SN7 SHORT NOTE 5M

Define drug dependence, tolerance and addiction. Describe the opioid antagonists and the principles of managing dependence.

Pharmacology · 2nd Professional — Para-Clinical

Definitions

Term	Meaning
Dependence	A state in which the drug is required for normal function; may be physical (withdrawal on cessation) or psychological (craving)
Addiction	Compulsive drug-seeking and use despite harm, with loss of control — a behavioural diagnosis, not a pharmacological one
Tolerance	Reduced effect on repeated use, requiring a larger dose
Habituation	Psychological desire without physical dependence
Withdrawal (abstinence) syndrome	Characteristic symptoms on cessation, usually opposite to the drug’s acute effects

CLINICAL PEARL

Tolerance and physical dependence are expected pharmacology; addiction is a disease of behaviour. A cancer patient on morphine for months is tolerant and physically dependent, and is not addicted. Confusing the three leads directly to the under-treatment of severe pain — the commonest practical consequence of getting these definitions wrong, and a widespread problem in India.

Common Drugs of Dependence

Drug	Withdrawal features	Management
Opioids	Lacrimation, rhinorrhoea, yawning, sweating, dilated pupils, gooseflesh ("cold turkey"), cramps, diarrhoea, agitation. Intensely unpleasant but rarely life-threatening	Substitution with methadone or buprenorphine; clonidine for autonomic symptoms; naltrexone to maintain abstinence
Alcohol	Tremor, seizures, delirium tremens — potentially fatal	Benzodiazepine taper; thiamine before glucose
Benzodiazepines	Rebound anxiety and insomnia, tremor, perceptual disturbance, seizures — also potentially fatal	Slow taper, often via long-acting diazepam
Nicotine	Irritability, craving, poor concentration, increased appetite	Nicotine replacement, varenicline, bupropion
Cannabis	Irritability, insomnia, reduced appetite	Supportive; psychological therapy
Stimulants (cocaine, amphetamine)	"Crash" — profound fatigue, hypersomnia, depression and suicidal ideation	Supportive; no established substitution therapy

Opioid Antagonists

Drug	Route and duration	Use
Naloxone	Intravenous, intramuscular or intranasal; acts in 1–2 minutes but lasts only 30–60 minutes — shorter than most opioids	Acute opioid overdose. Repeated doses or an infusion are needed, with prolonged observation; take-home naloxone kits for users and their families save lives
Naltrexone	Oral, long-acting (24–48 hours)	Maintenance of abstinence in opioid and alcohol dependence; must not be started until the patient is fully detoxified, or severe withdrawal follows
Methylnaltrexone, naloxegol	Do not cross the blood–brain barrier	Opioid-induced constipation without reversing analgesia — another use of a barrier to gain selectivity
Nalmefene	Long-acting	Reduction of alcohol consumption

Principles of Management

Detoxification is the beginning, not the treatment — relapse is the rule without sustained psychological and social support
Harm reduction — needle exchange, opioid substitution therapy, take-home naloxone, and testing for HIV, hepatitis B and C; these reduce death and transmission even in those not ready to stop
Treat coexisting psychiatric illness, which is present in a large proportion and drives relapse if untreated
Relapse is part of the course and should be treated as such, not as failure or grounds for withdrawing care

Applied Aspects

Tolerance to respiratory depression falls rapidly during abstinence, so a person who relapses after detoxification or release from prison and takes their previous dose frequently dies — this must be explained explicitly before discharge
Naloxone should be titrated in a dependent patient, aiming to restore adequate respiration rather than full consciousness; a large bolus precipitates violent withdrawal
Do not stop opioids abruptly in a hospitalised dependent patient; untreated withdrawal causes them to leave against advice and often to die outside
India has a substantial burden of opioid and alcohol dependence, and the NDPS Act governs prescribing; recent amendments have improved access to oral morphine for cancer pain, which had been severely restricted
Prescribers contribute to the problem — long courses of benzodiazepines, opioids for chronic non-cancer pain, and repeat prescriptions issued without review are all avoidable sources of iatrogenic dependence

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