamate (excitatory) receptors  Positive modulator of inhibitory GABA receptors  Depresses the inhibition centers first so appears to be a stimulant  Decreases levels of NO in brain medulla → decreased blood flow to the brain o Increased levels of dopamine and endogenous opioids in the mesolimbic pathway (reward pathway), o release of endotoxin (lipopolysaccharide) from gram-negative bacteria in the intestinal flora → stimulates the production of TNF (tumor necrosis factor) and other cytokines from macrophages Clinical syndromes  Acute alcoholic intoxication o Blood alcohol concentration (BAC) - measured in (mg/dl)  50mg/dl (0.05 %): impairs, fine motor skills and reaction times; induces euphoria, talkativeness, relaxation, pleasure, joyfulness  100 mg/dl produces CNS depression, ataxia, sedation, nausea, impaired memory & cognition  200 mg/dl drowsiness  300 mg/dl stupor  400-500 mg/dl death occurs o Acute liver injury  Toxic acetaldehyde metabolite major in the liver  Consumption of NAD → lac c acidosis and increase FA accumulation o Hemolytic anemia o Acute gastritis o Factors the influence the BAC  Rate of ingestion  Rate of absorption  Rate of tissue distribution  Rate of metabolism  Rate of excretion Dr M Hossu Notes 181   Average rate of metabolism is 150 mg/kg/hr  20ml of alcohol per hour for a 70 kg individual  1 can of beer, one shot of whisky or one glass of wine /hr o A concentration of 80 mg/dL in the blood constitutes the legal definition of drunk driving in the United States. o For an average individual, this alcohol concentration may be reached after consumption of three standard drinks, about three (12 ounce) bottles of beer, 15 ounces of wine, or 4 to 5 ounces of 80 proof distilled spirits.  Chronic alcohol intoxication o 9th leading cause of death in the US o Chronic alcoholic liver disease – Intake of 50 g/day.:  fatty liver, alcoholic hepatitis, and cirrhosis,  →portal hypertension  ↗ risk for development of hepatocellular carcinoma. o Chronic pancreatitis o Alcoholic cardiomyopathy o Nervous system abnormality o Associated malnutrition o Inadequate intake of food o Vitamin deficiency  Deficiencies of vitamin A – amblyopia  Thiamin – Wernicke encephalopathy, Korsakoff’s psychosis  Folic acid- megaloblastic anemia  Pyridoxine- sideroblastic anemia (looks like iron deficiency but iron levels are normal) o ↗ risk factor for cancers of the oral cavity, larynx, and esophagus.  The risk is greatly increased by concurrent smoking or use of smokeless tobacco.  Fetal alcohol syndrome o First described in France in 1968. o Dose related fetal growth retardation and increased perinatal mortality rates. o Consumption during the first trimester of pregnancy is particularly harmful. o the prevalence of frequent and binge drinking among pregnant women is ~6% & fetal alcohol syndrome affects 1 to 4.8 per 1000 children born in the United States o Heavy drinking leads to mental retardation.  Alcohol withdrawal syndrome o Psychological dependency o Physical dependency o upregulation of NMDA receptors due to chronic consumption (brain is attempting to reestablish homeostasis)→ excitotoxicity Dr M Hossu Notes 182  o Delirium tremens o Dehydration, electrolyte imbalance, excitability and autonomic system hyperactivity  Light / Moderate / Social drinking o increased overall survival o possible protective effects against coronary heart disease.  increase high-density lipoprotein (HDL) levels,  inhibit platelet aggregation,  lower fibrinogen levels Psychotropic drug abuse Types of drugs involved 1. Stimulants such as cocaine and amphetamines 2. Depressants such as heroin, barbiturates and benzodiazepines 3. Hallucinogens such as marijuana, LSD and PCP Methods of administration of the drug 1. Ingestion 2. Smoking 3. Inhalation 4. Sniffing 5. Injecting into the skin 6. Injected intravenously Effects of psychotropic drugs  Direct effects o All psychotropic drugs have effects on the nervous system o Alteration in mental function increases risk of traffic accidents, criminal behavior, and acts of violence including suicide o Habitual use leads to emotional and physical dependence o Severe withdrawal symptoms occur if the drug is withheld o Cocaine can produce hypertension and arrhythmias  Indirect effects o Effects of contaminants o Infections- at site of injection, bacteremia and endocarditis, HIV Hepatitis B  Long term effects o Marijuana: Chronic bronchitis and bronchial epithelial abnormalities, Reproductive abnormalities o Cocaine sniffing destroys the nasal septum Dr M Hossu Notes 183