Steven Lippmann, MD

Electronic cigarettes (e-cigarettes) have become increasingly popular over the last decade. Although they are perceived by many to be safer than traditional cigarettes, many of the devices still contain nicotine, and inhaling their vapors exposes users to toxic substances, including lead, cadmium, and nickel—heavy metals that are associated with significant health problems.¹ (For more on how e-cigarettes work, see “Cigarettes vs e-cigarettes: How does the experience (and cost) compare?”)

In addition, many people use e-cigarettes as a means to stop smoking, but few who do so achieve abstinence.^2,3 They frequently end up utilizing both, increasing their health risks by exposing themselves to the dangers of 2 products instead of one.¹

Further complicating the issue is that the manufacture and distribution of e-cigarettes has not been well regulated. Without regulation, there is no way to know with certainty how much nicotine the devices contain and what else is in them.

Things, however, are changing. The Food and Drug Administration (FDA) recently announced that e-cigarettes and other tobacco products like cigars and hookahs will now be regulated in the same way the government regulates tobacco cigarettes and smokeless tobacco.⁴ The rule will not take effect immediately because companies requested time to comply, but once it is enacted, packaging will be required to list what the products contain, among other changes.

Keeping up on the latest information on e-cigarettes is now—and will continue to be—important as family physicians are increasingly asked about them. What follows is a review of what we know about their potential risks.

© 2016 iStock

A nicotine system developed by a pharmacist

E-cigarettes, or electronic nicotine delivery systems, were patented in 2003 by a Chinese pharmacist.⁵ Since their introduction to North America and Europe in 2007, the devices have become known by over 400 different brand names.⁶ Consumption among adults doubled by 2012, and by 2014, about 4% of US adults used e-cigarettes every day or some days.⁷ Many of them are dual users of tobacco and electronic cigarettes. In fact, Jenkins and colleagues reports in this issue of JFP (see "E-cigarettes: Who's using them and why?") that over half of cigarette smokers (52%) in their study use e-cigarettes, usually to either lower their cigarette consumption or aid in smoking cessation. (Throughout this article, we will use “cigarettes” and “smoking” to refer to the use of traditional tobacco cigarettes.)

In addition to concern over an increase in use among the general population, there is significant concern about the increase in e-cigarette use among US middle and high school students.^1,8,9 In 2015, e-cigarettes were the most commonly used smoking product among middle and high school students, with 620,000 middle school students and nearly 2.4 million high school students using the battery-powered devices in the past 30 days.¹⁰

Many factors have contributed to the growing popularity of e-cigarettes.

• Perceived safety. With tobacco’s dangers so thoroughly documented, many advertising campaigns tout e-cigarettes as less dangerous than conventional cigarettes in terms of their ability to cause cardiac and lung diseases and low birth weights. This is largely because e-cigarettes do not produce the combustion products of tar, ash, or carbon monoxide. In addition, many consumers are mistakenly less fearful about the nicotine added to many e-cigarettes.
• Expectation that it helps smokers quit. Many smokers view e-cigarettes as an aid to smoking cessation.⁶ In fact, testimonials of efficacy in tobacco cessation abound in promotional materials and on the Web, and e-cigarettes are recommended by some physicians as a means to quit or lessen smoking of tobacco cigarettes.¹¹
• Wide availability and opportunities for use. The use of electronic nicotine delivery devices is sometimes permitted in places where smoking of conventional cigarettes is banned, although rules vary widely in different parts of the country. In addition, e-cigarettes are readily available for purchase on the Internet without age verification.
• Extensive advertising. There are increasing concerns that advertising campaigns unduly target adolescents, young adults, and women.^12-155 In addition to advertising, the media and social influences play significant roles in young people’s experimentation with “vaping,” the term for inhaling electronic cigarette aerosols.^14,15
• Regulation, legislation remain controversial. Currently, e-cigarettes are not required to be tested before marketing,¹⁶ but that may change with the FDA’s new regulations. The British National Public Health body, Public Health England, has documented public health benefits of e-cigarettes when used as a way to quit smoking, and provides evidence that the devices are less dangerous than traditional cigarettes.¹⁷ But this issue and public policy are the subject of ongoing debate. In 2015, the United Kingdom made it illegal to sell e-cigarettes or e-liquids to people younger than 18 years of age and urged child-proof packaging.

What’s “in” an e-cigarette—and are the ingredients toxic?

Because e-cigarettes are relatively new to the global marketplace, little research exists regarding the long-term effects and safety of their use, especially among habitual users.

Vapor/refills. E-liquids may contain a variety of substances because they have been largely unregulated, but they generally include some combination of nicotine, propylene glycol, glycerin, and flavorings. In fact, up to 7000 flavors are available,⁶ including such kid-friendly flavors as chocolate, cherry crush, and bubble gum.

Since many individuals continue to use traditional and electronic cigarettes, they end up in double jeopardy of toxicity through exposure to the dangers of both.

When the refills do contain nicotine, users generally derive less of the substance from the electronic devices than they do from a conventional cigarette. Researchers found that individual puffs from an e-cigarette contained 0 to 35 µg nicotine per puff.^1,18 Assuming an amount at the high end of the spectrum (30 µg nicotine), it would take about 30 puffs of an e-cigarette to derive the same amount of nicotine (1 mg) typically delivered by a conventional cigarette.

The chemical make-up of the vapor and the biologic effects on animal models have been investigated using 42 different liquid refills.^19,20 All contained potentially harmful compounds, but the levels were within exposure limits authorized by the FDA. These potentially dangerous chemicals include the known toxins formaldehyde, acrolein, and hydrocarbons.²⁰

An inflammatory response to the inhalation of the vapors was demonstrated in mouse lungs; exposure to e-cigarette aerosols reduced lung glutathione—an important enzyme in maintaining oxidation-reduction balance—to a degree similar to that of cigarette smoke exposure.²⁰ Less of the enzyme facilitates increased pulmonary inflammation.

In addition, human lung cells release pro-inflammatory cytokines when exposed to e-cigarette aerosols.²⁰ Other health risks include:

Harm to indoor air quality/secondhand exposure. Even though e-cigarettes do not emit smoke, bystanders are exposed to the aerosol or vapor exhaled by the user, and researchers have found varying levels of such substances as formaldehyde, acetaldehyde, isoprene, acetic acid, acetone, propanol, propylene glycol, and nicotine in the air. However, it is unclear at this time whether the ultra-fine particles in the e-cigarette vapor have health effects commensurate with the emissions of conventional cigarettes.^1,21,22

Cartridge refill ingestion by children. Accidental nicotine poisonings, particularly among children drawn to the colors, flavors, and scents of the e-liquids, have been problematic. In 2014, for example, over 3500 exposures occurred and more than half of those were in children younger than 6 years of age. (Exposure is defined as contact with the substance in some way including ingestion, inhalation, absorption by the skin/eyes, etc; not all exposures are poisonings or overdoses).²³ Although incidence has tapered off somewhat, the American Association of Poison Control Centers reports that there were 623 exposures across all age groups between January 1, 2016 and April 30, 2016.²³

Many people use e-cigarettes as a means to stop smoking, but few who do so achieve abstinence.

Environmental impact of discarded e-cigarettes. Discarded e-cigarettes filling our landfills is a new and emerging public health concern. Their batteries, as do all batteries, pollute the land and water and have the potential to leach lead into the environment.²⁴ Similarly, incompletely used liquid cartridges and refills may contain nicotine and heavy metals, which add to these risks.²⁴

Explosions. Fires and explosions have been documented with e-cigarette use, mostly due to malfunctioning lithium-ion batteries.²⁵ Thermal injuries to the face and hands can be significant.

Heavy metals. The presence of lead, cadmium, and nickel in inhaled e-cigarette vapor is another area of significant concern, particularly for younger people who might have long-term exposure.¹ All 3 heavy metals are known to be toxic to humans, and safe levels of inhalation have not been established.

Inhalation and/or ingestion of lead, in particular, can cause severe neurologic damage, especially to the developing brains of children.²⁶ Lead also results in hematologic dysfunction. Because of the risks associated with inhalation of this heavy metal, the substance was removed from gasoline years ago.

Inhaled cadmium induces kidney, liver, bone, and respiratory tract pathology²⁷ and can cause organ failure, hypertension, anemias, fractures, osteoporosis, and/or osteomalacia.²⁸ And inhaling nickel produces an inflammatory pulmonary reaction.²⁹

Pregnancy/lactation. Since no clear evidence exists on the safety of e-cigarette use during pregnancy, women should avoid exposure to these vapors during the entire perinatal period. Similarly, the effects of e-cigarettes on infants who are breastfeeding are not established. Pregnant and breastfeeding women should not replace cigarettes with e-cigarettes.^30,31 For pregnant women who smoke, the US Preventive Services Task Force (USPSTF) advises using only behavioral methods to stop cigarette use.³² And until more information becomes available, exposing infants and young children to e-cigarette vapor during breastfeeding is not recommended.

On the flip side, without tobacco, tar, ash, or carbon monoxide, e-cigarettes may have some advantages when compared with the use of traditional cigarettes, but that has not been substantiated.

Don’t substitute one form of nicotine for another

The presence of lead, cadmium, and nickel in inhaled e-cigarette vapor is an area of significant concern.

The USPSTF has not determined the benefit-to-harm ratio of using e-cigarettes as a smoking cessation aid, but recommends prescribing behavioral techniques and/or pharmacologic alternatives instead.³² Because the devices have been promoted as an aid to smoking cessation, intention to quit using tobacco products is a reason often stated for utilizing e-cigarettes.^2,33,34 Indeed, use of e-cigarettes is much more likely among those who already utilize tobacco products.^35-37

At least one study reports that e-cigarettes have efficacy similar to nicotine patches in achieving smoking abstinence among smokers who want to quit.³⁸ Former smokers who used e-cigarettes to quit smoking reported fewer withdrawal symptoms than those who used nicotine skin patches.³⁹ In addition, former smokers were more likely to endorse e-cigarettes than nicotine patches as a tobacco cigarette cessation aid. Significant reduction in tobacco smoke exposure has been demonstrated in dual users of tobacco and electronic cigarettes;^40,41 however, both of these nicotine delivery systems sustain nicotine addiction.

