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Home , Ataxia, Road rage

CONTINUING EDUCATION

Medication Use and Risks by Tammie Lee Demler, BS Pharm, PharmD

pon successful completion of this ar- the influence of has Useful Websites ticle, pharmacists should be able to: long been accepted as one 1. Identify the key functional ele- of the most important causes ■ www.dot.gov/ or http://www.dot.gov/ ments that are required to ensure of accidents and driv- odapc/ competent, safe driving. ing fatalities. Driving under Website of the U.S. Department of 2. Identify the side effects associated with pre- the influence of alcohol has Transportation, which contains trends Uscription, over-the-counter and herbal medi- been studied not only in ex- and law updates. It also contains an cations that can pose risks to drivers. perimental research, but also excellent search engine. 3. Describe the potential impact of certain medi- in epidemiological side ■ www.mayoclinic.com/health/herbal- cation classes on driving competence. studies. The effort that society supplements/SA00044 4. Describe the pharmacist’s duty to warn re- has made to take serious le- Website for the Mayo Clinic, with garding medications that have the potential to gal action against those who information about herbal supplements. impair a patient’s driving competence. choose to drink and drive It offers an expert blog for further exploration about specific therapies and 5. Provide counseling points to support safe driv- has resulted in the significant to receive/share insight about personal ing in all patients who are receiving medication. deterrents of negative social driving impairment with herbal drugs. stigma and incarceration. ■ www.icadts.nl/ Upon successful completion of this article, phar- Recently, laws in some states Website of the International Council on macy technicians should be able to: were strengthened even fur- Alcohol, Drugs and Traffic Safety, which 1. Identify the key functional elements that are ther by making driving while works to reduce morbidity and mortality required to ensure competent, safe driving. intoxicated (DWI) a felony if brought about by use of alcohol and 2. List side effects associated with the use there is a child in the car. drugs by operators of vehicles using all of herbal remedies, over-the-counter and While the impact of modes of transportation. prescription medications that can pose risks alcohol on driving abilities to drivers. is well known, there are few 3. Describe the potential impact of certain medi- epidemiologic studies about the role of herbal remedies, cation classes on driving competence. over-the-counter and prescription drugs in motor vehicle 4. Describe situations when the pharmacist accidents. There are some lab experiments in which the should be alerted to counsel patients on the therapeutic doses of several drugs have been shown potential of a medication to impair driving to impair psychomotor skills related to driving. It is also competence. important to note that many medications may potentiate the impairing effects of alcohol and other drugs. Less INTRODUCTION attention has been given to driving under the influence We are all well aware of the impact of drink- of medication, whether prescription or OTC medication. ing and driving through the media coverage Illicit drug use also seems to receive less media attention of drinking related accidents and through the than alcohol, and is much more difficult to detect. Field public service announcements sponsored by tests and detection systems have law and advocacy groups. Driving while under been in place for some years to detect alcohol, but as yet

www.americaspharmacist.net March 2012 | america’s PHARMACIST 35 there is no valid test to measure impairment from other severity of the effects differ between the medica- substances. Departments of motor vehicles (DMV) across tions studied, often depending on the half lives, the United States have tried to address this issue, and the dose, and formulation of the medications. New York state DMV medical advisory board tackled the There has been research looking at the issue of the impact of OTC medications on driving as a residual effects of and non- specific focus of community outreach years ago. hypnotics (z-hypnotics), using The issue of tracking the absolute impact of medi- single dose 20 mg and eszopiclone cations on driving is difficult unless there is an accident 7.5 mg in older drivers. Even though these two which requires further investigation and confirmatory medications would be expected to cause sig- blood tests that can be evaluated. The question remains, nificant residual side effects equally, the results however, whether appropriate use of herbal remedies and of the study do not support this hypothesis. The FDA approved medications poses a sufficiently significant study reported that single dose temazepam- potential hazard to suggest that these agents should not impaired driving performance in elderly patients be used while driving. Researchers must consider that the until 10 hours after bedtime administration, same dose of a certain medication can have wide vari- whereas eszopiclone impaired driving signifi- ability in both the intended therapeutic action of the drug, cantly until 11 hours after the dose. but also the side effects for individuals of different ages Antidepressants were evaluated for similar and states of health. People often drive without adequate effects. In a study of nefazodone, it was found knowledge of the degree of impairment their prescribed that impairment is the same for both elderly and and OTC medications can have on their driving skills. younger patients. It may be suggested that the Individual differences in the absorption, distribution, testing parameters may not have been sensitive metabolism and elimination of medications all cause enough to detect effects on specific features a difference in the effect of a drug on the body. As we of elderly drivers, especially when the same age, these differences become even more pronounced. medications have demonstrated moderate Coupled with the age-specific decline in physical and impairment in younger subjects. Some studies cognitive ability to drive and operate machinery, changes have examined the effects of chronic use versus of organ function and lean body mass can also play a role intermittent use of benzodiazepines with no dif- in driving deficits as we grow older. However, it is impor- ference noted, so caution should be extended tant to note that organ changes can be seen in younger even for those who use sedating medications on patients with chronic disease and comorbidities condi- a regular basis. tions as well. The impairment of behavioral, mental and Another factor to be considered is that while physical functions such as psychomotor performance, some drugs known to cause driving impairment , attention, memory and information pro- can be isolated and avoided, other substances cessing are all potential issues with medications. Aging which cause significant impairment are com- in itself is not the key to impairment. However, diseases bined with less impairing substances. Alcohol that are more likely to be experienced with increasing age, is known to impair driving, but also amplifies such as and other medical comorbidities that what might be minor or insignificant impairment. can impact physical strength and executive function, are Multi-ingredient combinations may be perceived the real factors which must be considered as potential by the general population as less danger- contributions to decreased driving competence. With the ous products and sold to patients who would number of aging drivers expected to increase over time, otherwise not use the single source product. An these factors must be taken into account. One would example of this can be seen with OTC products expect that medications most commonly associated such as the combination of acetaminophen and with sedation, such as sleep medicines and/or sedative- , which is marketed for pain hypnotics, would significantly increase risk. However, even relief at bedtime while improving sleep. The with these well-known offending drugs, the duration and diphenhydramine portion of this product is used

