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Chapter 15: Cardiovascular Drugs Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Chapter 15 Outline Cardiovascular Drugs Dental implications of cardiovascular disease Cardiac glycosides Antiarrhythmic agents Antianginal drugs Antihypertensive agents Antihyperlipidemic agents Drugs that affect blood coagulation Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 2 Cardiovascular Drugs Haveles (p. 186) Cardiovascular disease refers to diseases of the heart and blood vessels Includes hypertension, angina pectoris, coronary artery disease, cerebrovascular accident, and congestive heart failure (CHF) A leading cause of death in the United States 25% of the top 200 drugs are in this group Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 3 Dental Implications of Cardiovascular Disease Haveles (p. 187) Contraindications to treatment Vasoconstrictor limit Infective endocarditis Cardiac pacemakers Periodontal disease and cardiovascular disease Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 4 Contraindications to Treatment Haveles (p. 187) (Box 15-1) Acute or recent myocardial infarction (MI) (within the preceding 3 to 6 months) Unstable or recent onset of angina pectoris Uncontrolled CHF Uncontrolled arrhythmias Significant, uncontrolled hypertension Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 5 Vasoconstrictor Limit Haveles (p. 187) The majority of cardiovascular patients should benefit from the use of epinephrine in the local anesthetic agent The amount and effect of epinephrine administered must be weighed against the fact that discomfort can cause the release of endogenous epinephrine Limiting the dose to the cardiac dose (0.04 mg) may be warranted in a few severely affected patients Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 6 Infective Endocarditis Haveles (p. 187) When a risk of producing infective endocarditis exists, prophylactic antibiotics should be prescribed, if warranted by the dental procedure being performed Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 7 Cardiac Pacemakers Haveles (p. 187) A cardiac pacemaker is an electrical device implanted in a patient’s chest to regulate the heart rhythm If not appropriately shielded, some electrical devices used in dentistry may interfere with pacemaker activity Consult with physician may be appropriate before treatment Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 8 Periodontal Disease and Cardiovascular Disease Haveles (p. 187) Research has found a relationship between periodontal disease and both cardiovascular disease and stroke An inherited phenotype, MO, is under both genetic and environmental influences, placing the patient at increased risk for severe periodontal disease, insulin-dependent diabetes mellitus, atherosclerosis, and emboli production cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 9 Periodontal Disease and Cardiovascular Disease Monocytes in these patients secrete abnormally high levels of cytokines, including prostaglandin (PG)E2, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α, all of which are associated with both periodontal and cardiovascular disease An increase in dietary intake of fat leads to an increase in low-density lipoproteins (LDL, bad cholesterol), which are known to upregulate the destructive monocyte response Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 10 Cardiac Glycosides Haveles (pp. 187-189) CHF Digitalis glycosides Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 11 Heart Failure Haveles (pp. 187-188) (Fig. 15-1) In CHF, the heart does not provide adequate cardiac output Blood accumulates in the failing ventricle(s), the ventricle(s) enlarges and finally becomes ineffective as a pump • Left side failure backs into pulmonary circulation (lungs) leading to edema, dyspnea and orthopnea • Right side failure causes systemic congestion, leading to peripheral edema with fluid accumulation evidenced by pitting edema (pedal edema) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 12 Digitalis Glycosides Haveles (pp. 188-189) Pharmacologic effects Uses Adverse reactions Management of the dental patient taking digoxin Other drugs cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 13 Digitalis Glycosides The most common type of drug used in the treatment of CHF Haveles (p. 188) Not considered first-line therapy digoxin (Lanoxin) is used as the prototype Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 14 Pharmacologic Effects of