Despite many ongoing studies to determine if e-cigarettes are useful as a smoking cessation aid, the results vary widely and are inconclusive at this time.⁴²

E-cigarettes do not increase long-term tobacco abstinence

Contrary to popular belief, research shows that e-cigarette use among smokers is not associated with long-term tobacco abstinence.¹ E-cigarette users, however, may make more attempts to quit smoking compared with smokers not using them.⁴³ In addition, even though there is some evidence that e-cigarettes help smokers reduce the number of cigarettes smoked per day, simply reducing the daily number of cigarettes does not equate with safety.⁴⁴ Smoking just one to 4 cigarettes per day poses 3 times the risk of myocardial infarction and lung cancer compared with not smoking.⁴⁴ And since many individuals continue to use traditional and electronic cigarettes, they end up in double jeopardy of toxicity through exposure to the dangers of both.

A gateway to other substances of abuse?

Pregnant and breastfeeding women should not replace tobacco cigarettes with e-cigarettes.

There is also fear that nicotine exposure via e-cigarettes, especially in young people, serves as a “gateway” to tobacco consumption and other substance abuses, and increases the risk for nicotine addiction.³⁴ Such nicotine-induced effects are a result of changes in brain chemistry, and have been documented in humans and animals.³⁴

These concerns about negative health consequences, combined with the fact that e-cigarettes are undocumented as a smoking cessation aid, add urgency to the need for legislative and regulatory actions that hopefully can curb all nicotine exposures, particularly for our nation’s youth. In the meantime, it is important for physicians to advise patients—and the public—about the risks of e-cigarettes and the importance of quitting all forms of nicotine inhalation because nicotine—regardless of how it is delivered—is still an addictive drug.

CORRESPONDENCE
Steven Lippmann, MD, University of Louisville School of Medicine, 401 E. Chestnut Street, Suite 610, Louisville, KY 40202; [email protected].

Electronic cigarettes (e-cigarettes) have become increasingly popular over the last decade. Although they are perceived by many to be safer than traditional cigarettes, many of the devices still contain nicotine, and inhaling their vapors exposes users to toxic substances, including lead, cadmium, and nickel—heavy metals that are associated with significant health problems.¹ (For more on how e-cigarettes work, see “Cigarettes vs e-cigarettes: How does the experience (and cost) compare?”)

In addition, many people use e-cigarettes as a means to stop smoking, but few who do so achieve abstinence.^2,3 They frequently end up utilizing both, increasing their health risks by exposing themselves to the dangers of 2 products instead of one.¹

Further complicating the issue is that the manufacture and distribution of e-cigarettes has not been well regulated. Without regulation, there is no way to know with certainty how much nicotine the devices contain and what else is in them.

Things, however, are changing. The Food and Drug Administration (FDA) recently announced that e-cigarettes and other tobacco products like cigars and hookahs will now be regulated in the same way the government regulates tobacco cigarettes and smokeless tobacco.⁴ The rule will not take effect immediately because companies requested time to comply, but once it is enacted, packaging will be required to list what the products contain, among other changes.

Keeping up on the latest information on e-cigarettes is now—and will continue to be—important as family physicians are increasingly asked about them. What follows is a review of what we know about their potential risks.

© 2016 iStock

A nicotine system developed by a pharmacist

E-cigarettes, or electronic nicotine delivery systems, were patented in 2003 by a Chinese pharmacist.⁵ Since their introduction to North America and Europe in 2007, the devices have become known by over 400 different brand names.⁶ Consumption among adults doubled by 2012, and by 2014, about 4% of US adults used e-cigarettes every day or some days.⁷ Many of them are dual users of tobacco and electronic cigarettes. In fact, Jenkins and colleagues reports in this issue of JFP (see "E-cigarettes: Who's using them and why?") that over half of cigarette smokers (52%) in their study use e-cigarettes, usually to either lower their cigarette consumption or aid in smoking cessation. (Throughout this article, we will use “cigarettes” and “smoking” to refer to the use of traditional tobacco cigarettes.)

In addition to concern over an increase in use among the general population, there is significant concern about the increase in e-cigarette use among US middle and high school students.^1,8,9 In 2015, e-cigarettes were the most commonly used smoking product among middle and high school students, with 620,000 middle school students and nearly 2.4 million high school students using the battery-powered devices in the past 30 days.¹⁰

Many factors have contributed to the growing popularity of e-cigarettes.

• Perceived safety. With tobacco’s dangers so thoroughly documented, many advertising campaigns tout e-cigarettes as less dangerous than conventional cigarettes in terms of their ability to cause cardiac and lung diseases and low birth weights. This is largely because e-cigarettes do not produce the combustion products of tar, ash, or carbon monoxide. In addition, many consumers are mistakenly less fearful about the nicotine added to many e-cigarettes.
• Expectation that it helps smokers quit. Many smokers view e-cigarettes as an aid to smoking cessation.⁶ In fact, testimonials of efficacy in tobacco cessation abound in promotional materials and on the Web, and e-cigarettes are recommended by some physicians as a means to quit or lessen smoking of tobacco cigarettes.¹¹
• Wide availability and opportunities for use. The use of electronic nicotine delivery devices is sometimes permitted in places where smoking of conventional cigarettes is banned, although rules vary widely in different parts of the country. In addition, e-cigarettes are readily available for purchase on the Internet without age verification.
• Extensive advertising. There are increasing concerns that advertising campaigns unduly target adolescents, young adults, and women.^12-155 In addition to advertising, the media and social influences play significant roles in young people’s experimentation with “vaping,” the term for inhaling electronic cigarette aerosols.^14,15
• Regulation, legislation remain controversial. Currently, e-cigarettes are not required to be tested before marketing,¹⁶ but that may change with the FDA’s new regulations. The British National Public Health body, Public Health England, has documented public health benefits of e-cigarettes when used as a way to quit smoking, and provides evidence that the devices are less dangerous than traditional cigarettes.¹⁷ But this issue and public policy are the subject of ongoing debate. In 2015, the United Kingdom made it illegal to sell e-cigarettes or e-liquids to people younger than 18 years of age and urged child-proof packaging.

What’s “in” an e-cigarette—and are the ingredients toxic?

Because e-cigarettes are relatively new to the global marketplace, little research exists regarding the long-term effects and safety of their use, especially among habitual users.

Vapor/refills. E-liquids may contain a variety of substances because they have been largely unregulated, but they generally include some combination of nicotine, propylene glycol, glycerin, and flavorings. In fact, up to 7000 flavors are available,⁶ including such kid-friendly flavors as chocolate, cherry crush, and bubble gum.

Since many individuals continue to use traditional and electronic cigarettes, they end up in double jeopardy of toxicity through exposure to the dangers of both.

When the refills do contain nicotine, users generally derive less of the substance from the electronic devices than they do from a conventional cigarette. Researchers found that individual puffs from an e-cigarette contained 0 to 35 µg nicotine per puff.^1,18 Assuming an amount at the high end of the spectrum (30 µg nicotine), it would take about 30 puffs of an e-cigarette to derive the same amount of nicotine (1 mg) typically delivered by a conventional cigarette.

The chemical make-up of the vapor and the biologic effects on animal models have been investigated using 42 different liquid refills.^19,20 All contained potentially harmful compounds, but the levels were within exposure limits authorized by the FDA. These potentially dangerous chemicals include the known toxins formaldehyde, acrolein, and hydrocarbons.²⁰

An inflammatory response to the inhalation of the vapors was demonstrated in mouse lungs; exposure to e-cigarette aerosols reduced lung glutathione—an important enzyme in maintaining oxidation-reduction balance—to a degree similar to that of cigarette smoke exposure.²⁰ Less of the enzyme facilitates increased pulmonary inflammation.

In addition, human lung cells release pro-inflammatory cytokines when exposed to e-cigarette aerosols.²⁰ Other health risks include:

Harm to indoor air quality/secondhand exposure. Even though e-cigarettes do not emit smoke, bystanders are exposed to the aerosol or vapor exhaled by the user, and researchers have found varying levels of such substances as formaldehyde, acetaldehyde, isoprene, acetic acid, acetone, propanol, propylene glycol, and nicotine in the air. However, it is unclear at this time whether the ultra-fine particles in the e-cigarette vapor have health effects commensurate with the emissions of conventional cigarettes.^1,21,22

Cartridge refill ingestion by children. Accidental nicotine poisonings, particularly among children drawn to the colors, flavors, and scents of the e-liquids, have been problematic. In 2014, for example, over 3500 exposures occurred and more than half of those were in children younger than 6 years of age. (Exposure is defined as contact with the substance in some way including ingestion, inhalation, absorption by the skin/eyes, etc; not all exposures are poisonings or overdoses).²³ Although incidence has tapered off somewhat, the American Association of Poison Control Centers reports that there were 623 exposures across all age groups between January 1, 2016 and April 30, 2016.²³

Many people use e-cigarettes as a means to stop smoking, but few who do so achieve abstinence.

Environmental impact of discarded e-cigarettes. Discarded e-cigarettes filling our landfills is a new and emerging public health concern. Their batteries, as do all batteries, pollute the land and water and have the potential to leach lead into the environment.²⁴ Similarly, incompletely used liquid cartridges and refills may contain nicotine and heavy metals, which add to these risks.²⁴

Explosions. Fires and explosions have been documented with e-cigarette use, mostly due to malfunctioning lithium-ion batteries.²⁵ Thermal injuries to the face and hands can be significant.

Heavy metals. The presence of lead, cadmium, and nickel in inhaled e-cigarette vapor is another area of significant concern, particularly for younger people who might have long-term exposure.¹ All 3 heavy metals are known to be toxic to humans, and safe levels of inhalation have not been established.

Inhalation and/or ingestion of lead, in particular, can cause severe neurologic damage, especially to the developing brains of children.²⁶ Lead also results in hematologic dysfunction. Because of the risks associated with inhalation of this heavy metal, the substance was removed from gasoline years ago.

Inhaled cadmium induces kidney, liver, bone, and respiratory tract pathology²⁷ and can cause organ failure, hypertension, anemias, fractures, osteoporosis, and/or osteomalacia.²⁸ And inhaling nickel produces an inflammatory pulmonary reaction.²⁹

Pregnancy/lactation. Since no clear evidence exists on the safety of e-cigarette use during pregnancy, women should avoid exposure to these vapors during the entire perinatal period. Similarly, the effects of e-cigarettes on infants who are breastfeeding are not established. Pregnant and breastfeeding women should not replace cigarettes with e-cigarettes.^30,31 For pregnant women who smoke, the US Preventive Services Task Force (USPSTF) advises using only behavioral methods to stop cigarette use.³² And until more information becomes available, exposing infants and young children to e-cigarette vapor during breastfeeding is not recommended.