36 america’s PHARMACIST | March 2012 www.americaspharmacist.net alone as an OTC sleep aid. Other OTC medica- as being able to see a red light as a with discrete tions, such as anti-diarrheals, can also be very meaning when compared to a streetlight without meaning. sedating and impairing, so no medication should be considered entirely safe without consulting Visual Attention first with a health care professional. Another well- Visual attention is defined as the selection of visual stimuli studied category of impairing medication seen based on location in space. This is a key function for detect- prescribed in combination with other medica- ing road side targets, and impairment in this category can tions is the benzodiazepine class. Research be a reliable early indicator of many disorders including, but has demonstrated that use of multiple sedat- not limited to, dementia. Tests to determine the intactness of ing agents, such as duplicate benzodiazepine visual attention are available to specialists, however, are not therapy and benzodiazepines combined with widely available to most general practitioners. one or more antidepressants increases the risk Visual attention requires being able to pay attention of traffic accidents, so polypharmacy should be to peripheral objects and their position in space and time, avoided when trying to reduce risk to drivers. On while maintaining one’s ability to reach one’s destination. a positive note, researchers have concluded that This would be manifest by being able to see pedestrians in some cases, patients comply with recommen- on the side of the road while still avoiding a collision with dations to not drive—especially with opiate medi- a vehicle in front of you which is stopped at a stop sign. cations for pain and sedating antihistamines. Visual attention also requires being able to retrieve informa- tion from one’s field of vision for further analysis in order AGE AND DRIVING to respond appropriately to the stimulus. Further, visual The ability to identify hazardous situations, read attention requires the ability to focus one’s gaze on a target the road and navigate the environment while containing important information and filter it out from other driving are essential components of safe driving. visual background noise to anticipate problems and see A requirement for safe driving is the integration ways to avoid conflicts. It also requires being able to detect of high-level cognitive function and perception landmarks, information for direction or orientation in space with coordinated physical activities. “Driving Fit- and time, and the ability to organize information received ness” is a between safety and mobility, through the visual sensatory means so that it is identifiable. and it is important for society to identify factors that reduce the fitness of certain drivers. The Visual Perception function of driving can be seen as the ultimate Visual perception is defined as the extraction and appropri- activity of daily living (ADL) in our current envi- ate interpretation of visual information. Intact visual percep- ronment. However, it can be the most challeng- tion is required to read and understand traffic signs, to ing competency to sustain in that it requires the establish correct orientation while on the road, and to main- highest level of integrated visual, motor, and tain stability in directions on the road. Abnormal detection cognitive functions. of line orientation, altered visual perception, and impaired recognition of traffic signs have all been implicated in motor WHAT IS REQUIRED FOR SAFE DRIVING? vehicle crashes, and have been linked to Lewy Body de- Cognition Competence mentia. Visual perception requires the driver be able to shift Cognitive competence requires being able to visual focus from the automobile’s dashboard display back receive, filter, and assimilate information that is to the road quickly and effectively to ensure safety and critical to driving tasks, such as turning in time to driving competence. There is also the need for vision to be avoid danger, maneuvering the vehicle concur- corrected when there is a case of diagnosed nearsighted- rently and detecting dangerous conflicts. It also ness or farsightedness. The vision tests performed at the requires being able to focus one’s attention on state DMV are just one small step in the identification of the most critical information while filtering out drivers who may be at baseline risk of visual deficits. Other the extraneous, less important distractions such visual factors include being able to interpret the speed of

www.americaspharmacist.net March 2012 | america’s PHARMACIST 37 cars approaching our vehicles, intersecting our paths, or driver can manage to perform the required task when weather and light conditions change. should he/she be disabled or impaired in other ways. Specific physical tasks include, but are not Executive Function limited to, pushing the brake and gas pedal— Executive function is defined as the ability to adapt to new and being able to move ones foot quickly to the situations effectively. This high level of function re- correct pedal. Further, it is necessary to be able quires anticipation, planning, and effective performance. Im- to demonstrate a sufficient range of motion when pairment in this cognitive domain can be expressed through turning the head to the rear in order to back out personality changes, altered insight, and decreased im- of a spot or to be sure there is no vehicle pulse control. When operating a motor vehicle, an individual in the blind spot prior to making a lane change with executive function impairment may respond by overes- on the . The act of turning the steering timating their driving skill or by making dangerous decisions wheel sufficient range and speed is also a nec- and may lack insight. Many factors, including medication essary physical requirement for safe driving. therapy, can affect executive function. This ability to rea- There has been a significantly increased in- son and make decisions allows one to accurately choose terest in elderly drivers. This interest has resulted within a range of possibilities a safe appropriate action. This from population and travel trends. Driving a car executive function becomes extremely significant when an is the most common method of travel for elderly unexpected event occurs and it allows the individual to take people in the United States. A driver’s license action to keep him/her and passengers safe. Additionally, represents independence and evidence of there is a factor of vigilance, which is one’s ability to main- continued competence, in addition to the right tain focused attention for a long period of time, for example, to operate an automobile. That said, the elderly while driving long distances or on monotonous routes that drive less with increasing age. In the United can induce boredom or sleepiness. States, those over 65 years of age drive less than half the average of all the miles traveled by Memory (procedural, semantic, and episodic) other age groups. Memory is defined as the acquisition and coding of Elderly drivers tend to compensate for age information for use by the brain at a later time. Episodic related decreases in driving capabilities by memory, though not required for driving in a familiar loca- modifying their driving habits, such as shifting to tion, is generally the first phase of compromise seen in driving during the day to avoid night driving and dementia. Semantic memory, conversely, includes global its associated risks of reduced night vision and knowledge of the world, such as a green light equating to glare. Further, there is more purposeful avoid- “proceed” versus red for “stop.” Procedural memory is the ance of rush hour and high traffic times, bad application of a learned skill, such as turning off the car weather and unfamiliar travel routes. While the when parking or using a clutch when engaging the gears focus on the older driver has been highly sensa- in a car with a standard transmission. Semantic memory tionalized in the media, not all driving issues are and procedural memory are affected later in the progres- related to aging. Here are some issues related sion of dementia and Alzheimer’s disease. to younger drivers that can be worsened with medications that can cause driving impairments: Physical Competence • Less experienced drivers can have reduced A driver must possess intact muscle strength and tone capacity to drive once darkness falls. Even in order to perform the extremely physical task of driving under conditions where no medication is safely and effectively. Any impairment in this coordination involved, the less experienced driver’s auto- and balance can lead to slowed reflexes and increased matic reflexes and driving skills are in the early reaction time. There can be slowed physical movements developing stages during the first months of related to physical and mental illness—called psychomotor driving. Darkness is an extra variable for the retardation, and this must be evaluated fully to ensure the young driver to cope with.

38 america’s PHARMACIST | March 2012 www.americaspharmacist.net • Less experienced drivers can be more easily that is necessary to ensure that we arrive at our intended distracted and more willing to operate within destination is just one of the many factors to consider in an environment of distraction (such as when driving safety. Decreases in one’s ability to process infor- driving with friends.) Teens are safer driving ei- mation, whether due to an age-related decline in cognition ther by themselves or with family. One strategy or due to the influence of drugs, make safe arrival at one’s to ensure young drivers acquire good skills destination less likely. A decrease in cognitive processing is by shadowing an experienced driver as a impacts an additional factor in driving, spatial ability. This mentor who can model responsible behavior further complicates navigation by limiting one’s ability to and driving habits. extract information from maps and also to predict the time • Less experienced drivers may not understand needed when stopping or turning. the importance of wearing a safety belt and Restricted visual fields can create yet another chal- avoiding driving just for fun. New drivers lenge by altering one’s ability to correctly read road signs should try to gain their experience driving for and to recognize landmarks. Psychomotor retardation, school and work, especially during the early defined as slowed physical movement, is a frequent stages of learning. This practice should focus side effect of certain medications and this on the road and not allow distraction by cell further reduces one’s ability to respond quickly to urgent phones, texting, drinking and eating. situations that frequently occur while driving—such as the • Less experienced drivers are more likely to need to brake in order to avoid a crash, to navigate in icy believe they are invincible and not impacted by or other hazardous weather conditions, and to maneuver drowsy driving. A key part of learning to drive through sharp turns on tight curvy roadways. Medica- should be how to respond to any sleepiness, tion may not directly impact visual fields; however when especially a state made worse by medications. peripheral visual fields are compromised either by age or Sleepiness may cause even more accidents other health conditions, the side effects of medication can than alcohol and is often underestimated. worsen one’s overall driving competence. • Less experienced drivers must be taught Multiple medications that are prescribed in combina- about the dangers of driving and drinking tion with each other (polypharmacy) increase the chances alcohol or taking medications. Alcohol will im- of adverse drug reactions and of a greater difficulty in pair the judgment and reaction time of anyone an accurate identification of the medication causing the who drinks. Abuse of prescription and OTC problem. Whenever possible, and only if it is necessary medications can be even more dangerous to use polypharmacy, it is best to add a single new drug than alcohol. Young adults may be more likely to a current regimen so that the first dose effect of the to experiment with Food and Drug Administra- combination can be safely monitored. A prescriber and tion-approved medications, and evidence of pharmacist should always work together to reduce the misusing standard medication therapies, such number of medications a patient is on, as even the most as , is on the rise. This trend sophisticated pharmacokineticist cannot predict the exact of abusing what is perceived as “safer” drugs metabolic impact of multiple agents through various over illicit and more “traditional” drugs such as competing enzymatic systems. We are also learning more marijuana or cocaine, has given some youth a about ethnic predisposition and the resulting altered clear- false sense of safety in driving under the influ- ance of medications, which poses yet another nuance of ence of these substances. uncertainty for our patients. Although driving under the influence of any substance POTENTIAL RISKS OF PRESCRIPTION, which alters perception and judgment must be avoided, OTC AND HERBAL MEDICATIONS it is a clear dilemma for a physician to avoid prescribing A significant issue we must be concerned with any and all agents that may pose such a risk. In today’s is the impact of medication on the ability to drive world, personal transportation is a minimum daily activ- safely. The cognitive process of decision making ity in which we must engage, and it is unrealistic for a

