Chapter 7

Management of the medically compromised dental patient

I. American Heart Association (AHA) guidelines for antibiotic prophylaxis

a. Prevention of infective endocarditis: Antibiotic prophylaxis for the dental patient

Q. What year are the most current guidelines for prevention of infective endocarditis in dental patients?

A. 2007. Published in Circulation (The Journal of the American Heart Association). The title of the article is: Prevention of infective endocarditis. Guidelines from the American Heart Asssociation. A guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Online version: http://circ.ahajournals.org.

Q. What are the major changes in the updated recommendations?

A. The Committee concluded that only a very small number of cases of infective endocarditis (IE) might be prevented by antibiotic prophylaxis for dental procedures even if prophylactic therapy were 100% effective.

Q. Why were new recommendations needed?

A. The committee concluded that infective endocarditis was more likely to develop from frequent exposure to random bacteremias associated with daily activities (e.g., intraoral trauma, flossing and brushing) than from bacteremia caused by a dental, GI tract, or genitourinary (GU) tract procedure. Additionally, the committee recommended that maintenance of meticulous oral hygiene may reduce the incidence of bacteremia from daily activities and is more important than prophylactic antibiotics for a dental procedure to reduce the risk of IE.

Q. What are the current medical conditions cited in the 2007 Guidelines that require antibiotic prophylaxis?

A. See Table 7.1.

Q. Does a patient with a cardiovascular implantable electronic device (e.g., pacemaker) require antibiotic prophylaxis according to the American Heart Association (AHA)?

A. There does not seem to be any scientific studies to support the use of antibiotic prophylaxis in these patients for ­invasive dental procedures (Baddour et al., 2011).

Q. Are there other medical conditions that may also require antibiotic prophylaxis?

A. Yes. When in doubt get a medical consultation from the patient’s physician. Other conditions possibly requiring premedication prior to invasive dental treatment include (Lockart et al., 2007):

• Renal transplants/dialysis
• Hemophilia
• Shunts
• Immunosuppression secondary to cancer and cancer chemotherapy
• Immunosuppression secondary to HIV/AIDS
• Systemic lupus erythematosus
• Poorly controlled insulin-dependent diabetes mellitus.

Table 7.1 Conditions recommended for prophylactic antibiotics.

Q. Is antibiotic prophylaxis required for patients that have been treated for heart disease (e.g., blocked arteries)?

A. No. For patients with blocked arteries angioplasty can be performed to open blocked heart arteries. Stent placement is another option that can be done during angioplasty. A cardiac stent is a small mesh tube used to treat narrow or weak arteries. Balloon angioplasty involves a specially designed catheter with a small balloon tip is guided to the point of narrowing in the artery. Once in place, the balloon is inflated to compress the fatty matter into the artery wall and stretch the artery open to increase blood flow to the heart.

Q. According to the most current 2007 guidelines what dental procedures are required for patients to have antibiotic prophylaxis?

A. See Table 7.2.

Q. Is antibiotic prophylaxis required for patients taking low-dose aspirin?

A. No. Antibiotic prophylaxis is not indicated for patients taking low-dose aspirin.

Q. According to the 2007 guidelines which is the antibiotic of choice for prophylaxis against IE?

A. The bacterium most commonly associated with endocarditis following dental and oral procedures is Streptococcus viridans (α-hemolytic streptococci). Amoxicillin remains the most recommended antibiotic for endocarditis ­prophylaxis. Agents such as ampicillin and penicillin VK have an equal antimicrobial effect against α-hemolytic streptococci, but amoxicillin is better absorbed in the gastrointestinal tract and provides higher, more sustained serum levels than the other penicillins (Lockart et al., 2007).

Q. What are the most current AHA guidelines for antibiotic dosing for prophylaxis against IE?

A. See Table 7.3.

Q. What happens if the patient forgot to take the antibiotic 30 to 60 minutes before the dental procedure?

A. If the dosage of antibiotic was not taken before the procedure, the full amount may be taken up to 2 hours after the dental procedure (Wilson et al., 2007; Dajani et al., 1997).

Q. What happens if a patient is already taking an antibiotic for either a medical or dental reason?

A. Patients receiving antibiotics for other reasons at the time of a routine dental visit who are considered at risk for endocarditis have specific recommendations. The antibiotic that the patient is already taking is not adequate to prevent a dentally induced bacteria. Rather than increasing the dose of the drug currently being used, it is advisable to select an agent from a different class of antibiotic. Remember, if you have to choose another antibiotic, it must have the same bactericidal or bacteriostatic activity as the antibiotic taken for prophylaxis. For instance, if the patient is taking tetracycline (a bacteriostatic drug), he or she cannot take amoxicillin (a bactericidal antibiotic), but can take clindamycin, azithromycin, or clarithromycin, which are all bacteriostatic. If possible, the dental procedure is best postponed until at least 9 to 14 days after completion of the antibiotic. This will allow the normal oral flora to re-establish and help to reduce the incidence of bacterial resistance (Wilson et al., 2007; Dajani et al., 1997).

Q. Can I prescribe erythromycin to a patient who is allergic to penicllin?

A. Erythromycin, which was originally approved as an effective prophylactic agent for endocarditis in cases of penicillin allergy, is no longer among the recommended drugs. Erythromycin can cause severe gastrointestinal upset, and certain formulations (e.g., erythromcyin ethylsuccinate) have complicated pharmacokinetics. Instead, second-generation erythromycins, azithromycin, or clarithromycin can be prescribed because they have better absorption and produces less adverse effects.

Q. Is it advisable to see a patient taking antibiotic prophylaxis more than once a week or even once a week?

A. No. Since repeated use of antibiotics can lead to the emergence of antibiotic-resistant microorganisms in the oral cavity, it is recommended that there be an interval of at least 7 days between dental treatment appointments. There needs to be adequate time for the patient’s normal oral flora to be re-established and prevent the development of resistant strains.

