The scope of oral medicine practice and practitioner competencies is euolutionary in nature. This section of Oral Medicine Quintessence International is committed to presenting evidence-based ciinical practice guideiines in coi- Clinical Practice Guidelines iahoration with oral and nanoral tiealtti care providers.

The patient with hypertension

Catherine K. Riley, DDS, MSVGeza T. Terezhalmy, DDS, MA^

Elevated blood pressure appears to be an affliction that is more ccmmon in developed than in developing countries. However, the blood pressure consistently increases with age in most pcpuiations in the world, modified only by genetic and environmentai factors. In tfie United States, it is estimated that there may be as many as 58 million people witb hypertension; fewer than 5% of these cases have a curabie cause. Oral health care providers can expect tc be caiied on to care for patients with this progressively debilitating dis- ease. To provide competent care tc patients with bypertensicn, clinicians must understand fbe disease, its treatment, and its impact on the patient's ability to undergo and respond to dental care, (Quintessence Int 2001;32:671-690)

ETIOLOGY AND EPIDEMIOLOGY Defects in sodium transport have also been described in hypertensive patients.^' Abnormal sodium Hypertension is characterized by the elevation of sys- transport across the eellular membrane increases tolic and/or diastolic arterial blood pressures and may intracellular sodium eoncentrations. Increased sodium be either primary or secondary'. Primary, or essential, concentration leads to increased intracellular calcium hypertension is of unknown etiology but appears to be ion concentration and increased vascular smooth related to hereditary and environmental factors. muscle sensitivity to sympathetic stimulation. Stimu- Although the exact mechanism is unclear, the heritable lation of the sympathetic nervous system raises the component of hypertension has been documented in blood pressure. Specialized cells located in the ¡uxta- familial and twin studies.' glomerular apparatus sense tubular sodium ion con- Environmental factors (dietary sodium, obesity, and centrations and signa! appropriate changes in glomer- stress) appear to increase the likelihood of hyperten- ular filtration rate and renin production." The juxta- sion in genetically susceptible persons. Several popula- glomerular apparatus also has a dense sympathetic tions are known to be prone to salt sensitivity, includ- nerve supply, and sympathetic stimulation has been ing African Americans, those with a family history of shown to increase renin synthesis,' hypertension, the obese, and the elderly''^ Studies have There is also evidence that hypertensive persons demonstrated that the prevalence of hypertension is sig- may have decreased nitric oxide activity. Nitric oxide nificantly higher in individuals who are overweight.^'^ is a vasodilating substance produced by endothelial cells.'" The mosaic theory holds that multiple factors sustain elevated blood pressure even though initially 'Assistant Professor, Department of Dentai Diagnostic Science, University of Texas, Health Science Center al San Antonro, Dentai Schooi, San only one aberrant factor may have been responsible.'' Antonio, Texas. Secondary hypertension may be associated with ^Professor, Department of Denial Diagnostic Science, Uniuersity ot Texas, renal artery stenosis, pheochromocytoma, hyperaldos- Health Science Center at San Antonio, Dental School, San Antonio, Texas. teronism, coarctation of the aorta, and the use of Rsprint requests: Dr Geza T Terezhalmy, Protessor, Department ot Den- drugs (alcohol, oral contraceptives, sympathomimet- tal Diagnostic Science, University ol Texas, Health Science Center at San Antonio, Dentai School, 7703 Fioyd Curi Drive, San Antonio, Texas 72484 ics, corticosteroids, cocaine, licorice [glycyrrhiza], E-mail: [email protected] and others).'^

Quintessenoe internationai 671 • Riley/Terezhalmy

Fig 1 Classjficafion system ff.' pressure adopted frain fhe fifth i the Joint Nafional Commiftee oc tion, Evaluation, and Treatment Blood Pressure.'"

Opttmai Normai High- Stage 1 Stage 2 Sfage 3 Sfage 4 ^ normal iHyperfension

Eievated blood pressure appears to he more com- Large-scale studies have also demonstrated a linear monly found in developed than in deveioping relationship between increasing blood pressure and countries.'^''* The biood pressure consistently increases cardiovascular diseases," Chief cardiovascular compli- with age in most populations in tbe world; this trend, cations include left ventricular hypertrophy, which however, is modified by genetic and environmental fac- progresses to cardiac myopathy, dilation, and ultimate- tors.'•'''" It is estimated that in the United States there ly failure, and arterioscierotic and atherosclerotic may be as many as 58 miilion people witb bypertension; changes in coronary arteries.^^"^'* Coronary artery dis- of tbese, probably fewer than 5% have a curable cause.^' ease leads to angina pectoris and myocardial infarc- tion. Hypertensive events (arterioscierotic vessel dis- ease and increased vascular resistance) increase tbe CLINICAL MANIFESTATIONS incidence of iscbemic and bemorrhagic stroke.-' The risk increases in a relatively constant fashion as the Primary hypertension is asymptomatic until complica- blood pressure increases,"* Peripheral vascular disease tions develop in target organs, particularly the kidney, is characterized hy the absence of one or more major cardiovascular system, cerebrovascular system, peripb- pulses in the extremities, while hypertensive retinopa- eral vascular system, and eyes. Common to tbe patho- thy is characterized by bemorrhages or exudates, with genesis in ali of these organ systems is vascular dam- or without papiliedema. age described histologically as either arteriolosclerosis or arteriosclerosis. Additionally, hypertension leads to increased atherosclerosis.^^ The kidney is a major tar- DIAGNOSIS get for the ill effects oí hypertension, although this damage may be occult until late in the progression oí The diagnosis of pritnary hypertension depends on ele- the disease.^' vated systolic and/or diastolic blood pressure in the Clinically, the ultimate pathophysiologic condition absence of secondary causes. Repeated determinations is hypertensive nephrosclerosis, characterized by of the blood pressure are obtained on eacb of 3 days decreased glomerular filtration and tubular dysfunc- before a patient is diagnosed as hypertensive according tion, which can progress to end-stage renal disease. to the classification system adopted by the fifth Joint Hypertensive nephrosclerosis may predispose patients, National Committee on Detection, Evaluation, and especially African American individuals, to refractory Treatment oí High Blood Pressure QNC-V) {Fig 1}.^' hypertension." When systolic and diastolic pressures fall into different

672 Volume 32, Number 9, 2001 Riley/Tereztialmy • categories, the higher category is used to determine TABLE 1 Basic evaluation recotnmended for treatment strategies. patients with elevated blood pressure^i-^s The basic evaluation recommended for patients diagnosed witb bypertension includes a review of the History medical history, physical examination, and laboratory • Duration of elevated blood pressure (it known] studies (Table l).''-^' • All prescribed and over-the-counter medications taken Fewer than 5'^/o of hypertensive patients have sec- • Any symptoms of target-organ disease (catdiovascuiar, cerebrovascuiar. renal, peripheral vascular disease, and ondary hypertension caused by pheocbromocytoma, retinopattiy] renovascular bypertension, primary aldosteronism, • Any symptoms suggesting secondary hypertension Cusbing's syndrome, or coarctation of tbe aorta.^' (pheochromocytoma, renovascular hypertension, primary Indications for specialized diagnostic procedures to aldosteronism, Cushing's syndrom. coarctation ot the aorta) rule out secondary hypertension are onset of hyper- • Family history ot hypertension, prematuie cardiovascular tension before age 30 or after age 60, diastolic blood disease, diabetes mellitus, or dyslipidemia pressure greater than 120 mm Hg, abrupt onset of • Social history of cigarette smoking, alcohol use or abuse, hypertension, hypertensive retinopathy, or refractory and sedentary lifestyle hypertension.^'-" Renovascular disease is the most Physicalexamlnation likely etiologic factor in younger and older patients • Blood pressure measurements at least twice (2 minutes suffering from severe hypertension. apart) with the patient either seated or supine, and atter standing for at least for 2 minutes • Verification of blood pressure in the contralaterai arm: if signilicant and consistent differences are found, the PRINCIPLES OF MEDICAL MANAGEMENT higher value is used • Examination of the optic tundi, heart, and abdomen Historically, physicians based treatment decisions on • Palpation of the renal areas tor masses tbe diastolic blood pressure. Yet systolic blood pres- • Auscultation far bruits in the neck and abdomen sure more reliably predicts cardiovascular morbidity • Palpation ot the peripheral pulses and mortality.^''-''' Elevated systolic pressure imposes a Laboratory studies greater burden on tbe heart tban does elevated dias- • Complete blocd count tolic pressure, potentially leading to heart failure. Tbe • LJrinalysis pulse pressure, which closely correlates with the sys- • Determinations of serum creatinine, sodium, pofassium, uric acid, calcium, lasting blood sugar, total cholesterol, tolic pressure, is a reliable cofactor.^' The "hammer- low-density and high-density lipoproteins, and fasting ing" effect of wide pulse pressure damages arterial triglycérides walls, contributes to atberosclerosis, and leads to tar- • Electrocardiogram tc evaluate the heart as a target organ get-organ damage. According to the sixth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI)^^:

Tbe goal of prevention and management of strategy includes restriction of daily dietary sodium hypertension is to reduce morbidity and mor- intake to 2 g of sodium or 5 g of sodium chloride; tality by the least intrusive means possible. weight reduction, when appropriate; limitation of This may be accomplished by achieving and daily alcohol intake to no more than 1 oz of ethyl maintaining systolic blood pressure below 140 alcohol; and participation in aerobic exercise, such as mm Hg and diastolic blood pressure below 90 brisk walking for 30 to 45 minutes, three to five times mm Hg and lower if tolerated, wbile control- per week.^* This strategy carries over to all stages of ling other modifiable risk factors for cardio- hypertension and tends to minimize the doses of anti- vascular disease. Treatment to lower levels hypertensive drugs required to achieve and maintain may be useful, particularly to prevent stroke, optimal blood pressure. Epidemiologic studies have to preserve renal function, and to prevent or shown tbat tbe optimal blood pressure is less tban slow beart failure progression. 120/80 mm Hg,'^''''^