On the flip side, without tobacco, tar, ash, or carbon monoxide, e-cigarettes may have some advantages when compared with the use of traditional cigarettes, but that has not been substantiated.

Don’t substitute one form of nicotine for another

The presence of lead, cadmium, and nickel in inhaled e-cigarette vapor is an area of significant concern.

The USPSTF has not determined the benefit-to-harm ratio of using e-cigarettes as a smoking cessation aid, but recommends prescribing behavioral techniques and/or pharmacologic alternatives instead.³² Because the devices have been promoted as an aid to smoking cessation, intention to quit using tobacco products is a reason often stated for utilizing e-cigarettes.^2,33,34 Indeed, use of e-cigarettes is much more likely among those who already utilize tobacco products.^35-37

At least one study reports that e-cigarettes have efficacy similar to nicotine patches in achieving smoking abstinence among smokers who want to quit.³⁸ Former smokers who used e-cigarettes to quit smoking reported fewer withdrawal symptoms than those who used nicotine skin patches.³⁹ In addition, former smokers were more likely to endorse e-cigarettes than nicotine patches as a tobacco cigarette cessation aid. Significant reduction in tobacco smoke exposure has been demonstrated in dual users of tobacco and electronic cigarettes;^40,41 however, both of these nicotine delivery systems sustain nicotine addiction.

Despite many ongoing studies to determine if e-cigarettes are useful as a smoking cessation aid, the results vary widely and are inconclusive at this time.⁴²

E-cigarettes do not increase long-term tobacco abstinence

Contrary to popular belief, research shows that e-cigarette use among smokers is not associated with long-term tobacco abstinence.¹ E-cigarette users, however, may make more attempts to quit smoking compared with smokers not using them.⁴³ In addition, even though there is some evidence that e-cigarettes help smokers reduce the number of cigarettes smoked per day, simply reducing the daily number of cigarettes does not equate with safety.⁴⁴ Smoking just one to 4 cigarettes per day poses 3 times the risk of myocardial infarction and lung cancer compared with not smoking.⁴⁴ And since many individuals continue to use traditional and electronic cigarettes, they end up in double jeopardy of toxicity through exposure to the dangers of both.

A gateway to other substances of abuse?

Pregnant and breastfeeding women should not replace tobacco cigarettes with e-cigarettes.

There is also fear that nicotine exposure via e-cigarettes, especially in young people, serves as a “gateway” to tobacco consumption and other substance abuses, and increases the risk for nicotine addiction.³⁴ Such nicotine-induced effects are a result of changes in brain chemistry, and have been documented in humans and animals.³⁴

These concerns about negative health consequences, combined with the fact that e-cigarettes are undocumented as a smoking cessation aid, add urgency to the need for legislative and regulatory actions that hopefully can curb all nicotine exposures, particularly for our nation’s youth. In the meantime, it is important for physicians to advise patients—and the public—about the risks of e-cigarettes and the importance of quitting all forms of nicotine inhalation because nicotine—regardless of how it is delivered—is still an addictive drug.

CORRESPONDENCE
Steven Lippmann, MD, University of Louisville School of Medicine, 401 E. Chestnut Street, Suite 610, Louisville, KY 40202; [email protected].

Electronic cigarettes (e-cigarettes) have become increasingly popular over the last decade. Although they are perceived by many to be safer than traditional cigarettes, many of the devices still contain nicotine, and inhaling their vapors exposes users to toxic substances, including lead, cadmium, and nickel—heavy metals that are associated with significant health problems.¹ (For more on how e-cigarettes work, see “Cigarettes vs e-cigarettes: How does the experience (and cost) compare?”)

In addition, many people use e-cigarettes as a means to stop smoking, but few who do so achieve abstinence.^2,3 They frequently end up utilizing both, increasing their health risks by exposing themselves to the dangers of 2 products instead of one.¹

Further complicating the issue is that the manufacture and distribution of e-cigarettes has not been well regulated. Without regulation, there is no way to know with certainty how much nicotine the devices contain and what else is in them.

Things, however, are changing. The Food and Drug Administration (FDA) recently announced that e-cigarettes and other tobacco products like cigars and hookahs will now be regulated in the same way the government regulates tobacco cigarettes and smokeless tobacco.⁴ The rule will not take effect immediately because companies requested time to comply, but once it is enacted, packaging will be required to list what the products contain, among other changes.

Keeping up on the latest information on e-cigarettes is now—and will continue to be—important as family physicians are increasingly asked about them. What follows is a review of what we know about their potential risks.

© 2016 iStock

A nicotine system developed by a pharmacist

E-cigarettes, or electronic nicotine delivery systems, were patented in 2003 by a Chinese pharmacist.⁵ Since their introduction to North America and Europe in 2007, the devices have become known by over 400 different brand names.⁶ Consumption among adults doubled by 2012, and by 2014, about 4% of US adults used e-cigarettes every day or some days.⁷ Many of them are dual users of tobacco and electronic cigarettes. In fact, Jenkins and colleagues reports in this issue of JFP (see "E-cigarettes: Who's using them and why?") that over half of cigarette smokers (52%) in their study use e-cigarettes, usually to either lower their cigarette consumption or aid in smoking cessation. (Throughout this article, we will use “cigarettes” and “smoking” to refer to the use of traditional tobacco cigarettes.)

In addition to concern over an increase in use among the general population, there is significant concern about the increase in e-cigarette use among US middle and high school students.^1,8,9 In 2015, e-cigarettes were the most commonly used smoking product among middle and high school students, with 620,000 middle school students and nearly 2.4 million high school students using the battery-powered devices in the past 30 days.¹⁰

Many factors have contributed to the growing popularity of e-cigarettes.

• Perceived safety. With tobacco’s dangers so thoroughly documented, many advertising campaigns tout e-cigarettes as less dangerous than conventional cigarettes in terms of their ability to cause cardiac and lung diseases and low birth weights. This is largely because e-cigarettes do not produce the combustion products of tar, ash, or carbon monoxide. In addition, many consumers are mistakenly less fearful about the nicotine added to many e-cigarettes.
• Expectation that it helps smokers quit. Many smokers view e-cigarettes as an aid to smoking cessation.⁶ In fact, testimonials of efficacy in tobacco cessation abound in promotional materials and on the Web, and e-cigarettes are recommended by some physicians as a means to quit or lessen smoking of tobacco cigarettes.¹¹
• Wide availability and opportunities for use. The use of electronic nicotine delivery devices is sometimes permitted in places where smoking of conventional cigarettes is banned, although rules vary widely in different parts of the country. In addition, e-cigarettes are readily available for purchase on the Internet without age verification.
• Extensive advertising. There are increasing concerns that advertising campaigns unduly target adolescents, young adults, and women.^12-155 In addition to advertising, the media and social influences play significant roles in young people’s experimentation with “vaping,” the term for inhaling electronic cigarette aerosols.^14,15
• Regulation, legislation remain controversial. Currently, e-cigarettes are not required to be tested before marketing,¹⁶ but that may change with the FDA’s new regulations. The British National Public Health body, Public Health England, has documented public health benefits of e-cigarettes when used as a way to quit smoking, and provides evidence that the devices are less dangerous than traditional cigarettes.¹⁷ But this issue and public policy are the subject of ongoing debate. In 2015, the United Kingdom made it illegal to sell e-cigarettes or e-liquids to people younger than 18 years of age and urged child-proof packaging.

What’s “in” an e-cigarette—and are the ingredients toxic?

Because e-cigarettes are relatively new to the global marketplace, little research exists regarding the long-term effects and safety of their use, especially among habitual users.

Vapor/refills. E-liquids may contain a variety of substances because they have been largely unregulated, but they generally include some combination of nicotine, propylene glycol, glycerin, and flavorings. In fact, up to 7000 flavors are available,⁶ including such kid-friendly flavors as chocolate, cherry crush, and bubble gum.

Since many individuals continue to use traditional and electronic cigarettes, they end up in double jeopardy of toxicity through exposure to the dangers of both.

When the refills do contain nicotine, users generally derive less of the substance from the electronic devices than they do from a conventional cigarette. Researchers found that individual puffs from an e-cigarette contained 0 to 35 µg nicotine per puff.^1,18 Assuming an amount at the high end of the spectrum (30 µg nicotine), it would take about 30 puffs of an e-cigarette to derive the same amount of nicotine (1 mg) typically delivered by a conventional cigarette.

The chemical make-up of the vapor and the biologic effects on animal models have been investigated using 42 different liquid refills.^19,20 All contained potentially harmful compounds, but the levels were within exposure limits authorized by the FDA. These potentially dangerous chemicals include the known toxins formaldehyde, acrolein, and hydrocarbons.²⁰

An inflammatory response to the inhalation of the vapors was demonstrated in mouse lungs; exposure to e-cigarette aerosols reduced lung glutathione—an important enzyme in maintaining oxidation-reduction balance—to a degree similar to that of cigarette smoke exposure.²⁰ Less of the enzyme facilitates increased pulmonary inflammation.

In addition, human lung cells release pro-inflammatory cytokines when exposed to e-cigarette aerosols.²⁰ Other health risks include:

Harm to indoor air quality/secondhand exposure. Even though e-cigarettes do not emit smoke, bystanders are exposed to the aerosol or vapor exhaled by the user, and researchers have found varying levels of such substances as formaldehyde, acetaldehyde, isoprene, acetic acid, acetone, propanol, propylene glycol, and nicotine in the air. However, it is unclear at this time whether the ultra-fine particles in the e-cigarette vapor have health effects commensurate with the emissions of conventional cigarettes.^1,21,22

Cartridge refill ingestion by children. Accidental nicotine poisonings, particularly among children drawn to the colors, flavors, and scents of the e-liquids, have been problematic. In 2014, for example, over 3500 exposures occurred and more than half of those were in children younger than 6 years of age. (Exposure is defined as contact with the substance in some way including ingestion, inhalation, absorption by the skin/eyes, etc; not all exposures are poisonings or overdoses).²³ Although incidence has tapered off somewhat, the American Association of Poison Control Centers reports that there were 623 exposures across all age groups between January 1, 2016 and April 30, 2016.²³

Many people use e-cigarettes as a means to stop smoking, but few who do so achieve abstinence.