Q. How are prescriptions written for the different antibiotics for IE prophylaxis (Wilson et al. 2007)?

A. See Table 7.4. If allergic to penicillins then prescribe as shown in Table 7.5.

Table 7.2 Antibiotic prophylaxis recommendations for dental procedures.

Walter et al. (2007) Prevention of infective endocarditis. Guidelines from the American Heart Asssociation. A guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation, 116(15): 1736–54 with permission from Wolters Kluwer Health. Online version: http://circ.ahajournals.org.

Table 7.3 Prophylactic antibiotic regimens for oral and dental procedures.

Walter et. al. (2007) Prevention of infective endocarditis. Guidelines from the American Heart Association. A guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation, 116(15): 1736–54 with permission from Wolters Kluwer Health. Online version: http://circ.ahajournals.org.

* Cephalosporins should not be given to an individual with a history of anaphylaxis, angioedema, or urticaria with penicillins or ampicillin.

II. Antibiotic prophylaxis for total joint replacement

Q. What is the concern about antibiotic prophylaxis for dental patients with total joint replacement?

A. A problem arises in patients with total joint replacements because if an infection develops the bacteria cannot be easily eliminated from a joint replacement implant. Bacteremias can cause hematogenous seeding of a joint implant soon after the surgery and for years afterward. This is why antibiotic prophylaxis is very important in dental patients with total joint replacements.

Q. What are the current guidelines for antibiotic prophylaxis for dental patients with total joint replacements?

A. In 2009, the American Academy of Orthopedic Surgery (AAOS) safety committee recommended that dentists ­consider antibiotic prophylaxis for all patients with total joint (e.g., knee, hip) replacement before any dental procedure whether or not that person was even at a high risk for developing an infection forever. The AAOS stated that “given the potential adverse outcomes and cost of treating an infected joint, replacement, the AAOS ­recommends that clinicians consider antibiotic prophylaxis of all total joint replacement patients prior to any invasive procedure that may cause bacteremia” (American Dental Association: American Academy of Orthopaedic Surgeons, 2003). This recommendation followed an earlier guideline by the AAOS and the American Dental Association, who in 2003 said that antibiotic prophylaxis should only be considered within 2 years post-implant surgery in high-risk patients who have high-risk dental procedures such as dental extraction, periodontal procedures, endodontic procedures, initial placement of orthodontic bands, implant placement and oral prophylaxis with anticipated bleeding. Readers are referred to this article to review (American Dental Association: American Academy of Orthopaedic Surgeons, 2003). It is emphasized that ­dentists must use their own clinical judgment in determining whether a patient requires antibiotic prophylaxis.

Q. Why is there controversy regarding the use of antibiotic prophylaxis in patients with total joint replacement?

A. There is some controversy regarding the 2009 guidelines. A recent article suggests that the 2009 guidelines should not replace the 2003 guidelines until further review (Little et al., 2010). Some sources say that staphylococci, the most common cause of prosthetic joint infection, are relatively uncommon commensals of the oral flora and have been rarely implicated in bacteremia occurring after dental procedures. On the other hand, viridans-group streptococci make up most of the facultative oral flora and are the most common cause of transient bacteremia after dental procedures that result in trauma to the gingival or oral mucosa. However, viridans-group streptococci account for only 2% of all hematogenous prosthetic joint infections. Additionally it is stated that concerns about promoting antimicrobial resistance and about adverse reactions from antimicrobial use may outweigh any hypothetic benefit related to prevention of prosthetic joint infection (Deacon et al., 1996). (http://www.ccjm.org/content/78/1/36.short). Another 2011 article, reported that dental procedure are not associated significantly with a risk for prosthetic joint infections (PJIs) and the use of prophylactic antibiotics in these patients may be questioned (Skaar et al., 2011).

Q. What is the suggested antibiotic prophylaxis 2009 AAOS regimen for dental patients with total joint replacement?

A. See Table 7.6.

Q. How are prescriptions written for antibiotics used as prophylaxis for dental patients with total joint replacement?

A. Oral antibiotic prophylaxis for total joint replacement

Standard regimen (Table 7.7).

If allergic to penicillin (Table 7.8).

Q. Why is cephalexin suggested as an antibiotic?

A. Cephalexin (Keflex) is a cephalosporin that has excellent bone penetrating properties and is an ideal antibiotic in patient with total joint replacement. However, there is approximately a 10% cross sensitivity between penicillins and cephalosporins, which precludes the prescribing a cephalosporin to patients allergic to penicillins. In these cases an alternative antibiotic is clindamycin (see Table 7.6).

Q. Is a patient with a titanium rod or plate in the neck required to have antibiotic prophylaxis?

A. No. According to the American Dental Association and the American Academy of Orthopedic Surgeons (AAOS) antibiotic prophylaxis is not indicated for dental patients with pins, plates, screws or rods (American Dental Association: American Academy of Orthopaedic Surgeons, 2003; Rubin et al., 1976).

Q. Is antibiotic prophylaxis indicated for patients with pins, plates, or screws?

A. No. Antibiotic prophylaxis is not indicated for dental patients with pins, plates or screws in any part of the body (American Dental Association: American Academy of Orthopaedic Surgeons, 2003).

Q. If the patient is allergic to penicillin can cephalexin be prescribed?

A. No. If the patient is allergic to penicillin, cephalexin, which is a cephalosporin, should not be prescribed as there is a 10% cross-sensitivity in patients allergic to penicillin. Instead, clindamycin can be prescribed (Table 7.8).

Table 7.4 How the prescription is written for oral prophylactic antibiotic regimens.

Table 7.5 How the prescription is written for oral prophylactic antibiotic regimens if allergic to penicillin.