Pharmacologie therapy Lifestyle modifications In an analysis of 12 studies, it was found that hyper- For patients with stage 1 hypertension and no evi- tension progressed to higher levels or caused left ven- dence of cardiovascular complications, tbe therapeutic tricular hypertrophy or congestive heart failure in

Quintessence International 673 Riley/Terezhalmy

TABLE 2 Risk-based strategies for the treatment ot hypertension^»

Risk group A Risk group B Risk group C * No risk factor • At ieast one • Target-org an * No target-organ risk factor, damage, clinical damage not including evidence of * No clinical diabetes mellitus cardiovascular evidence of • No target-organ disease, or cardioi/ascular damage diabeles meilitus, disease • No clinical evidence wifh or without of cardiovascular other risk factors Blood pressure disease • High-normal • Lifestyle • Lifestyle • Lifestyle 130/85 to 139/89 modification modification modification mm Hg only only • Drug therapy for those with heart failure, renal insufficiency, or diabetes mellitus • Hypertension: • Lifestyle • Lifestyle • Lifestyle Stage 1 modification modification modification 140/90 to 159/99 trial for up to trial for up to • Drug therapy mm Hg 12 months 6 months or • Drug therapy lor pafients with muitiple risk factors • Hypertension: • Lifestyle • Lilestyle • Lifestyie Stages 2 and 3 modification modification modification 160/100 mm Hg - Drug therapy • Drug therapy • Drug therapy ot greater

11,2% of the patients who received a placebo, com- TABLE 3 Initial drug choices for the treatment of hypertension^*"'-" pared with only 0.7% of the patients who received active drug therapy.-'" However, the urgency of start- Uncomplicated hypertension - Diuretics ing antihypertensive drug therapy depends not only or • Beta-ad re ne rgic blocking on the patient's blood pressure but also on his or her agents overall level of risk and evidence of target-organ Diabetes mellitus (type 1 ) • ACE inhibitors damage. Risk factors include smoking, dyslipidemia, with proteinuria diabetes mellitus, age greater tban 60 years, gender iHeart failure caused by • ACE inhibitors (men and postmenopausal women), and family histo- systolic dysfunction or • Diuretics ry of cardiovascular diseases in men younger than 55 Isolated systolic hypertension • Diuretics (preferred) years and women younger tban 65 years. Target- {older persons] or organ damage includes beart diseases (left ventricular • Long-acling hypertrophy, angina pectoris, previous myocardial dihydropyridine calcium channel-blocking agents infarction, previous coronary revasctilarization, and Postmyocardial infarction • Beta-ad re ne rgic biocking heart failure), nephropathy, peripheral artery disease, agent without intrinsic retinopathy, transient ischémie attacks, and stroke- sympathetic activity Based on these data, the JNC-VI devised a tbree- or ' ACE inhibitors for pafients tiered risk classification system for patients with with systolic dysfunction hypertension (Table 2).'» ACE = Angiotensin-coni/erdng enzyme. The JNC-VI report recommends diuretics and beta-adrenergic blocking agents as initial drugs of choice for the treatment of hypertension uncompli- cated by concomitant diseases.^^ These are still the only classes of drugs proven in large randomized prospective trials to reduce the incidence of cardio- vascular disease and death.-"-^^ The JNC-VI report

674 Voiume 32, Number 9, 2001 Riley/Terezhalmy •

emphasizes four compelling indications for using coronary heart disease, no association between other classes of drugs for the treatment of hyperten- markers of clinical inflamtitation and coronary heart sion (Table 3).-"^-52 if the systolic blood pressure is disease, and little evidence to suggest that treatment greater than 200 tiim Hg or the dlastolic blood pres- of oral infections affects the incidence of ischémie sure is greater than 115 mm Hg, a single agent is heart disease.™ Although further study of the iink unlikely to control the blood pressure satisfactorily. between periodontal disease and coronary bcart dis- Under these circumstances, antihypertensive therapy ease is necessary to determine the true nature of the is initiated with two agents concurrently. relationship, periodontai infection in patients with If a full dose of the initial drug has no effect on the hypertension appears to represent another major risk blood pressure or causes troublesome side effects, the factor for ischémie JNC-VI recommends substitufing a dntg from a differ- ent class. If the initial drug produces only a partial Lichenoid stomatitis response, but the drug is well tolerated, a drug from a different class (preferably a diuretic if not already Lichen planus {LP) is a relatively common infiamma- used) is added to the regimen. tory mucocutaneous disease of unknown origin. Oral LP may be reticular, characterized by fine white striae and/or papules found on intact oral tissues with mini- PREVALENCE OF ORAL DISEASE mal or no inflammation. Reticular LP is usually asymptomafic and Is most often discovered during a Periodontal disease roufine oral examination. Erosive oral LP is character- ized by an erythematous, atrophie oral epithelium. Large-scale studies have demonstrated a linear rela- Patients typically complain of soreness, pain, burning, tionship between increasing blood pressure and car- and inability to eat or drink spicy, acidic, or rough tex- diovascular diseases.^''"^" Chief cardiovascular compli- tured foods (tomatoes, citrus fruits, caffeine-contain ing cations include atherosclerotic changes in coronary beverages, or chips). arteries.^' It has also been noted that the classic risk The clinical appearance of lichenoid lesions is indis- factors (hypertension, diabetes mellitus, obesity, smok- tinguishable from oral LP (Figs 2a and 2b). Like oral ing, and dyslipidemia) associated with ischémie heart LP, these lesions most often affect the buccal mucosa, disease and stroke account for only one half to two gingivae, and lateral borders of the tongue. Various thirds of the cases.^** antihypertensive drugs, including thiazides, furosemide, Several observational studies have suggested a pos- spironoiactone, labetaiol, propranolol, metbyldopa, sible link between periodontal disease and coronary and captopril, bave been implicated as etiologic agents heart disease.^''"" Inflammation associated with perio- in tbe development of iichenoid lesions.''"" The diag- dontal disease provides an environment for transient nosis is confirmed when the condition resolves after bacteremias to occur during activities of daily living, the offending drug is discontinued. such as eating, toothbrushing, and ñossing. Invasion of the endothelial and smooth muscle cells of the arterial Xerostomia wall by bacterial pathogens could initiate and/or exac- erbate the inflammatory response of atherosclerosis, Xerostomia is a relatively common complication of which in turn could increase the formafion of arterial antihypertensive drug therapy {Figs 3a and 3b). plaques.^^'^' Current research suggests that periodontal Reduced salivary flow is generally related to a drug's disease may also play a role in the thromboemboHc parasympatholytic or antimuscarinic eftect. The site of aspect of coronary heart disease.^^-^' Oral bacteria acfion of these drugs may be in the central nervous such as Streptococcus sanguis and Porphyromonas system, at parasympathetic and some sympathetic gan- gingivalis may activate tbe coagulation system, thus glia and at parasympathetic and some sympathetic increasing the risk of a thromboembolic event via eftector junctions. Other related salivary gland prob- platelet aggregation.^"-^' lems may include drug-induced fluid and electrolyte It has been documented tbat patients with athero- imbalances, glandular vasoconstriction, and acinar or sclerotic disease tend to suffer from poor oral health ductal dysfunction. compared to controls matched for age, gender, and Chronic xerostomia may result in painfijl (burning) socioeconomic status,^^^'' and patients with ischémie oral soft tissue problems and poor tissue adaptation to heart disease and periodontai disease are at 1.5 to 2.7 prostheses. The patient may relate difticulties with mas- times higher risk of experiencing a fatal cardiovascu- ticafion, swallowing, and speech. As the dryness per- lar event.^^""-^^ A more recent report found only a sists, the oral mucosa becomes atrophie and susceptible slight positive association between periodontitis and to candidiasis and other superinfections. The reduced

Quintessence International 675 Riiey/Terezhalmy

Figs 2a and Zb Patieni with an ti hyper tensive d'ug-induced lichenotd stomatitis.

Figs 3a and 3b Patient v^ith antlhypertensive drug-induced xerostomia.

buffering capacity of the saliva also contributes to a high incidence of dental caries and affects the sensitivi- ty of taste buds, which contributes to dysgeusia. Antihypertensive agents with xerostomic side effects include diuretics; beta-adrenergic blocking agents such as propranolol; guanethidine;

Gingivai hyperplasia

Calcium channel blockers are used extensively for the management of hypertension. Nifedipine was the first such drug to be associated with gingival hyperplasia (Fig 4), Subsequent reports have confirmed the asso- Fig 4 Patient with antihypeitensive drug-induced gingivai fiyper- ciation and implicated most other calcium channel- piasia. blocking agents.^'-'*' Gingival enlargement is usually noted within 1 to 2 months after the initiation of

676 Volume 32, Number 9, 2001 Riiey/Terezhalmy • therapy and appears to affect primarily the labial and facial interdental papillae. TABLE 4 Essential elements of a patient's historical profile in the oral health care setting Although the enlarged tissue may be firm and pain- less, it is often associated witb erythematous and ede- Patient identification matous chronic inflammation. The patient may report • Demographic data pain, gingival bleeding, and difficulty with mastication because of the hyperplastic tissue. Chief complaint • Characfer, duration, progression, domain, and reiafion to physio i ogic tiinction

PRINCIPLES OF DENTAL MANAGEMENT Dental history • Frequency of derifai visits • Date ot most recent dental radiographie examination Goais • Types of care received • History of orofacial injuries (date, cause, and fype of Patients witb hypertension are at increased risk for injury} acute hypertensive syndromes {hypertensive encepha- • Difficuifjes with past treatment lopatby and aortic dissection), angina pectoris, myo- • Adverse reactions to iocal anesthetic agents, iatex cardial infarction, congestive heart failure, puimonary gloves, rubber dam, or dental maferiais edema, cerebrovascular accidents, renai failure, peri- Medical history pheral vascular disease, and hypertensive retinopathy. • Known drug-reiatad allergies and other adverse effects Although hypertension does not directly contribute to • Current medications, vitamins, dietary supplements, tbe prevalence of oral disease, periodontal disease or special diet • Serious illnesses, previous hospital i zati o ns, and appears to be a risk factor for atherosclerotic compii- significant surgery cations. Furthermore, pharmacotherapeutic interven- • A review of the organ systems tion to control hypertension may aftect orai tissues. When patients with hypertension are treated in an Family history • Diabetes mellitus, high blood pressure, heart disease, oral health care setting, the goals are to develop and seizure disorders, bleeding probiems, cancer, and other implement timely preventive and therapeutic strategies factors compatible with the patient's physical and emotional Social history ability to undergo and respond to dental care and tbe • Tobacco, alcohol, recreational drugs (type, amount, patient's social, psycbological, and emotional needs and frequency) and other factors and desires.