www.americaspharmacist.net March 2012 | america’s PHARMACIST 39 prescriber to make recommendations to avoid this activity observed compensatory slowing and more very while taking medication long term. slow driving. In Figure 1, we see what the mmol/L Previous efforts to maintain the driving skills of aging is equivalent to the mg/dl measure. adults have included modifying the driving environment, In Europe we see that the government has improving and offering educational programs and enhanc- progressively restricted driving permits for people ing vehicle design. Ostrow’s research group explored the with insulin dependent diabetes, while the United effects of physical fitness training on the driving perfor- States has loosened its restriction. A key bar- mance of older adults. The results demonstrated that in- rier for confirming the effect of on creased flexibility and trunk rotations allowed the driving has been the inability to assess driving driver a better score when measured while driving. Thus performance, as actual driving exercises are not further underscoring the need for the physical strength feasible or ethical because of difficulties con- needed to properly handle a vehicle. trolling and replicating conditions among study subjects. When considering the elements of driv- CHRONIC DISEASE TREATMENT AND ing performance we look at steering and speed DRIVING COMPETENCE control and the factors affecting these. Thus, A common health condition that requires chronic medica- we consider the smoothness of braking (which tion is diabetes, which is well known to carry significant requires adequate pressure on the brake pedal), long term, serious sequellae. The outcome of experiencing smoothness of acceleration (which requires con- a hypoglycemic state can significantly impair one’s abil- trolled foot pressure on the gas pedal), speeding ity to drive, so caution must be given to administration of (as defined by seconds driving with 10 percent insulin and other medications that can cause hypoglycemia. greater than posted speed), versus slow driving Diabetic hypoglycemia can translate into impaired cognitive (by seconds driven at less than 30 percent of motor function, which is assumed to increase the risk of mo- posted speed limits). These variables can all add tor vehicle accidents. The results of driving simulators under up to erratic operation of the motor vehicle and conditions or varying blood glucose measures provided increase the chances of a crash. The Cox study further support that hypoglycemia can cause significant found that mild hypoglycemia (3.6 mM or 65 mg/ impairment. Driving performance was not altered with mild dL) and recovery from brief moderate hypogly- hypoglycemia, nor was there a difference when a patient cemia were not associated with impaired driving was recovering from low blood glucose. However, when performance when measure during brief testing. moderate hypoglycemia was present (a value defined as 2.6 However, moderate hypoglycemia was associ- mM or 47 mg/dL or less) there was disrupted steering, more ated with impaired performance. The impairment swerving and time over midline and off road. There was also was seen in 35 percent of the study subjects and primarily affected steering. Of those studied, 55 percent did not expect to be impaired and stated Figure 1. mmol/L Equivalent to Mg/dl Measure that they would be willing to drive under these Mg/dL mmol/L Comparison of Blood Average Glucose values A1C% same conditions. The significant increase in very 65 3.5 4 slow driving may be a compensatory effort used by patients who felt some level of impairment. The 100 5.5 5 research group recommends that people should 135 7.5 6 be instructed not to drive without treating blood 170 9.5 7 glucose below 3.6 mM or 65 mg/dL. Pharmacists 205 11.5 8 should discuss with patients who experience 240 13.5 9 hypoglycemia what their plan is to identify symp- 275 15.5 10 toms prior to driving, while operating a motor 310 17.5 11 vehicle and to subsequently treat hypoglycemia. 345 19.5 12 When we consider the effects of diabetes-

40 america’s PHARMACIST | March 2012 www.americaspharmacist.net related hypoglycemia on our patients, we should antihistamines and, consequently, people purchase these also consider the potential of any drug to cause brands to avoid the effects of drowsiness. It is important drug induced hypoglycemia in non-diabetes pa- to note that even these newer non-sedating agents can tients, including (but not limited to) quinine and still cause drowsiness and dizziness in many patients. sulfamethoxazole. Also consider beta-blocker Examples of second generation antihistamines include therapy, which may mask tachycardia associ- loratadine, fexofenadine, and cetirizine. ated with hypoglycemia. Another disease state, arthritis, may pose disease specific limitations— Antihypertensives with altered joint performance and pain—but While no consistent neuropsychological changes have also the side effects of medications used for been observed with diuretic therapy or treatment with ACE- palliative treatment of the condition. inhibitors, there have been clinical reports of drowsiness and psychomotor retardation with beta blockers. However, EFFECTS OF FIRST DOSE MEDICATIONS researchers have shown that the overall effects of beta- It is important to note that any first dose of blockers on neurological function are few and are offset medication should be taken in a controlled by the benefits of reduced blood pressure. Note that the environment to ensure that the patient is not al- hypotensive effects of all antihypertensives can lead to diz- lergic to and/or impaired by the new substance. ziness in the driver and warrants warning, especially with Even medications that have a low risk of causing first doses or changes of medication. Alpha-2 agonists drowsiness or dizziness in most of the popula- such as clonidine and guanfacine can be sedating, but tion can result in significant impairment in certain also can alter sleep architecture by decreasing REM sleep patients, often without warning. While we explore and has been reported to cause insomnia. The effects of the categories of the medications available, it is insomnia on patients can be a significant contribution to important for pharmacists and physicians to re- excessive daytime sleepiness and increased driving risk. mind their patients of the first dose phenomenon of all new medications and for dose changes to Anti-infectives pre-existing medication regimens. Another category of medication to be evaluated is the class of anti-infectives. Pharmacists may fail to consider MEDICATION AND DRIVING this group of medications as potential contributors to in- COMPETENCE creased driving risk, but many of these medications have The following reviews a sample of the more documented adverse effects that can be problematic. commonly prescribed drug classes used in Anti-infective products that are available for parenteral ambulatory care settings. For a comprehensive administration (IM or IV) only have been excluded from review of all medication American Hospital For- the summarized review due to the lower probability of a mulary Service (AHFS) categories and specific driving while still under the influence of these agents when drug events within these classes, please refer to administered as injections. the AHFS 2011 Red Book. Cephalosporins: The central effects Antihistamines that have been reported following oral and intramuscu- We begin the exploration of the potential ad- lar administration of cephalosporins include dizziness, verse effects of medication on driving with the headache and . However, some patients have first category of medication in the AHFS listing- reported the opposite effect, such as nervousness and antihistamines. First generation antihistamines, anxiety. Alterations in color perception and somnolence such as diphenhydramine, chlorpheniramine, have also been reported. Altered color perception could brompheniramine and are well known be considered a significant risk when one approaches an for their sedating effects. The second generation with a green or red light, or even a stop sign antihistamines are marketed as “non-sedating” that triggers our mental process to use our brake when we