Table 7.6 Suggested antibiotic prophylaxis regimen in dental patients with total joint replacement.

Adapted from: American Dental Association; American Academy of Orthopedic Surgeons (2003) Advisory Statement. Antibiotic prophylaxis for dental patients with total joint replacements. Journal of the American Dental Association 134: 895–898.
Prevention of infective endocarditis. Guidelines from the American Heart Association. A guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Online version: http://circ.ahajournals.org.

Table 7.7 How the prescriptions are written for oral antibiotic prophylaxis for total joint replacement.

Table 7.8 How the prescriptions are written for oral antibiotic prophylaxis for total joint replacement if allergic to penicillin.

Table 7.9 Classification of high blood pressure.

Reprinted from Chobanian et al. (2003) with permission from Wolters Kluwer Health.

III. Cardiovascular diseases

a. Hypertension

Q. What is the most current classification of blood pressure for adults?

A. The 2003 Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (7th Report) classifies blood pressure as shown in Table 7.9.

Q. Should blood pressure be taken on all dental patients?

A. Blood pressure should be taken on all new patients on the initial visit and hypertensive patients at every dental visit (Yagiela & Haymore, 2007).

Q. What are the effects of epinephrine on the sympathetic receptors in the body?

A. Theoretically, epinephrine binds to all sympathetic receptors (α₁, β_1, β₂) in the body. The α₁-receptors are locate predominantly on blood vessels under the skin, mucous membranes and GI tract. The β₂-receptors are located predominantly on blood vessels on certain internal organs like the lungs, liver and brain, and in blood vessels in skeletal muscle. B₁-receptors are primarily located on the heart. The coronary arteries have both α₁-and β₂-receptors.

    Epinephrine in low concentrations (up to two or three cartridges) achieved systemically after anesthetic injections in dentistry is fairly selective for β₂-receptors rather than α-receptors. Epinephrine has some α₁-receptor effects resulting in vasoconstriction. The β₂– receptors, when activated by epinephrine, cause a decrease in peripheral vascular resistance by selectively causing vasodilation in skeletal muscle blood vessels. This opposing vasodilation of epinephrine limits the potential vasopressor effects thus lowering peripheral resistance and therefore diastolic blood pressure which is governed by peripheral vascular resistance. At the same time, the β₁– (and β₂)-receptors in the heart are activated to increase cardiac output and therefore systolic blood pressure; this is influenced by peripheral vascular resistance as well, but is also heavily influenced by the cardiac output, which epinephreine increases strongly. With an increase in systolic blood pressure and a decrease in diastolic blood pressure, there is no real change in mean blood pressure; these two influences cancel each other out regarding mean blood pressure.

    Higher doses, as used to treat anaphylaxis, stimulate α₁-receptors. Since there are more of them, the net effect is ­vasoconstriction throughout the body, and an increase in peripheral resistance. This results in an increase in both systolic and diastolic blood pressure, and a possible reflex slowing of the heart mediated by the vagus nerve releasing acetylcholine onto the SA node (Yagiela, 1999).

Q. If more than three cartridges are needed in these patients is it adequate to space the doses apart rather than injecting all at one time?

A. When epinephrine is injected and absorbed into the blood it is rapidly converted to inactive metabolites. So, injections can be administered over minutes (e.g., 30 minutes) to avoid having too much cumulative doses (Yagiela & Haymore, 2007).

Q. It is a major concern of dentist whether to use epinephrine in hypertensive patients. Does the amount of epinphrine need to be limited in the controlled hypertensive patient?

A. By knowing the mechanism of how epinephrine effects the α and β receptors in the body in low and high doses should help with answering this question. See above question and answer. Remember, epinephrine is an endogenously produced neurotransmitter so that there is no real total contraindication for its use. The question that arises then, is how much epinephrine can be injected? It also depends on the medication used to treat the hypertension.

    There is no real need to limit the amount of epinephrine used in dental local anesthesia in hypertensive patients who are controlled so long as there are no drug interactions and no intravascular injections; however, the American Dental Association recommends that the total dosage of epinephrine be limited to 0.04 mg (two or three cartridges) in cardiac risk patients. In uncontrolled hypertensive patients, studies have shown that a few cartridges (up to two or three ­cartridges) of lidocaine with 1:100 000 epinephrine can be used without changing the blood pressure; however, it is recommended to delay dental treatment in uncontrolled hypertensive patients until the blood pressure is under control. Of course, extra care must be taken aspirate to avoid intravascular injection (Yagiela & Haymore, 2007; Budenz, 2000).

Q. Can levonordefrin be used instead of epinephrine?

A. Levonordefrin (Neo-Cobefrin) is half as potent a vasoconstrictor as epinephrine. However, it primarily stimulates α-adrenergic (sympathetic) receptors, with little to no effect on the α-adrenoceptor. Stimulation of α₁-receptors on ­tissues/organs causes vasoconstriction of blood vessels, resulting in hypertension (increased systolic and diastolic blood pressure). Epinephrine produces a greater stimulation of β₂ -receptors than β₁-receptors, causing vasodilatation and decreasing diastolic blood pressure. Higher doses produce more vasoconstriction and increased blood pressure. Since it is less effective/potent than epinephrine, it is used in higher concentrations (e.g., 2% mepivacaine with 1:20 000 levonordefrin) and has similar adverse effects as 1:100 000 epinephrine. So, levonordefrin can be used in patients taking nonselective beta-blockers.

Q. Is there a local anesthetic that contains less of a concentration than 1:100 000 epinephrine as a vasoconstrictor?

A. Yes. Recommendations in cardiac patients include administering block anesthesia with mepivacaine 3% (Carbocaine, Polocaine plain) and then infiltrating with articaine 4% (Septocaine) that contains 1:200 000 epinephrine, which is half the concentration of 1:100 000 epinephrine.