Environmental impact of discarded e-cigarettes. Discarded e-cigarettes filling our landfills is a new and emerging public health concern. Their batteries, as do all batteries, pollute the land and water and have the potential to leach lead into the environment.²⁴ Similarly, incompletely used liquid cartridges and refills may contain nicotine and heavy metals, which add to these risks.²⁴

Explosions. Fires and explosions have been documented with e-cigarette use, mostly due to malfunctioning lithium-ion batteries.²⁵ Thermal injuries to the face and hands can be significant.

Heavy metals. The presence of lead, cadmium, and nickel in inhaled e-cigarette vapor is another area of significant concern, particularly for younger people who might have long-term exposure.¹ All 3 heavy metals are known to be toxic to humans, and safe levels of inhalation have not been established.

Inhalation and/or ingestion of lead, in particular, can cause severe neurologic damage, especially to the developing brains of children.²⁶ Lead also results in hematologic dysfunction. Because of the risks associated with inhalation of this heavy metal, the substance was removed from gasoline years ago.

Inhaled cadmium induces kidney, liver, bone, and respiratory tract pathology²⁷ and can cause organ failure, hypertension, anemias, fractures, osteoporosis, and/or osteomalacia.²⁸ And inhaling nickel produces an inflammatory pulmonary reaction.²⁹

Pregnancy/lactation. Since no clear evidence exists on the safety of e-cigarette use during pregnancy, women should avoid exposure to these vapors during the entire perinatal period. Similarly, the effects of e-cigarettes on infants who are breastfeeding are not established. Pregnant and breastfeeding women should not replace cigarettes with e-cigarettes.^30,31 For pregnant women who smoke, the US Preventive Services Task Force (USPSTF) advises using only behavioral methods to stop cigarette use.³² And until more information becomes available, exposing infants and young children to e-cigarette vapor during breastfeeding is not recommended.

On the flip side, without tobacco, tar, ash, or carbon monoxide, e-cigarettes may have some advantages when compared with the use of traditional cigarettes, but that has not been substantiated.

Don’t substitute one form of nicotine for another

The presence of lead, cadmium, and nickel in inhaled e-cigarette vapor is an area of significant concern.

The USPSTF has not determined the benefit-to-harm ratio of using e-cigarettes as a smoking cessation aid, but recommends prescribing behavioral techniques and/or pharmacologic alternatives instead.³² Because the devices have been promoted as an aid to smoking cessation, intention to quit using tobacco products is a reason often stated for utilizing e-cigarettes.^2,33,34 Indeed, use of e-cigarettes is much more likely among those who already utilize tobacco products.^35-37

At least one study reports that e-cigarettes have efficacy similar to nicotine patches in achieving smoking abstinence among smokers who want to quit.³⁸ Former smokers who used e-cigarettes to quit smoking reported fewer withdrawal symptoms than those who used nicotine skin patches.³⁹ In addition, former smokers were more likely to endorse e-cigarettes than nicotine patches as a tobacco cigarette cessation aid. Significant reduction in tobacco smoke exposure has been demonstrated in dual users of tobacco and electronic cigarettes;^40,41 however, both of these nicotine delivery systems sustain nicotine addiction.

Despite many ongoing studies to determine if e-cigarettes are useful as a smoking cessation aid, the results vary widely and are inconclusive at this time.⁴²

E-cigarettes do not increase long-term tobacco abstinence

Contrary to popular belief, research shows that e-cigarette use among smokers is not associated with long-term tobacco abstinence.¹ E-cigarette users, however, may make more attempts to quit smoking compared with smokers not using them.⁴³ In addition, even though there is some evidence that e-cigarettes help smokers reduce the number of cigarettes smoked per day, simply reducing the daily number of cigarettes does not equate with safety.⁴⁴ Smoking just one to 4 cigarettes per day poses 3 times the risk of myocardial infarction and lung cancer compared with not smoking.⁴⁴ And since many individuals continue to use traditional and electronic cigarettes, they end up in double jeopardy of toxicity through exposure to the dangers of both.

A gateway to other substances of abuse?

Pregnant and breastfeeding women should not replace tobacco cigarettes with e-cigarettes.

There is also fear that nicotine exposure via e-cigarettes, especially in young people, serves as a “gateway” to tobacco consumption and other substance abuses, and increases the risk for nicotine addiction.³⁴ Such nicotine-induced effects are a result of changes in brain chemistry, and have been documented in humans and animals.³⁴

These concerns about negative health consequences, combined with the fact that e-cigarettes are undocumented as a smoking cessation aid, add urgency to the need for legislative and regulatory actions that hopefully can curb all nicotine exposures, particularly for our nation’s youth. In the meantime, it is important for physicians to advise patients—and the public—about the risks of e-cigarettes and the importance of quitting all forms of nicotine inhalation because nicotine—regardless of how it is delivered—is still an addictive drug.

CORRESPONDENCE
Steven Lippmann, MD, University of Louisville School of Medicine, 401 E. Chestnut Street, Suite 610, Louisville, KY 40202; [email protected].

Firearms are the most common means of suicide in the United States, accounting for approximately 20,000 adult deaths annually,1 which is approximately two-thirds of the more than 32,000 gun-related fatalities each year in the United States. Of approximately 3,000 American children who are shot to death annually, one-third are suicides.^1-4

Firearms are dangerous; it has been documented that even guns obtained for recreation or protection increase the risk of suicide, homicide, or injury.^2,3 This problem has become a public health concern.^3-8 Because most suicide attempts with firearms are fatal, psychiatrists have an interest in reducing such outcomes.^1-8

Risk factors for suicide by firearm
Easy availability of a gun in the home, with ammunition present—especially a gun that is kept loaded and not locked up—is the one of the biggest risk factors for suicide by firearms.⁴ Unrestricted, quick access allows people who are impulsive little time to reconsider suicide. The risk presented by easy availability is magnified by dangerous concomitant intoxication (see below), distress, and lack of supervision (of children).

Alcohol consumption is associated with suicide. Approximately one-fourth of the people who commit suicide are intoxicated at the time of death.⁹ Alcohol use, especially binge drinking, is observed in an even larger percentage of suicide attempts than individuals using guns while sober.

Female sex. In recent years, gun use by women has increased, along with firearm-related suicide. Simply having a gun at home greatly increases the suicide rate for women.^2-4

People with a history of high impulsivity, impaired judgment, violence, or psychiatric and neurologic disorders places people at greater risk of shooting themselves, especially those with depression, suicidal ideation, substance abuse, psychosis, or dementia.⁴

Older age, particularly men who live alone, increases the risk of suicide by firearms, especially in the context of chronic pain or other health problems. Gunfire is the most common means of suicide among geriatric patients of both sexes.⁸

Lethality. In general, suicide attempts with guns are more likely to be fatal than overdosing, poisoning, or self-mutilation.^1,2 Most self-inflicted gunshot wounds result in death, usually on the day of the shooting.^1,2

Evidence about these risk factors has led the American Medical Association and other health care groups to encourage physicians—in particular, psychiatric clinicians who focus on suicide prevention—to counsel patients about gun safety.

What can you do to minimize risk?
Gun-related inquiry and counsel by psychiatrists can benefit patients and their family.⁴ Be aware, however, of restrictions on such discussions by health care providers in some states (Box).¹⁰

Ask about the presence of firearms in the home. Our advice and our “doctor’s orders” are a means to promote health; suggestions in the context of a supportive physician-patient relationship could result in compliance.^3,4 Firearm-focused discussions might be uncomfortable or unpopular but are critical for preventing suicide. Openly discussing such issues with our patients could avoid tragedies.⁴ Involving family or significant others in these interventions also might be helpful.

Ask about access to and storage of firearms. Simply talking about gun safety is helpful.⁴ Seeking information about gun usage is especially called for in psychiatric practices that treat patients with suicidal ideation, depression, substance abuse, and cognitive impairment.⁸ Discuss firearm availability with patients who have a history of substance use, impulsivity, anger, or violence, or who have a brain disorder or neurologic condition. Talking about firearms with patients and educating them about safety is indicated whenever you observe a risk factor for suicide.

Advise safe storage. Aim to have the entire family agree to a safety policy. Guns should be kept unloaded and not stored with ammunition (eg, keep guns in the attic and ammunition in the basement), which might diminish the risk of (1) an impulsive shooting and (2) a planned attempt by giving people time to consider options other than suicide. Firearm safety includes locking ammunition and weapons in a safe and applying trigger locks. Try to get patients and their family to plan for compliance with such recommendations whenever possible.

Guide dialogue and educate patients about handling guns safely. Be sure that patients know that most firearm deaths that happen inside a home are suicide.^2-4 Advise patients, and their family, that firearms should not be handled while intoxicated.⁴ Encourage families to remove gun access from members who are suicidal, depressed, abusing pharmaceuticals or using illicit drugs, and those in distress or with a significant mental or neurologic illness.

In such circumstances, institute a protective plan to prevent shootings. This can be time-limited, or might include removing guns or ammunition from the home or deactivating firing mechanisms, etc. For safety reasons, some families do not keep ammunition in their home.

Additionally, firearms in the hands of children ought to include close monitoring by a responsible, sober adult. Keeping guns in locked storage is especially important for preventing suicide in children. Despite suicide being less frequent among younger people than in adults, taking steps to avoid 1,000 child suicides each year in the United States is a valuable intervention.

Conclusion
Specific inquiry, overt discussion, and face-to-face counseling about gun safety can be a life-saving aspect of psychiatric intervention. With such recommendations and education, psychiatrists can play a productive role in reducing firearm-related suicide.

Firearms are the most common means of suicide in the United States, accounting for approximately 20,000 adult deaths annually,1 which is approximately two-thirds of the more than 32,000 gun-related fatalities each year in the United States. Of approximately 3,000 American children who are shot to death annually, one-third are suicides.^1-4

Firearms are dangerous; it has been documented that even guns obtained for recreation or protection increase the risk of suicide, homicide, or injury.^2,3 This problem has become a public health concern.^3-8 Because most suicide attempts with firearms are fatal, psychiatrists have an interest in reducing such outcomes.^1-8

Risk factors for suicide by firearm
Easy availability of a gun in the home, with ammunition present—especially a gun that is kept loaded and not locked up—is the one of the biggest risk factors for suicide by firearms.⁴ Unrestricted, quick access allows people who are impulsive little time to reconsider suicide. The risk presented by easy availability is magnified by dangerous concomitant intoxication (see below), distress, and lack of supervision (of children).

Alcohol consumption is associated with suicide. Approximately one-fourth of the people who commit suicide are intoxicated at the time of death.⁹ Alcohol use, especially binge drinking, is observed in an even larger percentage of suicide attempts than individuals using guns while sober.

