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Pharmacology and Toxicology
PHAR 100
Hisham Elbatarny

Drug Tolerance, Physical and Psychological Dependence Outline • Introduction • Drug Dependence ◦ Tolerance ◦ Dependence ◦ Addiction • DrugAbuse ◦ Medical Perspective ◦ Social Perspective • Abuse Potential ◦ Intrinsic Dependence Liability ◦ Availability ◦ Inherent Harmfulness Introduction • drug addiction and dependence is a serious social and financial problem for many individuals and for society • can cause illness and death • may lead to crime to financially support use • occurs across all social groups and ages ◦ young: Illicit drugs, alcohol, tobacco ◦ older adults: benzodiazepines, barbiturates, alcohol, tobacco Magnitude of the Problem Canadian Centre on SubstanceAbuse: • “The Costs of SubstanceAbuse in Canada 2002” : survey released in 2006 • economic impact of substance abuse in Canada is $39.8 billion annually ◦ alcohol = $14 billion (37%) ◦ tobacco = $17 billion (43%) ◦ illegal drugs = $8.2 billion (21%). Have to take data w/ a grain ofsalt:some people maylie Alcohol Specifically • economic impact of alcohol is about $14 billion ◦ $7.1 billion to lost productivity due to illness and premature death ◦ $3.3 billion for direct health care costs ◦ $3.1 billion for enforcement costs • of the 33 million people in Canada (2011), estimated 4% dependent on alcohol = 1.32 million people • 27 034 hospital admissions per year related to alcohol • highest rate of alcoholism between ages of 20-24 • Centre for Addiction and Mental Health (March 2013) ◦ Canadians drink more than 50% above the global average ◦ alcohol is the third leading cause of the global burden of disease and injury Drug Dependence • a state of periodic or chronic intoxication produced by repeated consumption of a drug (natural or synthetic). Characteristics: • desire to take the drug and obtain it by any means • tendency to increase the dose • addiction to and physical dependence on the effects of the drug • compulsive and harmful behaviour Characteristics of Compulsive and Harmful Behaviour Compulsive • takes larger doses, for a longer period than intended • may express desire to discontinue drug, but are unsuccessful • lots of time is spent obtaining and using the drug • daily activities revolve around the drug • withdrawal from family and friends Harmful • a pattern of psychoactive use that is causing damage to health • continue to use the drug even though the user recognizes the potential damage • damage can be physical (hepatitis) or mental (depression) Drug Dependence • three important aspects of drug dependence: 1. Tolerance 2. Dependence (physical dependence) 3. Addiction (psychological) Tolerance • repeated administration of a given dose of drug has progressively less effect • in other words: the dose of a drug must be increased to obtain the same magnitude of pharmacological effect that was first achieved Tolerance • not all effects achieve tolerance at the same rate ◦ occurs with opioids and alcohol ◦ different mechanism must govern different rates of tolerance • once the drug has been stopped, tolerance can also disappear (depending on the drug) • tolerance can develop to drugs other than CNS drugs ◦ eg. nitroglycerin (for angina aka pain in heart) and antihypertensive • cross-tolerance: usually between similar acting drugs Cross Tolerance • when taking drug “A” not only leads to tolerance to that drug but also to drug “B” • cross tolerance occurs when: ◦ drug “B” interacts with the same receptor as drug “A” ▪ ex: methadone and heroin both act on same exact opioid receptor (same spot!) ◦ drug “B” has a similar interaction at the same receptor system used by drug “A”, but, Drug “B” interacts with a different receptor ▪ ex: benzodiazepine and alcohol: both bind to GABAreceptors, but different sites Mechanisms of Tolerance Metabolic Tolerance: • drug metabolism and elimination increased ◦ up-regulation of enzymes: break down more drug ◦ less drug at site of action Pharmacodynamic (Physiological) Tolerance: • body compensates for the effect of the drug ◦ homeostasis (need to maintain normal function) ▪ ex: can increase or decrease # of receptors at site (tolerance usually decreases #) Dependence • abnormal physiological state produced by repeated administration of a drug that leads to the appearance of a characteristic and specific group of symptoms when drug administration is discontinued or decreased • aka withdrawal syndrome Dependence • severity of withdrawal syndrome determines magnitude of dependence • symptoms of withdrawal syndrome often opposite of drug effects ◦ i.e. withdrawal from CNS stimulant is depressant effects • relief of symptoms occurs by taking the drug: negative reinforcement • withdrawal symptoms usually occur hours after the drug is discontinued ◦ can be manipulated by antagonists: n
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