Patient assessment

According to tbe National Health and Nutrition Exam- These and other data indicate that oniy a minority ination Survey (NHANES III) conducted between of persons with hypertension are aware of it, receive 1988 and 1991, only 53% of bypertensive patients treatment for it, or have it under control.*^ This were receiving antihypertensive therapy, only 29% of should alert oral health care providers to the reality the patients with hypertension had their blood pressure tbat patients witb hypertension are not being diag- controlled to less than 140/90 mm Hg, and 35% were nosed or treated aggressively enough. Dentists must unaware that they even had hypertension."^ In another recognize the importance of their role in monitoring report, the NHANES estimated that, between 1991 the hlood pressure of known bypertensive patients and 1994, only 27.4% of patients with hypertension and the need for their active participation in detection had their blood pressure controlled to levels below efforts. 140/90 mm Hg.^^ Emerging evidence also suggests that, because hyper- Medicai history tension is undertreated, cases of end-stage renal disease continue to increase (hypertension is the second-leading Although 70% of patients with hypertension have cause, after diahetes melhtus).'"*' Recent epidemiologic stage 1 disease^' and their risk of experiencing a medi- studies have also found that the incidence of age-adjust- cal emergency in the dental office is relatively low, the ed stroke rates, after declining for many years, have risen other 30% represent a significant high-risk population slightly since 1993-^=^^ Hospitalization rates for heart and must be identified. The most important compo- iailure in older people have steadily increased over the nent of the pretreatment evaluation of the dental last 20 years and continue to increase.*^ The majority of patient is the establishment of a historical profile heart iailure patients have antecedent hypertension.^^ (Tahle 4). An initial medical history must be obtained

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from all patients, and it should be reviewed with the number of antihypcrtensive agents taker -'i' ^^•• patient at each appointment. patient the more labile the patient's hypertens:vc state. History or symptoms of cardiovascular, cerebro- Famiiy history. Family history of hypertens on, pre- vascular, renal, and ocular diseases. Although the mature cardiovascular disease (in men youni'T than causes and mechanisms of the development of hyper- 55 years and in women younger than 65 years), -"haöe- tension are still controversial, target-organ damage tes mellitus, or dyslipidemia are high-risk prédis; Mng from prolonged high blood pressure, particularly in factors to hypertension.'* . the kidneys, the heart, the cerebrovascular system, and Social history. Social history of ctgarette smokmg, the eyes, have been extensively elucidated.^^-^*"'^^ A his- drug use or ahuse (alcohol, oral contracephves, sym- tory or symptoms of cardiovascular disease (angina pathomimetics, steroids, cocaine, licorice, and others), pectoris, myocardial infarction, left ventricular hyper- or sedentary lifestyle are high-risk predisposmg factors trophy, left ventricular dysfunction, congestive heart to hypertension."" failure, or aneurysm), cerehrovascular disease (tran- sient ischémie attacks or stroke), renal disease (pro- Physical examination teinuria or serum creatinine greater than 1.5 mg/dL), or hypertensive retinopathy all suggest hypertension of Vital signs. The most important clue from the physical long duration. A history or symptoms of pheochromo- examination that will either confirm or rule out signif- cytoma, renovascular hypertension, primary aldostero- icant hypertensive disease Is the patient's blood pres- nism, Cushing's syndrome, or coarctation of the aorta sure. It sbould be recorded for all new patients at the may suggest the presence of secondary hypertension.'^ time of initial appointment and at all subsequent Drug history. Diuretics and beta-blockers are tbe appointments for all patients witb a bistory of hyper- recommended initial drug choices for hypertension tension, cardiovascular diseases, diabetes mellitus, thy- uncomplicated by concomitant disease.'"-'•^ However, roid disorders, adrenal disease, renal dysfunction, or tbere are a number of compelling indications for using significant use of tobacco, coffee, or alcobol. otber classes of drugs."""^^ A hypertensive patient taking Botb the systolic and diastolic pressures sbould be an angiotensin-converting enzyme (ACE) inhihitor is measured.^'-" If tbe blood pressure is abnormal, it likely to have type 1 diabetes mellitus with proteinuria. sbould be measured at least twice (2 minutes apart) The use of an ACE inhibitor or a diuretic may indicate wbile the patient is in eitber a supine or seated posi- concomitant beart failure with systolic dysfunction. tion, and it should be verified in the contralateral arm. Older patients with systolic hypertension will be taking If a significant and consistent difference is found, the a diuretic (preferred), or a long-acting dibydropyridine higher value should be recorded. In a nonpregnant calcium channel-blocking agent. The use of a beta- adult, a reading of 140/90 mm Hg or higber is byper- blocker or an ACE inbibitor may help to identify a tension. A drop in blood pressure to below 90/50 mm hypertensive patient who has suffered a myocardia! Hg is a reliable sign of sbock. infarction. There are also a number of otber, less com- The pulse pressure, wbich closely correlates with peliing indications for specific classes of drugs, such as the systolic pressure, is a reliable cofactor.^' Tbe bam- beta-blockers for hypertbyroidism, alpha-blockers for mering effect of the wide pulse pressure damages the dyslipidemia and prostatic hypertrophy, and calcium arterial walls, contributes to atherosclerosis, and leads antagonists for cyciosporine-induced hypertension in to target-organ damage. The rate, rhythm, and force of patients who have received an organ transplant. the pulse should be checked for a full minute after the In clinical practice, the treatment of hypertension patient has been comfortably seated. Tbe "at-rest" involves a sequential care program, which may consist pulse rate for an adult should be 60 to 72 beats per of lifestyle modification'^ and use of one or a number minute. Any adult who has an at-rest rate of less tfian of agents in a predetermined regimen to be modified 50 or greater than 120 (if symptomatic: sweating, on a regular basis as clinical judgment dictates.'* If the weakness, dyspnea, and/or chest pain) should be initial drug prescribed for the treatment of byperten- treated as an emergency. sion produces only a partial response but is well toler- In patients with hypertension, coronary heart dis- ated, another drug from a different class, preferably a ease, congestive heart failure, and valvular disease, diuretic if not already used, is added to tbe regimen. If premature ventricular contractions, characterized by a tbe systolic blood pressure is greater than 200 mm Hg pronounced pause in an otherwise normal rhythm, are or the diastolic blood pressure is greater tban 115 mm a significant finding. The incidence of premature ven- Hg, a single agent is unlikely to satisfactorily control tricular contractions may increase with age, fatigue, the blood pressure. Under these circumstances, antihy- emotional stress, and the use of coffee and tobacco pertensivc therapy may include the concurrent use of and may also be an occasional, insignificant finding in two or more agents. It is axiomatic that the greater the healthy adults.

678 Volume 32, Number 9, 2001 Riley/Terezhalmy •

TABLE 5 Preventive and therapeutic strategies for the management of iiypertensive patients in the oral health care setting

Blood pressure Strategies 120/eO mm Hg or less • Optimal blood pressure • Record BP at each recall appointment. • Risk status 1 • Provide routine office care. 130/85 mm Hg or less • Normal blood pressure • Reoord BP at each recall appointment - Risk status 1 • Provide routine otfice care. 130/35 to 139/69 mm Hg • High-normal blood pressure • Record BP at each recali appointment. • Risk status 1 • Provide routine office care. 140/90 to 159/99 mm Hg • Stage 1 hypertension * Record BP at each appointment. - Risk status II' • Provide routine office care: • Medically stable • Record BP after local anesthesia • No limitation on physical with epinephrine. activity • Provide routine medical referral. 160/100 to 179/109 mm Hg • Stage 2 hypertension • Record BP at each appointment. • Risk status III: • Provide limited office care. • Medically stable • Record BP after local anesthesia • Limited tolerance for exercise with epinephrine. • Provide routine medicai referrai. 180/110 to 209/119 mm Hg * Stage 3 hypertension • Record BP • Risk status IV: • Provide emergency office care: • Medical i y unstable • Monitor BP during treatment • Very limited toierance for • Use local anesthesia without exercise epinephrine • Provide urgent medical referral. 210/120 or greater - Stage 4 hypertension • Record BP, - Risk status V: • Provide emergency office care: • No tolerance for exercise * Monitor BP during treatment • Hypertension is constant • Use locai anesthesia without threat to life epinephrine. • Provide emergency medical referral. BP r^ Blood pressure.

