Textbook Notes (369,035)
Canada (162,359)
Psychology (9,698)
PSYC62H3 (313)
Chapter 10

Chapter 10 notes.doc

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Department
Psychology
Course
PSYC62H3
Professor
Suzanne Erb
Semester
Winter

Description
Chapter 10 sedative-hypnotics, Anxiolytics, and anticonvulsants - drug with sedative hypnotic properties perhaps the most commonly use and abused drugs in US - alcohol tops list - readily accepted in both recreational and medicinal contexts - alcoholics alone rep 20% of people seen in psych wards and 4% of deaths are related to alcohol (9% in the group of age between 15 and 29) - sedative-hypnotic low doses of these drugs have a psychological calming effect, and higher doses have a hypnotic, or sleep-inducing effect; drugs at lower doses can also induce activating effects - alcohol aka ethyl alcohol or ethanol; most used/abused recreational sedative-hypnotic in world - barbiturates and benzodiazepines are most frequently abused prescription sedative hypnotics - drugs with similar properties: qualitative effects are dose-related; low doses: mild activational effect, moderate doses: sedation and sleep; high doses: anesthesia, higher doses: coma, respiratory arrest, death ALCOHOL - most widely consumed; almost half of all men and one-third of all women - the alcohol in wine, hard cider, and beer is derived through interaction of yeast and sugar (fermentation) in fruits or grains, thus, it cannot reach alcohol concentrations high than 12-20% of total volume before the yeast is inactivated - Spirits are produced from concentration (distillation) of fermented solutions, and have a higher alcohol content (more than 20%) - The alcohol content is specified in terms of proof, which is exactly double the actual percentage of ethanol a beverage contains. 90-proof whiskey is 45% ethanol CHARACTERISTICS: - Not very potent drug, requiring several grams to exert noticeable effects on behaviour, rather than milligram amount - Takes between 25mg and 50mg of ethanol per 100 milliliters of blood (a blood alcohol content, or BAC, of 0.025% to 0.05%) to exert measurable effects in most individuals - Legal BAC limits for driving: between 0.0% and 0.05% - Alcohol also has somewhat different pharmacokinetic properties than most other drugs - Ethanol molecule is small, neutrally charged molecule it is readily absorbed from all compartments of the GI tract - Water soluble, unlike many psychoactive drugs - Readily passes through the blood-brain barrier and placenta due to sufficiently high oil/water partition coefficient - The onset of action is quick and its duration of action is short - Low fat solubility = females achieving higher plasma concentrations of alcohol than males, even when same amount of booze is ingested and they weigh the same - Metabolization - Alcohol is metabolized by alcohol dehydrogenase (ADH) at a fairly constant rate (zero-order kinetics when drugs are metabolized at a fairly constant rate, regardless of the amount taken) - With liver is responsible for the metabolism it also occurs at the upper GI tract site - Women only have about half the ADH in their stomachs as men, which (in addition to possessing a higher body fat to water ratio) explains their higher levels of intoxication when consuming similar amounts of alcohol as men - There are also differences among people of different ethnic backgrounds - East Asians have lower level of ADH in the stomach than Caucasians - Alcohol is a high calorie liquid and it provides the body with a ready source of calories 1 - The characteristics above contribute to some of the unique problems associated with alcohol - Chronic users of alcohol often suffer from liver damage because the liver spends a lot of time and energy trying to metabolize alcohol - Chronic users of alcohol also suffer from brain damage because the individuals are consuming a large portion of their calories in alcohol and neglecting to eat proper amounts of other foods containing proteins, nutrients, etc - Relative margin of safety is not high: - The BAC of persons who have died of acute alcohol exposure is around 0.5% (165 pound dude drinking 23 drinks in 4 hours) - Because responsible social drinking results in BACs of around 0.05% (165 pound dude drinking 4 drinks in 4 hours) therapeutic index of alcohol is around 10 not high - THERE ARE TWO BUILT IN MECHANISM THAT PREVENT LETHAL LEVELS OF ALCOHOL BEING REACHED: - If one approaches a BAC of 0.12% rapidly