Digitalis Glycosides Haveles (p. 188) Increases force and strength of contraction of the myocardium (positive inotropic effect) Allows the heart to do more work without increasing the use of oxygen The heart becomes more efficient, and cardiac output increases cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 15 Pharmacologic Effects of Digitalis Glycosides In CHF, the heart rate is increased due to increased sympathetic action resulting from decreased carbon monoxide (CO) As digoxin increases CO, sympathetic tone is decreased, with a decrease in heart rate Digoxin also reduces edema that occurs with CHF The size of the heart is reduced as excess blood volume is removed via the kidneys Digoxin can affect automaticity, conduction velocity, and refractory periods of different parts of the heart in different ways Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 16 Uses of Digitalis Glycosides Most common usage is treatment of CHF Haveles (p. 188) Also used for atrial arrhythmias, including atrial fibrillation (AF) and paroxysmal atrial tachycardia (PAT) A recent trial found digoxin did not reduce mortality; for this reason use of digoxin is decreasing Angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) and βadrenergic blockers are used more often Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 17 Adverse Reactions of Digitalis Glycosides Haveles (pp. 188-189) Narrow therapeutic index: slight changes in dose, absorption, or metabolism can trigger toxic symptoms Gastrointestinal (GI): signs of toxicity include anorexia, nausea, vomiting, copious salivation Arrhythmias: if sufficient overdose is given (note: digitalis is used to treat arrhythmias, its toxicity can cause them) Neurologic: signs of toxicity include headache, drowsiness, and visual disturbances cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 18 Adverse Reactions of Digitalis Glycosides Oral: increased salivation is associated with digoxin toxicity Dental drug interactions: interaction with sympathomimetics can increase chances of arrhythmias; in severe cardiac disease, the epinephrine dose may be limited to the cardiac dose (0.04 mg) Erythromycin and tetracycline can increase toxicity of digoxin in some patients Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 19 Management of the Dental Patient Taking Digoxin Haveles (p. 189) (Box 15-2) Watch for overdose side effects such as nausea, vision changes, and copious salivation Use epinephrine with caution to minimize arrhythmias Monitor pulse to check for bradycardia Tetracycline and erythromycin can increase digoxin levels (in approximately 10% of patients) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 20 Other Drugs Haveles (p. 189) (Note: these are not cardiac glycosides) ACEIs: now first-line therapy for CHF ARBs: for patients who cannot tolerate ACEIs; also first-line therapy β-Adrenergic blockers Vasodilators: hydralazine and isosorbide dinitrate Diuretics: to relieve edema Aldosterone antagonists Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 21 Antiarrhythmic Agents Haveles (pp. 189-191) Automaticity Action potential Arrhythmias Antiarrhythmic agents Adverse reactions Dental implications cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 22 Antiarrhythmic Agents Arrhythmias may result from abnormal impulse generation or abnormal impulse conduction Haveles (p. 189) Cardiac diseases such as myocardial anorexia, arteriosclerosis, and heart block can produce arrhythmias Antiarrhythmic agents are used to prevent arrhythmias Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 23 Automaticity Haveles (pp. 189-190) (Fig. 15-2) Cells of cardiac muscles have an intrinsic rhythm called automaticity The sinoatrial (SA) node in right atrium has the fastest rate of depolarization and directs other cells of the heart • It is innervated by both the parasympathetic and sympathetic nervous system It signals the atrioventricular (AV) node, which sends signals through the bundle of His to Purkinje fibers and ventricles Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 24 Action Potential Electrical excitation from the nerve produces movement of ions across the membrane, generating an action potential Haveles (p. 190) (Fig. 15-2) Visualized as an electrocardiogram (ECG) A relationship exists between the action potential and the ECG tracing Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 25 Arrhythmias Arrhythmias are divided into supraventricular (atrial) and ventricular types Haveles (p. 