Inhalants are CNS depressants and influence gamma-aminobutyric acid (GABA). Physiologic effects of inhalant use include a variety of body functions. Most of the damage initially affects the brain, observed through tremors and uncontrolled shaking. Headaches and seizures are common. Personality changes, memory loss, and decreased cognitive functioning may also develop. Inhalants can also cause lung damage with hypoxia, sinus discharge, coughing, and cyanosis. Arrhythmias, heart block, and heart failure are also possible with inhalant use. Other medical effects associated with inhalant use include gastrointestinal, liver, and kidney failure; bone marrow damage; and peripheral nervous system effects. Venous thromboembolism can be associated with inhalant use. Psychological effects of inhalant use include impaired judgment, hyperactivity, aggressive behavior, speech problems, and increased accidents, especially unplanned suicides in children who use inhalants. 52 Inhalation of hydrocarbons in the setting of catecholamine surge has resulted in fatal overdoses in otherwise young healthy patients. Sudden sniffing death is a rare but dangerous complication of inhalant use disorder. It is thought to be due to myocardium sensitization to catecholamines that is possibly accentuated by hypoxia associated with inhalant misuse, causing fatal dysrhythmias. 139 Individuals who try to quit inhalants may experience withdrawal symptoms including nausea, loss of appetite, diaphoresis, problems sleeping, and mood changes. Treatment of Inhalant Use Disorder and Intoxication Like many other drugs of abuse, no specific antidote or reversal agent exists for inhalant use or intoxication. Supportive care for the respiratory effects of stimulants may include oxygen or beta- agonists to treat bronchospasm. Nitrous oxide that is commonly found in whipped cream canisters may have effects on vitamin B 12 metabolism, and the neurotoxicity found in chronic use of this inhalant may be reversible with administration of vitamin B 12 (cyanocobalamin). 140 Chronic inhalant abuse can lead to withdrawal symptoms in absence of use, with symptoms similar to other withdrawal syndromes, such as irritability, nausea, vomiting, diaphoresis, tachycardia, hallucinations, or delusions. Treatment of inhalant use disorder can include pharmacotherapy or behavioral interventions. Multiple medications have been suggested for treatment of inhalant use disorder such as benzodiazepines, barbiturates, antipsychotic agents, lamotrigine, and buspirone. Tobacco Use Disorders/Vaping Tobacco use is widespread in the United States, and its deleterious effects are well documented. Smoking cigarettes lead to disease and disability in almost every organ in the body. Heart disease, stroke, lung disease, diabetes, and chronic obstructive pulmonary disease as well as multiple types of cancer are directly associated
with smoking. Additionally, there is an increased risk for tuberculosis, eye diseases, and immune diseases. Secondhand smoke is also detrimental to nonsmoking adults and children including stroke, lung cancer, sudden infant death syndrome, middle ear disease, worsening asthma, acute respiratory infections, and slowed lung growth. The strongest predictors of nicotine addiction are the time to first cigarette and total cigarettes per day. 53 The cigarette is a highly efficient drug delivery system. On average, the individual takes in 1-2 milligrams of nicotine per lit cigarette and takes 10 puffs over a 5 minute period. This equates to 200 hits of nicotine to the brain daily. 54 Nicotine stimulates catecholamine release by an activation of nicotine acetylcholine receptors, and this results in increases in increases in blood pressure, respiratory, and heart rates. It also stimulates reward pathways in the brain and is highly addictive. Frequent dosing is necessary to prevent withdrawal symptoms in most patients. Tobacco Withdrawal Withdrawal symptoms are often a barrier to stopping tobacco use, which is often due to nicotine deprivation. Withdrawal symptoms begin within 24 hours of abruptly quitting tobacco and include • Irritability, frustration, or anger • Anxiety • Difficulty concentrating Symptom intensity is higher in individuals who smoke cigarettes or use smokeless tobacco but peaks 2-3 days after abstinence and typically lasts approximately 2-3 weeks. However, nicotine replacement therapies (NRT) and other medications are available to augment the treatment of nicotine addiction. 55 Although thought to be beneficial, NRT must be initiated with caution and the most recent clinical practice guideline suggested cautious initiation within 2 weeks of acute myocardial infarction. 141 More recently, a study demonstrated that the use of NRT was not associated with any differences in short-term outcomes in smokers hospitalized with coronary heart disease. 142 NRTs come in a variety of delivery systems, and no standard dosing regimens are recommended. Starting at the lower doses available for each NRT is recommended with careful titration upward to control cravings but avoid the side effects associated with nicotine administration. 143 Table 5 represents a sample of NRTs, but it is not an inclusive list, and treatments must be individualized to each patient. E-cigarettes/Vaping Vaping was new to the U.S. market in 2007 with the introduction of the first electronic cigarette (e-cigarette) as a form of smoking cessation therapy. At the time, it was available by prescription only. Devices containing both nicotine and tetrahydrocannabinol (TCH) became available, and the popularity of this delivery device soared. 56 Use of vape products doubled between 2017 and • Increased appetite • Depressed mood • Insomnia
2019, prompting U.S. government policy makers to introduce age restrictions and ban the use of flavored e-cigarettes due to the concern for the general health of the young adults who were increasingly using these products. 144 Unfortunately, there is not enough data to determine short-term or long-term effects or the type of components that are to blame. Vaping is a delivery system similar to a nebulizer; however, the vaping system coats the lungs in harmful chemicals masked in a variety of flavorings and aromatic additives. Vitamin E is often used as part of the delivery system and thickening agent in the e-liquid, which is thought to be an irritant to the lungs. Other common substances found in the e-liquid include (1) diacetyl, which is a food additive (buttery taste in microwave popcorn) known to damage small passages in the lungs; (2) formaldehyde, which contributes to lung and heart disease; and (3) acrolein, which is used as a weed killer and can also damage lungs. Several lung diseases listed subsequently are associated with vaping. 57 •
Bronchiolitis obliterans (popcorn lung) is a rare condition resulting from damage of the small airways from diacetyl. Inhaling this additive causes coughing, wheezing, chest pain, and shortness of breath. Symptomatic treatment is available; however, there is no lasting treatment. Vaping-related lipoid pneumonia develops when fatty acids enter the lungs from the oily substances found in the e-liquid. This induces inflammatory responses in the lungs demonstrated by chronic cough, shortness of breath, and blood-tinged mucus. The single most important treatment is to eliminate vaping while the lungs heal themselves. Primary spontaneous pneumothorax may develop due to vaping due to the development of bullous lung disease. Rapid lung growth found in adolescence makes this complication more common. The development of lung bullae is typically painless as opposed to the symptoms associated with pneumothorax that include sharp chest or shoulder pain along with dyspnea. E-cigarette/vaping associated lung injury (EVALI) presents as an acute respiratory illness with nonspecific symptoms such as cough, shortness of breath, and chest pain, and may produce hemoptysis. Gastrointestinal symptoms, fever, fatigue, and weight loss may occur over days to weeks after starting to use vaping products. EVALI is strongly associated with vitamin E, which is found in lung fluid of individuals with EVALI but not in those without EVALI. EVALI is a diagnosis of exclusion and is considered strongly when pulmonary infiltrates are found on imaging of the lung in patients with recent initiation of these vaping delivery systems. Laboratory tests should be guided by clinical findings as well as practice guidelines.
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