Q. What is a safe way to administer epinephrine in a hypertensive patient?

A. It is best to inject a small amount of anesthetic solution containing epinephrine and to wait about 5 minutes while monitoring the patient.

Q. Can gingival retraction cord be used safely in hypertensive patients?

A. Gingival retraction cord is made of cotton with a range of options of nonimpregnated and chemically impregnated cords that have astringent (contraction–retraction; shrinkage of gingival tissues and sulcular displacement) or hemostatic (vasoconstriction; coagulation) actions. Examples of astringent/hemostatic agents include aluminum chloride, aluminum sulfate, and aluminum potassium sulfate, racemic epinephrine [equal amounts of dextrorotatory (d) and levorotatory (l) isomers] and ferric sulfate. 20–25% aluminum chloride and 15.5–20% ferrie sulfate are most commonly used (Strassler & Boksman, 2011). The ADA has been stated that 5 to 10% aluminum chloride is safe and effective (American Dental Association, 2002). Gingival retraction cords are also impregnated with epinephrine. About 92% of the epinephrine is systemically absorbed (Malamed, 1993; Kellam, et al. 1992; Pallasch, 1998). In fact, the amount of epinephrine absorbed may be equal to about 3.9 cartridges of a local anesthetic with 1:100 000 epinephrine (Kellman et al. 1992). This provides a concentration of about 4% (equals 40 mg/ml) of active epinephrine which is about 40 times the concentration given for cardiac arrest or allergic anaphylaxis (Malamed, 1993). Since there is controversy regarding the adverse effects of epinephrine-impregnated gingival retraction cord, it is advised to limit or avoid their use especially in in cardiac patients.

Q. What is the different classification of medications the patient could be taking for hypertension and what are common dental adverse effects and how are they managed in the dental office?

A. See Table 7.10.

Q. If a patient is taking multiple antihypertensive medications, are the adverse effects additive?

A. Yes. If a patient is taking more than one antihypertensive drug that causes xerostomia, the xerostomia effect will be greater (Yagelia & Haymore, 2007).

Q. Are many of these antihypertensive medications also used for other heart conditions?

A. Yes. Some are used as anti-arrhythmic drugs, for angina, and for congestive heart failure.

Q. If a patient is taking a nonselective beta-blocker can epinephrine be administered?

A. There are nonselective and selective cardiac beta-blockers. Non-cardioselective beta blockers block both β₁ and β₂ receptors, which means that both β-receptors will be blocked allowing binding to the α-receptors, which cause vasoconstriction and possible hypertensive effects. Non-cardioselective beta-blockers include: propranolol (Inderal), timolol (Blocadren), and nadolol (Corgard). Epinephrine should be limited to 0.04 mg or two cartridges of 1:100 000 epinephrine.

    Cardioselective beta blockers selectively block only β₁-receptors. Thus, there is little concern for using epinephrine in these patients.

Q. Which cardiac drugs can cause gingival enlargement?

A. Calcium channel blockers especially nifedipine (Adalat, Procardia), amlodipine (Norvasc) and less likely, diltiazem (Cardizem) can cause gingival enlargement.

Q. Is the correct term for gingival enlargement gingival hyperplasia or hypertrophy?

A. No. Hyperplasia is a histologic term defined as an abnormal increase in noncellular connective tissue components of the gingiva (Yagiela & Haymore, 2007). Hypertrophy is a term describing the enlargement of an organ or tissue from the increase in size of its cells. Both terms are used incorrectly when describing drug induced gingival enlargement.

Table 7.10 Dental management of patients taking drugs for hypertension.