190) May result in tachycardia or bradycardia of supraventricular or ventricular parts of the heart May result from ectopic foci “emergent leaders” that preempt the SA or AV nodal rate Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 26 Antiarrhythmic Agents Haveles (pp. 190-191) (Tables 15-1, 15-2) Placed in four groups designated by numeral I through IV according to mechanism of action Subsets of these Roman numerals use capital letters (A, B, C) cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 27 Antiarrhythmic Agents Antiarrhythmic agents work by depressing parts of the heart that are beating abnormally They may decrease the velocity of depolarization, decrease impulse propagation, and inhibit aberrant impulse propagation cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 28 Antiarrhythmic Agents Haveles (p. 191) Digoxin: although digoxin is not included in the other groups of antiarrhythmics, it is used to treat some arrhythmias Shortens the refractory period of atrial and ventricular tissues while prolonging the refractory period and diminishing the conduction velocity in the Purkinje fibers Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 29 Adverse Reactions of Antiarrhythmic Agents Haveles (p. 191) Antiarrhythmic agents have a narrow therapeutic index and are difficult to manage Only used for patients with arrhythmias that prevent the proper functioning of the heart Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 30 Classification and Mechanism of Action of the Antiarrhythmic Agents Class IA sodium (Na+) channel blocker (medium) Quinidine, procainamide, disopyramide Class IB Na+ channel blocker (fast) Haveles (p. 191) (Table 15-1) lidocaine Class IC Na+ channel blocker (slow) Flecainide, encainide, propafenone cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 31 Classification and Mechanism of Action of Antiarrhythmic Agents Class II β-blockers Class III potassium (K+) channel blockers Propranolol, esmolol, acebutolol, sotalol Bretylium and d-sotalol (non–β-blocking enantiomer) Class IV calcium channel blockers (CCBs) Verapamil, diltiazem Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 32 Management of Dental Patients Taking Antiarrhythmic Agents Haveles (p. 191) (Table 15-2) All: Check for abnormal or extra beats when taking blood pressure and pulse AF: pt. on warfarin-check international normalized ratio (INR) Amiodarone: liver toxicity, blue skin, photosensitivity CCBs: gingival enlargement Disopyramide: anticholinergic xerostomia Procainamide: reversible lupus-like syndrome, 25%-30%, central nervous system (CNS) depression xerostomia Quinidine: nausea, vomiting, diarrhea; cinchonism with large doses; atropine-like effect, xerostomia Phenytoin: gingival enlargement β-Blockers, nonspecific: interaction with epinephrine Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 33 Antianginal Drugs Haveles (pp. 191-194) Angina pectoris Nitroglycerin (NTG)-like compounds CCBs β-Adrenergic blocking agents Ranolazine Dental implications Prevention of an anginal attack MI Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 34 Angina Pectoris Characterized by pain or discomfort in the chest radiating to the left arm and shoulder Haveles (pp. 191-192) Pain can also radiate to neck, back, and lower jaw Jaw pain may be confused with a toothache Occurs when coronary arteries do not supply enough oxygen to the myocardium cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 35 Angina Pectoris At one time, NTG-like compounds were the only drugs that could relieve the symptoms Haveles (pp. 191-192) (Table 15-3) Today, β-adrenergic blockers and CCBs have added a new dimension The effect of these drugs is to reduce the workload of the heart Oxygen requirement of myocardium is reduced, relieving painful symptoms Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 36 Nitroglycerin-Like Compounds Haveles (pp. 191-192) (Box 15-3) NTG is by far the most often used nitrate for management of acute anginal episodes Also to prevent anginal attacks induced by stress or exercise Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 37 Mechanism of Nitroglycerin-Like Compounds Haveles (p. 192) NTG is a vasodilator Releases free nitrite ion and nitric oxide • Nitric oxide activates guanylyl cyclase and increases cyclic guanosine monophosphate (cGMP), producing relaxation of vascular smooth muscle throughout the body By reducing workload on the heart, NTG decreases the oxygen demand cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 