Preventive strategies be alert for tbe onset of adverse reactions, particularly during drug administration. Preventive medicinG. Prior to tbe initiation of dental Use of local anesthetic agents. Local anestbetics treatment, reasonable control of bypertension should sbould always be administered slowly, and measures be assured (Table 5). Long, stressful procedures should must be taken to avoid accidental intravascular injec- be avoided. Psychosedation, ora! (benzodiazepines) tions. Tbe selection of a local anesthetic agent and the sedation, or inhalation (nitrous oxide) sedation may type and concentration of the vasoconstrictor, particu- be helpful to reduce anj;iety. If nitrous oxide is admin- larly in the management of patients with cardiovas- istered, adequate oxygénation (35% nitrous oxide: cular disease, is the topic of considerable debate."-'"^ 65% oxygen) must be used to avert rebound hyperten- Several investigators have found no significant in- sion secondary to hypoxia. During treatment, the clin- crease in blood pressure during dental treatment'"*-™ ician should always observe the patient's response and In one study comparing blood pressures during dental

Quintessenceinternatlonai 679 Riley/Terezhalmy

examination and dentai treatment, a mean diñerence duce drug-drug, drug-disease, or drug-food ra'^ of only 8 tnm Hg (systolic) and 1 mm Hg (diastolic) tions or drug-induced illness. was noted with the most traumatic procedure {oral Preventive dentistry. Plaque removal. Den -i": surgery).'"^ Mean changes related to restorative den- agement plans for patients with hypertension should tistry were 4 mm Hg (systolic) and 3 mm Hg (dias- include appropriate preventive strategies. Such i^trate- tolic). Another report concluded that while the actual gies should take into considerafion toothbrush -sign administration of the local anesthetic agent may pro- and technology to increase the effectiveness of pi.que duce a transient increase in blood pressure, the hlood removal For patients with average dextertty, no spectf- pressure decreases after the needle is removed from ic manual toothbrush design has been shown to be the mouth."" superior for plaque removal.'" The new electro- A recent report presented an antipodal approach to mechanical brushes employ variations of a rotary or resolve the issue of safety, as it relates to the use of oscillating motion at a "sonic" speed. In both short- local anesthetic agents containing a vasoconstrictor."' term and long-term studies, electromechanical brushes The investigators started with the proven premise that have been shown to be more effective than conven- exercise capacity is a simple and reliable index to esti- fional brushes in reducing plaque and gingivitis in all mate cardiac function in patients with heart disease."^ age groups.""-"^ They compared the cardiovascular effects of infiltrafion In three clinical studies designed to determine anesthesia, 2% lidocaine with epinephrine (1:80,000), whether the use of an ultrasonic toothbrush was supe- with those produced by ergometric exercise. rior to a manual toothbrush in removing supragingival The hemodynamic eftects of infiltration anesthesia, plaque and reducing gingiva! bleeding, it was found 72 mg of lidocaine and 0.045 mg of epinephrine, were that in individuals with average motivation, compli- less than those produced by ergometer stress tesfing at ance, and abilifies, the ultrasonic toothbrush was high- 25 W in young pafients and at 15 W in older subjects. ly efi'ective in removing plaque and reducing the bleed- In this study, there were no differences in hemody- ing index.'^'-'^ä Another study confirmed that the ultra- namic responses (evaluated by echocardiography) sound generated by the toothbrush alters Streptococcus between normotensive and hypertensive patients. The mutans ceil wall and intracellular components and workload of ergometer stress testing at 25 W in inhibits the adherence of S mutans to the enamel sur- younger patients and at 15 W in older subjects is less face.'^" The ultrasonic toothbrush improves gingival tban 4 metabolic equivalents (METS)."' health and may reduce systemic dissemination of oral Tbe vaiued of 4 METS is approximately equivalent infection, independent of operator skills. A recent to tbe workload produced by walking 4.8 k/h, doing design modification to the ultrasonic toothbrush used light yard work (raking leaves, weeding, or pushing a in the aforementioned studies (Ultrasonex ultrasonic power mower), painting, or doing light carpentry. "••-"* tootbbrush, Sonex) added an 18,000 strokes per Based on this report, local dental anesthesia, lidocaine minute sonic carrier wave to the previous 1.5-MHtz 2% (72 mg) with epinephrine 1:80,000 (0.045 mg) can ultrasonic wave, which may futiher enhance scrubbing be administered safely to patients who have exercise and foaming action for plaque removal. capacity of 4 METS or more (can tolerate the afore- Fluorides. For hypertensive patients with xerostomia mentioned activities with minimal or no symptoms and a high incidence of dental caries, preventive such as shortness of breath, chest pain, or fatigue). modalities such as dietary analysis, and dietary coun- Based on the US formulafion of local dental anesthet- seling, and prophylaxis should he combined witb over- ic agents, 0.045 mg of epinephrine is equivalent to 5 the-counter home ftuoride use. The use of topical fluo- mL of a local dental anesthetic agent with epinephrine ride gel in a carrier is another alternative, however, 1:100,000. This study provides a scienfific rather than more cooperation is required from the patient. The an anecdotal basis to the clinical observation that the application of topical fluorides, including a 5% fluoride critical determinant for the safe use of local anesthefic varnish, should be part of office-hased preventive care. agents containing a vasoconstrictor is the patient's Sialagogues. Qualitative and quantitative changes in abiUty to tolerate physical and/or emotional stress and saliva lead to reduced lubrication, antibacterial, antivi- not the diagnostic label. ral, and antifungal activity; loss of mucosai integrity; Adverse drug effects. It bas been emphasized loss of buffering capacity; reduced lavage and cleans- repeatedly that therapeutic agents seldom exert their ing of oral fissues; interference witb normal remineral- beneficial effects without also causing adverse drug ization of teeth; and altered digestion, taste, and effects. An awareness of the various medications com- speech. Patients with xerostomia whose salivary glands monly prescribed for patients with hypertension will can respond to stimulation may henefit from simple assist clinicians to anticipate these potential adverse dietary measures such as eating carrots or celery or drug effects and avoid prescribing drugs that may pro- from chewing sugarless or xylitol-containing gums.

680 Volume 32, Number 9, 2001 Riley/Terezhalmy •

Pilocarpine hydrochloride, 2.5 mg to 5.0 mg, mm Hg) are classified as ASA risk status III. Tbey are administered orally in two to six increments up to a medically stable, but tbey usually have limited exercise maximum daily dose of 30.0 mg (see Drug Mono- tolerance characterized by symptoms such as short- graph, page 689), may more predictably increase sali- ness of breath, chest pain, or fatigue. These patients vary activity. Recently, cevimeline bydrochloride {see may undergo limited office care under local anesthesia Drug Monograph, page 690}, an acetylcholine deriva- with a vasoconstrictor in the amount compatible with tive, has been approved by tbe US Food and Drug the patient's ability to tolerate pbysical and emotional Administration for the treatment of dry mouth caused stress. Limited office care may include dental prophy- by Sjogren's syndrome. Presumably it could also be laxis, restorative procedures, simple periodontal and used to treat drug-induced xerostomia. In tbose endodonfie procedures, and roufine extractions. patients with no residual salivary gland function, sali- The ASA risk status IV patient. Patients with stage vary substitutes, oral moisturizers, and artificial saliva 3 hypertension (blood pressure of 180/110 to 209/119) may provide some relief for xerostomia. arc classified as ASA risk status IV. They are medically unstable and usually have very limited exercise toler- Therapeutic strategies ance. Tbese patients are candidates for emergency office care under local anesthesia without a vasocon- The treatment plan for a patient with hypertension strictor. Such care should be based on firm evidence should be compatible with the patient's physical and that the benefits achieved by therapeutic intervention emotional ability to undergo and respond to dental outweigh the risk of complications associated with the care and the limitations imposed on the clinical hypertensive state and may include activities related to process by such preventive strategies as the length of pain relief, the treatment of infection (may include the appointment and the formulation and maximum simple incision and drainage), and the induction of allowable dose of the local anesthetic agent (see Table hemostasis. The use of epinephrine for the control of 5). A system ot risk status classification, adopted by local bleeding should be avoided. the American Society of Anesthesiologists (ASA), is a The ASA risk status V patient. Patients with stage valuable instrument for risk management in the oral 4 hypertension (blood pressure of 210/120 mm Hg or health care setting. The primary purpose of the ASA greater) have no tolerance for physical and emotional classification is to quickly and easily place each stress. Their hypertensive state is usually an immediate patient into an appropriate risk category and thereby threat to life. Any therapeutic intervention (limited to provide guidelines for the course of therapy. The clas- pain relief, the treatment of infection [may include sification is flexible, and the clinician should develop a simple incision and drainagcj, and the induction of realistic, common sense approach to its use in den- hemostasis [avoiding the use of epinephrine for the tistry. By definition, a patient classified as ASA risk control of local bleeding]) should be based on firm status I has no overt systemic disease. evidence tbat the benefits achieved hy therapeutic The ASA risk status II patient. The goal of preven- intervention outweigh the risk of complications asso- tion and management of hypertension is to reduce ciated with the hypertensive state. morbidity and mortality hy the least intrusive means possible- This may be accomplished by achieving and Hypertensive urgencies and emergencies maintaining systolic blood pressure of ¡ess than 140 mm Hg and diastolic blood pressure of 90 mm Hg or Any disorder that causes hypertension can give rise to lower if tolerated, while controlling other modifiable a hypertensive urgency or emergency (Table 6).'^^ A risk factors for cardiovascular disease. These patients hypertensive urgency is defined as a situafion in which by definition are ASA risk status II. They are medical- the blood pressure should be lowered within a few ly stable and they usually have no limitation on physi- hours.'^2 Patients presenting with significantly raised cal activity. Patients with stage 1 hypertension (blood blood pressure but without evidence of target-organ pressure of 140/90 to 159/99 mm Hg) are also classi- injury need urgent, but not emergency, blood pressure fied as ASA risk status II (medically stable and usually reduction. This can be achieved by the use of oral have no limitation on physical activity). The type and agents without intensive monitoring. A hypertensive extent of therapeutic intervention to eliminate the oral emergency is defined as a situation that requires disease burden in these patients requires minimal if immediate blood pressure reduction to prevent or any deviation from comprehensive office care, and, limit target-organ damage.'^^ Patients with target- consequently, no hypertension-specific modifications organ damage, such as hypertensive encephalopathy of the treatment plan arc indicated. or aortic dissection, require emergency blood pressure The ASA risk status III patient. Patients with stage reduction witb parenteral drug therapy and intensive 2 hypertension (blood pressure of 160/100 to 179/109 monitoring.