www.americaspharmacist.net March 2012 | america’s PHARMACIST 41 recognize that color code for traffic control. be counseled on the specific drug regimen they are receiving. Many of these antiretrovirals have Macrolides: Though rare, drugs such as erythromycin, the capacity to increase the drug concentra- azithromycin, clarithromycin, and telithromycin have been tions of other sedating medications, so extreme reported to cause dizziness, vertigo and somnolence caution should be employed when providing (ranging from 1–4 percent and dependant on the dose combination therapy to HIV patients. and indication of the antibiotic). The use of long term high dose azithromycin has resulted in reports of reversible Autonomic Agents hearing loss in roughly 5 percent of patients. Hearing loss Parasympathetic (cholinergic) agents and tinnitus are reported to resolve within five weeks of Parasympathetic (cholinergic) agents such as discontinuation of the medication. Clarithromycin has also donepezil, and rivastigmine are had documented reports of confusion, tinnitus and . agents used in Alzheimer’s disease. They can cause dizziness, drowsiness and tremor. The ill- Fluoroquinolones: This class of medication, including ness itself poses the danger of significant cogni- ciprofloxacin, levofloxacin, moxifloxacin, and gemifloxi- tive decline, which ultimately irreversibly impairs cin is associated with an increased risk of tendonitis and one’s ability to drive. Deficits in memory and tendon rupture for all age groups. Though tendon injury is executive function are so significant that patients seen more often in those over 60 years of age and those often become progressively homebound and who are more physically active, patients who are not within unable perform the basic activities of daily living these risk categories should also be counseled about this (ADL). In the case of these supplemental medi- possible injury. Tendonitis and tendon rupture cause pain, cation therapies, it is best to counsel patients decreased agility and decreased strength. The more com- and their caretakers on the anticipated decline in mon tendons affected are the shoulder, hand and Achilles function and the use of caution when using any tendon. Each is involved in the strength and reflex abilities medication that can compound memory deficits. required by competent drivers. The (CNS) effects of ciprofloxacin are related to the GABA inhib- agents iting action of the fluoroquinolones, so CNS stimulation can Many medications are known to cause undesir- be expected, including tremor, nervousness and confu- able effects and primary care providers may sion. Some patients, however, do still experience sedation overlook the role a drug may play in causing with this group of antibiotics. Additional reports of altered cognitive impairment. Acetylcholine is a key neu- glucose control has been reported, causing either hyper or rotransmitter which can produce significant side hypoglycemia, so diabetes patients receiving insulin or oral effects when its action is blocked or altered. therapy should be cautioned about this potential impair- The current debate among health care provid- ment when driving. In general, maintaining blood glucose ers questions the impact of one medication with control during an infection requires close monitoring. pronounced anticholinergic effects or a cumula- Sulfonamides, tetracyclines and antifungal anti-infec- tive consumption of multiple agents with varying tive agents all exhibit central nervous system side effects degrees of anticholinergic properties. No one for patients with varying degrees of incidence and inten- can question, however, the cognitive impact sity. It is imperative that pharmacists review the package of anticholinergic agents. Some research has inserts prior to dispensing so that proper consultation may looked at the long-term use of these products be provided. and the cumulative exposure linked to poor memory in older men and found a correlated Antiretrovirals: The most common adverse CNS effects negative long term effect so caution is advised. related to decreased driving potential in patients receiving Researchers at Harvard Medical School these HIV therapies include insomnia, peripheral neuro- developed a scale to assess the anticholinergic logic symptoms, dizziness and myalgia. Patients should cognitive burden and have rated drugs by giving

42 america’s PHARMACIST | March 2012 www.americaspharmacist.net Table 1. Findings of the Harvard Medical School Research Score Medications 1 , bupropion HCl, , , risperidone), trazodone, codeine, possible anticholinergic potential fentanyl, morphine, prednisone, theophylline, colchicine, atenolol, captopril, chlorthalidone, digoxin, dipyridamole, disopyramide phosphate, isosorbide dinitrate , isosorbide mononitrate, metoprolol, triamterene, nifedipine, quinidine, brompheniramine, cimetidine, loperamide 2 , belladonna alkaloids, carbamazepine, loxapine, , pimozide, some relevant anticholinergic potential , cyproheptadine, meperidine 3 Amitriptyline, , , desipramine, doxepin, imipramine, nortriptyline, definitive anticholinergic potential , , perphenazine, thioridazine, trifluoperazine, trimipramine, flavoxate, oxybutynin, tolterodine, procyclidine, orphenadrine, benztropine, carbinoxamine, chlorpheniramine, , dicyclomine, , hydroxyzine, meclizine, trihexyphenidyl, scopolamine, promethazine scores ranging from 1 (if there were possible anti- other agents in the same class, there are considerations cholinergic effects based on lab simulation but no such as aspirin induced tinnitus that must also be fac- clinical relevant cognitive effects) to 3. (See Table tored into reduced driving competence. The non-steroidal 1.) Scores of 2 or 3 were given if the drug had anti-inflammatory agents (such as ibuprofen) are not as established and relevant anticholinergic effects. sedating as their opiate counterparts, but they still may Drugs without any noted effect were not named. pose risk of dizziness. This anticholinergic cognitive burden scale is intended to serve as a tool for practitioners to Opiate agonists: The opiate agonists such as morphine, add up the scores of the multiple drugs a patient codeine, oxycodone, hydrocodone, hydromorphone, metha- is taking. In cases where the summed score is 3 done, fentanyl, butorphanol, meperidine, and tramadol have or more, it would be advisable for the medication a well-established profile of side effects which impair driving regimen to be reviewed in order to recommend ability. A 2007 random-stop roadside survey by the National medications with lower anticholinergic profile and Highway Transportation Safety Administration found that a reduced overall anticholinergic cognitive burden. 5 percent of drivers tested positive for medications which Other medications in this same AFHS cat- could cause impairment. A Swedish study of drivers arrested egory include antimuscarinic, antispasmodics for drugged driving detected morphine or codeine in 19 (such as scopolamine), sympathomimetic (ad- percent of the 14,000 arrested subjects. It can be difficult to renergic) agents such as clonidine and methyl- predict the degree of impairment expected based on serum dopa, beta agonists such as albuterol, sympa- level, and tolerance is an unpredictable mitigating factor. thomimetic (adrenergic) blocking agents such Patients beginning opioid therapy must be counseled as the non selective beta-blockers (propranolol), to avoid driving following the first few doses to properly cardioselective beta-blockers (atenolol and assess the effects on reaction time, wakefulness and metoprolol), and skeletal the muscle relaxants attention. A low risk of driving impairment may be ob- and baclofen. All of these agents served in opioid tolerant patients on stable doses in stable have drowsiness and dizziness as frequently condition. Opioid tolerant patients should be cautioned documented adverse effects. that a dose increase may impair driving. Likewise, inap- propriate dose reduction or other events which precipitate Central Nervous System Agents withdrawal symptoms may impair driving. Common side Analgesics: The category of pain relievers effects of opiate agonists which lead to impaired driving has a vast array of mechanisms of action and include somnolence, lethargy, dizziness and hallucination. potential adverse effects. While many medica- Reaction time is slowed and attention span is shortened. tions, such as acetaminophen and aspirin, are Symptoms of withdrawal which lead to impaired driving less likely to cause drowsiness than some of the include agitation, muscle aches and cramping.