38 Mechanism of Nitroglycerin-Like Compounds Amyl nitrite is a volatile agent in a closed container Sublingual (SL) NTG is available as an SL tablet (Nitrostat) or spray used sublingually (Nitroingual) It is administered by crushing the container and inhaling the fumes SL isosorbide dinitrate is also effective for an acute anginal attack One of the NTG products should be in the dental office emergency kit; the patient should bring their NTG to each appointment Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 39 Adverse Reactions of Nitroglycerin-Like Compounds Most reactions are caused its effect on vascular smooth muscle Haveles (p. 193) Severe headaches are often reported Flushing, hypotension, light-headedness, and syncope can also result SL NTG can produce a localized burning or tingling Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 40 Significant Drug Interactions and Contraindications Haveles (p. 193) Phosphodiesterase 5 (PDE5) inhibitors include sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis) The administration of any of these drugs with doses of any nitrate is contraindicated The combination can cause dangerously low blood pressure Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 41 Storage of Nitroglycerin-Like Compounds NTG is degraded by heat and moisture but not by light Haveles (p. 193) Tablets should be stored in the original dark-brown glass container • If opened it should be discarded between 3 and 6 months NTG spray is effective until its expiration date Long-acting NTG-like products are available for long-term prophylaxis of anginal attacks Dose forms include tablets and topical products cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 42 Storage of Nitroglycerin-Like Compounds With long-term regular use, tolerance develops Prophylactic nitrates should be given with an 8- to 12- hour “vacation” every day The mononitrate dose form requires a 7-hour “vacation” daily Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 43 Examples of Antianginal Preparations Haveles (pp. 192-193) (Table 15-3) Acute attacks Nitrites • Amyl nitrite Short-acting nitrates • NTG (Nitrostat) (Nitrolingual) • isosorbide dinitrate cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 44 Examples of Antianginal Preparations Prophylactic use Long-acting nitrates • NTG (Nitro-Bid) (Nitro Dur, Minitran) • isosorbide dinitrate (Isordil, Sorbitrate-DSC) • isosorbide mononitrate (Imdur, Ismo, Monoket) • pentaerythritol tetranitrate (Peritrate) β-Blockers • Propranolol CCBs* (See Box 15-4) • verapamil (Calan, Isoptin) • nifedipine (Procardia) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 45 Calcium Channel Blocking Agents Mechanism of action of CCBs for treatment of angina is related to inhibition of movement of calcium during the contraction of cardiac and vascular smooth muscle Haveles (pp. 193-194) (Table 15-4) Vasodilation and a decrease in peripheral resistance results, decreasing the work of the heart CCBs are also used in treatment of cardiac arrhythmias and hypertension Adverse effects include dizziness, weakness, constipation, and hypotension Nifedipine is associated with gingival enlargement and dysgeusia Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 46 β-Adrenergic Blocking Agents Used in the treatment of angina (as well as hypertension) Haveles (p. 194) Block the beta response to catecholamine stimulation reducing both chronotropic and inotropic effects Net result is a reduced myocardial oxygen demand Adverse effects include bradycardia, CHF, headache, dry mouth, blurred vision, and unpleasant dreams Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 47 ranolazine (Ranexa) Haveles (p. 194) A new drug for treatment of chronic angina Exact mechanism of action is unknown Should only be used in patients that have not responded to long-acting nitrates, CCBs, and βblockers Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 48 Dental Implications Haveles (p. 194) Treatment of an acute anginal attack Prevention of anginal attack MI Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 49 Treatment of an Acute Anginal Attack Before administering NTG, the dental team should make sure the patient has not used a PDE5 inhibitor within the past 24 hours; if such is the case, call 911 The patient’s personal NTG tablets or spray should be available Long-acting nitrates and topical products are not useful for the treatment of an acute anginal attack cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 50 