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Addiction and Drug Abuse By S.Bohlooli, PhD Cultural Consideration Licit or Illicit ?! Resultant criminal activity leads to make an agent considered as illicit. Activity like: robbery, prostitution and other antisocial activity. •Drug Misuse A drug might be used for a wrong indication, or wrong dosage, and or too long period •Drug Abuse abuse might be construed as any use of drug for non medical purpose substance dependence (addiction) cluster of symptoms indicating that the individual continues use of the substance despite significant substance-related problems. PHYSICAL AND PSYCHOLOGICAL DEPENDENCE Physical dependence is a state that develops as a result of the adaptation (tolerance) produced by a resetting of homeostatic mechanisms in response to repeated drug use. Psychological dependence is manifested by compulsive drug seeking behavior in which the individual uses the drug repetitively for personal satisfaction often in the face of known risks to health Tolerance is the most common response to repetitive use of the same drug and can be defined as the reduction in response to the drug after repeated administrations Types of Tolerance •Innate (preexisting sensitivity or insensitivity) •Acquired Pharmacokinetic (dispositional or metabolic) Pharmacodynamic Learned tolerance Behavioral •Conditioned Acute tolerance Reverse tolerance (sensitization) Cross-tolerance Origins of Substance Dependence Agent (drug) Host (user) Environment Agent (drug) Availability Cost Purity/potency Mode of administration: Chewing (absorption via oral mucous membranes) Gastrointestinal Intranasal Subcutaneous and intramuscular Intravenous Inhalation Speed of onset and termination of effects Pharmacokinetics: combination of agent and host Host (user) Heredity Innate tolerance Speed of developing acquired tolerance Likelihood of experiencing intoxication as pleasure Psychiatric symptoms Prior experiences/expectations Propensity for risk-taking behavior Environment Social setting Community attitudes Peer influence, role models Availability of other reinforcers (sources of pleasure or recreation) Employment or educational opportunities Withdrawal Syndrome Withdrawal signs and symptoms occur when drug administration in a physically dependent person is abruptly terminated. Withdrawal symptoms have at least two origins: (1) removal of the drug of dependence, (2) central nervous system hyperarousal due to readaptation to the absence of the drug of dependence. VII. Co-administration/Coabuse Many of these drugs are used in combination with other drugs from one or more categories. Alcohol is used, for example, with almost everything else. Smoking (nicotine intake) is prevalent in patients using other drugs. Be aware of the possibility of combination of drugs when treating intoxication, withdrawal or overdose, each drug will require a specific treatment. Neurobiology of Abused Drugs Many drugs acts through G protein coupled receptor (dopamine, opioid and cannabinoid) Chloride Ion channel associated with GABA (benzodiazepines) Excitatory amino acid receptors (phencyclidine) I. Animal Studies A) Drug-self administration Drugs as reinforcers animals. High correlation with human dependence liability. in Morphine/Heroin Self-Administration II. Brain Reward System Changes in brain function => Reward=> Craving Involve the Dopaminergic System Mesolimbic pathway:Ventral tegmental area (VTA), medial forebrain bundle, nucleus accumbens and the prefrontal cortex. Nigrostriatal pathway: Sustantia nigra, striatum. Mesocortical pathway: VTA, cingulate and frontal CTX. Tubero-Infundibular: Arcuate N. in hypothalamus. THE DOPAMINERGIC SYSTEM THE MESOLIMBIC DOPAMINERGIC REWARD PATHWAY Tyrosine Tyrosine L-DOPA DA Dopamine Synapse Dopamine Reuptake System Alcohol consumption Sedation Relief of anxiety Slurred speech Ataxia Impaired judgment Disinhebited behavior Alcohol Withdrawal Syndrome Alcohol craving Tremor, irritability Confusion Visual hallucinations Nausea Sleep disturbance Fever, profuse sweating Tachycardia Tachycardia Hypertension Nausea, diarrhea Dilated pupils Sweating Perceptual distortion Seizures (12 to 48 hours after last drink) Severe agitation Delirium tremens (rare in uncomplicated withdrawal) Benzodiazepine Withdrawal Symptoms Following moderate dose usage Anxiety, agitation Increased sensitivity to light and sound Paresthesias, strange sensations Muscle cramps Myoclonic jerks Sleep disturbance Dizziness Following high-dose usage Seizures Delirium Nicotine Withdrawal Syndrome Irritability, impatience, hostility Anxiety Dysphoric or depressed mood Difficulty concentrating Restlessness Decreased heart rate Increased appetite or weight gain Clinical aspect of opioid use Rush: an orgasm like reaction Euphoria Feeling of tranquility and sleepiness Opioid Withdrawal SYMPTOMS SIGNS Regular Withdrawal Craving for opioids Pupillary dilation Restlessness, irritability Sweating Increased sensitivity to pain Piloerection ("gooseflesh") Nausea, cramps Tachycardia Muscle aches Vomiting, diarrhea Dysphoric mood Increased blood pressure Insomnia, anxiety Yawning Fever Protracted Withdrawal Anxiety Insomnia Drug craving Cyclic changes in weight, pupil size, respiratory center sensitivity CNS stimulants Clinical aspects of stimulants Rush Mental alertness Marked euphoria Delusion (bugs are crawling under skin!) Spree use ( up to 4000 mg /day amphetamine) Lack of food Lack of sleep Cocaine Withdrawal Symptoms and Signs Dysphoria, depression Sleepiness, fatigue Cocaine craving Bradycardia Clinical effect of marijuana Being high Euphoria Uncontrollable laughter Alteration of time sense Depersonalization Sharpened vision Late: becoming relaxed, experience of introspective and dream-like effect Difficulty in concentration and thinking Marijuana Withdrawal Syndrome Restlessness Irritability Mild agitation Insomnia Sleep EEG disturbance Nausea, cramping Drugs Kill the Brain