www.americaspharmacist.net March 2012 | america’s PHARMACIST 43 Benzodiazepines: Benzodiazepines such as alpra- the diagnoses of and schizophrenia. zolam, , diazepam and , have Research, labeling changes, and promotion a wide range of adverse effects, ranging from the well for use as augmenting agents for refractory known sleep inducing effects to the less considered lack depression and for insomnia has brought a of coordination. Single dose and short-term studies have greater reach to a broader population taking even demonstrated altered ability to learn visual and these medications. First generation antipsy- verbal information as well as psychomotor retardation and chotic agents, such as haloperidol and fluphen- lessened vigilance. Supportive research demonstrates azine, have been burdened with the primary improved cognition upon the withdrawal of these medica- side effect of dystonic reactions and muscle tions from the regimen of elderly patients. The best way due to the inhibition of dopamine in the to avoid driving impairments is to educate patients about nigrostriatal system. Extrapyramidal symptoms the risks of using benzodiazepines when driving, espe- (EPS) have made adherence and tolerance of cially when used in combination with other central nervous this class of antipsychotic agents a challenge system , and to only use short acting agents for the psychiatric community. While this mus- at the lowest doses during times outside of driving. cular side effect is notable and may impact the physical ability of a person to operate a motor : The neuropsychological effects of this vehicle safely and competently, it is the seda- medication class are complicated by not only the effects tion and light headedness that pose the great- of the targeted seizure disorder, but also the individual est risk. The potential to cause cognitive effects differences in the metabolism of these drugs. The anti- within this class may be related in part to the epileptic drugs can be ranked on their intrinsic ability to anticholinergic properties, however even those cause drowsiness. Carbamazepine has fewer reports of agents with lower anticholinergic burden have sedation than or . However when been reported to cause impaired cognition. factors of serum concentrations differences and impact Second generation agents are also known of drug interactions must be considered it becomes very as the atypical antipsychotic agents and have challenging for the prescriber and pharmacist to predict become a popular choice over the first gen- the degree of risk. When evaluating this total impact on eration agents due to the reduced potential driving competence, the dose, duration of treatment and of extrapyramidal side effects. The impact of subjective complaints of sedation must be considered. sedation, dizziness and hypotensive effects of medications such as aripiprazole, quetiapine, Psychotherapeutic Agents risperidone and olanzapine continue however Antidepressants: This class of medication is well known to pose risks to drivers who are taking these for the first dose effects of drowsiness and dizziness. medication. Further, the FDA has included a Discontinuation of antidepressants also causes dizziness class effect warning for all these agents for the in many patients. The agents within the class vary in their potential to cause metabolic syndrome and dia- potential contribution to this effect, however. Tricyclic an- betes. In the case of any blood sugar changes, tidepressants are highly anticholinergic as compared to there can be significant impairment in judgment the SSRI medications, such as paroxetine and sertraline. and autonomic stability. While the SSRIs are not anticholinergic, they are frequent offenders responsible for lightheadedness and dizziness. Sedatives and Hypnotics To avoid problems while driving, a pharmacist should rec- Many adults in United States have reported ommend an agent with the least anticholinergic proper- some level of daytime sleepiness sufficient to ties and use caution to observe potential additive effects have negatively impacted their lives. While we of multiple medications with potential impairing qualities. strive to be productive in our professional and personal lives, many of us operate in a sleep- Antipsychotics: The prescribing of antipsychotic deprived state. Cases in which excessive day- medications has been expanded for treatment beyond time sleepiness which is self inflicted, perhaps

44 america’s PHARMACIST | March 2012 www.americaspharmacist.net by long hours at work or studying, the resolution mended is that a person plan to get a full eight-hour rest is simply increasing one’s amount of sleep. when taking medications to induce sleep, as opposed to However, when excessive daytime sleepi- taking these agents for short naps. The Epworth Sleepi- ness is caused by other reasons, such as ness Scale and Stanford Sleepiness Scale can be helpful insomnia, the solution is more challenging. tools that the pharmacist can recommend to physicians Improved sleep hygiene and clear diagnosis to screen patients for excessive daytime sleepiness if of the source of the insomnia is key. However, presenting with this chief complaint. medication is often the only intervention to help Modafinil has emerged as a safer medication inter- individuals resolve their excessive daytime vention to treat excessive daytime sleepiness due to the sleepiness. improved side effect profile over the older stimulant medi- It is estimated that sleep disorder and cations which include dextroamphetamine, methylpheni- related complications contribute to more than date, and pemoline. However, even this agent can cause 100,000 motor vehicle crashes, resulting in lightheadedness. Pharmacists may also see an increased 71,000 personal injuries and 1,500 deaths an- use of modafinil over the older standard therapies because nually. Sleep-related motor vehicle crashes tend of the reduced (though not absent) potential for abuse. to involve the driver asleep in almost 18 Some of the side effects of the older stimulant medication percent of these reported cases, and young interventions include tremor and agitation. There has been adult male drivers are noted to be the most likely limited research evaluating the potential contribution of to be involved. It is difficult to get a clear sense medications that cause agitation on or of the impact of medication in these events, but “road .” However, to ensure total medication safety, the role must be considered when investigating further research in this area is warranted. the events for future safety recommendations. A prescribing physician in partnership with a pharma- While it seems counterintuitive, some of the cist should observe, discuss, and document adherence medications used to alleviate insomnia can cause to prescribed medication therapy, especially for patients other sleep problems. Most sleep medications who have careers which require responsibility for the decrease sleep latency, which is defined as the safety of others such as school bus drivers, airplane pilots time to fall asleep. Most medications used to treat and those with history of accidents related to previous insomnia can alter the sleep architecture, which in excessive daytime sleepiness. Failure to adhere to the turn can lead to continued sleepiness during the medication instructions which further poses risk for safe day and, hence, impaired driving ability. driving should be documented, and the patient should be Some individuals seek to overcome exces- educated about the shared societal obligation to make sive daytime sleepiness caused by medication our roadways safe. therapy by using stimulants such as amphet- It is important to remember that alcohol is consid- amines and caffeine. When overused or used ered a drug and is associated with excessive daytime inappropriately, stimulants can cause significant sleepiness, and is the most widely used substance with lightheadedness. sedative effects. Pharmacists must always consider and The newer sleep medications have been counsel patients on the confounding effects of alcohol on launched touting an improved side effect profile, medications with known potential somnolence effects. It is chiefly, less next day lag-over effects of the drug. also critical for clinicians in the field to consider the impact While drug half life plays one role, metabolic of illicit drug use, such as amphetamine or cocaine abuse, differences exhibited can be the primary factor on daytime sedation and impaired driving competence. to consider in predicting the possible negative When individuals seek treatment for insomnia, they impact on alertness and driving behavior the anticipate that medication will help bring refreshed next day. Manufacturers of the z-hypnotics and sleep and reduced next day sleepiness. However, many benzodiazepine agonists have been required to medications used for sleep can cause next day lag- include in their FDA packaging label the warning over drowsiness due to the altered sleep architecture. of possible driving without memory. Also recom- Intact sleep architecture requires a defined, progressive