Treatment of an Acute Anginal Attack For acute emergencies, the office should have a supply of SL NTG The patient should be seated Three tablets or doses of spray, each 5 minutes apart • If the anginal attack is not stopped, the patient should be taken to the emergency room Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 51 Prevention of Anginal Attack Haveles (p. 194) Two methods to prevent an acute anginal attack include pretreatment with either an anxiolytic agent or SL NTG Anxiolytics: an antianxiety agent, or anxiolytic (benzodiazepine) may be prescribed to allay anxiety and prevent an acute anginal attack NTG: premedicating an anxious patient with SL NTG can reduce the chance of an attack Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 52 Myocardial Infarction Haveles (p. 194) An anginal attack not relieved by three doses of SL NTG may be experiencing an MI If the patient who has not been previously diagnosed as having angina experiences chest pain, he or she should be taken to an emergency room for diagnosis Any patient with an anginal attack not relieved by NTG should go to the hospital emergency room Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 53 Antihypertensive Agents Haveles (pp. 194-205) Patient evaluation Treatment of hypertension Diuretic agents β-Adrenergic blocking agents CCBs Angiotensin-related agents Renin inhibitors α1-Adrenergic blocking agents Other antihypertensive agents Management of the dental patient taking antihypertensive agents cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 54 Antihypertensive Agents Haveles (pp. 194-196) (Box 15-4) Hypertension is the most common cardiovascular disease (28.6% of Americans) Even blood pressure within the formerly “normal” range is associated with an increase in morbidity and mortality Eventually, elevated blood pressure damages internal organs More likely to have kidney and heart disease and cardiovascular problems cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 55 Antihypertensive Agents Haveles (pp. 195, 197) (Table 15-5) Hypertension is divided into categories based on the cause or progression of the disease Essential (idiopathic, primary): from an unknown cause, 85% to 90% of patients Secondary: cause can be identified and associated to a disease process of endocrine or renal system (10% of patients) Malignant: high or rapidly rising blood pressure, develops in about 5% of patients with primary or secondary hypertension Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 56 Patient Evaluation Haveles (p. 195) Three objectives To assess lifestyle and identify other cardiovascular risk factors or concomitant disorders that may affect prognosis and treatment To reveal identifiable causes of hypertension To assess for the presence or absence of targetorgan damage or cardiovascular disease Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 57 Treatment of Hypertension A stepped-care approach as blood pressures become greater than 140/90 or less than 130/80 mm Hg in patients with diabetes or chronic kidney disease Lifestyle modification: stage 1 or stage 2 and everyone Haveles (pp. 195, 197) (Fig. 15-4; Table 15-6) Weight reduction, physical activity, a diet rich in fruits and vegetables, reduced contents of saturated and total fats, sodium restriction Initial drug choices: once diagnosed with stage 1 or stage 2 hypertension Sex, race, presence of diabetes or hyperlipidemia, and renin activity are taken into consideration cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 58 Treatment of Hypertension Haveles (pp. 195, 199) (Box 15-5) The Big Five antihypertensive groups Diuretics β-Blockers CCBs ACEIs ARBs Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 59 Diuretic Agents for Hypertension Haveles (pp. 197-200) (Fig. 15-6) The three major types of diuretics are found Thiazides (-like) diuretics Loop diuretics Potassium-sparing diuretics Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 60 Thiazide Diuretics Haveles (pp. 197, 199-200) Among the most common agents for treatment of hypertension hydrochlorothiazide (HCTZ) is the most commonly used thiazide Many patients with stage 1 hypertension are treated solely with HCTZ Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 61 Mechanism of Action of Thiazide Diuretics Haveles (pp. 197, 199) (Table 15-8) The exact mechanism by which thiazide diuretics lower blood pressure has not been determined Initially inhibit sodium reabsorption from the distal convoluted tubule and part of the