Mechanism of habituation


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Mechanism of habituation

  1. 1. Mechanism of habituation Dr. S. Parasuraman M.Pharm., Ph.D., Senior Lecturer, Faculty of Pharmacy, AIMST University, Bedong 08100, Malaysia.
  2. 2. • Variables factors simultaneously influence the likelihood that a given person will become a drug abuser or an addict. • These variables can be organized into three categories: – agent (drug) – host (user) – environment Mechanism of habituation
  3. 3. • Drugs vary in their capacity to produce immediate good feelings in the user. • Drugs that produce intensely pleasant feelings (euphoria) are more likely to be taken repeatedly. • • Reinforcement refers to the capacity of drugs to produce effects that make the user wishing to take them again. • Stronger the reinforcement, the drug produces, the greater is the likelihood for the drug to be abused. Agent (Drug) Variables
  4. 4. • Reinforcing  increase neuronal activity in brain. • Cocaine, amphetamine, ethanol, opioids, cannabinoids, and nicotine all reliably increase extracellular fluid dopamine levels in the ventral striatum. • Serotonin, glutamine, norepinephrine, opiates, and g-aminobutyric acid (GABA) are also involved in mediating the reinforcing effects of drugs. Agent (Drug) Variables
  5. 5. • In general, effects of drugs (pharmacokinetic and pharmacodynamic effects) vary among individuals. • Genetics (polymorphism of genes that encode enzymes) plays major role in drug absorption, metabolism, and excretion and in receptor- mediated responses. • Genetic factors contribute to different degrees of reinforcement or euphoria observed among individuals. Host (User) Variables
  6. 6. • Children of alcohol abuse  Innate tolerance to alcohol may contribute to the development of alcoholism  innate tolerance increases vulnerability to alcoholism, impaired metabolism (alcohol, metabolized by alcohol dehydrogenase), due to mutation in ALDH2 gene  poor metabolizer. • Poor metabolizer (alcohol)  excess accumulation of acetaldehyde after the ingestion of alcohol  These people experience a very unpleasant facial flushing reaction 5 to 10 minutes after ingesting alcohol. Host (User) Variables
  7. 7. • Taking drugs may be seen initially as a form of rebellion against authority. • Other factors like pleasure, diversion, or income are particularly important in communities where educational levels are low and job opportunities scarce. Environmental Variables
  8. 8. • Tolerance can be defined as the reduction in response to the drug after repeated administrations. Pharmacological Phenomena Tolerance • Drug (dose) increases ↑ --- drug effect ↑ • Repeated drug administration  tolerance • Thus a higher dose is required to produce the same effect that was once obtained at a lower dose. Example: Diazepam produces sedation at doses of 5 to 10 mg in a first-time user  repeated user may required several hundreds of milligrams to produce desired effect (due to development of tolerance)
  9. 9. • Dispositional tolerance/ Pharmacokinetic tolerance • Pharmacologic tolerance/ Pharmacodynamic tolerance • Behavioral tolerance/ learned tolerance • Reverse tolerance • Acute tolerance • Inverse tolerance • Conditioned tolerance Types of tolerance
  10. 10. • Pharmacokinetic tolerance: changes in the distribution or metabolism of a drug after repeated administrations. • Eg. Antihypertensive agents, barbiturates. Barbiturates stimulate the production of higher levels of hepatic CYPs (enzyme induction), causing more rapid removal of barbiturates from the circulation  results in reduction of drug in systemic circulation. Types of tolerance
  11. 11. • Pharmacodynamic tolerance: Adaptive changes that have taken place within systems affected by the drug. • Eg.: drug induced changes in receptor density or efficiency of receptor coupling to signal-transduction pathways. • Behavioral/ Learned tolerance refers to a reduction in the effects of a drug due to compensatory mechanisms that are acquired by past experiences. Eg.: repeated experiences to function normally despite a state of intoxication (alcoholism). • High levels of intoxication behavioral alteration  physical and psychological defect will be observed. Types of tolerance
  12. 12. • Reverse tolerance: A drug user may actually become more sensitive to a drug when that drug destroys brain tissue and make it less enjoyable. Eg.: MDMA, cocaine, amphetamine • Acute tolerance: – Also known as tachyphylaxis. – Immediate tolerance to the effect of a drug as the body adapts to it. – Example, a single dose of most hallucinogens causes a reduced effect if the drug is taken. Eg.: hallucinogen, psilocybin, LSD-25. Types of tolerance
  13. 13. • Inverse tolerance: Repeated use of some drugs can suddenly cause a increased sensitivity to it, as the brain antcipates and enhances its effects. Eg.: Long-term marijuana or cocaine • Conditioned tolerance: – Also known as situation-specific tolerance. – develops when environmental cues such as sights, smells, or situations are consistently paired with the administration of a drug. – When a drug affects homeostatic balance by producing sedation and changes in blood pressure, pulse rate, gut activity, etc.,. Types of tolerance
  14. 14. • Physical dependence is the physiological adaptation of the body to the presence of an agent. • Abrupt discontinuation or dosage reduction of chronic use of a drug results negative physical symptoms of withdrawal. • Eg.: naloxone, pentazocine Physical Dependence
  15. 15. • Physical dependence is the physiological adaptation of the body to the presence of an agent. • Abrupt discontinuation or dosage reduction of chronic use of a drug results negative physical symptoms of withdrawal. • Eg.: µ-opioids, all GABA agonists, gabapentin, neuroleptic, antidepressants, androgenic-anabolic steroids, glucocorticoids, naloxone, pentazocine Symptoms Physical Dependence
  16. 16. • Symptoms which may be experienced during withdrawal or reduction in dosage include increased heart rate and/or blood pressure, sweating, and tremors. More serious withdrawal symptoms such as confusion, seizures, and visual hallucinations indicate a serious emergency and the need for immediate medical care. • Abrupt withdrawal from opioids can cause an extremely physiologically and psychologically painful withdrawal that is very rarely fatal in patients of general good health and with medical treatment. Acute withdrawal of opioid causes hypertension, arrhythmia, constant diarrhea and vomiting. Withdrawal Syndrome
  17. 17. • Methadone used for heroin withdrawal treatment • Opioid acts – 4to 6 hr • Methadone acts – 24-36 hr • Methadone has ability to eliminate cravings • Its also act μ (mu) and NMDA receptor • Used for treatment of heroin withdrawal • Heroin withdrawal can be treated by – Methadone maintenance therapy (MMT) – Buprenorphine therapy – Buprenorphine + naloxone therapy – Behavioral therapy How methadone will work?
  18. 18. • patient under treatment for a medical disorder who has become "addicted" to the available prescribed drugs. • Addiction leads to conception of excess dose, out of control. • An example would be a patient with chronic pain, anxiety, or insomnia who begins using the prescribed medication more often than directed by the physician. • If the physician restricts the prescriptions, the patient may begin seeing several doctors without the knowledge of the primary physician. • Such a patients may need emergency admission in hospital. Medical addict
  19. 19. Thank you