www.americaspharmacist.net March 2012 | america’s PHARMACIST 45 percentage of time spent in structured sleep stages. If an individual gets too little sleep, or if sleep is interrupted, MEDICATIONS WITH MEDICAL AND these critical stages of sleep are not experienced and RECREATIONAL USES therefore complete physically and mentally restorative Dextromethorphan: is widely available as an sleep cannot be attained. Many medications can improve OTC antitussive medication for temporary relief the time to fall asleep, but due to the deviation from the of coughs caused by minor throat and bronchial natural required staged sleep architecture, this sleep irritation. A recent trend among young adults medication leaves most feeling “hung over” the next day. exploring sources of euphoric effects has been Additionally, the newer z-hypnotic agents have a more the recreational use of dextromethorphan. At rec- rapid onset and shorter duration of effects compared to ommended doses, dextromethorphan produces older therapies; though it should be noted that eszopi- little or no CNS depression. At recreational doses, clone has longer duration of effects. positive effects may include acute euphoria, In the case of chronic administration of these agents, elevated mood, dissociation of mind from body, patients may be at risk of withdrawal if abruptly discon- creative, dream-like experiences, and increased tinued. Withdrawal syndromes can also cause driving perceptual awareness. Other effects include dis- impairment, including adverse effects such as , orientation, confusion, mydriasis, and altered time convulsions, fatigue, flushing, lightheadedness, nervous- perception, visual and auditory hallucinations. ness, and panic attacks. Altered driving competence can Recreational doses of dextromethorphan are be a result of drug induced unsteady gait, confusion, approximately 100–200 mg. This dose is reported disorientation, and significant cognitive and psychomo- to produce mild, stimulant effects. Doses of tor impairment which can be observed within one to five 200–500 mg produce a more impaired effect, and hours following zolpidem doses of 10–20 mg. Memory 500–1,000 mg may result in hallucinations and a impairment, which is measured by learning, recall, and mild reaction with an overall distur- recognition of words, pictures, and numbers; psychomo- bance in senses, thinking and memory. Misuse tor slowing; reduced capacity to sustain attention and and abuse of dextromethorphan will impair the impaired balance due to ataxia and dizziness have been user’s judgment, memory, language, and other reported. Visual disturbances and a reduced ability to es- mental performances related to driving safely. timate time and distance have also been reported. Dose- dependent psychomotor impairment can be caused by Marijuana hypnotic drugs and can be found up to five hours after a Prevalence of treating a variety of symptoms with single 15 mg oral dose of zolpidem. Memory and learning marijuana means pharmacists and health care impairment can be found up to eight hours following a providers must be prepared to counsel the pa- 10–20 mg dose. tients seeking information about drug interactions There has been no significant residual effect on and adverse effects. Dronabinol is a synthetic memory or actual driving when subjects have been tested tetrahydrocannabinol (THC) and the only FDA- the morning after a single 10 mg dose of zolpidem. Fol- approved cannabinoid product. The manufactur- lowing a single 10–20 mg dose of zaleplon, studies have er of dronabinol recommends that patients using shown no continued effects on actual driving after five to this medication should be educated to avoid 10 hours or on body sway, reasoning, retrieval and spatial operating a motor vehicle until they are able to memory after four to nine hours. However, significant tolerate the drug and perform such driving tasks impairment has still been reported within one to three safely. Epidemiology data from road traffic arrests hours of taking a dose of these medications. The drug and fatalities indicate that after alcohol, marijuana manufacturer recommends that patients be warned about is the most frequently detected psychoactive the potential impairment of mental alertness and motor substance among driving populations. Marijuana coordination, which is required when operating machinery has been shown to impair performance on driv- or driving a motor vehicle ing simulator tasks and on open and closed driv-

46 america’s PHARMACIST | March 2012 www.americaspharmacist.net ing courses for up to approximately three hours. tive side effects or cognitive impairment adverse actions Decreased car handling performance, increased can be considered an additive risk. reaction times, impaired time and distance Unlike FDA-approved drug products, herbal remedies estimation, inability to maintain road navigation, are not labeled with standardized drug information provid- travel orientation, subjective sleepiness, motor ing dosing guidelines, common adverse effects, contraindi- in-coordination, and impaired sustained vigilance cations and side effects observed during research. Howev- have all been reported. Paradoxically, some driv- er, it is important that we remember that the package insert ers may actually be able to improve performance is continually updated to reflect post marketing surveillance for brief periods by overcompensating for self- on side effects and other emerging safety information. perceived impairment. The greater the demands Clear, concise reporting of the post marketing “pa- placed on the driver, however, the more critical tient experience” on all prescription and non-prescription the likely impairment. Marijuana may particularly agents becomes even more important as we move ahead impair monotonous and prolonged driving in in our advocacy for safer driving recommendations related particular. Decision times to evaluate situations to drug therapy. Of additional concern is the impact on and determine appropriate responses increase. drug interactions that increase adverse effects and should Mixing alcohol and marijuana dramatically inten- be considered whenever driving while medicated. Recog- sifies effects of the combination than with either nizing the adverse effects of herbal therapies is more chal- drug on its own. Furthermore, it is important to lenging and the reporting of these events is infrequent. recognize the increased bioavailability of inhaled Unlike the required reporting which is in place for manu- marijuana over the oral and that the potential facturers that produce FDA-approved medications, ad- impairment will be based on the dosage form the verse event reporting instruction is not required for makers patient is using. of herbal medication products. Patients who wish to report an herbal remedy adverse event may use MedWatch and HERBAL REMEDIES the toll-free reporting hotline, 1-800-FDA-1088. Though All medications have potential side effects, the most common general reactions involve the liver and and herbals products offer no improved safety gastrointestinal tract, herbal drugs can cause significant over the FDA-approved drug therapies. Herbal neurologic effects such as dizziness and drowsiness and remedies, also known as complementary play a role in the impairment of drivers. alternative medications (CAM) are often revered by patients for their “natural” ingredients and POTENTIAL FACTORS LEADING “safety” profiles. The risk of unexpected adverse TO INCREASED IMPAIRMENT effects can be potentiated by the age and health Smoking Cessation of the patient; however, the side effect possibili- Many medications, including sedating antipsychotic medi- ties may be less well known then those that are cations, are extensively metabolized by the liver, mainly regulated by the FDA. Further, doses of herbal by the CYP 1A2 enzyme system. It is well documented products may vary in strength and quality, dif- that products of incomplete combustion called polycyclic fering between manufacturing lots or within the aromatic hydrocarbons (PAH) are found in tobacco smoke same bottle being purchased by the patient. and induce this same enzyme system. For this reason, There are also concerns about contamination smokers who take medications that rely on the 1A2 and adulteration of herbal therapies with pesti- metabolic pathway will have lower plasma concentrations cides and microorganisms which would other- of these agents compared with their non-smoking coun- wise remain unknown to the public without the terparts. Smoking cessation has been shown to increase high level scrutiny as is given to FDA approved the incidence of side effects of the medications that are medications. The impact of such variability and metabolized via this hepatic metabolic pathway. contamination cannot be measured in terms of This increase in side effects occurs as a result of in- driving capacity, but clearly an increase in seda- creased serum concentrations of these drugs when the in-