Female sex. In recent years, gun use by women has increased, along with firearm-related suicide. Simply having a gun at home greatly increases the suicide rate for women.^2-4

People with a history of high impulsivity, impaired judgment, violence, or psychiatric and neurologic disorders places people at greater risk of shooting themselves, especially those with depression, suicidal ideation, substance abuse, psychosis, or dementia.⁴

Older age, particularly men who live alone, increases the risk of suicide by firearms, especially in the context of chronic pain or other health problems. Gunfire is the most common means of suicide among geriatric patients of both sexes.⁸

Lethality. In general, suicide attempts with guns are more likely to be fatal than overdosing, poisoning, or self-mutilation.^1,2 Most self-inflicted gunshot wounds result in death, usually on the day of the shooting.^1,2

Evidence about these risk factors has led the American Medical Association and other health care groups to encourage physicians—in particular, psychiatric clinicians who focus on suicide prevention—to counsel patients about gun safety.

What can you do to minimize risk?
Gun-related inquiry and counsel by psychiatrists can benefit patients and their family.⁴ Be aware, however, of restrictions on such discussions by health care providers in some states (Box).¹⁰

Ask about the presence of firearms in the home. Our advice and our “doctor’s orders” are a means to promote health; suggestions in the context of a supportive physician-patient relationship could result in compliance.^3,4 Firearm-focused discussions might be uncomfortable or unpopular but are critical for preventing suicide. Openly discussing such issues with our patients could avoid tragedies.⁴ Involving family or significant others in these interventions also might be helpful.

Ask about access to and storage of firearms. Simply talking about gun safety is helpful.⁴ Seeking information about gun usage is especially called for in psychiatric practices that treat patients with suicidal ideation, depression, substance abuse, and cognitive impairment.⁸ Discuss firearm availability with patients who have a history of substance use, impulsivity, anger, or violence, or who have a brain disorder or neurologic condition. Talking about firearms with patients and educating them about safety is indicated whenever you observe a risk factor for suicide.

Advise safe storage. Aim to have the entire family agree to a safety policy. Guns should be kept unloaded and not stored with ammunition (eg, keep guns in the attic and ammunition in the basement), which might diminish the risk of (1) an impulsive shooting and (2) a planned attempt by giving people time to consider options other than suicide. Firearm safety includes locking ammunition and weapons in a safe and applying trigger locks. Try to get patients and their family to plan for compliance with such recommendations whenever possible.

Guide dialogue and educate patients about handling guns safely. Be sure that patients know that most firearm deaths that happen inside a home are suicide.^2-4 Advise patients, and their family, that firearms should not be handled while intoxicated.⁴ Encourage families to remove gun access from members who are suicidal, depressed, abusing pharmaceuticals or using illicit drugs, and those in distress or with a significant mental or neurologic illness.

In such circumstances, institute a protective plan to prevent shootings. This can be time-limited, or might include removing guns or ammunition from the home or deactivating firing mechanisms, etc. For safety reasons, some families do not keep ammunition in their home.

Additionally, firearms in the hands of children ought to include close monitoring by a responsible, sober adult. Keeping guns in locked storage is especially important for preventing suicide in children. Despite suicide being less frequent among younger people than in adults, taking steps to avoid 1,000 child suicides each year in the United States is a valuable intervention.

Conclusion
Specific inquiry, overt discussion, and face-to-face counseling about gun safety can be a life-saving aspect of psychiatric intervention. With such recommendations and education, psychiatrists can play a productive role in reducing firearm-related suicide.

Firearms are the most common means of suicide in the United States, accounting for approximately 20,000 adult deaths annually,1 which is approximately two-thirds of the more than 32,000 gun-related fatalities each year in the United States. Of approximately 3,000 American children who are shot to death annually, one-third are suicides.^1-4

Firearms are dangerous; it has been documented that even guns obtained for recreation or protection increase the risk of suicide, homicide, or injury.^2,3 This problem has become a public health concern.^3-8 Because most suicide attempts with firearms are fatal, psychiatrists have an interest in reducing such outcomes.^1-8

Risk factors for suicide by firearm
Easy availability of a gun in the home, with ammunition present—especially a gun that is kept loaded and not locked up—is the one of the biggest risk factors for suicide by firearms.⁴ Unrestricted, quick access allows people who are impulsive little time to reconsider suicide. The risk presented by easy availability is magnified by dangerous concomitant intoxication (see below), distress, and lack of supervision (of children).

Alcohol consumption is associated with suicide. Approximately one-fourth of the people who commit suicide are intoxicated at the time of death.⁹ Alcohol use, especially binge drinking, is observed in an even larger percentage of suicide attempts than individuals using guns while sober.

Female sex. In recent years, gun use by women has increased, along with firearm-related suicide. Simply having a gun at home greatly increases the suicide rate for women.^2-4

People with a history of high impulsivity, impaired judgment, violence, or psychiatric and neurologic disorders places people at greater risk of shooting themselves, especially those with depression, suicidal ideation, substance abuse, psychosis, or dementia.⁴

Older age, particularly men who live alone, increases the risk of suicide by firearms, especially in the context of chronic pain or other health problems. Gunfire is the most common means of suicide among geriatric patients of both sexes.⁸

Lethality. In general, suicide attempts with guns are more likely to be fatal than overdosing, poisoning, or self-mutilation.^1,2 Most self-inflicted gunshot wounds result in death, usually on the day of the shooting.^1,2

Evidence about these risk factors has led the American Medical Association and other health care groups to encourage physicians—in particular, psychiatric clinicians who focus on suicide prevention—to counsel patients about gun safety.

What can you do to minimize risk?
Gun-related inquiry and counsel by psychiatrists can benefit patients and their family.⁴ Be aware, however, of restrictions on such discussions by health care providers in some states (Box).¹⁰

Ask about the presence of firearms in the home. Our advice and our “doctor’s orders” are a means to promote health; suggestions in the context of a supportive physician-patient relationship could result in compliance.^3,4 Firearm-focused discussions might be uncomfortable or unpopular but are critical for preventing suicide. Openly discussing such issues with our patients could avoid tragedies.⁴ Involving family or significant others in these interventions also might be helpful.

Ask about access to and storage of firearms. Simply talking about gun safety is helpful.⁴ Seeking information about gun usage is especially called for in psychiatric practices that treat patients with suicidal ideation, depression, substance abuse, and cognitive impairment.⁸ Discuss firearm availability with patients who have a history of substance use, impulsivity, anger, or violence, or who have a brain disorder or neurologic condition. Talking about firearms with patients and educating them about safety is indicated whenever you observe a risk factor for suicide.

Advise safe storage. Aim to have the entire family agree to a safety policy. Guns should be kept unloaded and not stored with ammunition (eg, keep guns in the attic and ammunition in the basement), which might diminish the risk of (1) an impulsive shooting and (2) a planned attempt by giving people time to consider options other than suicide. Firearm safety includes locking ammunition and weapons in a safe and applying trigger locks. Try to get patients and their family to plan for compliance with such recommendations whenever possible.

Guide dialogue and educate patients about handling guns safely. Be sure that patients know that most firearm deaths that happen inside a home are suicide.^2-4 Advise patients, and their family, that firearms should not be handled while intoxicated.⁴ Encourage families to remove gun access from members who are suicidal, depressed, abusing pharmaceuticals or using illicit drugs, and those in distress or with a significant mental or neurologic illness.

In such circumstances, institute a protective plan to prevent shootings. This can be time-limited, or might include removing guns or ammunition from the home or deactivating firing mechanisms, etc. For safety reasons, some families do not keep ammunition in their home.

Additionally, firearms in the hands of children ought to include close monitoring by a responsible, sober adult. Keeping guns in locked storage is especially important for preventing suicide in children. Despite suicide being less frequent among younger people than in adults, taking steps to avoid 1,000 child suicides each year in the United States is a valuable intervention.

Conclusion
Specific inquiry, overt discussion, and face-to-face counseling about gun safety can be a life-saving aspect of psychiatric intervention. With such recommendations and education, psychiatrists can play a productive role in reducing firearm-related suicide.

Dementia—“major neurocognitive disorder” in DSM-5—manifests as progressive decline in cognitive function.In tandem with that decline, approximately 80% of nursing home patients with dementia exhibit behavioral disturbances,¹ including irritability, insomnia, wandering, and repetitive questioning.^1,2 These disturbances can erode their quality of life and can frustrate caregivers and providers.³

Causative pathology
Before designing a therapeutic intervention for cognitively impaired people with behavioral disturbances, a precise diagnosis of the causative pathology must be determined. This affords therapies that specifically address the patient’s problems. Other related and unrelated somatic or mental health concerns should be identified to specify the optimal approach.

Patients in whom dementia is suspected require that a thorough medical, psychiatric, substance use, and family history be taken to identify predisposing factors for their illness²; exhaustive review of the history might reveal drug interactions or polypharmacy that can cause or exacerbate symptoms, including behavioral manifestations. Physical examination, cognitive function testing, laboratory tests, and neuroimaging also help reveal the etiologic diagnosis of the dementia.^1,3

Identifying the diagnosis directs the treatment; for example, a behaviorally discontrolled person with a cognitive, stroke-induced encephalopathy requires an entirely different regimen than a comparatively compromised individual with Alzheimer’s disease or frontotemporal dementia. Early detection of dementia also is helpful for managing its cognitive and behavioral problems more effectively.¹Once a diagnosis of dementia is established, it might be behavioral symptoms and poor insight that become more worrisome to the patient’s caregivers and providers than cognitive deficits. Your task is then to apply behavioral approaches to management, with consistency, to maximize, at all times, the patient’s safety and comfort.⁴

How you approach behavioral management is important
Consider these interventions:

• Ensure that you appropriately treat associated depression, pain, and somatic illness—whether related or unrelated to dementia.
• Offer caregivers and staff a plan for attending to supportive measures, including nutrition, hydration, and socialization.
• Provide family and caregivers with disease education, social support, and management tips^1,2; be respectful to family members in all interactions.³
• Offer caregivers and staff a plan for attending to supportive measures, including nutrition, hydration, and socialization.

