Nicotine replacement and related drugs

Key examples

• Nicotine
• Varenicline
• Bupropion

 

Common indications

• In smoking cessation, drug therapy to control physical symptoms of nicotine withdrawal is used alongside non-pharmacological measures to address the psychological and behavioural aspects of dependence.

 

Mechanisms of action

• Nicotine obtained from tobacco use has complex actions. In the central nervous system it activates nicotinic acetylcholine receptors, increasing neurotransmitter levels and causing euphoria and relaxation. Nicotine withdrawal causes intense craving, anxiety, depression and irritability with increased appetite and weight gain. During abstinence from tobacco, nicotine replacement therapy prevents withdrawal symptoms by maintaining receptor activation. Varenicline, a partial agonist of the nicotinic receptor, reduces both withdrawal symptoms and the rewarding effects of smoking by preventing binding of tobacco-derived nicotine to receptors. Bupropion increases concentrations of noradrenaline and dopamine in the synaptic cleft by inhibiting reuptake. The mechanism underlying its benefits in smoking cessation are not fully understood.

 

Important adverse effects

• It is generally considered safer for smokers to take nicotine replacement therapy than to continue smoking. Adverse effects include local irritation (for example from patches, lozenges, nasal spray) or gastrointestinal upset with oral nicotine. Palpitations and abnormal dreams may occur.
• Common side effects of varenicline include nausea, headache, insomnia and abnormal dreams. Rarely, patients may develop suicidal ideation.
• Bupropion commonly causes dry mouth, gastrointestinal upset, neurological (e.g. headache, impaired concentration, dizziness) and psychiatric (e.g. insomnia, depression, agitation) adverse effects. Hypersensitivity is common and more often manifests as a skin rash (for example urticaria) than a severe reaction (such as anaphylaxis).

 

Warnings

• Nicotine replacement therapy should be used with caution in people who are haemodynamically unstable, for example following myocardial infarction. Bupropion and varenicline should be used with caution in people at risk of seizures as they can precipitate convulsions. This includes people with prior seizures or head injury and those who abuse alcohol or who take other drugs that lower the seizure threshold. They should be used with care in people with psychiatric disease due to risk of suicidal ideation. All these drugs should be used with caution in people with hepatic or renal impairment.

 

Important interactions

• Nicotine replacement and varenicline have no clinically significant drug interactions. Bupropion is metabolised by cytochrome P450 enzymes, so its plasma levels are increased by P450 inhibitors, e.g. valproate, and reduced by inducers, e.g. phenytoin, carbamazepine. Use of bupropion with monoamine oxidase inhibitors or tricyclic antidepressants increases stimulation of catecholaminergic pathways and risk of adverse effects.