ascending loop of Henle of the kidney Water and chloride ions passively accompany the sodium, producing diuresis Potassium excretion is also increased Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 62 Adverse Reactions of Thiazide Diuretics Haveles (pp. 199-200) (Table 15-9) Common adverse reactions include hypokalemia (secondary to sodiumpotassium exchange) and hyperuricemia (inhibits uric acid secretion) Hyperglycemia, hyperlipidemia, hypercalcemia, and anorexia are other side effects Hyperuricemia is of special concern if the patient has gout cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 63 Adverse Reactions of Thiazide Diuretics Oral adverse reactions include xerostomia and, rarely, oral lichenoid eruptions indistinguishable from lichen planus Nonsteroidal antiinflammatory drugs (NSAIDs) can reduce the antihypertensive effect of the thiazide diuretics Thiazides can cause hypokalemia and can sensitize the myocardium to developing arrhythmias The potential for arrhythmias is exacerbated in patients taking digoxin, especially if digitalis toxicity is present Epinephrine also has arrhythmic potential; limit to cardiac dose when patient is taking thiazide diuretics and digitalis toxicity may be present Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 64 Examples of Thiazide Diuretics Haveles (p. 196) (Box 15-4) chlorothiazide (Diuril) hydrochlorothiazide (HCTZ, Esidrix) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 65 Loop Diuretics Haveles (p. 200) The “strong cousins of thiazides” furosemide (Lasix) is the most commonly used loop diuretic Acts on the ascending limb of the loop of Henle and has some effect on the distal tubule Inhibits reabsorption of sodium with concurrent loss of fluids cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 66 Loop Diuretics Side effects include hypokalemia and hyperuricemia Used in management of hypertensive patients with CHF Can be used when rapid diuresis is desired Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 67 Examples of Loop Diuretics Haveles (p. 196) (Box 15-4) bumetanide (Bumex) furosemide (Lasix) torsemide (Demadex) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 68 Potassium-Sparing Diuretics Haveles (p. 200) “Puny” diuretics with “potassium-catching” ability (weak diuretic action) Spironolactone: competitively antagonizes the action of aldosterone • Result is sodium excretion through diuresis and loss of fluid volume Triamterene: interferes with potassium-sodium exchange in the distal and cortical collecting tubules and the collecting duct by inhibiting sodiumpotassium adenosine triphosphate (ATPase) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 69 Examples of Potassium-Sparing Diuretics Haveles (p. 196) (Box 15-4) amiloride (Midamor) spironolactone (Aldactone) triamterene (Dyrenium) eplerenone (Inspra) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 70 Potassium Salts Potassium salts are not cardiac drugs Haveles (p. 200) Lack of potassium caused by diuretics must be managed, often with potassium supplementation The most common adverse reaction relates to the GI tract; includes nausea and abdominal discomfort Patients taking calcium salts should be questioned about their use of diuretics Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 71 β-Adrenergic Blocking Agents for Hypertension β-Adrenergic blockers are frequently used to treat hypertension Haveles (pp. 200-201) β1-receptor stimulation is associated with increased heart rate, cardiac contractility, and AV conduction β2-receptor stimulation causes vasodilation of skeletal muscle and bronchodilation in pulmonary tissues β-Adrenergic blockers inhibit these actions cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 72 β-Adrenergic Blocking Agents for Hypertension Haveles (pp. 196, 201) (Box 15-4) Nonselective β-adrenergic blocking drugs such as propranolol, block both β1- and β2-receptors In usual doses selective β-adrenergic blocking drugs such as metoprolol, block β1-receptors more than β2-receptors (β1 > β2 ) At larger doses, the selectivity disappears • Pindolol and acebutolol have partial agonist activity and cause some beta stimulation while blocking catecholamine action cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 73 β-Adrenergic Blocking Agents for Hypertension Haveles (pp. 200-201) β-Adrenergic blockers lower blood pressure by decreasing cardiac output Side effects: bradycardia, mental depression, and decreased sexual ability CNS effects: confusion, hallucinations, dizziness, and