Minimize psychosocial and environmental stressors

• Avoid unnecessary environmental changes, such as rearranging or refurbishing the patient’s living space.¹
• As noted, ensure that the patient is comfortable and safe in his (her) surroundings, such as providing wall-mounted handrails and other aids for ambulation.
• Provide access to television, proper lighting, and other indicated life-enhancing devices.^1,2
• Consider a pet for the patient; pets can be an important adjunct in providing comfort.
• Provide music to reduce agitation and anxiety.⁴
• Appeal to institutional administration to provide a higher staff−patient ratio for comfort and security.^2,5
• Because social contact is helpful to build a pleasant environment, preserve opportunities for the patient to communicate with others, and facilitate socialization by encouraging friendly interactions.¹
• Provide stimulation and diversion with social activities, support programs, and physical exercise—sources of interaction that can promote health and improve sleep.
• Redirection and validation are helpful to divert a patient’s attention from stressful situations and keep him (her) calm.^2,5
• Pharmacotherapy should be implemented if psychosocial methods of behavioral management fail or the patient’s behavior becomes threatening.¹
• Provide access to television, proper lighting, and other indicated life-enhancing devices.Provide music to reduce agitation and anxiety.Redirection and validation are helpful to divert a patient’s attention from stressful situations and keep him (her) calm.Pharmacotherapy should be implemented if psychosocial methods of behavioral management fail or the patient’s behavior becomes threatening.

Other considerations

• Identify and treat primary and secondary causes of the underlying major neurocognitive disorder.
• Use an integrative, multidisciplinary approach to manage behavioral problems in dementia.
• Utilize a social worker’s expertise to faciliate family, financial, or related social issues and better cooperation. This promotes comfort for patients, families, and staff.
• Physical therapy aids in maintaining physical function, especially preservation of gait, balance, and range of motion. Thus, with greater stability avoiding a fall can be a life-saving event.
• Socialization, mental outlook, and emotional health are improved by occupational therapist interventions.
• Individual psychotherapy helps to improve self-esteem and personal adjustment. Group activities reinforces interpersonal connections.
• Refer the family and caregivers for supportive therapy and education on dementia; such resources help minimize deleterious effects of the patient’s behavioral problems on those key people.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Dementia—“major neurocognitive disorder” in DSM-5—manifests as progressive decline in cognitive function.In tandem with that decline, approximately 80% of nursing home patients with dementia exhibit behavioral disturbances,¹ including irritability, insomnia, wandering, and repetitive questioning.^1,2 These disturbances can erode their quality of life and can frustrate caregivers and providers.³

Causative pathology
Before designing a therapeutic intervention for cognitively impaired people with behavioral disturbances, a precise diagnosis of the causative pathology must be determined. This affords therapies that specifically address the patient’s problems. Other related and unrelated somatic or mental health concerns should be identified to specify the optimal approach.

Patients in whom dementia is suspected require that a thorough medical, psychiatric, substance use, and family history be taken to identify predisposing factors for their illness²; exhaustive review of the history might reveal drug interactions or polypharmacy that can cause or exacerbate symptoms, including behavioral manifestations. Physical examination, cognitive function testing, laboratory tests, and neuroimaging also help reveal the etiologic diagnosis of the dementia.^1,3

Identifying the diagnosis directs the treatment; for example, a behaviorally discontrolled person with a cognitive, stroke-induced encephalopathy requires an entirely different regimen than a comparatively compromised individual with Alzheimer’s disease or frontotemporal dementia. Early detection of dementia also is helpful for managing its cognitive and behavioral problems more effectively.¹Once a diagnosis of dementia is established, it might be behavioral symptoms and poor insight that become more worrisome to the patient’s caregivers and providers than cognitive deficits. Your task is then to apply behavioral approaches to management, with consistency, to maximize, at all times, the patient’s safety and comfort.⁴

How you approach behavioral management is important
Consider these interventions:

• Ensure that you appropriately treat associated depression, pain, and somatic illness—whether related or unrelated to dementia.
• Offer caregivers and staff a plan for attending to supportive measures, including nutrition, hydration, and socialization.
• Provide family and caregivers with disease education, social support, and management tips^1,2; be respectful to family members in all interactions.³
• Offer caregivers and staff a plan for attending to supportive measures, including nutrition, hydration, and socialization.

Minimize psychosocial and environmental stressors

• Avoid unnecessary environmental changes, such as rearranging or refurbishing the patient’s living space.¹
• As noted, ensure that the patient is comfortable and safe in his (her) surroundings, such as providing wall-mounted handrails and other aids for ambulation.
• Provide access to television, proper lighting, and other indicated life-enhancing devices.^1,2
• Consider a pet for the patient; pets can be an important adjunct in providing comfort.
• Provide music to reduce agitation and anxiety.⁴
• Appeal to institutional administration to provide a higher staff−patient ratio for comfort and security.^2,5
• Because social contact is helpful to build a pleasant environment, preserve opportunities for the patient to communicate with others, and facilitate socialization by encouraging friendly interactions.¹
• Provide stimulation and diversion with social activities, support programs, and physical exercise—sources of interaction that can promote health and improve sleep.
• Redirection and validation are helpful to divert a patient’s attention from stressful situations and keep him (her) calm.^2,5
• Pharmacotherapy should be implemented if psychosocial methods of behavioral management fail or the patient’s behavior becomes threatening.¹
• Provide access to television, proper lighting, and other indicated life-enhancing devices.Provide music to reduce agitation and anxiety.Redirection and validation are helpful to divert a patient’s attention from stressful situations and keep him (her) calm.Pharmacotherapy should be implemented if psychosocial methods of behavioral management fail or the patient’s behavior becomes threatening.

Other considerations

• Identify and treat primary and secondary causes of the underlying major neurocognitive disorder.
• Use an integrative, multidisciplinary approach to manage behavioral problems in dementia.
• Utilize a social worker’s expertise to faciliate family, financial, or related social issues and better cooperation. This promotes comfort for patients, families, and staff.
• Physical therapy aids in maintaining physical function, especially preservation of gait, balance, and range of motion. Thus, with greater stability avoiding a fall can be a life-saving event.
• Socialization, mental outlook, and emotional health are improved by occupational therapist interventions.
• Individual psychotherapy helps to improve self-esteem and personal adjustment. Group activities reinforces interpersonal connections.
• Refer the family and caregivers for supportive therapy and education on dementia; such resources help minimize deleterious effects of the patient’s behavioral problems on those key people.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Dementia—“major neurocognitive disorder” in DSM-5—manifests as progressive decline in cognitive function.In tandem with that decline, approximately 80% of nursing home patients with dementia exhibit behavioral disturbances,¹ including irritability, insomnia, wandering, and repetitive questioning.^1,2 These disturbances can erode their quality of life and can frustrate caregivers and providers.³

Causative pathology
Before designing a therapeutic intervention for cognitively impaired people with behavioral disturbances, a precise diagnosis of the causative pathology must be determined. This affords therapies that specifically address the patient’s problems. Other related and unrelated somatic or mental health concerns should be identified to specify the optimal approach.

Patients in whom dementia is suspected require that a thorough medical, psychiatric, substance use, and family history be taken to identify predisposing factors for their illness²; exhaustive review of the history might reveal drug interactions or polypharmacy that can cause or exacerbate symptoms, including behavioral manifestations. Physical examination, cognitive function testing, laboratory tests, and neuroimaging also help reveal the etiologic diagnosis of the dementia.^1,3

Identifying the diagnosis directs the treatment; for example, a behaviorally discontrolled person with a cognitive, stroke-induced encephalopathy requires an entirely different regimen than a comparatively compromised individual with Alzheimer’s disease or frontotemporal dementia. Early detection of dementia also is helpful for managing its cognitive and behavioral problems more effectively.¹Once a diagnosis of dementia is established, it might be behavioral symptoms and poor insight that become more worrisome to the patient’s caregivers and providers than cognitive deficits. Your task is then to apply behavioral approaches to management, with consistency, to maximize, at all times, the patient’s safety and comfort.⁴

How you approach behavioral management is important
Consider these interventions:

• Ensure that you appropriately treat associated depression, pain, and somatic illness—whether related or unrelated to dementia.
• Offer caregivers and staff a plan for attending to supportive measures, including nutrition, hydration, and socialization.
• Provide family and caregivers with disease education, social support, and management tips^1,2; be respectful to family members in all interactions.³
• Offer caregivers and staff a plan for attending to supportive measures, including nutrition, hydration, and socialization.

Minimize psychosocial and environmental stressors

• Avoid unnecessary environmental changes, such as rearranging or refurbishing the patient’s living space.¹
• As noted, ensure that the patient is comfortable and safe in his (her) surroundings, such as providing wall-mounted handrails and other aids for ambulation.
• Provide access to television, proper lighting, and other indicated life-enhancing devices.^1,2
• Consider a pet for the patient; pets can be an important adjunct in providing comfort.
• Provide music to reduce agitation and anxiety.⁴
• Appeal to institutional administration to provide a higher staff−patient ratio for comfort and security.^2,5
• Because social contact is helpful to build a pleasant environment, preserve opportunities for the patient to communicate with others, and facilitate socialization by encouraging friendly interactions.¹
• Provide stimulation and diversion with social activities, support programs, and physical exercise—sources of interaction that can promote health and improve sleep.
• Redirection and validation are helpful to divert a patient’s attention from stressful situations and keep him (her) calm.^2,5
• Pharmacotherapy should be implemented if psychosocial methods of behavioral management fail or the patient’s behavior becomes threatening.¹
• Provide access to television, proper lighting, and other indicated life-enhancing devices.Provide music to reduce agitation and anxiety.Redirection and validation are helpful to divert a patient’s attention from stressful situations and keep him (her) calm.Pharmacotherapy should be implemented if psychosocial methods of behavioral management fail or the patient’s behavior becomes threatening.

Other considerations

• Identify and treat primary and secondary causes of the underlying major neurocognitive disorder.
• Use an integrative, multidisciplinary approach to manage behavioral problems in dementia.
• Utilize a social worker’s expertise to faciliate family, financial, or related social issues and better cooperation. This promotes comfort for patients, families, and staff.
• Physical therapy aids in maintaining physical function, especially preservation of gait, balance, and range of motion. Thus, with greater stability avoiding a fall can be a life-saving event.
• Socialization, mental outlook, and emotional health are improved by occupational therapist interventions.
• Individual psychotherapy helps to improve self-esteem and personal adjustment. Group activities reinforces interpersonal connections.
• Refer the family and caregivers for supportive therapy and education on dementia; such resources help minimize deleterious effects of the patient’s behavioral problems on those key people.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

When a patient who smokes enters a tobacco-free medical facility and has access to caffeinated beverages, he (she) might experience toxicity to many pharmaceuticals and caffeine. Similarly, if a patient is discharged from a smoke-free envi­ronment with a newly adjusted medication regimen and resumes smoking or caffeine consumption, alterations in enzyme activ­ity might reduce therapeutic efficacy of pre­scribed medicines. These effects are a result of alterations in the hepatic cytochrome P450 (CYP) enzyme system.