Quintessence international 681 • R il Gy/Terezhalmy vasodilation.'^' Nitric acid is released under TABLE 6 Potential causes of hypertensive ence of endotheliai agonists such as acety syndromes norepinephrine, and substance P.''« Nitric acri is also Essential hypertension released hy the endotheiium in response to mechani- • No discernible organic cause cal forces such as shear stress. Drug-related causes When hypertension is sustained or severe, tí c com- • Ant i hypertensive drug withdrawal pensatory endotheiial vasodilator responses are -over- • Cocaine whelmed, leading to endotheiial decompensation, • Sympathomimeticagents which promotes lurther rise in blood pressure and hir- • Cyclosporine tber endotheiial dysfunction. The exact cellular mecha- • Eryfhopoietin nisms leading to loss of endotheiial function in acute • Drug-drug interactions (Monoamine oxidase inhibitors, hypertension are poorly understood, but putative amphetamines, ginseng, St John's wort] mechanisms include proinflammatory responses Renovascular disease induced by angiotensin II, cytokines, and monocyte • Henal attery stenosis cbemotactic protein I; increased endotbehal-ceil Renal parenchymal disease cytosoiic calcium concentrations; release of the vaso- • Acute glomerulonephritis, uasculifis, hemoiytic uremic constrictor endotheiin 1; and upregulated expression of syndrome, and thrombotic thrombocyfopenic purpura endotheiial adhesion molecules.'""'^' Piatelet aggrega- tion and degranulation on damaged endotheiium pro- Pregnancy • Eclampsia mote iurther inflammation, vasoconstriction, and thrombosis. Ultimately, these molecular events trigger Endocrine disorders increases in endotheiial permeahility, inhibit local • Cushing's syndrome, pheochromocyfoma, and endotheiial fibrinoiytic activity, activate the coagulation renin-secreting fumors cascade, and result in acute target-organ damage. Central nervous system disorders IÍ inadequately treated, a hypertensive syndrome • Head injury, infection, hemorrhage, and brain tumors (urgency or emergency) can progress to cerebral hem- Autonomie hyperactiwity orrhage, coma, and death. In the medical setting, the • Guiilain-Barré syndrome and acute intermittent porphyna patient's history and results oí the physical examina- tion determine the nature, severity, and subsequent management of acute hypertension syndromes (Tahle Supervised long-term treatment of hypertension 7). In the oral health care setting, clinicians must lowers tbe incidence of hypertensive complications.'" recognize symptoms and signs associated with a Preexisting chronic hypertension may lower the proba- hypertensive crisis and initiate first-response therapy bility of a hypertensive urgency or emergency at a par- appropriate íor the setting (Table 8). ticular blood pressure through adaptive vascular changes that protect end organs from acute changes in Hypotensive emergencies the blood pressure. Conversely, in patients without pre- existing chronic bypertension, a hypertensive urgency Orthostatic hypotension. When a patient assumes an or emergency can develop at substantiaily iower blood upright posture, approximately 500 to 700 mL of pressures.'^- Patients with unrecognized bypertension blood is pooled in the lower extremities and in the or undertreated hypertension are at increased risk for splanchnic and pulmonary tissues. In response to this the development of hypertensive urgencies or emergen- decrease in the venous blood return to the heart, there cies, as well as their more insidious consequences. is a transient reduction in cardiac output and reflex The pathophysiology of hypertensive syndrome is stimulation of the cardiopulmonary, aortic, and unclear, but a rise in vascular resistance seems to be a carotid baroreceptors, wbich in turn increase sympa- necessary initial step. Increased vasoreactivity can be thetic outflow and inhibit parasympatbctic activity.'''^ precipitated by the release of vasoconstrictive suh- As a result, the heart rate and vascular resistance stances such as angiotensin II or norepinephrine or increase to maintain the systemic blood pressure. can occur as a result of relative hypovolemia. There is Orthostatic hypotension may result from an excess evidence that angiotensin II activates tbe expression reduction in blood volume when the patient is upright of genes for proinflammatory cytokines that have or from inadequate cardiovascular compensation for direct cytotoxlc efiects on vascular endothelium.'"•"'' the deciine in cardiac preioad associated with the Endothelial cells contribute to blood pressure home- change to an upright posture. Patients become predis- ostasis by secreting substances such as nitric acid and posed to orthostatic hypotension as a result of age- prostracyclin, which modulate vascular tone through related physiologic changes and diseases or medications

682 Voiume 32, Number 9, 2001 Riiey/Terezhalmy • that impair the homeostatic mechanisms of blood pres- TABLE 7 Factors affecting the management of sure regulation. hypertensive syndrome in a medical setting The adverse effects of antihypertensive medications are among the most common etiologic factors associ- History ated with orthostatic hypotension. The medications • Duration and severity of preexisting hypertension include diuretics, antihypertensive medications with • Presence of end-organ damage (cardiovascuiar, central nervous system effects (such as clonidine and renal, and cerebrovascular) • Details ot antihypertensive drug therapy methyldopa), and those with peripheral vasodilatory • Degree of blood pressure controi actions (such as prazosin, hydralazine, and guanethi- • intake of over-the-counter preparations such as dine). Orthostatic hypotension often occurs at thera- sympathomimetic agents and hertial medicine peutic blood levels of these medications. • Use of illicit drugs such as cocaine Orthostatic hypotension is commonly defined in Symptoms suggesting end-organ compromise the medical literature as a decline of 20 mm Hg or • Chest paih (myocardial ischemia or infarction: aortic more in the systolic blood pressure or 10 mm Hg in dissection) the diastolic blood pressure and tbe presence of • Dyspnea (pulmonary edema or congestive heart faiiure] accompanying symptoms of cerebral bypoperfusion on - Lethargy, cohfusion, headache, visual disturbances (inciuding blindness), and seizures (hypertensive tbe assumption of an uprigbt posture. A reduction of encephalopathy) 20 mm Hg or more in the systolic blood pressure Blood pressure within 3 minutes of standing up has been sbown to be • With patient in both supine and standing positions a significant risk factor for syncope and falls.'''^'''•' (if possible) to assess for volume depletion Anotber study concluded tbat a decline of 20 mm Hg • in both arms: a significant difference raises ihe or more in the systolic blood pressure within 3 to 4 suspicion of aortic dissection minutes of a change from a sitting to a standing posi- tion is associated with an excess 5-year mortality rate in diahetic patients with hypertension. Medications TABLE 8 Diagnosis and treattnetit of hypertensive and diseases, particularly hypertension and its seque- crisis in an oral health care setting lae, appear to be major determinants.'"'^ Consequently, any decline of 20 mm Hg or more in the systolic blood Symptoms and signs Treatment pressure of patients witb bypertension sbould be con- • Restlesshess - Elevate head. sidered a potentially dangerous hypotensive response. • Flushed face • Administer oxygen Orthostatic hypotension, often observed in older • Headache (6 L/min by nasal cannula). patients, may resuh in substantial morbidity and mor- • Dizzihess • Administer nitroglycerin tality from associated syncope and falls. The lack of • Tinnitus (0.4-mg tablet/spray, sublirigually]. • Biood pressure • Activate emergency medicai symptoms associated with orthostatic hypotension in > 180/110 mm Hg services (rapid transport]. susceptible patients sbould prompt oral health care • 'Hammering" pulse • ii/onitor vital signs (blood pressure. providers to take preemptive action. Because meals • Altered mental state pulse rate, and pulse character). and many antihypertensive medications can cause • Chest pain major blood pressure reductions in susceptible (espe- cially elderly) patients,"'^ it is prudent to scheduie den- tal appointments 30 to 60 minutes after the ingestion TABLE 9 Diagnosis and treatment of orthostatic of meals and medications. hypotension in an oral health care setting The blood pressure and pulse rate should be deter- mined after the patient has been in a supine position for Symptoms and signs Treatment at least 5 minutes to ensure a stable base line. Following • Lack of symptoms • Return patient to supine position. completion of dental treatment, tbe blood pressure and in susceptibie patients • Administer oxygen pulse rate should be measured after the patient is • Syncope when the ¡6 L7min by nasal cannula). allowed to assume a sitting position for at least 2 min- patient assumes an * Monitor vitai signs utes and then allowed to stand for 2 minutes. Some upright posture (blood pressure, pulse rate. patients with orthostatic hypotension have an immedi- • Decline of 20 mm Hg and puise character]. ate decline in blood pressure on standing, whereas oth- or more in the systolic • Allow patient to assume a ers have incremental declines that are usually evident biood pressure sitting position for at ieast after 2 minutes.'« In the oral health care setting, clini- or 2 minutes. • Oaciineof 10 mm Hg • Ailow patient to stand for cians must recognize symptoms and signs associated or more in the diastolic 2 minutes. with orthostatic hypotension and initiate first-response blood pressure therapy appropriate for the setting (Table 9).