fatigue have been reported GI tract effects: diarrhea, nausea, and vomiting Can produce xerostomia (very mild) or worsen a patient’s lipid profile May exacerbate asthma, angina, or peripheral vascular disease Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 74 Dental Drug Interactions of βAdrenergic Blocking Agents Nonselective β-blockers can have a drug interaction with epinephrine Haveles (p. 201) May have a two- to fourfold increase in vasopressor response resulting in hypertension In patients with cardiovascular disease or higher blood pressure, the amount of epinephrine given to patients taking nonspecific β-blockers should be limited to the cardiac dose unless blood pressure monitoring accompanies the use of larger doses Usual doses can be given to patients taking specific β-blockers or α- and β-blockers Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 75 α- and β-Adrenergic Blocking Drug for Hypertension Haveles (p. 201) Labetalol is a nonselective β-adrenergic receptor blocking drug that also has αreceptor blocking activity Reduces peripheral resistance through its αblocking action Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 76 Examples of β-Adrenergic Blocking Agents for Hypertension Haveles (p. 196) (Box 15-4) β-Adrenergic blockers atenolol (Tenormin) betaxolol (Kerlone) bisoprolol (Zebeta) metoprolol (Lopressor) (Toprol-XL) nadolol (Corgard) propranolol (Inderal [LA]) timolol (Blocadren) cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 77 Examples of β-Adrenergic Blocking Agents for Hypertension β-Blockers with intrinsic sympathomimetic activity acebutolol (Sectral) penbutolol (Levatol) pindolol (Visken) β-Blockers with α-blocking activity carvedilol (Coreg) labetalol (Normodyne, Trandate) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 78 Calcium Channel Blocking Agents for Hypertension Haveles (pp. 201-202) Many CCBs end in the suffix -dipine Used to treat hypertension and other cardiac conditions such as arrhythmias and angina Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 79 Mechanism of Calcium Channel Blocking Agents Haveles (p. 201) Inhibit the movement of extracellular calcium ions into cells, including vascular smoothmuscle and cardiac cells Produces vasodilation, which produces coronary vasodilation and reverses vasospasms By producing systemic vasodilation CCBs reduce the afterload on the heart Useful in treatment of both angina pectoris and hypertension cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 80 Mechanism of Calcium Channel Blocking Agents At least four types of calcium channels (L, T, N, and P) have been discovered Current CCBs are all of the L type The decrease in transmembrane calcium current results in relaxation of vascular smooth-muscle cells and a reduction in cardiac contractility and conduction Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 81 Pharmacologic Effects of Calcium Channel Blocking Agents for Hypertension Haveles (p. 201) Smooth muscle: vascular smooth muscle is relaxed and dilation of coronary and peripheral arteries and arterioles occur, reducing preload Cardiac muscle: may reduce heart rate, decrease myocardial contractility (negative inotropic effect), and slow AV nodal conduction Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 82 Adverse Reactions of Calcium Channel Blocking Agents Haveles (pp. 201-202) Extensions of pharmacologic effects CNS: can produce excessive hypotension, which can cause dizziness and lightheadedness, headache GI: nausea, vomiting, and constipation Cardiovascular: bradycardia and edema Other: shortness of breath due to pulmonary edema has been reported Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 83 Oral Manifestations of Calcium Channel Blocking Agents Haveles (p. 202) Include xerostomia, dysgeusia, gingival enlargement On discontinuation of the CCB, the gingival enlargement usually reverts to normal tissue and does not reappear If not, gingivectomy or gingivoplasty may be required Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 84 Dental Drug Interactions of Calcium Channel Blocking Agents carbamazepine (Tegretol) is used for trigeminal neuralgia Haveles (p. 202) Diltiazem and verapamil may increase serum levels of carbamazepine, resulting in toxicity Both nausea and constipation, side effects of CCBs, could be additive with side effects produced by NSAIDs (nausea) and opioids (constipation) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 85 Examples of Calcium Channel