Antihypertensive drug	Adverse effects	Dental management
Diuretics Thiazide diuretics Chlorothiazide (Diuril) Hydrochlorothiazide (Hydrodiuril) (HCTZ) Loop Diuretics Bumetanide (Bumex) Furosemide (Lasix) Potassium-sparing Diuretics Amiloride (Midamore) Spironolactone (Aldactone) Triamterene (Dyrenium) Combination Diuretics Aldactazide (HCTZ + spironolactone) Dyazide (HCTZ + triamterene) Maxzide (25/50 mg HCTZ + 37.5/75 mg triamterene) Moduretic (HCTZ + amiloride)	Xerostomia (loop diuretics cause the most xerostomia) Orthostatic hypotension Drug interaction with NSAIDs Lichenoid reactions (e.g., lichen planus-like lesions)	Xerostomia Xerostomia: monitor for caries, candidiasis and periodontal disease If xerostomia is severe, contact patient’s physician to change to a different classification of medication For xerostomia: recommend OTC products Saliva substitutes: effects only last for a few hours. Most contain either carboxymethylcellulose or hydroxyethylcellulose (e.g., Moi-Stir® spray or oral Swabsticks, Optimoist® spray, Salivart® aerosol;, Xero-Lube® spray OR mucopolysaccharide solutions (e.g., MouthKote® spray) OR Saliva stimulants: Natrol Dry Mouth Relief Saliva lubricants/moisturizers: Biotene Dry Mouth: toothpaste, mouthwash, gum, moisturizig gel drink plenty of water chew sugarless gum or candy use of sodium fluoride gels or rinses if severe, prescribe salivary stimulants (cholinergic agents) such as pilocarpine (Salgan) or cevimeline HCL (Evoxac) Pilocarpine is contraindicated in patients with uncontrolled asthma, narrow-angle glaucoma or iritis. Pregnancy category C. Adverse effects include excessive sweating and gastrointestinal distress. Recommended dose: Comes in 5 mg tabs: Initial dose 5 mg tid or qid; up to 3 to 6 tabs per day; not to exceed 2 tabs (10 mg) per dose. Can take up to 6 to 12 weeks to see results. Cevimeline (Evoxac) contraindicated in patients with uncontrolled asthma, narrow-angle glaucoma or iritis. Pregnancy category C. Adverse effects include sweating and nausea. Orthostatic hypotension Make slow, careful changes in position. After being in a supine position for dental care slowly raise the dental chair to an upright position and have the patient sit in the upright position for a few minutes before getting out of the chair. Assistance in helping the patient out of the chair is important. Monitor vital signs. NSAIDs use Reduce effectiveness of antihypertensive drug Limit use of NSAID to 5 days. Have blood pressure monitored. Lichenoid reactions Refer to patient’s physician for either treatment of the reaction with topical corticosteroids or change in medication Use of epinephrine No precautions or contraindications with the use of epinephrine with these medications. Take vital signs. Medical consultation is required if hypertension is not controlled. Medical consultation is required if hypertension is not controlled.
Beta-blockers Acebutolol (Sectral) Atenolol (Tenormin) *Carvedilol (Coreg) *Labetalol (Normodyne) Metoprolol (Lopressor) *Nadolol (Corgard) *Pindolol (Visken) *Propranolol (Inderal) *Sotalol (Betapace) *Timolol (Blocadren) __________________ *Nonselective cardiac beta-blockers (blocks both β1 and β2-adrenergic receptors)	Xerostomia, dizziness, oral lesions, orthostatic hypotension	Xerostomia: see above recommendations Orthostatic hypotension: see above recommendations NSAIDs use Limit use of NSAID to 5 days. Have blood pressure monitored. Oral lesions (Kalmer, 2009) Lichen planus-like lesions, pemphigus like lesions (especially with propranolol) Use of epinephrine Take vital signs. Noncardiac selective beta-blockers: limit epinephrine to two cartridges of 1:100 000 because nonselective beta- blockers block both β1 and β2 receptors leaving α receptors for binding which causes increased blood pressure. Medical consultation is required if hypertension is not controlled.
α-Adrenergic blockers Doxazosin (Cardura) Prazosin (Minipress) Tamsulosin (Flomax) Terazosin (Hytrin)	Xerostomia, dizziness, vertigo	Xerostomia: see above recommendations Orthostatic hypotension: see above recommendations NSAIDs use: see above recommendations Use of epinephrine No precautions or contraindications with the use of epinephrine with these medications.
ACE inhibitors
Benazepril (Lotensin) Captopril (Capoten) Enalapril (Vasotec) Fosinopril (Monopril) Lisinopril (Zestril, Prinivil) Quinapril (Accupril) Ramipril (Altace)	Cough (highest incidence with ramipril), orofacial angioedema (swelling of the oral cavity; tongue, soft palate and uvula) (Yagiela & Haymore, 2007), less xerostomia	Orthostatic hypotension: see above recommendations NSAIDs use: see above recommendations Orofacial angioedema: refer to physician or hospital (Rees & Gibson, 1997). Orofacial angioedema is a condition with lip, facial or oral swelling. The danger of this condition is the possibility of airway obstruction (laryngeal edema). (Scully & Porter, 2003). Use of epinephrine No precautions or contraindications with the use of epinephrine with these medications. Oral vesiculobullous lesions: Pemphigoid like lesions: captopril
Calcium channel blockers Amlodipine (Norvasc) Diltiazem (Cardizem) Felodipine (Plendil) Nisoldipine (Sular) Nifedipine (Adalat, Procardia) Nicardipine (Cardene) Isradipine (DynaCirc) Verapamil (Calan, Isoptin)	Gingival enlargement, dizziness	Orthostatic hypotension: see above recommendations Use of epinephrine No precautions or contraindications with the use of epinephrine with these medications. Gingival enlargement More commonly seen with nifedipine and amlodipine Strict home care (plaque control) Surgical removal of gingiva, if necessary (as long as the patient is taking the calcium channel blocker the gingiva will return to an overgrowth state).
Angiotensin receptor blockers (ARBs) Candesartan (Atacand) Eprosartan (Teveten) Irbesartan (Avapro) Losartan (Cozaar)	Dizziness, cough	Orthostatic hypotension: see above recommendations NSAIDs use: see above recommendations Use of epinephrine No precautions or contraindications with the use of epinephrine with these medications.
Central anti-adrenergic Clonidine (Catapres) Methyldopa (Aldomet)	Rebound hypertension, orthostatic hypotension, oral lichenoid lesions, xerostomia	Xerostomia: see above recommendations Orthostatic hypotension: see above recommendations NSAIDs use: see above recommendations Oral lesions: Pemphigoid-like oral reaction Use of epinephrine No precautions or contraindications with the use of epinephrine with these medications.

Q. What is the mechanism of calcium channel blocker-induced gingival enlargement?

A. The exact mechanism of action is not clear. However, a proposed hypothesis involves inflammatory factors within the gingival tissue whereby numerous inflammatory cells in the connective tissue are replaced by collagen. An alteration of the intracellular calcium level in gingival cells by nifedipine, local inflammatory factors (plaque or biofilm accumulation), is important in causing gingival enlargement (Ciancio, 2004).

Q. What is the treatment of calcium channel blocker induced gingival enlargement?

A. It is recommended to teach the patient optimum oral home care. If there is no underlying periodontal disease and adequate keratinized gingiva, a gingivectomy can be performed but it must be understood that as long as the patient is taking the drug the gingival enlargement will return. If there is underlying periodontal disease, then periodontal flap surgery is advised. Referral to the periodontist may be necessary.

Q. What are dental implications if the patient is taking antihypertensives?

A. See Table 7.10.

A. Xerostomia or dry mouth is a common adverse effect of heart medication, especially diuretics, but it may not be so severe to interfere with oral function. Orthostatic hypotension is common. There are no drug–drug interactions with epinephrine except for noncardiac selective beta blockers, where the maximum amount of 1:100 000 epinephrine is two cartridges.