Taking a careful history of tobacco and caffeine use, and knowing the effects that these substances will have on specific medi­cations, will help guide treatment and man­agement decisions.

The role of CYP enzymes
CYP hepatic enzymes detoxify a variety of environmental agents into water-soluble compounds that are excreted in urine. CYP1A2 metabolizes 20% of drugs handled by the CYP system and comprises 13% of all the CYP enzymes expressed in the liver. The wide interindividual variation in CYP1A2 enzyme activity is influenced by a combina­tion of genetic, epigenetic, ethnic, and envi­ronmental variables.¹

Influence of tobacco on CYP
The polycyclic aromatic hydrocarbons in tobacco smoke induce CYP1A2 and CYP2B6 hepatic enzymes.² Smokers exhibit increased activity of these enzymes, which results in faster clearance of many drugs, lower con­centrations in blood, and diminished clinical response. The Table lists psycho­tropic medicines that are metabolized by CYP1A2 and CYP2B6. Co-administration of these substrates could decrease the elimina­tion rate of other drugs also metabolized by CYP1A2. Nicotine in tobacco or in nicotine replacement therapies does not play a role in inducing CYP enzymes.

The turnover time for CYP1A2 is rapid— approximately 3 days—and a new CYP1A2 steady state activity is reached after approxi­mately 1 week,⁴ which is important to remember when managing inpatients in a smoke-free facility. During acute hospitaliza­tion, patients could experience drug toxic­ity if the outpatient dosage is maintained.⁵

When they resume smoking after being discharged on a stabilized dosage of any of the medications listed in the Table, previous enzyme activity rebounds and might reduce the drug level, potentially leading to inad­equate clinical response.

Caffeine and other substances
Asking about the patient’s caffeine intake is necessary because consumption of coffee is prevalent among smokers, and caffeine is metabolized by CYP1A2. Smokers need to consume as much as 4 times the amount of caffeine as non-smokers to achieve a similar caffeine serum concentration.² Caffeine can form an insoluble precipitate with antipsychotic medication in the gut, which decreases absorption. The interac­tion between smoking-related induction of CYP1A2 enzymes and forced smoking ces­sation during hospitalization, with ongo­ing caffeine consumption, could lead to caffeine toxicity.^4,5

Other common inducers of CYP1A2 are insulin, cabbage, cauliflower, broccoli, and charcoal-grilled meat. Also, cumin and tur­meric inhibit CYP1A2 activity, which might explain an ethnic difference in drug toler­ance across population groups. Additionally, certain genetic polymorphisms, in specific ethnic distributions, alter the potential for tobacco smoke to induce CYP1A2.⁶

Some of these polymorphisms can be genotyped for clinical application.³

Asking about a patient’s tobacco and caffeine use and understanding their inter­actions with specific medications provides guidance when prescribing antipsychotic medications and adjusting dosage for inpatients and during clinical follow-up care.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

When a patient who smokes enters a tobacco-free medical facility and has access to caffeinated beverages, he (she) might experience toxicity to many pharmaceuticals and caffeine. Similarly, if a patient is discharged from a smoke-free envi­ronment with a newly adjusted medication regimen and resumes smoking or caffeine consumption, alterations in enzyme activ­ity might reduce therapeutic efficacy of pre­scribed medicines. These effects are a result of alterations in the hepatic cytochrome P450 (CYP) enzyme system.

Taking a careful history of tobacco and caffeine use, and knowing the effects that these substances will have on specific medi­cations, will help guide treatment and man­agement decisions.

The role of CYP enzymes
CYP hepatic enzymes detoxify a variety of environmental agents into water-soluble compounds that are excreted in urine. CYP1A2 metabolizes 20% of drugs handled by the CYP system and comprises 13% of all the CYP enzymes expressed in the liver. The wide interindividual variation in CYP1A2 enzyme activity is influenced by a combina­tion of genetic, epigenetic, ethnic, and envi­ronmental variables.¹

Influence of tobacco on CYP
The polycyclic aromatic hydrocarbons in tobacco smoke induce CYP1A2 and CYP2B6 hepatic enzymes.² Smokers exhibit increased activity of these enzymes, which results in faster clearance of many drugs, lower con­centrations in blood, and diminished clinical response. The Table lists psycho­tropic medicines that are metabolized by CYP1A2 and CYP2B6. Co-administration of these substrates could decrease the elimina­tion rate of other drugs also metabolized by CYP1A2. Nicotine in tobacco or in nicotine replacement therapies does not play a role in inducing CYP enzymes.

The turnover time for CYP1A2 is rapid— approximately 3 days—and a new CYP1A2 steady state activity is reached after approxi­mately 1 week,⁴ which is important to remember when managing inpatients in a smoke-free facility. During acute hospitaliza­tion, patients could experience drug toxic­ity if the outpatient dosage is maintained.⁵

When they resume smoking after being discharged on a stabilized dosage of any of the medications listed in the Table, previous enzyme activity rebounds and might reduce the drug level, potentially leading to inad­equate clinical response.

Caffeine and other substances
Asking about the patient’s caffeine intake is necessary because consumption of coffee is prevalent among smokers, and caffeine is metabolized by CYP1A2. Smokers need to consume as much as 4 times the amount of caffeine as non-smokers to achieve a similar caffeine serum concentration.² Caffeine can form an insoluble precipitate with antipsychotic medication in the gut, which decreases absorption. The interac­tion between smoking-related induction of CYP1A2 enzymes and forced smoking ces­sation during hospitalization, with ongo­ing caffeine consumption, could lead to caffeine toxicity.^4,5

Other common inducers of CYP1A2 are insulin, cabbage, cauliflower, broccoli, and charcoal-grilled meat. Also, cumin and tur­meric inhibit CYP1A2 activity, which might explain an ethnic difference in drug toler­ance across population groups. Additionally, certain genetic polymorphisms, in specific ethnic distributions, alter the potential for tobacco smoke to induce CYP1A2.⁶

Some of these polymorphisms can be genotyped for clinical application.³

Asking about a patient’s tobacco and caffeine use and understanding their inter­actions with specific medications provides guidance when prescribing antipsychotic medications and adjusting dosage for inpatients and during clinical follow-up care.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

When a patient who smokes enters a tobacco-free medical facility and has access to caffeinated beverages, he (she) might experience toxicity to many pharmaceuticals and caffeine. Similarly, if a patient is discharged from a smoke-free envi­ronment with a newly adjusted medication regimen and resumes smoking or caffeine consumption, alterations in enzyme activ­ity might reduce therapeutic efficacy of pre­scribed medicines. These effects are a result of alterations in the hepatic cytochrome P450 (CYP) enzyme system.

Taking a careful history of tobacco and caffeine use, and knowing the effects that these substances will have on specific medi­cations, will help guide treatment and man­agement decisions.

The role of CYP enzymes
CYP hepatic enzymes detoxify a variety of environmental agents into water-soluble compounds that are excreted in urine. CYP1A2 metabolizes 20% of drugs handled by the CYP system and comprises 13% of all the CYP enzymes expressed in the liver. The wide interindividual variation in CYP1A2 enzyme activity is influenced by a combina­tion of genetic, epigenetic, ethnic, and envi­ronmental variables.¹

Influence of tobacco on CYP
The polycyclic aromatic hydrocarbons in tobacco smoke induce CYP1A2 and CYP2B6 hepatic enzymes.² Smokers exhibit increased activity of these enzymes, which results in faster clearance of many drugs, lower con­centrations in blood, and diminished clinical response. The Table lists psycho­tropic medicines that are metabolized by CYP1A2 and CYP2B6. Co-administration of these substrates could decrease the elimina­tion rate of other drugs also metabolized by CYP1A2. Nicotine in tobacco or in nicotine replacement therapies does not play a role in inducing CYP enzymes.

The turnover time for CYP1A2 is rapid— approximately 3 days—and a new CYP1A2 steady state activity is reached after approxi­mately 1 week,⁴ which is important to remember when managing inpatients in a smoke-free facility. During acute hospitaliza­tion, patients could experience drug toxic­ity if the outpatient dosage is maintained.⁵

When they resume smoking after being discharged on a stabilized dosage of any of the medications listed in the Table, previous enzyme activity rebounds and might reduce the drug level, potentially leading to inad­equate clinical response.

Caffeine and other substances
Asking about the patient’s caffeine intake is necessary because consumption of coffee is prevalent among smokers, and caffeine is metabolized by CYP1A2. Smokers need to consume as much as 4 times the amount of caffeine as non-smokers to achieve a similar caffeine serum concentration.² Caffeine can form an insoluble precipitate with antipsychotic medication in the gut, which decreases absorption. The interac­tion between smoking-related induction of CYP1A2 enzymes and forced smoking ces­sation during hospitalization, with ongo­ing caffeine consumption, could lead to caffeine toxicity.^4,5

Other common inducers of CYP1A2 are insulin, cabbage, cauliflower, broccoli, and charcoal-grilled meat. Also, cumin and tur­meric inhibit CYP1A2 activity, which might explain an ethnic difference in drug toler­ance across population groups. Additionally, certain genetic polymorphisms, in specific ethnic distributions, alter the potential for tobacco smoke to induce CYP1A2.⁶

Some of these polymorphisms can be genotyped for clinical application.³

Asking about a patient’s tobacco and caffeine use and understanding their inter­actions with specific medications provides guidance when prescribing antipsychotic medications and adjusting dosage for inpatients and during clinical follow-up care.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Electronic cigarettes (e-cigarettes) have become popular in the United States over the past decade.¹ They have been widely marketed as an alternative to tobacco and as a way to quit smoking.

While the negative effects of smoking tobacco are well known (having as few as one to 4 cigarettes a day triples the risk of coronary artery disease and pulmonary neoplasia²), the potential risks of e-cigarettes are not as well known. There has been limited regulation and insufficient research into the harmful effects of inhaling their vapor.

The potentially harmful compounds within e-cigarette vapors include both organic and inorganic toxins.³ A study of the contents of numerous e-cigarette refills found formaldehyde and acrolein, along with several hydrocarbons.³ Lead, cadmium, and nickel were also found in e-cigarette refills and their inhaled vapors.¹ Lead causes severe neurotoxicity,⁴ cadmium can cause organ damage,⁵ and inhaled nickel causes an inflammatory reaction in the lungs.⁶

The risk-to-benefit ratio of e-cigarettes as a means of tobacco cessation and the health consequences of breathing their vapors cannot be established until research is completed. What we do know is that the nicotine in e-cigarette vapors maintains continued addiction.