www.americaspharmacist.net March 2012 | america’s PHARMACIST 47 duced CYP1A2 enzyme returns to the baseline metabolic Table 2. Substrates of CYP 1A2 rate as a result of the removal of PAH upon smoking ces- • Alosetron sation, despite no change in prescribed doses (See Table • Caffeine 2.). The addition of nicotine replacement to the patient’s • Clozapine* • Flutamide regimen will help reduce the withdrawal from nicotine, but • Estrogens will not lessen the impact of the metabolic consequences • Frovatriptan • Melatonin and increased serum concentrations of drugs affected by • Mexiletine the 1A2 enzymatic pathway. • Mirtazapine • Olanzapine • Ramelteon Drug Interactions • Rasagiline • Ropinirole Pharmacokinetic interactions occur when combinations • Tacrine of drugs, or a drug and another substance, result in a • Theophylline* • Tizanidine change in the way the body affects a drug. In other words, • Triamterene how the combination affects drug absorption, distribution, • Zolmitriptan metabolism, and elimination (ADME). An example of this *Narrow therapeutic index, requires monitoring was discussed earlier with the metabolic consequences of smoking on the 1A2 enzymatic system. operate motor vehicles. However it may be those Pharmacodynamic interactions occur when the drug medications less likely implicated in impairment affects the body, such as a confounding effect of bone that may pose greatest risk due to the less promi- marrow suppression with carbamazepine and clozapine. nent warnings and consultations. The combination of these two medications creates a more How can we keep our patients safe? Some intense risk of adverse effects than either drug alone, and suggested things to consider when counseling cannot be otherwise explained by metabolism through the your patients in order to fulfill your duty to warn: liver. Polypharmacy, in the absence of enzymatic pathway • For patients who are in high risk driving oc- competition, may pose an increased risk of pharmacody- cupations or for those who have specific namic interactions, which result in elevated serum con- concerns about driving, pharmacists must centrations and intensified adverse effects of the drug. advocate that the patient seek advice and ask for specific warnings that could impair driving PHARMACIST DUTY TO WARN competence. Pharmacists can assist patients How far should we go with the duty to warn patients about by providing medications that pose less risk driving risk? It is key for pharmacists to know the likelihood, of driving impairment. Most OTC medications by percentages, for certain medications to cause increased will also provide warnings in their packaging driving risk. about driving risk and altered sense of alert- As we consider our elderly patients, we must take into ness. Providing specific signage within your account the impact of the multiple-medication regimens pharmacy may be an important step in achiev- they are taking and balance this with the proposed legisla- ing a safer community. Suggestions for signs tion for renewed driving testing for ensured competence. can be “Ask your pharmacist if your medica- It is unlikely that we can make our elders go on a “drug tion can affect your ability to drive.” holiday” so they can pass their test, so let’s use our best • Patients should always start a new medication efforts to reduce the total number of medications for these therapy when they are in a controlled setting individuals. Increased risks of falls and hip fractures have to allow for full observation of any potential been identified as a medication issue for all those involved adverse effects. Some patients have a false in treating geriatric patients. Certain guidelines in long- sense of “tolerance” to the effects of medi- term care, such as the Beer’s list, ensure that this real risk cations, perhaps from previous exposure to is considered. Medications such as muscle relaxants and medication that had similar warnings but did antihistamines can be expected to reduce one’s ability to not affect their ability to function. Emphasize

48 america’s PHARMACIST | March 2012 www.americaspharmacist.net that each new medication has a unique set • Patients must remember that OTC and herbal therapy of side effects. When coupled with a patient’s can be problematic. individualized pharmacokinetics and phar- • Never drink alcohol and drive. It is critical that patients macodynamics, a new medication requires recognize that the intoxicating effect of alcohol with the same caution with first dose as previously sedating medications is additive. Even if not warned to initiated medication. avoid alcohol with the prescribed medications, teach • Patients must be encouraged to share the full patients that concomitant consumption of alcohol never comprehensive list of medications he/she is is safe. Any potential impairing side effect of medica- taking. This should include OTC, herbal, and tions will be exaggerated by the central nervous system any medication they are receiving from friends, effects of alcohol, a bad mix before driving. family or through the Internet. Even medica- • Though written medication information is generally tions/supplements that are obtained through provided to patients as a standard of practice, patients the health food stores can be a significant should make sure to ask if they don’t receive a medica- contribution to the medication repertoire and tion guide. These guides can be made available in dif- must be disclosed. Pharmacists should also ferent languages to promote culturally inclusive medica- encourage patients to divulge any illicit medi- tion literacy to all patients. cation use, as such substances can have an • Patients should be counseled not to crush, chew or individual or combined effect on driving, for alter medications that are slow release (SR) or extended example, hepatic metabolism can be signifi- release (ER), as this will cause an increased absorption cantly affected even through the inhalation of and higher serum concentrations of the drug. Impaired smoked marijuana. driving will be more likely with higher serum concentra- • Patients must communicate plans for smok- tions of sedating and CNS depressing substances. ing cessation. Health care providers should • Avoid alcohol while taking medication. There are few encourage all patients to stop smoking. medications that have demonstrated 100 percent safety However, we must also consider the impact with concurrent medication administration. Never drink of the cessation on liver metabolism. Smok- alcohol and drive, and don’t add extra risk by taking ers have increased clearance due to CYP medications along with even minimal ingestion of alco- 1A2 metabolic induction, which causes hol if planning on driving. some medications to be eliminated from • Whether taking a chronic course of the same medica- the body more quickly and serum concen- tion, or when doses change of something you have been trations to be lower because of this. Upon taking, always be prepared to recognize the signs of cessation, the body quickly resumes normal impaired driving performance (stop for rest if any occur): liver clearance, and if a patient continues to • Blurred vision consume the same amount of drug metabo- • Difficulty in concentrating or staying awake lized by CPY 1A2, he/she will experience a • Unusual surprise by ordinary traffic events serum concentration that can be double than • Not being able to remember how exactly you came prior to smoking cessation. at destination • Patients also must be reminded to adhere to • Difficulty in holding steady course in traffic lanes the medication instructions and not to double dose when missed or to alter extended release formulations. These decisions by patients can Tammie Lee Demler, BS Pharm, PharmD, director of the psychiatric result in unintended higher than recommended pharmacy residency program at the University at Buffalo School of serum concentrations. Most often drowsiness Pharmacy and Pharmaceutical Sciences, is past president of the Phar- and dizziness are directly correlated to serum macists Society of the State of New York. She is the first and only phar- concentration of medications and this will only macist to serve on the New York State Department of Motor Vehicles intensify the risk of impaired driving. Medical Advisory Board.