Q. Many antihypertensive drugs cause orthostatic hypotension. What precautions should the dentist follow?

A. According to the American Autonomic Society, orthostatic hypotension or postural hypotension is defined as a ­systolic blood pressure decrease of at least 20 mmHg or a diastolic blood pressure decrease of at least 10 mmHg within 3 minutes of standing (Bradley & Davis, 2003). Many cases of orthostatic hypotension are due to antihypertensive medications. Most antihypertensives, except calcium channel blockers, can potentially cause orthostatic hypotension. Medications that can cause orthostatic hypotension include: Diuretics; beta-blockers, alpha-blockers; angiotensin-­converting enzyme (ACE) inhibitors; erectile dysfunction drugs: sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis); antidepressants (tricyclic antidepressants).

Q. How do beta-blockers cause orthostatic hypotension?

A. Beta-blockers block the β-adrenoceptor in the body, preventing the heart from speeding up, preventing the heart from contracting as forcefully, and dilating blood vessels. All three of these effects affect the ability of the body to react to position changes.

Q. When can orthostatic hypotension happen in the dental patient?

A. 1) When lying down in a supine position and quickly sitting up in an upright position and then standing.
     2) Immediately after intravenous sedation (due to vasodilation).
     3) After nitroglycerin or other medication use.

Q. How can orthostatic hypotension be managed in the dental patient?

A. Make slow, careful changes in position. After being in a supine position for dental care slowly raise the dental chair to an upright position and have the patient sit in the upright position for a few minutes before getting out of the chair. Assistance in helping the patient out of the chair is important. Vital signs must be monitored.

Q. Is angioedema of the oral cavity dose related?

A. No. Angioedema from ACE inhibitors can occur at any time during therapy (Yagiela & Haymore, 2007).

Table 7.11 Dental management of patients taking drugs for angina.

b. Angina and other ischemic cardiac conditions

Q. What is angina?

A. Angina pectoris occurs when the metabolic demands of the heart exceed the ability of the coronary arteries to supply adequate blood flow and oxygen to the heart. There are different types of angina: stable angina (angina upon exercise); unstable angina (angina at rest); variant angina (Prinzmetal’s angina) due to a hart vasospasm, often occurring during sleep.

Q. What drugs are used to treat angina pectoris?

A. The purpose of medication for angina pectoris is to increase blood flow and oxygen to the heart. Table 7.11 reviews drugs are used in the management of angina:

Q. What adverse effects should be recognized in patients taking these medications?

A. Orthostatic hypotension (except for aspirin). Have the patient sit in an upright position for a few minutes before ­getting up from the dental chair. It is important to monitor for gingival enlargement in patients taking calcium channel blockers especially nifedipine and amlodipine.

Q. Is epinephrine contraindicated in patients with angina?

A. Management of stable angina patients without a history of a myocardial infarction includes the reduction of stress and anxiety so that epinephrine should be used for stress control but is limited to two cartridges of 1:100 000 epinephrine to avoid increased tachycardia. Profound anesthesia is necessary to prevent stressful situation whereby large amount of endogenous epinephrine are synthesized and released from the adrenal medulla in response to pain. A local anesthetic with 1:200 000 epinephrine can also be used (e.g., articaine 4% or prilocaine 4%). In a 1.7 ml cartridge, 1:200 000 dilution concentration contains 0.0085 mg of epinephrine versus 0.017 mg in 1:100 000 concentration. Short ­appointments are recommended. Mild or moderate (conscious) sedation may be indicated.

    Epinephrine should be avoided and no elective dental treatment in patients with unstable angina or in stable angina with myocardial infarction within 6 months of recent coronary artery bypass graft surgery. Medical consultation with the patient’s physician is recommended.

Q. What local anesthetic should be administered if emergency dental treatment is necessary in the unstable angina patient or had a myocardial infarction within the last 6 months?

A. Stress and anxiety reduction is important, as mentioned above, so it is safe to limit the amount of local anesthetic to one or two cartridges.

Q. Why is there 1.7 ml of local anesthetic in one cartridge?

A. Most US manufacturers of local anesthetics made a labeling change in 2005. Each anesthetic cartridge contains a minimum of 1.7 ml and a maximum of 1.8 ml and 1.7 ml is printed on the cartridge. The majority of cartridges are labeled 1.7 ml.

Q. If patients are taking nitroglycerin do they need to have it with them at every dental visit?

A. Yes. It should be out on the table in case it is needed quickly. However, the nitroglycerin in the emergency medical kit in the dental office may have “fresher” nitroglycerin than the pills the patient is taking.

c. Congestive heart failure

Q. What is heart failure?

A. Heart failure occurs when decreases in contractility prevent the heart from pumping forcefully enough to deliver blood to meet the body’s demands. Decreases in cardiac output activate reflex responses in the sympathetic nervous system, which attempt to compensate for the reduced cardiac output.

Q. What is the dental management of patients taking medications for heart failure?

A. See Table 7.12.

Q. Can epinephrine be used safely in a patient with congestive heart failure?

A. It is advised to limit the amount of epinephrine to two cartridges of 1:100 000 epinephrine especially if taking digoxin.

Q. Is lidocaine contraindicated in patients with heart failure?

A. Yes. Lidocaine is contraindicated in patient allergic to lidocaine, heart failure, cardiogenic shock, second-or third -degree heart block (if no artificial pacemaker), Wolff-Parkinson-White syndrome (this may be controversial), and Stokes-Adams syndrome.

d. Patient on low-dose aspirin and other antiplatelet drugs

Q. Should the term “baby aspirin” be used?

A. No. All products containing 81 mg are called “low-dose aspirin” and not “baby aspirin” because it was ambiguous and many people would give the “baby” aspirin to babies. All labeling is now “low-dose” aspirin. Low-dose aspirin products contain 81 mg of aspirin.