It’s up to us as physicians to educate our patients about the potential harm of e-cigarette chemical toxicity and encourage cessation of both tobacco products and e-cigarettes.

Kavitha Srinivasan, MD
Lee Smith, BA
Manasa Enja, MD
Steven Lippmann, MD
Louisville, Ky

Electronic cigarettes (e-cigarettes) have become popular in the United States over the past decade.¹ They have been widely marketed as an alternative to tobacco and as a way to quit smoking.

While the negative effects of smoking tobacco are well known (having as few as one to 4 cigarettes a day triples the risk of coronary artery disease and pulmonary neoplasia²), the potential risks of e-cigarettes are not as well known. There has been limited regulation and insufficient research into the harmful effects of inhaling their vapor.

The potentially harmful compounds within e-cigarette vapors include both organic and inorganic toxins.³ A study of the contents of numerous e-cigarette refills found formaldehyde and acrolein, along with several hydrocarbons.³ Lead, cadmium, and nickel were also found in e-cigarette refills and their inhaled vapors.¹ Lead causes severe neurotoxicity,⁴ cadmium can cause organ damage,⁵ and inhaled nickel causes an inflammatory reaction in the lungs.⁶

The risk-to-benefit ratio of e-cigarettes as a means of tobacco cessation and the health consequences of breathing their vapors cannot be established until research is completed. What we do know is that the nicotine in e-cigarette vapors maintains continued addiction.

It’s up to us as physicians to educate our patients about the potential harm of e-cigarette chemical toxicity and encourage cessation of both tobacco products and e-cigarettes.

Kavitha Srinivasan, MD
Lee Smith, BA
Manasa Enja, MD
Steven Lippmann, MD
Louisville, Ky

Electronic cigarettes (e-cigarettes) have become popular in the United States over the past decade.¹ They have been widely marketed as an alternative to tobacco and as a way to quit smoking.

While the negative effects of smoking tobacco are well known (having as few as one to 4 cigarettes a day triples the risk of coronary artery disease and pulmonary neoplasia²), the potential risks of e-cigarettes are not as well known. There has been limited regulation and insufficient research into the harmful effects of inhaling their vapor.

The potentially harmful compounds within e-cigarette vapors include both organic and inorganic toxins.³ A study of the contents of numerous e-cigarette refills found formaldehyde and acrolein, along with several hydrocarbons.³ Lead, cadmium, and nickel were also found in e-cigarette refills and their inhaled vapors.¹ Lead causes severe neurotoxicity,⁴ cadmium can cause organ damage,⁵ and inhaled nickel causes an inflammatory reaction in the lungs.⁶

The risk-to-benefit ratio of e-cigarettes as a means of tobacco cessation and the health consequences of breathing their vapors cannot be established until research is completed. What we do know is that the nicotine in e-cigarette vapors maintains continued addiction.

It’s up to us as physicians to educate our patients about the potential harm of e-cigarette chemical toxicity and encourage cessation of both tobacco products and e-cigarettes.

Kavitha Srinivasan, MD
Lee Smith, BA
Manasa Enja, MD
Steven Lippmann, MD
Louisville, Ky

Dementia affects 34 million people globally, with the most common cause of dementia, Alzheimer’s disease (AD), affecting 5.5 million Americans.^1,2 The connection between cerebrovascular disorders and AD means that antihypertensive agents may play a role in dementia prophylaxis and management.^1,2

Hypertension increases the risk of intellectual dysfunction by increasing susceptibility to heart disease, ischemic brain injury, and cerebrovascular pathology.¹ In addition to senile plaques, ischemic brain lesions are observed in autopsies of AD patients,¹ and brain infarctions are more common among AD patients than among controls.² Brain pathology suggestive of AD was found in 30% to 50% of postmortem examinations of patients with vascular dementia.¹

It is useful to note that dihydropyridines, a subgroup of calcium channel blockers, may inhibit amyloidogenesis.³

Hypertension and cognition

Hypertension-induced hyperdense lesions in cerebral white matter reflect pathology in small vessels, inflammatory change, and disruption of the blood-brain barrier, which may precede cognitive decline.¹ Even subclinical ischemic changes may increase the probability of developing dementia.² Hypertension also reduces cerebral perfusion, especially in the hippocampus, which may promote degeneration of memory function.¹ Prolonged cerebral hypoxia increases amyloid precursor protein production and β-secretase activity.^1,2 Patients who died of brain ischemia show prominent β-amyloid protein and apolipoprotein E in histopathologic analysis of the hippocampus.¹ Compression of vessels by â-amyloid protein further augments this degenerative process.¹

Inhibition of amyloidogenesis

Long-term administration of antihypertensive medications in patients age <75 decreases the probability of dementia by 8% each year.¹ Calcium channel blockers protect neurons by lowering blood pressure and reversing cellular-level calcium channel dysfunction that occurs with age, cerebral infarction, and AD.

Select dihydropyridines may inhibit amyloidogenesis in apolipoprotein E carriers:

•  amlodipine and nilvadipine reduce β-secretase activity and amyloid precursor protein-β production³

•  nilvadipine and nitrendipine limit β-amyloid protein synthesis in the brain and promote their clearance through the blood-brain barrier³

•  nilvadipine-treated apolipoprotein E carriers experience cognitive stabilization compared with cognitive decreases seen in non-treated subjects.

Dihydropyridines can produce therapeutic effects for both AD and cerebrovascular dementia patients, indicating the potential that certain agents in this class have for treating both conditions.

Disclosure
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Dementia affects 34 million people globally, with the most common cause of dementia, Alzheimer’s disease (AD), affecting 5.5 million Americans.^1,2 The connection between cerebrovascular disorders and AD means that antihypertensive agents may play a role in dementia prophylaxis and management.^1,2

Hypertension increases the risk of intellectual dysfunction by increasing susceptibility to heart disease, ischemic brain injury, and cerebrovascular pathology.¹ In addition to senile plaques, ischemic brain lesions are observed in autopsies of AD patients,¹ and brain infarctions are more common among AD patients than among controls.² Brain pathology suggestive of AD was found in 30% to 50% of postmortem examinations of patients with vascular dementia.¹

It is useful to note that dihydropyridines, a subgroup of calcium channel blockers, may inhibit amyloidogenesis.³

Hypertension and cognition

Hypertension-induced hyperdense lesions in cerebral white matter reflect pathology in small vessels, inflammatory change, and disruption of the blood-brain barrier, which may precede cognitive decline.¹ Even subclinical ischemic changes may increase the probability of developing dementia.² Hypertension also reduces cerebral perfusion, especially in the hippocampus, which may promote degeneration of memory function.¹ Prolonged cerebral hypoxia increases amyloid precursor protein production and β-secretase activity.^1,2 Patients who died of brain ischemia show prominent β-amyloid protein and apolipoprotein E in histopathologic analysis of the hippocampus.¹ Compression of vessels by â-amyloid protein further augments this degenerative process.¹

Inhibition of amyloidogenesis

Long-term administration of antihypertensive medications in patients age <75 decreases the probability of dementia by 8% each year.¹ Calcium channel blockers protect neurons by lowering blood pressure and reversing cellular-level calcium channel dysfunction that occurs with age, cerebral infarction, and AD.

Select dihydropyridines may inhibit amyloidogenesis in apolipoprotein E carriers:

•  amlodipine and nilvadipine reduce β-secretase activity and amyloid precursor protein-β production³

•  nilvadipine and nitrendipine limit β-amyloid protein synthesis in the brain and promote their clearance through the blood-brain barrier³

•  nilvadipine-treated apolipoprotein E carriers experience cognitive stabilization compared with cognitive decreases seen in non-treated subjects.

Dihydropyridines can produce therapeutic effects for both AD and cerebrovascular dementia patients, indicating the potential that certain agents in this class have for treating both conditions.

Disclosure
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Dementia affects 34 million people globally, with the most common cause of dementia, Alzheimer’s disease (AD), affecting 5.5 million Americans.^1,2 The connection between cerebrovascular disorders and AD means that antihypertensive agents may play a role in dementia prophylaxis and management.^1,2

Hypertension increases the risk of intellectual dysfunction by increasing susceptibility to heart disease, ischemic brain injury, and cerebrovascular pathology.¹ In addition to senile plaques, ischemic brain lesions are observed in autopsies of AD patients,¹ and brain infarctions are more common among AD patients than among controls.² Brain pathology suggestive of AD was found in 30% to 50% of postmortem examinations of patients with vascular dementia.¹

It is useful to note that dihydropyridines, a subgroup of calcium channel blockers, may inhibit amyloidogenesis.³

Hypertension and cognition

Hypertension-induced hyperdense lesions in cerebral white matter reflect pathology in small vessels, inflammatory change, and disruption of the blood-brain barrier, which may precede cognitive decline.¹ Even subclinical ischemic changes may increase the probability of developing dementia.² Hypertension also reduces cerebral perfusion, especially in the hippocampus, which may promote degeneration of memory function.¹ Prolonged cerebral hypoxia increases amyloid precursor protein production and β-secretase activity.^1,2 Patients who died of brain ischemia show prominent β-amyloid protein and apolipoprotein E in histopathologic analysis of the hippocampus.¹ Compression of vessels by â-amyloid protein further augments this degenerative process.¹

Inhibition of amyloidogenesis

Long-term administration of antihypertensive medications in patients age <75 decreases the probability of dementia by 8% each year.¹ Calcium channel blockers protect neurons by lowering blood pressure and reversing cellular-level calcium channel dysfunction that occurs with age, cerebral infarction, and AD.

Select dihydropyridines may inhibit amyloidogenesis in apolipoprotein E carriers:

•  amlodipine and nilvadipine reduce β-secretase activity and amyloid precursor protein-β production³

•  nilvadipine and nitrendipine limit β-amyloid protein synthesis in the brain and promote their clearance through the blood-brain barrier³

•  nilvadipine-treated apolipoprotein E carriers experience cognitive stabilization compared with cognitive decreases seen in non-treated subjects.

Dihydropyridines can produce therapeutic effects for both AD and cerebrovascular dementia patients, indicating the potential that certain agents in this class have for treating both conditions.

Disclosure
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.