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REFERENCES TABLE 10 Diagnosis and treatment of cardiogenic shock in an oral healthi care setting 1. Corvoi P, Jeuneinaitre X, Ciiarru N, Kotc!'' Symptoms and signs Treatment Soubrier F. Role of renin-angiotensinogen syster pressure regulation and in human hypertensi • Lethargy, confusion • Keep the patienf warm, with the insights from molecular genetics, Rec Prog H Res and somrioience legs raised siightly to improve t995;50:287-308. • Cold, moist and often venous return. 2. McNight [A, Moore T]. The effect of dietary f'aci rs on cyanotic hands and • Check airway and ventilation; blood pressure. Compr Ther 1994;20:511-517. feet provide supplemental oxygen by 3. Law MR, Frost CD, Wald NJ. By how much does dietary • Weak and rapid pulse lacemask immediately sait reduclion lower blood pressure? Ill, Analysis of data (tachycardia unless • Activate emergency medical from trials within populations. BM| 1991;302:819-824. heart biock or terminal services. The patient's baseline 4. Pan WH, Nanas S, Dyer A, et al. The role of weight in the bradycardia is present) pulse and blood pressure, the positive association between age and blood pressure. Am J • Engorged and current pulse rate and character. Epidemiol 1991;124:621-523. distended neck veins the blood pressure, other signs 5. Beilin LJ. Non-pharmacological management of hyperten- • Tachypnea (Apnea may or symptoms, and current sion: Optimal strategies for reducing cardiovascular risk, be a terminal event) medications and dosages I Hypertension 1994;t2(suppl 10):S71-SSt. • Hyperventilation and should be relayed to the medical 6. Hilton PJ. Cellular sodium transport in essential hyperten- signs of pulmonary personnel. sion. N EngI J Med 1986;3t4:222-229. congestion • Severe pain may be treated with 7. Bell PD, Mashburn N, Unlap MT Renal sodium/calcium • Dilated and morphine. (Administer 3 to 5 mg exchange: A vasodilator that is defective in s alt-sensitive nonreactive pupils intravenously over 2 minutes; may hypertension. Acta Physiol Scand 2000; 168:209-214. • Systolic blood pressure be repealed in 15 to 20 minutes if 8. Grienling KK, Alexander RW. Cellular mechanisms in less than 90 mm Hg there is no evidence of respiratory angiotensin H action. In: Swales JD (ed). Textbook of or a value of 30 mm Hg depression.] Hypertension, ed 1. London; Blackwell Scientific, 1994;11; below basal levels for • It at any time the patient loses 244-252. at ieast 30 minutes consciousness, initiate basic life 9. Lindop GB. The effects of hypertension on the structure of • Chest pain support. human resistance vessels. In; Swales JD (ed). Textbook of Hypertension, ed 1. London: Blackwell Scientific, 1994; 663-669. 10. Granger VP, Alexander BT. Abnormal pressure natriuresis in hypertension; Role of nitric oxide. Acta Physiol Scand 2000:168:161-168. 11. Takeda R, Myamori 1. Endocrine and auto-paracrine factors Cardiogenic shock. Tbe syndrome of cardiogenic in the pathogenesis of primary hypertension. Hypertens sbock has been defined as the inability of the beart (as Res 1995;18;171-179. a result of impairment of its pumping function) to 12. Compese VM, Nosrati S. Diagnosis and evaluation of sec- deliver sufficient blood to the tissues to meet resting ondary hypertension. Clin Cornerstone 1999;2;27-39. metabolic demands."' A presumptive diagnosis of car- 13. Carvalho JJ, Baruzzi RG, Howard PF, et al. Blood pressure diogenic sbock is indicated by low systolic blood pres- in four remote populations in the Intersait Study H™er- tension 1989;14;238-247. sure (less tban 90 mm Hg or a vaiue 30 mm Hg below basal levels for at least 30 minutes); evidence of poor 14. Poulter NR, Sever PS. Blood pressure in other populations In; Swales JD (ed). Textbook of Hypertension, ed 1. tissue perfusion such as cyanosis, cold extremities, or London' Blacicwell Scientific Publications, 1994;22, altered mentation; and tbe size and responsiveness of 15. Cost E, Rose G. IGein C, et al. Sah and blood pressure in the pupils to light (the pupils are dilated).''*'^ Cardio- Rio Granee do Sul, Brazil, Buli Pan Am Health Orean genic shock is generally associated witb left ventricu- 1995 ;24; 159-176. lar infarction.'^"-'^^ Compared witb patients wbo have 16. Joffres MR. Hamet P, Rabkin SW, Gelsky D, Hogan K, acute myocardial infarction without cardiogenic Fodor G. Canadian Heart Health Surveys Research Group! Prevalence, control and awareness of high blood pressure shock, patients who have shock are older, more often among Canadian adults. Can Med Assoc ] I992146- have had a previous infarction, and more commonly 1997-2005, have a history of angina pectoris, congestive heait fail- 17, Silagy CA, McNeil ]H. Epidemiologie aspects of isolated ure, and diabetes meliitus.'""'^*' systolic hypertension and implications for future research When there is evidence of inadequate tissue perfu- Am J Cardiol 1992;69:213-218. sion, resuscitative and supportive efforts should be ini- 18. Tiiomilehto J, Zimmet P, Taylor R, Bennett P Kana- tiated immediately. In the orai health care setting, clin- kaanpaa J, Wolf E. A cross-sect ion a I analysis of blood pres- icians must recognize symptoms and signs associated sure and Its determinants in eleven Pacifie populations | AmCollNutrl989;8;151-165. with cardiogenic shock and initiate first-response ther- apy appropriate for the setting {Table 10).

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54 Beck JD, Offenbacher S, Williams R, Gibbs P, Garcia R. 75. Robertson Wfi, Wray D. Ingestion of medicatiim amo'i^ Periodontitis: A risk factor for coronary heart disease. Ann patients with oral kératoses including lichen planus. fral Periodontol 1998;3:127-141. Surg Oral Med Oral Pathol 1992;74:183-185, 55. Syrjancn J, Peltola J, Valtonen V, livannnainen M, Kaste 76. Hay KD, lieade PC. Spectrum of oral disease induced by M, Huttunen JK. Dental infections in association with drugs and other bioactive agents. Drugs 1982;2ti 268-277. cerebral infarction in young and middle-aged men. J Intern 77, Eversole LE. Aliergic stomatilides. J Oral Mci: [979;34: Med 1989:25:179-184. 93-102. 56. Mattiia K], Nieminen MS, Valtonen V, et al. Association 73. Reed WD, Becker SW, Lichenoid drug eruptioi. from between dental health and acute myocardiai infarction. Br gold, chroroquine, and chlorothiazide. GP 1962:25: MedJ 1989:298:779-781. 118-123. 57. Genco RJ. Periodontal disease and risk for myocardial 79. Van Dis ML, Parks ET. Prevalence of oral lichen planus in infarction and cardiovascular disease. Cardiovasc Rev Rep patients with diabetes mellitus. Oral Surg Oral Med Oral 1998;19:34-40. Pathoi 1995:79:696-700, 58. Dorn BR, Dunn WA, Progulske-Fox A, Invasion of human 80. Zelickson BD, Rogers RS. Oral drug reactions. Dermatol coronary artery ceiis by periodontal pathogens. Infect din 1987:5:695-708, Immun 1999:67:5792-5798. Glass BJ, Van dis ML, 1.anglais RP, Miies DA. Xerostomia: 59. Beck JD, Pankow ), Tyroler HA, Offenbaeker S. Dental Diagnosis and treatment pianning considerations. Oral infections and atherosclerosis. Am Heart J 1999:158' Surg Oral Med Oral Pathol 1984:5:248-252, S528-S533. Schubert MM, Izutsu KT. latrogenic causes of salivary 60. Vaitonen VV. Role of infection in atherosclerosis. Am gland dysfunction. J Dent Res 1987:66:680-688. Heart I 1999;138:S431-S453. Felder RS, Miilar SB, Henry RH. Orai manifestations of 61. Position Paper, the American Academy of Peri odontology. drug therapy. Spec Care Dent 1988;May-June:l 19-124, Periodontai disease as a potential risk for systemic disease. Sreebny LM, Vaidini A, Yu A. Xerostomia. II. Relationsbip JPeriodontoi 1998:69:841-850. to nonoral symptoms, drugs, and disease. Oral Surg Oral 62. Nery EB, Meister F, Eliinger RF, Eslami A, McNamara TJ. Med Oral Pathoi l989;68:419-427 Prevalence of medical problems in periodontal patients Persson RE, Izusu KT, Truelove EL, Rersson R. Differences obtained from three different populations. J Clin Periodon- in salivary rates in elderly subjects using serostomic medi- toi 1987;5R:564-568. cations. Oral Surg Oral Med Oral Pathol 1991:72:42-46. 63. DeStefano F, Anda RF, Kahn HS, Williamson DF, Russell Hassell TM, Hefti AF, Drug-induced gingival overgrowth: CM. Dental disease and risk of coronary heart disease and Oid probiem, new probiem. Crit Rev Oral Biol Med 1991: mortality. Br Med J 1993:306:688-691. 2:103-137 64. Mattila KJ, Vaiie MS, Nieminen MS, Valtonen VV, Rees TD, Levine RA. Systemic drugs as a risk factor for Hietaniemi DL. Dental infections and coronary atheroscle- periodontal disease initiation and propogation. Compend rosis. Atherosclerosis 1993:103:205-211, Contin Edue Dent 1995; 16:20-42. 65. Umino M, Nagao M. Systemic diseases in elderly dental Burt VL, Whelton P, Roccelia EJ, et al. Prevalence of patients. Int Dent J 1993:43:213-218. hypertension in the US aduit population. Resuits from the 66. Mattila KJ, Valtonen VV, Nieminen M, Huttunen JK. Third National Heaith and Nutrition Examination Survey, Dental infection and the risk of new coronary events: 1988-1991. Hypertension 1995:25:205-313. Prospective study of patients with documented coronarj' National Center for Health Statistics. Health, United artery disease. Clin Infect Dis 1995;20:588-592. States, 1996. Hyattsvilie, MD: US Public Health Service, 67 Joshipura KJ, Rimm EB, Dougiass CW, Trichopoulos D, 1997 Ascherio A, Wiilet WC. Poor oral health and coronary 90. National High Blood Pressure Education Program heart disease. J Dent Res 1996:75:1631-1636, Working Group. 1995 Update of the Working Group 68. Beck JD, Garcia RI, Heiss G, Vokonas PS, Offenbacher S. Reports on Chronic Renal Faiiure and Renovascular Periodontai disease and cardiovascular disease. J Peri- Hypertension. Aich Intern Med 1996; 156:1938-1947. odontol 1996:67:1123-1137 gj US Renal Data System, USRDS 1997 Annual report. 69. Grau AJ, Buggle F, Ziegler C, et ai. Association between Bethesda, MD: US Dept of Health and Human Services, acute cerebro vascular ischetiiia and chronic and recurrent National Institute of Diabetes and Digestive and Kidney infection. Stroke 1997:28:1724-1729. Disease, 1997. 70. Hujoel PP, Drangsholt M, Spiekerman C, DeKouen TA, 92 Brown RD, Whisnant )P, Sicks JD, O'Fallon WM, Wiebers Periodontai disease and coronary heart disease risk. J Am DO. Stroke incidence, prevaience, and survivai. Secular Med Assoc 2000:284:1406-1410. trends in Rochester, Minnesota, through 1989. Stroke 7t. Hay KD, Reade PC. Methyldopa as a cause of orai mucous 1996;27:373-380. membrane reactions. BrDentJ 1978;145:195-203. 93 National Heart, Lung, and Blood Institute. Fact Book 72. Williams BG. Orai drug reaction to methyidopa. Oral Surg Fiscal Year 1996. Bethesda, MD: US Dept of Health and Oral Med Oral Pathol 1983 ;56.375-377 Human Services, National Institutes of Health, 1997 73. Brooks SL. Lichenoid reaction of oral mucosa and skin to 94. Graves EJ. Detailed diagnoses and procedure. National methyidopa. J Oral Med I982;37:42-44. Hospital Discharge Survey, 1989, Dept of Health and 74. Firth NA, Reade PC. Angiotensin-converting enzyme inhi- Human Services, publication 91-1769. Hyattsviile, MD: bitors implicated in oral mucosal lichenoid reactions. Nationai Center for Health Statistics, 1991. 1989:67:41-44,