Q. Is aspirin an antiplatelet or anticoagulant drug?

A. Aspirin is an antiplatelet drug with a totally different mechanism of action than warfarin and heparin which are ­anticoagulant drugs. Aspirin is also used as an antithrombotic agent because of its mechanism of action of inhibiting platelet aggregation.

Q. What are the different antiplatelet drugs?

A. Irreversible platelet inhibitors:

• Aspirin (acetylsalicylic acid or ASA)
• Clopidogrel (Plavix)
• Ticlopidine (Ticlid)
• Prasugrel (Effient)
• Aspirin-dipyridamole (Aggrenox).

Reversible platelet inhibitors

• Dipyridamole (Persantine).

Q. Which is the newest antiplatelet drug?

A. Prasugrel (Effient) is a antiplatelet (aggregation inhibitor) indicated to reduce the rate of thrombotic cardiovascular events such as stent thrombosis in patients with unstable angina, non-ST-segment elevation MI (myocardial infarction), or ST-elevation MI (STEMI) managed with percutaneous coronary intervention. There is a Black Box Warning that prasugrel may cause significant or fatal bleeding. Consult with the patient’s physician before dental procedures. There is no evidence for discontinuing prasugrel prior to dental surgery. Discontinuing prasugrel as well as any antiplatelet drug may lead to increased risk of cardiovascular events. However, consultation with the patient’s physician is important.

Q. What is dipyridamole (Persantine)?

A. Dipyridamole is sometimes used with aspirin to reduce the risk of death after a heart attack and to prevent another heart attack. Dipyridamole is used with other drugs to reduce the risk of blood clots after heart valve replacement. It works by preventing excessive blood clotting.

Q. What is clopidogrel?

A. Clopidogrel (Plavix) is a reversible platelet inhibitor. The combination of aspirin and clopidogrel is usually standard treatment for one month after heart stent placement and long-term use can significanlty reduce the risk of major cardiovascular events after percutaneous coronary intervention (Patrono et al., 2004). Clopidogrel work differently from aspirin by inhibiting the binding of fibrinogen to platelets which is an important step for platelets to clot or aggregate (Awtry & Loscalzo 2000). Clopidogrel is frequently used by patients that cannot tolerate the adverse ­gastrointestinal effects of aspirin or are allergic or intolerant to aspirin (American Dental Hygiene Association, 2011).

Q. What is the difference between irreversible platelet inhibitors and reversible platelet inhibitors?

A. Irreversible inhibitors of platelet aggregation drugs require new platelets (about 5–10 days) to be produced when the drug is stopped in order to get normal bleeding times. When reversible inhibitors of platelet aggreation drug are stopped the affected platelets regain aggreation function quicker, usually about 2 days (American Dental Association, 2011).

Q. Who should be taking low-dose aspirin?

A. Aspirin is to prevent a heart attack or stroke in individuals who have had a heart attack or stroke, in individuals to prevent a first and second heart attack who currently have coronary heart disease, after coronary bypass surgery, and individuals with stable and unstable angina. No benefit has been shown in men younger than age 45 and women younger than 55 who prophylactically take aspirin. Aspirin interferes with thrombus formation by decreasing platelet formation.

Q. What is the mechanism of action of aspirin’s antiplatelet action and does it differ from regular anti-inflammatory/analgesic dose aspirin?

A. Basically, the beneficial antiplatelet effects of aspirin for secondary or primary prevention of cardiovascular disease result from irreversible acetylation of the active site of cyclo-oxygenase (COX) in platelets which prevents the formation of thromboxane A₂ (TXA₂) resulting in inhibition of platelet aggregation or clotting (http://www.uptodate.com/­contents/benefits-and-risks-of-aspirin-in-secondary-and-primary-prevention-of-cardiovascular-disease?source=see_link). (See “Benefits and risks of aspirin in secondary and primary prevention of cardiovascular disease”.)

    How does this happen? From a pharmacologic point of view (e.g., arachidonic acid cascade) aspirin inactivates permanently the COX-1 and COX-2 activity in platelets, preventing the formation of TXA₂ and in endothelial cells, ­preventing the formation of prostacyclin (PGI₂). COX-1 is considered to be the “protective” enzyme and is normally found in the gastrointestinal tract, kidneys, uterus and platelets. Under the influence of COX-1 prostaglandins maintain and protect the gastric mucosa, maintain normal platelet function and regulate renal blood flow. COX-2 is produced only during inflammation and is found in low amounts in the tissues. The objective of using anti-inflammatory drugs is to reduce the inflammation and pain caused by COX-2. TXA_2, found in platelets, strongly induces platelet aggregation and vasoconstriction (prevents bleeding), while prostacyclin, formed in endothelial cells (lining of blood vessels), has the opposite effects of thromboxane and inhibits platelet aggregation and induces coronary artery vasodilation. Thus, prostacyclin has beneficial and desirable effects by protecting cells from platelet deposition and causing coronary artery vasodilation.

    The antiplatelet effect occurs when aspirin or acetylsalicylic acid gets hydrolyzed or metabolized to acetic acid and salicylic acid (salicylate). It is the acetic acid that irreversibly/permanently binds covalently to the COX enzyme in the platelet. However, in anucleated (without a nucleus) platelets, new COX is formed every about 10 to 14 days, which is how long a platelet lives; the antiplatelet effect will persist about 5 days which is when 50% of platelet function returns to normal. On the other hand, in endothelial cells which have a nucleus, more cyclooxygenase is formed immediately. This allows the endothelial cell to continue to produce prostacyclin (Page, 2005). Thus, since aspirin is very sensitive at low doses (75 to 325 mg/day) to COX-1 rather than to COX-2 and TXA₂ is derived from COX-1 in platelets it can be concluded that aspirin in low-doses and longer dosing intervals has a lasting antiplatelet affect by inhibiting platelet aggregation via inhibition of the formation of TXA₂ (Page, 2005).