enough, vomiting may occur, because of local irritation of the GI tract or disturbances in vestibular functioning - Most persons become stuporous or pass out when a BAC of around 0.35% is reached. Therefore the lethal limit would be achieved only by those who consume alcohol rapidly enough to achieve a higher concentrations before they pass out Ethanol Pharmacokinetics - It takes approximately 1 hour for 90% of the alcohol in a drink to get into the bloodstream - Alcohols accumulation in the brain is rapid enough to exert noticeable effects within minutes - Whereas solid food in the stomach increases the absorption time, carbonated alcoholic beverages tend to enhance the absorption of alcohol because the carbonation forces the alcohol into the small intestine, where there is greater surface area for the absorption to take place and, thus, more rapid accumulation of alcohol in the brain - There is considerable lack of correspondence between the peak plasma levels of alcohol in the blood and the peak behavioural and subjective effects induced. - The behavioural effects of alcohol are far greater when plasma levels are on the rise than when they are falling - The fact that the same brain concentrations of ethanol during the rising and falling portions of the time-concentration function (a matter of an hour or two) induce substantially different effects suggests the development of acute tolerance (Tachyphylaxis) - The oxidative metabolism of ethanol into its first metabolite acetaldehyde can involve several organs and multiple enzymes (ADH I, cytochrome P 2E1 [CYP2E450 and catalase-H O [CAT-H O ] 2 2 2 2 - The liver accounts for about 90% of the alcohol metabolized - Acetaldehyde is very efficiently metabolized in the liver into acetic acid (acetate), primarily by NAD- linked aldehyde dehydrogenase (ALDH), which is further metabolized into carbon dioxide and water and then excreted - Acetaldehyde can be formed locally in the brain from the ethanol that escapes liver metabolism - ADH I, the main enzyme that metabolizes ethanol in the liver is not widely present in the brain; thus, local formation of acetaldehyde in this organ after alcohol ingestion is done by the other two enzymatic systems: CYP2E1 and catalase (60% if brain ethanol metabolism by catalase, and 20% by CYP2E1) - Mice: higher levels of acetaldehyde = reduction in preference for ethanol - Acetaldehyde has been considered a highly toxic substance when accumulated in significant amount in the periphery, because it induces nausea, headache, and high blood pressure, and cellular damage - Acetaldehyde in small amounts in the brain psychoactive substance capable of regulating neuronal activity, and behavioural processes 2 - Acetaldehyde can have different effects depending on its concentration. This is an important factor that can explain some of the failures that can occur after the implementation of pharmacological treatments for alcoholism based on the aversive reaction induced by acetaldehyde accumulation Neurochemical effects of ethanol - Acute ethanol administration induces marked changes in the patterns of regional brain metabolism, with relative increases in some areas and decreases in others, which may be correlated with the different behavioural effects of alcohol - This effect is also mimicked by its second metabolite, acetate - NEUROPHARMACOLOGICAL LEVEL: - Alcohol at high doses: act directly on neuronal membranes by altering their basic structure and making them more fluidwhich may inhibit the movement of the Na+ and K+ ions across the membranes and interfere with the ability of the neuron to generate and conduct action potentials - Alcohol at low doses: intoxication, affects wide variety of neurotransmitter systems in the brain. this makes is difficult to determine which ones are most relevant to intoxication, tolerance, dependence, and withdrawal, as well as which ones might be targets for drug therapy - Acute exposure to ethanol dose-dependently increases the release of dopamine in the nucleus accumbens, thus promoting behavioural activation. Oral dose of ethanol promotes DA release in the human nucleus accumbens - Ethanol also appears to enhance activity of opioid receptors - Acetaldehyde produces very similar patterns of effects on the dopaminergic and opioid systems Two key receptors relevant to alcohols subjective effects and the development of tolerance and dependence with chronic us
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