Drug Dependence

Dispositional (metabolic) tolerance – Pharmacokinetic. Less drug gets to the site of action due to metabolism or distribution change. Continuous use.

Pharmacodynamic (functional) tolerance – Decreasing effects cannot be explained by change in metabolism or distribution. Same amount of drug gets to site of action, but changes in tissues or cells result in decreased response to drug. Doing interval is important. Continuous use.

Behavioral tolerance – Individual learns to compensate for effects of drug. Occurs with occasional use.

Degree of tolerance – Depends on doing interval, dose level, type of tolerance, and duration of treatment.

Requirements for production of physical dependence – Dose interval (continuous), dose level (sufficient depression of function), duration of treatment. Shorter-acting drugs have more intense withdrawl symptoms upon termination of administration.

Opioid tolerance – High degree of cross-tolerance. No tolerance to miosis, constipation, or excitatory effects. Withdrawal symptoms include lacrimation, rhinorrhea, sneezing, yawning, other muscarinic effects, and kicking movements. Opioid withdrawl is not life-threatening, except in newborns. Methadone and clonidine (autonomic symptoms) are used to suppress withdrawl symptoms during detoxification. Ultra-rapid opiate detoxification has been attempted with naltrexone. Maintenance therapy is administered using methadone orally. Acetylmethadol is also used for maintenance therapy as it is long-acting. Buprenoprhine (partial agonist) may be able to substitute for opiates and blocks the euphoria of opiates. Treatment of neonatal withdrawl involves methadone and diazepam in some cases. Clonidine is also used.

CNS depressant tolerance – The lethal dose (death by respiratory depression) is not much greater in addicts than in non-tolerant individuals. Tolerance develops to the psychic and motor effects but not to the respiratory depressing effects. Withdrawal from these agents is much more severe and life-threatening than withdrawal from opiates. Symptoms of withdrawal include hyperexcitability that can progress to seizures and status epilepticus. Abrupt withdrawal of short-acting agents can be fatal. A common approach to treatment of withdrawal us to suppress withdrawal with pentobarbital or Phenobarbital and then gradually reduce the dose. Diazepam is given to substitute for short-acting benzodiazepines and then gradually withdrawn.

Category: Forensic Medicine Notes , Pharmacology Notes , Psychiatry Notes