    In contrast, at daily regular analgesic/anti-inflammatory dosages of greater than 1000 mg (this is considered to an be anti-inflammatory dose, not an antithrombotic dose) aspirin inhibits both TXA₂ and prostacyclin, which negates the entire antiplatelet effect, while lower doses (antithrombotic) of 75 to 325 mg/day preferentially inhibit TXA₂ resulting in the antiplatelet phenomena (Page, 2005). The reason why higher doses and shorter dosing interval is required for an anti-inflammatory/analgesic effect is that COX-2, which is responsible for pain and inflammation, is much less sensitive to the actions of aspirin (Page, 2005). Therefore, regular anti-inflammatory doses most likely will not result in bleeding, while low-dose aspirin could result in bleeding.

Q. How soon after taking aspirin is an antiplatelet effect noticed?

A. Aspirin is absorbed in the upper gastrointestinal tract and within 60 minutes an antiplatelet effect is seen which is associated with a prolonged bleeding time (Awtry & Loscalzo, 2000; Patrono et al., 1998).

Q. Does low-dose aspirin inhibit both COX-1 and COX-2?

A. Yes. Low-dose aspirin inhibits both COX-1 and COX-2 but is a more potent inhibitor of COX-1, thereby suppressing TXA₂ production and irreversibly inhibiting platelet aggregation for the lifetime of the platelet, which is about 10–14 days.

Q. What happens to the antiplatelet effect when nonsteroidal anti-inflammatory drugs (NSAIDs) are given with aspirin?

A. The effect of oral ibuprofen on in vitro platelet aggregation was evaluated in a study in which healthy volunteers were treated with aspirin 2 hours before or 2 hours after ibuprofen. When ibuprofen was given before aspirin, TXA₂ production by activated platelets was approximately twofold higher and inhibition of platelet aggregation was negligible at 24 hours. Ibuprofen had no effect on the action of aspirin when given 2 hours after aspirin and neither acetaminophen nor diclofenac affected the activity of aspirin.

Q. Does aspirin cause gastrointestinal tract toxicity (e.g., GI tract bleeding)?

A. Yes. Although aspirin-induced gastrointestinal toxicity is dose-dependent even at lower doses, aspirin can cause serious GI bleeding, especially in preexisting lesions in patients with gastric ulcers (Patrono et al., 2004).

Q. What is the dosage of low-dose aspirin?

A. The accepted dosage of low-dose aspirin is controversial because aspirin is antithrombotic in a wide range of doses (Patrono et al., 2004). Low-dose can be considered to be between 81 mg/day to 325 mg/day or even twice weekly. This dosage is adequate because approximately 10% of the platelets are replenished every day so that once-a-day doing can completely inhibit the formation of TXA₂ (Patrono et al., 2004).

Q. Should I ask every patient if he/she is taking aspirin?

A. Yes. Sometimes patients may take the aspirin on their own without physician supervision. It is important to ask the patient if the aspirin was prescribed by the physician.

Q. Does low-dose aspirin interfere with bleeding time and are patients that take prophylactic low-dose aspirin more prone to bleeding during invasive dental procedures?

A. It has been published that low-dose aspirin may not significantly alter bleeding time (Ardekian et al., 2000; AAP, 1996). Only about 20% to 25% of patients taking aspirin have an abnormal bleeding time (Randall, 2007). The increase in bleeding time lasts for the lifetime of the platelet or until new platelets are formed, which is about 10 to 14 days. About 50% of platelet function returns to normal within 5 days after aspirin is stopped. Consultation with the patient’s physician is recommended.

Q. Should aspirin be discontinued before dental surgery (e.g., periodontal/implant/oral surgery) because of the risk of excessive bleeding?

A. It is the consensus that if an antiplatelet drug is used as monotherapy (only one drug) it does not need to be discontinued or alteration in doses. The frequency of oral bleeding complications after invasive dental procedures is low to negligible for patients who were taking antiplatelet drugs. Bleeding will still occur but the risks of altering or ­discontinuing use of antiplatelet medications outweigh the low risk of postoperative oral bleeding complications resulting from dental procedures and that can be usually controlled with local measures (Napeñas et al., 2009; Brennan et al., 2008; Madan et al., 2005; Ardekian et al., 2000). However, if more than one antiplatelet drug is being taken then the patient’s physician or cardiologist must be contacted because in-office procedures may not be possible and the patient may need to be referred to a hospital for treatment.

    A clinical study reported that the only significant relationship found between bleeding and all antiplatelet drugs, not just aspirin, was between bleeding and the number of teeth extracted. It was concluded by this research group that no more than three teeth should be extracted at one dental sitting and that the teeth should be adjacent to each other (Cardona-Tortajada et al., 2009).

Q. Does clopidogrel (Plavix) or other antiplatelet agents other than aspirin alter bleeding time?

A. Yes. Antithrombotic/antiplatelet agents may increase the risk of bleeding during invasive dental procedures (Little et al., 2002). In fact, clopidogrel is considered to be a more potent antiplatelet agent and can prolong the bleeding time by 1.5 to 3 times the normal value (Randall, 2007). Also, sensitivity to antiplatelet agents varies in different people (Randall, 2007). Some clinical reports have recommended continuing monotherapy aspirin or clopidogrel or dual therapy with more than one antiplatelet agent for invasive dental procedures (Napeñas et al., 2009). Consultation with the patient’s physician is recommended.

Q. Is there an increased risk of bleeding if a patient is taking two antiplatelet agents?

A. Yes. There is an increased bleeding tendency if two antiplatelet agents are used together. This must be taken into consideration before performing invasive dental procedures. Consultation with the patient’s physician is recommended.

Table 7.12 Dental management of patients taking medications for heart failure.

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