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95. Levy D. Larson MG, Vasan RS, Kännel WB, Ho KKL. The 114. Fox SM III, Naughton JP, Gorman PA. Physical activity progression of hypertension to congestive heart failure. ] and cardiovascular health, II. The exercise prescription: Am Med Assoc 1996:175:1557-1562. Intensity and duration. Mod Concepts Cardiovasc Dis 96. Berlowitz DR, Ash AS, Hickcy EC, Friedman RH, ef al. 1972;41:21-24. Inadequate management of blood pressure in a hyperten- 115. Froelicher VF, Quaglietti S. Handbook of Exercise Testing. sive population. N Engl J Med 1998;339:1957-1963. Boston: Little, Brown, 1996 62. 97. Allen LH, Ming KM, Neal RG. Blood pressure and elec- 116. Hlatky MA, Boineau RE, Higginbotham MB, et al. A brief trocardiographic response to dental treatment with use of self-administered questionnaire to determine functional local anesthesia. ] Am Dent Assoc 1986;113:639-642. capacity (The Duke Activity Status Index]. Am J Cardiol 98. Boakes A], Laurence DR, Lovel KW, O'Neil R, Verrill P]. 1989;64:651-654. Adverse reactions to local anaesthetic/vasoconstrictor 117 Mandel ID. The plaque fighters. J Am Dent Assoc 1993; preparations. Br Dent ] 1972; 135:137-140, 124:71-73. 99. Meiller TF, Overholser CD, Kutcher MJ, Bennett R. Blood lis. Youngblood JJ, Killoy W, Love JW, Drisko C. Effectiveness pressure fluctuations in hypertensive patients during oral of a new home plaque removal instrument in removing surgery. J Oral Maxiilofac Surg 1983;41:715-718. subgingival and interproximal plaque: A preliminary in 100. Lipp M, Dick W, Daublander M, Fuder H, Stanton-Hicks vivo report. Compend Contin Educ Dent 1985;6: M. Exogenous and endogenous plasma levels of epineph- S128-S132. riñe during dental treatment under local anesthesia. Reg 119. Baab DA, Johnson RH. The effect of new electric tooth- Anesth 1993;18:6-12, brush on supragingival plaque and gingivitis. J Periodontol 101. Massaiha R, Valdman S, Farkash P, Merkin L, Herishanu 19S9;60:336-34L Y Fatal intracerebral hemorrhage during dental treatment, 120. Killoy WJ, Love JW, Love J, Fedi PF Jr, Tira DE. The effec- Isr J Med Sei 1996;32:774-776. tiveness of a counterrotary action powered toothbrush and 102. Mito RS, Yagiela JA. Hypertensive response to levonorde- conventional toothbrush on plaque removal and gingival frin in a patient receiving propranoioi: Report of case. bleeding. A short-term study. ] Periodontol 19S9;60: JAm Dent Assoc 1988;116:55-57. 473-477. 103. Meyer FU. Hemodynamic changes of local anesthesia in 121. Wilcoxon DB, Ackerman RJ Jr, Killoy WS, Love JW, normotensive and hypertensive subjects. Int ] Clin Phar- Sakumura JS, Tira DE. The effectiveness of a counter-rota- macol Ther Toxicol 1986 ;24:477-4SI. tional action power toothbrush on plaque control in ortho- dontic patients. Am J Orthod Dentofac Orthop 1991; 104. Steinman HR, Patterson SS, Newton CW, Troup P, Zipes 99:7-14. DP. Cardiovascular changes during nonsurgical endodon- tics. J Endod 19S2;8:497-501. 122. Wilson S, Levine D, Dequincy G, Killoy W. Effects of two toothbrushes on plaque, gingivitis, gingival abrasion and 105. Singer J. Meiller TF, Rubinstein L, Blood pressure fluctua- recession: A one-year longitudinal study. Compend Contin tions during dental hygiene treatment. Dent Hyg 1983; Educ Dent 1993;Suppl 16:S569-S579. 57(S):24-28. 123. Wilson S, Levine D, Dequincy G, Kilioy WJ. Effects of two 106. Beck FM, Weaver JM. Blood presstire and heart rate toothbrushes on plaque, gingivitis, gingival abrasion and responses to anticipated high stress dental treatment. J recession: A one-year longitudinal study. Compend Contin Dent Res 1981;60:26-29. Educ Dent 1993;14(suppl 16):S69-S79, 107. Meiller TF, Overholser CD, Kutcher MJ, Bennet R Blood 124. Yukna RA, Shaklee RL. Interproximal vs midradicular pressure fluctuations in hypertensive patients during oral effects of a counterrotational powered brush during sup- surgery, J Oral Maxiilofac Surg 1983;41:715-718. portive periodontal therapy. Compend Contin Educ Dent 108. Cioffi GA, Chernow B, Glahn RF, Terezhalmy GT, Lake 1993;14(suppl 16):S80-S86. CR. The hemodynamic and plasma catecholamine respons- 125. Love JW, Driska CL, Killoy WJ, Tira DE, Love JD. Clinical es to routine restorative dental care. ] Am Dent Assoc assessment of the Interplak powered toothbrush vs a con- 1985;111:67-70. ventional brush plus floss. Compend Contin Educ Dent 109. Ship 11. The response of systolic and diasttilic blood pres- 1993;14(suppl 16):S87-S98. sures to dental stress. Oral Surg Oral Med Oral Fathol 126. Blahunt P. A clinical trial of the Interplak powered tooth- 1960;13:499-507. brush in a geriatric popuiation. Compend Contin Educ 110. Gortzak RAT, Ousting J, Abraham-lnpijn L. Blood pres- Dent 1993;14¡suppl 16¡:S606-S610. sure response to routine restorative dental treatment with 127 Terezhalmy GT, Gagliardi VB, Rybicki LA, Kauffman MJ. and without local anesthesia. Oral Surg Oral Med Oral Ciinicai evaluation of the efficacy and safety of the Ultra- Fathol 1992:73:677-681. Soex ultrasonic toothbrush: A 30-day study. Compend 111. Niwa H, Satoh Y, Matsuura H. Cardiovascular responses Contin Educ Dent 1994;15:866-874, to epinephrine-containing local anesthetics for dental use: 128. Terezhalmy GT, Iffland H, Jelepis C, Waskowski J. Clinical A comparison of hemodynamic responses to infiltration evaluation of the effect of an ultrasonic toothbrush on anesthesia and ergometer-stress testing. Oral Surg Oral plaque, gingivitis, and gingival bleeding: A six-month study. Med Oral Pathol 2000;90:171-181. J Prosthet Dent 1995 ;73:97-103. 112 Bruce RA, Exercise testing for evaluation of ventricular 129. Whitmyer CC, Terezhalmy GT, Miller DL, Hujer ME, function. N Engl J Mcd 1977;296:671-675. Ciinicai evaluation of the efficacy and safety of an ultra- 113. Kenney WL (ed). ACSM's Guidelines for Exercise Testing sonic toothbrush system in an elderly patient population. and Prescription, ed 5. Baltimore: Williams & Wdkins, 1998,19:29-33. 1995:93-94.

