J Am Board Fam Pract: first published as 10.3122/jabfm.7.5.417 on 1 September 1994. Downloaded from Use Of Transdermal Nicotine Systems In A Possible Suicide Attempt Norman Montalto, DO, Carolyn C. Brackett, PharmD, and Todd Sobol, MD Background: Transdennal drug delivery systems, a relatively recent development, are well accepted by physicians and patients because of reliability and ease of administration. The patch resen'oirs, however, contain large quantities of drug, and the potential for considerable toxicity exists if they are used incorrectly. A case is presented of an apparent suicide attempt that involved the use of nicotine transdennal patches. Methods: This case report involved a patient seen in the emergency department by one of the authors. Data were obtained from the patient's medical record while maintaining confidentiality. Results: The drug overdose was a potentially serious one. The patient recovered fully after an uneventful hospital course. Conclusions: Transdennal drug delivery systems now deliver many drugs, several of which are quite potent. Intentional or unintentional misuse of the systems can result in toxicity. The physician and phannacist should carefully instruct each patient in the appropriate use and handling of transdennal drug delivery systems. (J Am Board Fam Pract 1994; 7:417-20.) WIth the advancement of transdermal technol­ ing," "toxicology," "treatment," "management," ogy, such pharmaceutical agents as estrogen, sco­ and "contaminant." polamine, nitroglycerin, fentanyl, and recently nicotine can be administered by the transdermal Background route. Transdermal administration is not typi­ Nicotine is one of the most toxic of all poisons cally associated with acute drug overdosage, but and acts with great rapidity. It is well absorbed the following case appears to illustrate an attempt from the gastrointestinal and respiratory tracts at suicide using trans dermal nicotine patches in and through intact skin. Percutaneous absorption combination with ingestion of other substances. occurs many times more rapidly with the free Following the case presentation, we discuss the alkaloid than with any of its acid salts.1•2 symptoms and the treatment of nicotine toxicity The major effects of nicotine, in addition to and recommend safety guidelines to consider local caustic action, are transient stimulation and http://www.jabfm.org/ when prescribing transdermal nicotine therapy. then subsequent depression or paralysis of the central nervous system, all peripheral autonomic Methods ganglia, and motor end-plates in skeletal muscles. The case report was developed from informa­ Nicotine exerts an excitatory effect on smooth tion described by the attending physician and muscle, which could be responsible for the vaso­ from the patient's medical record. The patient's constriction and gastrointestinal hypermotility on 23 September 2021 by guest. Protected copyright. confidentiality was maintained. References that are observed following toxic exposures. 1 Fa­ for background literature were obtained from talities are traditionally believed to result from bibliography review, MEDLINE, and Interna­ respiratory arrest secondary to muscle paralysis, tional Pharmaceutical Abstracts. Key words used although there is now evidence that central de­ to search included "nicotine," "toxicity," "poison- pressant effects might contribute as well.2•3 A lethal dose of nicotine in adult humans is es­ timated to be 30 to 60 mg or 0.5 to 1.0 mglkg. Submitted, revised, 1 April 1994. From the Department of Family Medicine (NM), The Ohio Tolerance to the toxic effects of the alkaloid can State University Medical Center; the College of Pharmacy be acquired by habitual smokers, however, and (CCB), The Ohio State University, Columbus; and the Depan­ persons ingesting as much as 2.0 g of nicotine ment of Emergency Medicine (TS), Wright State University have survived.4 In fatal poisonings death is rapid, School of Medicine, Dayton, OH. Address reprint requests to Carolyn C. Brackett, PharmD, 500 W. 12th Avenue, Columbus, usually occurring within 1 hour and occasion­ OH43210. ally within 5 minutes. 1 Artificial ventilation and Transdermal Nicotine 417 J Am Board Fam Pract: first published as 10.3122/jabfm.7.5.417 on 1 September 1994. Downloaded from circulatory support are often effective in prevent­ place is 11 to 12 hours, which reflects continued ing death, and some patients have experienced percutaneous absorption of drug, and following complete recovery within hours.l-4 removal of a nicotine patch, absorption continues Most fatalities associated with nicotine poison­ for several more hours, indicating the persistence ing occurred in the 1920s and 1930s, when con­ of a cutaneous reservoir of drug. IS Plasma nico­ centrated nicotine solutions were commonly used tine levels in nonsmoking volunteers are unde­ as insecticides, and reports of fatal poisonings fre­ tectable in 10 to 12 hours following patch removal quently involved the mistaking of nicotine solu­ but would be expected to decrease more rapidly in tions for