Varenicline overdose in a teenager – a clinical pharmacology perspective

Rollema, Hans; Faessel, Hélène M.; Williams, Kathryn E

doi:10.1080/15563650902970689

Cited by 6 publications

(3 citation statements)

References 4 publications

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“…Thus, activation of α7 nAChRs but inhibition of α4β2 nAChRs may contribute to the antidepressant effects of nicotine. Further, varenicline is also a full agonist at 5-HT3 receptors 78, which are implicated in mood regulation 79, so the effects of varenicline in human depressed patients are likely to be complex.…”

Section: Activation or Desensitization? An Ongoing Controversy In Modmentioning

confidence: 99%

Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis

Mineur¹,

Picciotto²

2010

Trends in Pharmacological Sciences

232

150

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There is a well-established connection between smoking and depression, with depressed individuals over-represented among smokers and ex-smokers often experiencing increased depressive symptoms immediately after quitting. Nicotine in tobacco binds, activates and desensitizes nicotinic acetylcholine receptors (nAChRs), but it is not known whether activation or desensitization is more important for nicotine’s effects on depressive symptoms. In this article, we review the hypothesis that blockade rather than activation of neuronal nAChRs might be important for the effects of nicotinic agents on depressive symptoms based on clinical and preclinical studies of nicotinic drugs. The endogenous neurotransmitter for nAChRs is acetylcholine, and the effects of nicotine on depression-like behaviors support the idea that dysregulation of the cholinergic system might contribute to the etiology of major depressive disorder. Thus, pharmacological agents that limit acetylcholine signaling through neuronal nAChRs might be promising for the development of novel antidepressant medications.

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Section: Activation or Desensitization? An Ongoing Controversy In Modmentioning

confidence: 99%

Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis

Mineur¹,

Picciotto²

2010

Trends in Pharmacological Sciences

232

150

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show abstract

“…In fact, with high doses of varenicline (> 3 mg/day) the rapid onset of emesis limits the systemic exposure of varenicline [32]. Overdosing is therefore not expected to result in excessive systemic exposures that could potentially cause nicotinic toxic effects, as illustrated by a recently reported overdose case [51,52].…”

Section: Safety and Tolerability Of Vareniclinementioning

confidence: 99%

Pharmacodynamic and pharmacokinetic profiles of the α4β2 nicotinic acetylcholine receptor partial agonist varenicline, a smoking cessation aid

Faessel

Rollema

2016

J Pediatr Biochem

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This review describes the role of ?4?2 containing nicotinic acetylcholine receptors in the mesolimbic reward pathway in the neurobiology of nicotine addiction and discusses the rationale for targeting this receptor with partial agonists as novel smoking cessation agents. Varenicline is a ?4?2 nicotinic acetylcholine receptor partial agonist that is a smoking cessation aid with a dual mechanism of action: relief of craving and withdrawal symptoms, as well as attenuation of nicotine reinforcement. The pharmacological profile of varenicline is consistent with that of a potent and selective partial agonist at the target receptor, both in in vitro and in vivo neurochemical and behavioral models. Varenicline was nominated for full clinical development in 1997, and later approved in the US and Europe as a smoking cessation aid in 2006. The recommended dose of varenicline is 1 mg BID for 12 weeks after an initial titration week in adult smokers motivated to stop smoking. The pharmacokinetics of varenicline is linear and consistent regardless of smoking status, age, gender or ethnic background. Varenicline is largely eliminated unchanged in the urine, and consequently a dose adjustment is warranted for patients with severe renal insufficiency. Although varenicline is currently not approved for use in smokers under age 18, its pharmacokinetic and tolerability profile in adolescents appeared generally similar to adults. Several large clinical trials have consistently shown the efficacy, tolerability and safety of varenicline in various ethnic smoking populations and in adult smokers with co-morbid chronic pulmonary or cardiovascular disease. Additional clinical studies in special patient populations are currently ongoing.

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“…Nausea and vomiting may reduce risk of harm in case of overdose. 85 A meta-analysis of clinical trial safety data found that nausea occurs in about one-third of patients. 35 The next three most common adverse events were insomnia, abnormal dreams and headache.…”

Section: Tolerability and Safetymentioning

confidence: 99%

Varenicline: Smoking Cessation in Patients with Medical and Psychiatric Comorbidity

Tonstad

Els

2010

Clinical Medicine Insights: Therapeutics

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Smoking remains a major public health challenge. Nicotine is the main psychoactive drug responsible for the addictive nature of tobacco, explaining why many smokers fail to quit without assistance. Pharmacotherapy for smoking cessation is deemed effective for a broad range of populations and should be routinely offered to smokers interested in making a quit attempt. Varenicline, a partial agonist at the α4β2 nicotinic receptor increases chances of quitting three-fold compared to placebo in smokers without comorbidities, and in smokers with cardiovascular disease or chronic obstructive pulmonary disease. Persons with mental illness have high rates of smoking, and the potential impact of varenicline on mental status and the underlying pathophysiology of mental illness, has become a salient concern. Varenicline is an appropriate aid for smoking cessation in patients with medical and/or psychiatric comorbidity. This conclusion is supported by current evidence on the safety and tolerability of the drug.

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Varenicline overdose in a teenager – a clinical pharmacology perspective

Cited by 6 publications

References 4 publications

Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis

Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis

Pharmacodynamic and pharmacokinetic profiles of the α4β2 nicotinic acetylcholine receptor partial agonist varenicline, a smoking cessation aid

Varenicline: Smoking Cessation in Patients with Medical and Psychiatric Comorbidity

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