Learning Objectives: Drugs of Abuse 1 and 2 1. Distinguish drug abuse from drug dependency.

Abuse is repeated use in a pattern and amount that interferes with health and normal social/ occupational functioning of person. Dependency is overwhelming preoccupation with procurement and use of drug. Loss of control over drug use both within and between instances of use. When drug is withdrawn, there are reversible physiological and behavioral changes, often opposite to action of the drug. 2. Describe the toxicity and tolerance phenomena associated with abuse and dependency. Tolerance is reduced drug effect with repeated use and requirement of higher doses to achieve same effect. Cross-tolerance is when use of one drug induces tolerance to different drugs in same class. Metabolic tolerance is that the rate of drug elimination increases with chronic use because it stimulates its own metabolism. Cellular tolerance is biochemical adaptation to the drugs present, like change in neurotransmitter levels/storage/release or in their receptors (downregulation of receptors is most common). Cocaine toxicity causes hypertension, MI, strokes due to vasoconstriction. It is a local anesthetic contributing to seizures. Overdoses are usually fatal within minutes by arrhythmia, seizing, resp. depression. IV diazepam, propanolol, Ca-channel blockers are good treatments for overdose. Fetal morbitdity if used in pregnancy. Tolerance to euphoria and convulsant and cardiorespiratory stimulation develops. 3. Recognize withdrawal symptoms and therapeutic management for drugs of abuse. Withdrawal from opiates begins 8-10 hours after last dose, with lacrimation, rhinorrhea, yawning, sweating, restless sleep, weakness, chills, goosebumps, nausea, vomiting, muscle aches, involuntary movements, hyperpnea, hyperthermia, hypertension. It can last over a week, then lead to hypotension/bradycardia/hypothermia/mydriasis lasting 6 months or more. Methadone replacement therapy is very effective, being orally active, long-lasting, milder withdrawal, less euphoria so people can work and function. Buprenorphine, a partial agonist, is also good, but its more expensive. Clonidine is good to reduce sympathetic effects of initial detox phase. In very motivated people, naltrexone can be used to block the effects of heroin if it is ever used. Cocaine withdrawal causes paranoia, insomnia, depression, fatigue, agitation, sweating, nausea, vomiting (esp. free-base smokers), but withdrawal is usually not that bad compared to depressants or opiates.Therapy can be antipsychotics for overdose, and maybe dopaminergic agonists like amantadine or bromocriptine or antidepressants like desipramine to help during recovery.

4.

Describe the pharmacological basis for treating drug abuse.