Quintessence International 687 Riley/Terezhalmy

130. Shinada K, Hashizume LN, Teraoka K, Kurosaki N. Effect 144. Lipsitz LA, Pluchino FC, Wei JY, Rowe JW. öyncoi'- 'f of ultrasonic toothbrush on Streptococcus mutans. fpn J institutionalized elderly; The impact of multiplt: p^" '''*'^" ConservDent 1999:42:410-417. cal conditions and situational stress. J Chron c Di: I'^O"', 131. Vaughan CJ, Delanty N. Hypertensive emergencies. Lancet 39:619-630. 2000;356:411-417. 145. Davis BE!, Langford HG, Blaufox MD, Curb 0, P"lk BF, 132. Joint National Committee on Preventioti, Detection, Evaiu- Shulman NB. The association of postural chi. 'jiti- '" ^ï^' ation, and Treatment of High Blood Pressure. Sixth Report. tolic blood pressure and mortality in persons ith hyper- Arch Intern Med 1997;157:2413-2446. tension: The Hypertension Detection and I illow-tip Program experience. Circulation 1987;75:340-34ti 133. Funaltoshi Y, Jchiki T, Ito K, Takeshita A. Induction of interletikin-6 expression by angiotensin II in rat vascular 146. Lipsitz LA, Pluchino FC, Wei JY, Minaker KL, Rowe JW. smooth muscle cells. Hypertension 1999;34:118-125. Cardiovascular and norepinephrine responses following meal consumption in elderly (older than 75 years) persons 134. Mulier DN, Dechend R, Mervaaîa EM, et al. NF-kB inhihi- with post-prandial hypotension and syncope. Am J Cardiol tion ameliorates angiotensin Il-induced inflammatory 1986;58:810-815. damage in rats. Hypertension 2000;35:193-201. 147. Kennedy GT, Crawford MH. Optimal position and timing 135. Furchgott RF, Zawadzky ]V. The obligatory role of endo- of blood pressure and heart rate measurements to detect thelial cells in the relaxation of arterial smooth muscle hy orthostatic changes in patients with ischémie heart disease. acetylcholine. Nature 19aO;288:373-376. J Cardiac Rehabil 1984;4:219-223. 136. Kuchan MJ, Jo H, Frangos JA. Role of G proteins in shear stress-mediated nitric oxide production hy endotheiial 148. Dole WP, O'Rourke RA. Pathophysiology and manage- cells. Am J Physiol 1994;267.C753-C758. ment of cardiogenic shock. Curr Prohl Cardiol 1938j8: 1-72. 137. Okada M, Matsumori A, Ono K, et al. Cyclic stretch upreg- ulates production of interleukin-8 and monoeyte ehemo- 149. Califf RM, Bengtson JR. Cardiogenic shock. N Engl J Med tactic and activating factor/monocyte chemoattractant 1994:330:1724-1730. protein-1 in human endotheiial cells. Arterioscler Thromh 150. Harnarayan C, Bennett MA, Pentecost BL, Brewer DB, Vase Biol 1998;18:894-901. Quantitative study of infracted myocardium in cardiogenic 138. Wung BS, Cheng JJ, Chao YJ, Lin J, Shyy YJ, Wang DL. shock. Br Heart J 1970;32:728-732. Cyclic strain increases monoeyte chtmotactic protein-1 151. Page DL, Caulfield JB, Kastor JA, DeSanctis RW, Sanders secretion in human endotheiial cells. Am J Physiol 1996; CA. Myocardial changes associated with cardiogenic 270: H1462-H1468. shock. N Engl J Med I971;285:133-137 139. Touyz RM, Milne FJ. Alterations in intracellular cations 152. Alonso DR, Scheidt S, Post M, Killip T. Pathophysiology of and cell membrane ATPase activity in patients with malig- cardiogenic shock: Quantification of myocardial necrosis, nant hypertension. J Hypertens 1995;I3:867-874. clinical, pathologic and electro cardiographie correlations. 140. MacArthur H, Warner TD, Wood EG, Corder R, Vane JR. Circulation 1973:48:588-596. Endothelin-1 release from endotheiial eells in culture is 153. Scheidt S, Ascheim R, Killip T HI. Shock after acute elevated both acutely and chronically by short periods of myocardial infarction: A clinical and hemodynamic profile. mechanical stretch. Biochem Biophys Res Commun 1994; Am J Cardiol 1970;26:556-564. 200:395-400. 154. Hands ME, Rutherford JD, Müller JE, et al. The in-hospital 141. Verhaar MC, Beutler JJ, Gaillard CA, Koomans HA, development of cardiogenic shock after myocardial infarc- Fijnheer R, Rabelink TJ. Progressive vascular damage in tion: Incidence, predictors of occurrence, outcome and hypertension is associated with increased levels of circulat- prognostic factors. J Am Coll Cardiol 1989; 14:40-46. ing P-selectin. J Hypertens 1998;16:45-50. 155. Leor J, Goldbourt U, Reicher-Reiss H, Kaplinsky E, Behar 142. Eckberg D-L. Para sympathetic cardiovascular controi in S, SPRINT Study Group. Cardiogenic shock complicating human disease: A critical review of methods and results. acute myocardial infarction in patients without heart fail- Am J Physioi 1980;239.H581-H593. ure on admission: Incidence, risk factors, and outcome. 143. Tinetti ME, Williams TF, Mayewski R. Fall risk index for Am J Med 1993:94:265-273. elderly patients hased on number of chronic disabilities. 156. Wackers FJ, Lie KI, Becker AE, Dürrer D, Weliens HJ. Am J Med 1986;80:429-434. Coronary artery disease in patients dying from cardiogenic shock or congestive heart failure in the setting of acute myocardial infarction. Br Heart J 1976:38:906-910.

Volume 32, Number 9, Riley/Terezhalmy •

XEROSTOMrA: R, PILOCARPINE HYDROCHLORIDE

Pilocarpine hydrochloride is a parasympathomimetic drug extracted from the Pilocarpus plant, it exerts a broad spectrum d pharmacologie activities, with a predominantly miscannic-cholin- ergic action. Pilocarpine has been shown to stimulate lacrimal, salivary, gastric, intestinal, res- piratory, and pancreatic secretions. Pregnancy risk factor C.

1. Indications • To Stimulate salivary flow in patients with salivary giand dysfunction secondary to drug-induced xerostomia.

2. Contraindications • Piiooarpine is contraindicated in patients with known hypersensitivity to pilocarpine. • Pilocarpine should be used with caution in patients with cardiovascular disease, urinary tract obstruction, and Parkinsons disease, cr narrow-angie giaucoma.

3. Drug interactions • Pilocarpine increases myopia with sympathomimetic amines. 4. Administration • Orai. {route and dosage) • Dosage lorm; 5 mg tabiets. • initially, give 2.5 to 5.0 mg, three times daily; titration up to 30.0 mg per day at variable dosage intervals may be considered tor palients who have not responded adequately.

5. Monitored efficacy • The endpoint fcr therapeutic efficacy is increased salivary flow, which is not necessarily and toxicity accompanied by subjective improvement; • It may require up to 4 weei

6. Length of • Pilocarpine may be continued indefinitely as long as the salivary flow continues to be stimulated treatment and the patient experiences no serious side effects,

7. Cessation ot • Pilocarpine may be withdrawn immediately and completely without adverse effects. treatment

e. Instructions to • Use caution while driving at night or performing hazardous tasks in poor illumination because the patient the drug may affect adaptation tc the dark. Prcmplly report any adverse drug effect and inform ail health care professionals that you are taking pilccarpine.

For additional information, please review the manufacturer's recommendations.

Quintessence International 689 Riley/Terezhalmy

XEROSTOMIA: R CEVIMELINE HYDROCHLORIDE

Cevimeline hydrochloride is an acetyicholine derivative that has been approved by the US Food and Drug Administration for the treatment of xerostomia caused by Sjögren's syndrome. Presumably it could aiso be used to treat radiation- and drug-induced xerostomia. It has a high affinity for muscarinic-cholinergic receptors located on lacrimal and salivary giand celis and a much lower affinity for cardiac parasympathetic receptors. Pregnancy risk factor C.

1. Indications • To stimulate salivary flow in patients with salivary gland dystunction secondary to drug-induced xerostomia.

2. Contraindications • Cevimeline is oontraindicated in patients with known hypersensitivity to acetylchoiine. • Cevimeiine is contralndicated in patients with uncontroiled asthma, narrow-angle giaucoma, or iritis. • Cevimeline should be used with caution in patients with cardiovascular disease, urinary tract obstruction, or Parkinson's disease. 3. Drug interactions • Cevimeline has additive eftects in slowing cardiac conduction in patients taking a beta-blocker. • Cevimeline antagonizes the effects of antimuscarinic drugs such as atropine or scopolamine.

4. Administration • Oral. (route and dosage) • 30.0 mg, three times daily.

5. Monitored efficacy • The endpoint for therapeutic efficacy is increased salivary flow, which is not necessariiy and toxicity accompanied by symptomatic improvement. • Secondary indicators of efficacy, when applicable, include diminished oral mucositis and candidiasis, and decreased dysphagia. • The patient shouid be examined every 6 to 8 weeks to assess parameters of efficacy as well as evidence ot adverse drug effects. • Common adverse effects include sweating, nausea, rhinitis, diarrhea, and visuai disturbances (especially at night): the dosage can be titrated downward and/or the dosage interval can be increased. • Symptoms o! overdose may inciude bronchospasm, bradycardia, involuntary urination, vomiting, hypotension, and tremors: • Atropine, 0.5 to 1.0 mg, administered intravenously or intramuscularly, is the treatment of choice for toxicity manifesting as significant muscarinic symptoms. • Epinephrine, 0.1 tc 1.0 mg, administered subcutaneousiy, may be useiul in reversing severe cardiovascular or puimonary sequelae.

6. Length of • Cevimeline may be continued indefinitely as long as the salivary flow continues to be stimuiated treatment and the patient experiences no serious drug effects.

7. Cessation of • Cevimeiine may be withdrawn immediately and completeiy without adverse effects. treatment

8. Instructions to • Use oaution while driving at night or performing hazardous tasks in poor illumination because the patient the drug may affect adaptation to the dark. Promptly report any adverse drug effect and inform ali heaith care professionais that you are taking acetyicholine.

For additional information, please review the manufacturer's recommendations.

690 Volume 32, Number 9, 2001