Withdrawal, drug nicotine

Nicotine is responsible for the highly addictive properties of tobacco products. Addiction occurs in 30% of those who experiment with tobacco products, and more than 80% of those who attempt to quit smoking will relapse within a year. Withdrawal from nicotine produces a syndrome characterized by nicotine craving as well as dysphoria, anxiety, irritability, restlessness and increased appetite. It is treated with nicotine replacement therapies, such as nicotine gum and patches, and/or with buproprion, a drug that is classified as an antidepressant but has multiple and complex effects in brain. Buproprion reduces craving in some smokers. Nicotine addiction has been reviewed recently at cellular and systems levels [38-41]. 

Tennant FS, Tarver AL, Rawason RA (1983) Clinical evaluation of mecamylamine for withdrawal from nicotine dependence. In Harris LS (ed) Problems of drug dependence, NIDA Research Monograph 49. USDHHS publication no, 84-1316, pp 239-246 Tercyak KP, Herman C, Audrain J (2002) Association of attention-deficit/hyperactivity disorder symptoms with levels of cigarette smoking in a community sample of adolescents, J Am Acad Child Adolesc Psychiatry 41 799-805... 

Other clinical uses Tricyclic drugs are also used in the treatment of bipolar affective disorders, acute panic attacks, phobic disorders (compare with alprazolam Chapter 22), enuresis, and chronic pain states. Clomipramine and the selective serotonin reuptake inhibitors, including fiuvoxamine, are effective in obsessive-compulsive disorders. SSRls are also effective in patients who suffer from panic attacks, social phobias, bulimia, and premenstrual syndrome (PMS) and may also be useful in the treatment of alcohol dependence. Bupropion is used for management of patients attempting to withdraw from nicotine dependence. 

Tricyclics modify peripheral sympathetic effects in two ways through blockade of norepinephrine reuptake at neuroeffector junctions and through alpha adrenoceptor blockade. Sedation and atropine-like side effects are common with tricyclics, especially amitriptyline. In contrast to sedative-hypnotics, tricyclics lower the threshold to seizures. The answer is (B). Selective serotonin reuptake inhibitors cause sexual dysfunction in some patients, with changes in libido, erectile dysfunction, and anorgasmia. Tricyclic antidepressants may also decrease libido or prevent ejaculation. Of the heterocyclic antidepressants bupropion is the least likely to affect sexual performance. The drug is also used in withdrawal from nicotine dependence. The answer is (B). 

Dissection of the molecular mechanisms underlying tobacco addiction should lead to new and better treatments to achieve nicotine withdrawal. It seems clear that the dopamine D2 receptor is involved in nicotine dependence and drugs that block this receptor, such as tiapride, could be useful in the treatment of tobacco dependence. Tiapride has been shown to be successful in alcohol withdrawal [58] but would represent a new avenue for tobacco addiction therapy. 

Similarly opioid peptides are important in nicotine addiction and may have a role in causing nicotine withdrawal symptoms in some smokers [35]. Opioid antagonists such as naltrexone are licensed treatments for dependence syndromes arising from other addictive drugs and could also be of use in some smokers to aid nicotine withdrawal [59] although there is no definitive evidence overall that they are beneficial [60]. 

In a series of studies, Markou and her colleagues have sought to identify drugs that ameliorate the changes in brain reward function evoked by nicotine withdrawal (see Kenny and Markon 2001 for review). This review snmmarises the evidence that 5-hydroxytryptamine (5-HT) and, especially, 5-HTia receptors may play an important role in nicotine withdrawal, although the specific nature of the changes evoked... 

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Marks Ml, Stitzel lA, et al (1985) Time course study of the effects of chronic nicotine infusion on drug response and brain receptors. 1 Pharmacol Exp Ther 235(3) 619-628 Marshall DL, Redfem PH, et al (1997) Presynaptic nicotinic modulation of dopamine release in the three ascending pathways studied by in vivo microdialysis comparison of naive and chronic nicotine-treated rats. 1 Neurochem 68(4) 1511-1519 Martinez D, Gil R, et al (2005) Alcohol dependence is associated with blunted dopamine transmission in the ventral striatum. Biol Psychiatry 58(10) 779-786 McClernon El, Kozink RV, Rose IE (2007) Individual differences in nicotine dependence, withdrawal symptoms, and sex predict transient fMRl-BOLD responses to smoking cues. Neuropsychopharmacology 33(9) 2148-2147... 

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