other medications.2 Between 1930 and smokers whose hepatic enzymes have been in­ 1935,288 nicotine-associated fatalities occurred duced by the polycyclic aromatic hydrocarbon in the United States.5 Nonfatal poisonings were components of smoke. much more common than fatalities, however, Four nicotine transdermal patches are cur­ with some serious illnesses resulting from percu­ rently approved for use and marketed in the taneous exposure through clothing to as little as United States: Nicotrol (Parke-Davis), Nicoderm 7.5 mL of concentrated nicotine solution.5-9 (Marion Merrell Dow), Habitrol (Basel-Ciba­ Symptoms of nicotine toxicity are manifested Geigy), and Prostep (Lederle). All of the patches primarily by the gastrointestinal tract and the are applied every 24 hours, for 24 hours, except central nervous system. Features of gastrointes­ for Nicotrol, which is applied every 24 hours tinal cholinergic overstimulation are prominent but removed at bedtime, for an effective appli­ and include severe nausea, vomiting, salivation, cation time of approximately 16 hours. All patch and diarrhea. Central nervous system signs and strengths contain varying amounts of nicotine symptoms include headache, dizziness, confusion, (Table 1), but all brands contain nicotine as the seizures, and coma. In addition to central nervous free alkaloid, which is the form most readily system and gastrointestinal manifestations, severe absorbed through the skin.l°-I3 nicotine toxicity results in increased heart rate Percutaneous absorption from the drug-im­ and blood pressure and respiratory muscle paraly­ pregnated patch reservoir is generally excellent, sis, which are the events that can cause death. but to maintain a drug gradient across the system Treatment of nicotine poisoning includes re­ membranes, a substantial amount of drug must moving external sources of exposure, decontami­ remain in the controlled-release system after nating the gastrointestinal tract if vomiting and the 16-hour or 24-hour administration period diarrhea have not occurred, administering oxy­ (fable 1). For this reason safe disposal of the used gen, and supporting respiration and circulation, if patch is of the utmost importance, because chil­ http://www.jabfm.org/ necessary. In cases of nicotine toxicity caused by dren or pets discovering the used patch could be transdermal patches, removing the patches and poisoned by the remaining nicotine. washing the application sites with water only are recommended. The use of soap can actually drive Case Report nicotine on the skin surface further into the skin, A 15-year-old girl had a reported history of ad­ thus increasing the amount absorbed. IO-I3 Signs justment disorder with depressive features and at­ on 23 September 2021 by guest. Protected copyright. of toxicity are self-limiting, and recovery usu­ tention deficit disorder. She had a history of three ally occurs rapidly following discontinuation of previous suicide attempts. On the evening of ad­ exposure. mission to the emergency department she was Nicotine is eliminated primarily by the liver, found unresponsive, lying on her bed. She was and approximately 20 metabolites have been last seen at 4 PM in her usual state of health. Her identified. Following intravenous infusion, the parents discovered her at 6:45 PM and telephoned plasma half-life of nicotine is 1 to 2 hours in indi­ for emergency services. On arrival, the para­ viduals with normal hepatic function. The lung medics found the patient responsive only to deep and kidney also metabolize small amounts of the pain. She had placed 14 Habitrol patches on her drug. During percutaneous absorption of nico­ chest, abdomen, buttocks, and extremities. It is un­ tine, no important metabolism occurs in the skin. known how long the patches were in place. Para­ Nicotine has a large volume of distribution of 2 to medical personnel removed 12 of the patches, and 3 Ukg.14 Plasma half-life with a nicotine patch in the 2 remaining were removed in the emergency 418 JABFP Sept.-Oct.1994 Vol. 7 No.5 J Am Board Fam Pract: first published as 10.3122/jabfm.7.5.417 on 1 September 1994. Downloaded from Table 1. Characteristics of Nicotine Transdermal Systems. Nicotine Dose Time to Peak Plasma Residual Nicotine Maximum Plasma Absorbed Concentration Total Nicotine (mg) after Concentration Product (mgl24 hr)lO-13 (hours)IO-13 Content (mg)lO-13 24 hours lO- 13 (ng/mL) Nicoderm 21 2-4 114 83 23 (Marion Merrell Dow) 14 78 60 17 7 36 26 8 Habitrol 21 5-6 52.5 31.5 17 (Basel) 14 35 21 12 7 17 10.5 7 ProStep 22 8 30 8 16 (Lederle) 11 IS 4 ND Nicotrol 15* 8 24.9 6 13 (Parke-Davis) 10* 16.6 4 7 S* 8.3 2 3.5 ND=NoData *Nicotine absorbed over 16 hours department. The size and milligram strength of cardiac, respiratory, and mental status monitoring the patches were not known. On examination at and supportive care. Her recovery was rapid and the emergency facility her respirations were regu­ without complication; she was discharged after 48 lar at 12/min, blood pressure was 170/92 mmlHg, hours to the psychiatric unit for further care.