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CONTINUING EDUCATION QUIZ Which of the following medications is least Select the correct answer. likely to cause excessive daytime sleepiness? a. Loperamide Please base questions 1–2 on the following case: b. Dextromethorphan c. Modafinil A 65-year-old female patient arrives at your phar- d. Diphenhydramine macy counter with a new prescription for zolpidem for sleep. She is currently taking clonidine for hyper- Which of the following medications has tension, but otherwise is healthy and not taking any become more likely to be a driving risk due to other prescription or OTC medications. She is worried trends of misuse about the extra cost of the medication and asks your a. Loperamide opinion about taking some OTC Benadryl which is b. Dextromethorphan much more affordable. c. Modafinil d. Diphenhydramine Which of the following is an appropriate counseling response for this patient? BT, a 45-year-old female, arrives at your a. Benadryl is a better choice, considering that it does not pharmacy with the hope of embarking on her interact with her clonidine and is much less expensive. smoking cessation New Year resolution. She b. Clonidine may be causing her sleep disturbance; she currently takes olanzapine for a psychiatric may not need the zolpidem if she discusses alternative illness and hydrocodone for back pain. What antihypertensive therapy with her physician. concern do you share with her prior to her stop- c. Zolpidem is never safe for elderly patients to use and ping her smoking? should be avoided. a. Her olanzapine serum concentrations can be d. None of the above lowered due to the smoking cessation and resolution of hepatic metabolism: she may Which of the following is a reasonable goal for her to need more medication. ensure future safer driving? b. Her olanzapine serum concentration can be a. Taking any first dose of medication at home or in a increased due to the smoking cessation and controlled setting in order to assess possible side ef- resolution of hepatic metabolism: she may fects which may impact driving need less medication. b. Only taking medications without noted side effects of c. Her olanzapine will not be affected, but hy- dizziness or somnolence, everything else should be drocodone effects will be intensified and may avoided cause her daytime drowsiness. c. No medication should be taken when driving. d. Her olanzapine will not be affected nor will her d. Only prescription medications pose risk. hydrocodone, so driving will not be a problem.

AP is a 70-year-old male presenting to your phar- macy with complaints of episodes of hypoglycemia with his new insulin regimen. What “signs” of potential impaired driving would you offer the patient to ensure he knows the status of his driving competence related to his blood sugar? a. Blurred vision b. Unusual surprise by ordinary traffic events c. Difficulty in holding steady course in traffic lanes d. All of the above

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To prevent BT from experiencing potential As a pharmacist concerned about the driving compe- increased sedation and impaired driving, what tence of your patients, which of the following recommen- would you recommend for her therapeutic plan? dations would you make to prescribers? a. Application of a nicotine topical patch once a. A prescriber is better off giving two moderately sedating daily to offset the liver metabolism that oc- medications instead of one very sedating medication curs with smoking cessation b. Long-term administration of a sedating medication b. Inhalation of the nicotine inhaler, to mimic more always results in tolerance to the sedative effects naturally the smoking of cigarettes and to re- c. First doses of all new medications should be observed duce the changes in medication concentration before driving while medicated. c. Consider implementing a proactive dose d. A and C reduction of olanzapine during smoking cessation to accommodate the changes in Which of the following disease states can pose in- expected serum concentration. creased driving risk? d. Consider implementing a proactive dose a. Type 2 non insulin dependent diabetes increase of olanzapine during smoking b. Type 1 insulin dependent diabetes cessation to accommodate the changes in c. Arthritis expected serum concentration. d. All of the above

What is NOT an example of a factor of driving Which of the following physiologic states can signifi- competence? cantly increase driving risk a. Visual attention a. Moderate hyperglycemia b. Visual perception b. Mild hyperglycemia c. Executive memory c. Mild hypoglycemia d. Semantic memory d. None of the above

Which of the following statements is (are) true? Which of the following medications has been known a. All issues related to unsafe driving are related to cause hypoglycemia? to aging. a. Trimethoprim b. Young drivers may experience effects of b. Olanzapine medication impairment. c. Trimethoprim/Sulfamethoxazole c. Older drivers may experience effects of medi- d. Zaleplon cation impairment. d. B and C Patients are at greatest increase risk of driving impairment due to sedation with which of the following Young drivers may experience increased im- medications? paired driving due to which one of the following a. Second generation antihistamines of which most likely reason(s)? b. Acetaminophen a. They are likely to be consuming more sedat- c. Modafinil ing OTC medications. d. All are equally impairing. b. The organ systems of adolescents do not ef- ficiently metabolize drugs like older patients. Please select the appropriate ranking of medications c. Adolescents may think that prescription and based on a progressively worse ranking of anticholinergic OTC medications carry less risk than “illicit” side effect burden according to the Harvard Researchers drugs. (least

www.americaspharmacist.net March 2012 | america’s PHARMACIST 51

Please select the appropriate ranking of Medication Use and Driving Risks medications based on an equivalent ranking March 1, 2012 (expires March 1, 2015) • Activity Type: Knowledge-based of anticholinergic side effect burden accord- FREE ONLINE C.E. Pharmacists now have online access to NCPA’s ing to the Harvard Researchers (all drugs C.E. programs through Powered by CECity. By taking this test online— share a similar anticholinergic burden) go to the Continuing Education section of the NCPA Web site (www. ncpanet.org) by clicking on “Professional Development” under the a. Brompheniramine=cimetidine=benztropine Education heading you will receive immediate online test results and b. Cimetidine=oxcarbazepine=olanzapine certificates of completion at no charge. c. Amitriptyline=clozapine=scopolamine To earn continuing education credit: ACPE Program 207-000-12-003-H04-P d. Dicyclomine=amitriptyline=meperidine A score of 70 percent is required to successfully complete the C.E. quiz. If a passing score is not achieved, one free reexamination is permitted. Olanzapine can increase the likelihood Statements of credit for mail-in exams will be mailed to you approxi- mately four weeks after the completed program quiz and evaluation has of driving impairment with which of the fol- been received by NCPA. lowing factors most likely attributed to this therapy? Record your quiz answers and the following information on this form. q NCPA Member License a. Drug induced hypoglycemia NCPA Member No. ______State ______No. ______b. Daytime sleepiness q Nonmember State ______No. ______c. All fields below are required. Mail this form and $7 for manual processing to:NCPA, Attn: CE Processing; 100 Daingerfield Road Alexandria, VA 22314.Make check pay- d. Tinnitus able to NCPA. ______NABP eProfile ID MM-DD of birth Which of the following medication ______scenarios would put the patient at risk of Name ______driving impairment? Pharmacy name ______a. Using a benzodiazepine when a full night Address ______of rest is expected City State ZIP ______b. Using z-hypnotics when a full nights rest Phone number (store or home) is not expected ______Store e-mail (if avail.) Date quiz taken c. Taking a dose of a friend’s herbal medi- Quiz: Shade in your choice cation labeled for “sleep” a b c d e a b c d e d. All of the above 1. q q q q q 11. q q q q q 2. q q q q q 12. q q q q q 3. q q q q q 13. q q q q q Which of the following consultation tips 4. q q q q q 14. q q q q q to keep patients safe is most effective? 5. q q q q q 15. q q q q q a. If a medication package insert does not 6. q q q q q 16. q q q q q q q q q q q q q q q list alcohol as a contraindication, the 7. 17. 8. q q q q q 18. q q q q q combination of drug and alcohol poses 9. q q q q q 19. q q q q q no increased risk to the driver. 10. q q q q q 20. q q q q q b. Medication side effects which may impair driving always wear off with continued use. Quiz: Circle your choice c. If a patient has been taking his/her medi- 21. Is this program used to meet your mandatory C.E. requirements? a. yes b. no cation for a year or more, dose changes 22. Type of pharmacist: a. owner b. manager c. employee will not result in an increased potential for 23. Age group: a. 21–30 b. 31–40 c. 41–50 d. 51–60 e. Over 60 impairment. 24. Did this article achieve its stated objectives? a. yes b. no d. None of the above are true. 25. How much of this program can you apply in practice? a. all b. some c. very little d. none How long did it take you to complete both the reading and the quiz? ______minutes

NCPA® is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. NCPA has assigned 1.5 contact hours (0.15 CEU) 52 america’s PHARMACIST | AugustMarch 2012 2011 of continuing education credit to this article. Eligibility towww.americaspharmacist.net receive continuing education credit for this article expires three years from the month published.