Drug Dependence

Idiosyncrasy : 

Idiosyncrasy

Idiosyncrasy: 

Idiosyncrasy Idiosyncrasy , from Ancient Greek idiosynkrasía , "a peculiar temperament", "habit of body" ( idios "one's own", syn "with" and krasis "mixture") is defined as an individualizing quality or characteristic of a person or group, and is often used to express eccentricity or peculiarity An unusual individual reaction to food or a drug

Idiosyncrasy: 

Idiosyncrasy It is defined as qualitatively abnormal response to a drug Can be seen even after the first dose Highly unpredictable Has a genetic basis Seen only in small percentage in a population Can be fatal

Idiosyncrasy…: 

Examples Aplastic anemia with Chloramphenicol Broad spectrum antibiotic Occurs 1 in 32, 000 patients Can produce irreversible bone marrow suppression leading to inhibition of maturation & decrease in number of RBCs, on first administration Can be fatal Idiosyncrasy…

Idiosyncrasy…: 

Examples Individuals with G6PD (an enzyme that maintains the content of GSH in red cells, and thus prevent hemolysis) deficiency cannot tolerate primaquine or some sulfonamide drugs (well tolerated in most individuals) These individuals will suffer from hemolysis leading to severe anemia Primaquine and related substances reduce red cell GSH harmlessly in normal cells, but enough to cause hemolysis in G6PD-deficient cells Idiosyncrasy…

Slide 6: 

Drug Dependence or Drug Abuse

Drug Abuse?: 

Taking a Drug for any reason other than a medical one… To get a feeling of euphoria (high) To enhance athletic ability (steroids) Drug Abuse?

Slide 8: 

What is addiction?

Addictive? : 

If it causes, “uncontrollable compulsive drug seeking and use, even in the face of negative health and social consequences.” Results from both psychological and physical dependence on the drug Addictive?

Drug Dependence / Addiction : 

Drug Dependence / Addiction Condition in which person has a continuing desire to take the drug compulsive craving to take the drug The demand of the drug dominates the life style of the individual This state of periodic or chronic intoxication occurs after excessive, repeated and persistent self administration of certain drugs It is harmful for him and the community

Drug Dependence / Addiction… : 

WHO Definition A state, generally psychic but sometimes physical that results from interaction between the living organisms and certain drugs, leading to behavioral / other responses that always include a compulsion to take the drug periodically or constantly to obtain its psychic effects (Euphoria) or to avoid the discomfort of its absence Drug Dependence / Addiction…

Drug Dependence / Addiction… : 

Biological phenomena Having following components a. Euphoria b. Tolerance c. Psychic dependence (Habituation) d. Physical dependence e. Abstinence / Withdrawal syndrome Drug Dependence / Addiction…

Drug Dependence – Components… : 

Drug Dependence – Components… a. Euphoria Pleasant floating sensation & forgetfulness from worries. Person is happy irrespective of circumstances Major component responsible for drug abuse

Drug Dependence – Components… : 

b. Tolerance A ↓ response to a drug requiring ↑ in dose to achieve the initial effect. So person has to take ever increasing doses of drug Tolerance may be: Pharmacokinetic / metabolic Tolerance -- ↑ metabolism / disposition Pharmacodynamic or functional Tolerance ---- changes in receptor or effector systems involved in drug action Cross tolerance Drug Dependence – Components…

Drug Dependence – Components… : 

c. Psychic dependence (Habituation) / Addiction Personal is emotionally dependent on the drug Manifested by compulsive drug using behavior Drug is used repetitively for personal satisfaction No harm is done if drug is not provided It precedes physical dependence Exp: Tea, Coffee, Smoking Drug Dependence – Components…

Drug Dependence – Components… : 

d. Physical dependence The person depends upon the drug for normal physical activities The presence of certain amount of drug is necessary in body fluids especially ECF for the normal physical activities of life drug becomes a sort of essential food for the person Drug Dependence – Components…

Drug Dependence – Components… : 

d. Physical dependence… The body adjusts to a new level of homeostasis during the period of drug use & reacts in opposite fashion when this is disturbed Withdrawal of the drug produces symptoms & signs, frequently the opposite of those caused by the drug. Drug Dependence – Components…

Drug Dependence – Components…: 

Drug Dependence – Components… e. Abstinence / Withdrawal syndrome A condition to describe the signs & symptoms that occur on withdrawal of the drug in a physically dependent person The manifestations are opposite to the effect of drug e.g. Morphine produces sleep, relief of pain, constipation Withdrawal produces insomnia, pain all over the body & diarrhoea

Drug Addiction : 

Drug Addiction Addiction is a behavioral pattern characterized by a compulsive use of a drug. It indicates psychological dependence Addiction is used synonymously with drug dependence

Slide 20: 

How do drugs of addiction work? Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function Other pathways also involved!

Slide 21: 

Dopamine Pathways Functions reward (motivation) Pleasure, euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe

Mechanisms producing drug dependence : 

Mechanisms producing drug dependence Positive reinforcement Activation of reward pathways by the drug i. Related to binding of drug on specific receptors ii. Rate of change in synaptic levels of dopamine in nucleus accumbens iii. Other mediators like 5HT, glutamate & GABA may influence the dopamine

Mechanisms producing drug dependence : 

b. Changes at cellular level Responsible for tolerance e.g. increased activity of adenylyl cyclase , and other components of signaling pathway (G-Protein & Protein kinases) c. Negative reinforcement Produced by drug withdrawal, responsible for abstinence syndrome Mechanisms producing drug dependence

Mechanisms producing drug dependence : 

d. Neurobiological substrates Responsible for withdrawal symptoms. e.g. in opioids dependence activation of locus ceruleus during withdrawal ---- important in treatment by Clonidine. e. Genetic Factors Mechanisms producing drug dependence

Drugs Causing Dependence : 

Drugs Causing Dependence Mainly seen with drugs acting on CNS All increase the conc of Dopamine in target structures of mesolimbic projections Classified on the basis of molecular targets and underlying mechanisms

Drugs Causing Dependence : 

Drugs Causing Dependence a. Drugs that activate G 10 -coupled receptors Opioids: Heroin, Morphine & other strong opioids. Hallucinogens: Phencyclidine, Lysergic acid diethylamide (LSD) & related drugs Marijuana: Cannabinoids γ-hydroxybutyric acid

Drugs Causing Dependence : 

Drugs Causing Dependence b. Drugs that mediate their effects via ionotropic effects Nicotine, Alcohol Benzodiazepines, Barbiturates Inhalants Anaesthetics: Nitrous oxide, chloroform, diethylether. Industrial solvents: Benzene. Organic Nitrates: Amyl nitrite. Steroids Anabolic Steroids

Drugs Causing Dependence : 

Drugs Causing Dependence c. Drugs that bind to transporters of biogenic amines Cocaine Amphetamines ECSTASY

Controlled substance : 

Controlled substance Drug deemed to have abuse liability It is listed on governmental schedule of controlled substances Such schedule categorized illicit drugs, control prescribing practices & mandiate penalties for illegal possession, manufacture & sale of listed drugs

Approaches for treating drug dependence: 

Approaches for treating drug dependence 1. Pharmacological approaches a) Detoxification e.g. Methadone for Morphine. b) Specific therapy e.g. Disulfiram for Alcohol. 2. Psychotherapy 3. Rehabilitation 4. Community Education

The End!: 

The End!