Drugs of Abuse

Substance abuse and Dependence Substance abuse 

• It means use of an illicit drug or the excessive or nonmedical use of a licit drug or chemicals.
• A primary motivation for drug abuse appears to be the anticipated feeling of pleasure derived from the CNS effects of the drug.
• The older term ‘’physical dependence’’ is now denoted as dependence, whereas “psychological dependence’’ is more simply called addiction.
• At least one of the following four characteristics should be present in a person:

1. Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home.2. Recurrent substance use in situations in which it is physically hazardous (e.g. driving an automobile, etc.)3. Recurrent substance- related legal problems.4. Recurrent substance use despite having persistent or recurrent social or interpersonal problems. Dependence It is a physiological state of neuroadaptation resulting from repeated administration of the drug, necessitating its continued use to prevent the appearance of distressing withdrawal (abstinence) syndrome which is manifested as opposite to the pharmacological effects of the drug. Cross dependence It means the ability of a drug to suppress the manifestation of withdrawal (dependence) produced by another drug. Addiction It involves recurrent abuse of a drug despite adverse consequences which not only harm the individual but the society as well. The detrimental effects of drug abuse are due to:-

1. Intense craving to procure drug by any means to obtain its rewarding effect.
2. Development of tolerance and hence need to increase the dose to get the same rewarding experience.
3. Life threatening or alarming withdrawal effects after cessation of drug.

Tolerance When after repeated administration a given dose of a drug produces a decreased effect than expected, or conversely, when larger doses are needed to obtain the effects obtained with previous dose. It may be classified as

• Pharmacokinetic/drug disposition tolerance(as with barbiturates)
• Pharmacodynamics/cellular tolerance ( as with opioids)
• Reverse tolerance (sensitisation, as with cocaine)
• Cross tolerance-once tolerance to primary drug develops, the individual also exhibit cross tolerance to related classes of drugs.(as individuals tolerant to morphine are also tolerant to other opioids)

 Designer drugs To develop drugs of abuse, molecular modifications are produced in secret for profit by skilled and criminally minded chemists. Manipulation of fentanyl has produced compound of high potency with great addiction potential. Withdrawal syndrome The phenomenon of withdrawal is associated with

• Alcohol
• Amphetamines
• Cocaine
• Nicotine
• Sedatives
• Hypnotics
• Anxiolytics
• It develops within a few hours of stopping or reducing any of the above mentioned abuse substances.
• The signs and symptoms of withdrawal vary with the substance abused and their severity depends upon the amount and the duration of the addiction.
• Common symptoms of withdrawal are sweating, palpitation, agitation, insomnia, vomiting, diarrhoea, muscle cramps, seizures, dysphoria, fatigue, changes in appetite, etc.

  Volatile substance abuse 

• They are inhaled to seek ‘self gratifying high’ that may affect the CNS. These include nail varnish, petrol, lacquer-paint solvents, adhesives and butane liquid gas.
• Also solids, viz. paint scraping and old shoe polish may be volatized over a fire.
• Such substances are usually used by children because of easy accessibility at home.
• CNS effects are confusion, hallucination, ataxia, dysarthria, convulsions, coma and respiratory failure.
• Even lung, kidney, liver and heart damage can occur.
• Sudden cardiac death may occur due to sensitization of the heart to catecholamines.

  The Dopamine Hypothesis of Addiction 

• Dopamine in the mesolimbic system appears to play a primary role in the expression of ‘’reward’’.
• But excessive dopaminergic stimulation may lead to pathologic reinforcement.
• Such that behavior may become compulsive and no longer under control → common features of addiction.
• Most addictive drugs have actions that include facilitation of the effects of dopamine in the CNS.
• Mechanism for the development of tolerance, dependence and withdrawal effects
• A large range of neuroadaptations develop in response to chronic exposure of substance and these are thought to be more or less critical for expression of the major features of dependence: tolerance, withdrawal and processes that may contribute to compulsive use and relapse.
• The dependence syndrome results from the need for the drug to be present in the brain to maintain “near-normal” functioning.
• If the drug is eliminated from the body so that it no longer occupies its site of action, the adaptations that produced dependence are unmasked and manifested as an acute withdrawal syndrome that lasts until the system re-equilibrates to the absence of drug (days).
• Subsequently, a protracted withdrawal syndrome, characterized by craving for the drug (i.e., an intense preoccupation with obtaining the drug), may emerge and continue indefinitely (years).

 Schedule of controlled drugs 

 LSD, lysergic acid diethylamide; MDA, methylene dioxyamphetamine; MDMA, methylene dioxymethamphetamine; PCP, phencyclidine; STP (DOM), 2,5-dimethoxy-4-methylamphetamine.           Signs and symptoms of overdose and withdrawal from selected drug of abuse. 

 Principles of management

• Management of individuals with substance abuse and dependence based on:-

• Type of drug

• Duration of drug

• Pattern of use

• Psychological profile

• Sociocultural factors

• Physical complications

• It is a chronic relapsing disorder so multidisciplinary management using a team approach is best suited for these problems
• The therapeutic team should consist of a psychiatrist, a nurse, and a social worker for optimum benefit.
• Pharmacological interventions play a limited role in the overall management of substance abuse disorders.
• The medicines used for such disorders are grouped as follows:

1. Drugs for detoxification, i.e. for treating withdrawal symptoms, e.g. benzodiazepines and clonidine.

2. Drugs for discouraging repeated use of the abused substance, e.g. disulfiram for alcohol and naltrexone for opioids.

3. Drugs used for substitution of abused substance, e.g. methadone for opioids.

4. Drugs used for treatment of co-morbid psychiatric and physical illnesses.

5. Drugs used for treating the overdose of the abused substance, e.g. naloxone for opioids or flumazenil for diazepam.

• The management is symptomatic.
• Benzodiazepines are used for insomnia; anxiety, and agitation.
• Clonidine helps by controlling symptoms caused by autonomic over activity.
• Severe withdrawal symptoms last for 3-4 days and it takes about a forthnight for the physiological functions to stabilize.
• The ultra-rapid detoxification for opioids dependence has recently been introduced. It involves the use of naltrexone or naloxone (opioid antagonist) in combination with other medicines to minimize discomfort
• For the purpose of de-addiction opioid agonist therapy (methadone) is preferred.
• Naltrexone has been used for preventive purpose in cocaine and alcohol addicts.
• Disulfiram is expected to produce an aversion for alcohol by changing the pleasant effect of alcohol in to dysphoria and other troublesome physical symptoms like hot flush, nausea, vomiting and feeling of impending doom.
• Acamprosate, an amino acid derivative of gamma amino-butyric-acid and fluoxetine have been used to directly reduce daily alcohol consumption by directly reducing the craving for it.
• Control of nicotine withdrawal symptoms and prevention of its long term abuse, NRT (nicotine replacement therapy) is available in the form of patch, gum, spray and inhaler.
• NRT replaces nicotine without the harmful effects of cigarette smoke.
• Bupropion , an atypical antidepressant also used to help smokers to quit the habit.