Addiction

A-Pharmacological approaches to treating drug dependence

B-Clinical use of drugs in substance dependence

A-Pharmacological approaches to treating drug dependence

To alleviate withdrawal symptoms

1-Methadone (orally active) used short term to blunt opioid withdrawal2-Ibogaine (a naturally occurring psychoactive agent) used by some to reduce opioid withdrawal3-α2 Adrenoceptor agonists (e.g. clonidine, lofexidine) to diminish opioid, alcohol and nicotine withdrawal symptoms4-β Adrenoceptor antagonists (e.g. propranolol) to diminish excessive peripheral sympathetic activity5-Benzodiazepines, clomethiazole, topiramate and γ-hydroxybutyric acid (GHB) to blunt alcohol withdrawal

Long-term substitution

• Methadone, buprenorphine or legal heroin to maintain opioid-dependent patientsNicotine patches or chewing gumVarenicline (α4β2 nicotinic receptor partial agonist)

Blocking response

• 1-Naltrexone to block opioid effects in drug-withdrawn patients2-Mecamylamine to block nicotine effects3-Immunisation against cocaine and nicotine to produce circulating antibody (still being developed)

Aversive therapies

• Disulfiram to induce unpleasant response to ethanol

Reducing continued drug use (may act by reducing craving)

• 1-Bupropion (antidepressant with some nicotinic receptor antagonist activity) to reduce tobacco use2-Naltrexone to reduce ethanol use3-Clonidine (α2 adrenoceptor agonist) to reduce craving for nicotine4-Acamprosate (NMDA receptor antagonist) to treat alcoholism5-Topiramate and lamotrogine (antiepileptic agents) to treat alcoholism and cocaine use6-γ-Hydroxybutyric acid (GHB) reported to reduce craving for alcohol and cocaine7-Baclofen reported to reduce opioid, alcohol and stimulant use8-Ibogaine reported to reduce craving for stimulants and opioids

Clinical use of drugs in substance dependence

• A-Tobacco dependence

• Short-term nicotine is an adjunct to behavioural therapy in smokers committed to giving up; varenicline is also used as an adjunct but has been linked to suicidal ideation.

• Bupropion is also effective but lowers seizure threshold, so is contraindicated in people with risk factors for seizures (and also if there is a history of eating disorder).

Alcohol dependence

• 1-Long-acting benzodiazepines (e.g. chlordiazepoxide) can be used to reduce withdrawal symptoms and the risk of seizures; they should be tapered over 1-2 weeks and then discontinued because of their abuse potential.

• 2-Disulfiram is used as an adjunct to behavioural therapy in suitably motivated alcoholics after detoxification; it is contraindicated for patients in whom hypotension would be dangerous (e.g. those with coronary or cerebral vascular disease).

• 3-Acamprosate can help to maintain abstinence; it is started as soon as abstinence has been achieved and maintained if relapse occurs, and it is continued for 1 year.

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Opioid dependence

• 1-Opioid agonists or partial agonists (e.g., respectively, methadone or buprenorphine) administered orally or sublingually may be substituted for injectable narcotics, many of whose harmful effects are attributable to the route of administration.

• 2-Naltrexone, a long-acting opioid antagonist, is used as an adjunct to help prevent relapse in detoxified addicts (opioid free for at least 1 week).

• 3-Lofexidine, an α2 agonist (cf. clonidine;), is used short term (usually up to 10 days) to ameliorate symptoms of opioid withdrawal, and is then tapered over a further 2-4 days.