Blocking Agents CCBs Haveles (p. 196) (Box 15-4) diltiazem (Cardizem [SR], Dilacor [XR]) verapamil (Isoptin [SR], Calan [SR]) Dihydropyridines amlodipine (Norvasc) felodipine (Plendil) isradipine (DynaCirc) nicardipine (Cardene [SR]) nifedipine (Procardia [XL], Adalat [CC]) nisoldipine (Sular) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 86 Angiotensin-Related Agents Haveles (pp. 202-203) Two types of drugs whose mechanism involves angiotensin ACEIs ARBs Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 87 Angiotensin-Converting Enzyme Inhibitors Haveles (pp. 202-203) ACEIs prevent the conversion of angiotensin I to angiotensin II ACEI drugs are commonly used as antihypertensives Many ACEIs end in -pril Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 88 Mechanism of AngiotensinConverting Enzyme Inhibitors The renin-angiotensin-aldosterone system adjusts the quantity of sodium and water retained (circulatory volume) and the peripheral resistance (blood vessels) Haveles (p. 202) (Fig. 15-7) When the kidney senses a decrease in blood pressure or flow it releases renin Renin catalyzes the conversion of angiotensinogen (inactive precursor) to angiotensin I ACE converts angiotensin I to angiotensin II ACE is the enzyme blocked by ACEIs cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 89 Mechanism of AngiotensinConverting Enzyme Inhibitors Angiotensin II produces vasoconstriction and stimulates the adrenal cortex to release aldosterone, facilitating water retention By blocking these events, blood pressure is lowered Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 90 Adverse Reactions of AngiotensinConverting Enzyme Inhibitors Haveles (pp. 202-203) (Box 15-6) The most common adverse reactions are related to the cardiovascular system and the CNS Cardiovascular: hypotension has produced dizziness, lightheadedness, and fainting • Tachycardia and chest pain have been noted CNS: side effects may include dizziness, insomnia, fatigue, and headache cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 91 Adverse Reactions of AngiotensinConverting Enzyme Inhibitors Haveles (pp. 202-203) (Box 15-6) GI: nausea, vomiting, and diarrhea can occur Respiratory: an increase in upper respiratory symptoms, including a dry, hacking cough can occur It occurs because the ACE also inactivates bradykinin, a potent stimulator of allergic reactions cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 92 Adverse Reactions of AngiotensinConverting Enzyme Inhibitors Allergic-like reactions Angioedema: swelling of the extremities, face, lips, mucous membranes, tongue, glottis, or larynx can occur Rash Other: because teratogenicity can cause fetal and neonatal morbidity and mortality, ACEIs should not be given to women who could be or become pregnant Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 93 Oral Adverse Reactions of Angiotensin-Converting Enzyme Inhibitors Dysgeusia: an altered sense of taste is reported in about 6% of patients taking captopril Haveles (pp. 202-203) Usually reversible after a few months, even with continued drug treatment Autoimmune oral lesions: lichenoid or pemphigoid reactions may produce oral manifestations May have a photosensitivity factor Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 94 Dental Drug Interactions of Angiotensin-Converting Enzyme Inhibitors The antihypertensive effectiveness of ACEIs is reduced by administration of the NSAIDs Haveles (p. 203) Chronic administration for several days may result in an increase in the patient’s blood pressure ACEIs may be used alone or in combination with a β-blocker, thiazide diuretic, or CCB Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 95 Examples of Angiotensin-Converting Enzyme Inhibitors for Hypertension Haveles (p. 196) (Box 15-4) benazepril (Lotensin) captopril (Capoten) enalapril (Vasotec) fosinopril (Monopril) lisinopril (Zestril, Prinivil) moexipril (Univasc) perindopril (Aceon) quinapril (Accupril) ramipril (Altace) trandolapril (Mavik) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 96 Angiotensin Receptor Blockers Haveles (p. 203) ARBs attach to the angiotensin II receptor and block the effect of angiotensin II losartan (Cozaar) is the prototype losartan a high affinity and selectivity for the AT1receptor It blocks the vasoconstrictor and aldosteronesecreting effects of angiotensin II An increase in plasma renin level follows Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 97 Adverse Reactions of Angiotensin Receptor Blockers Haveles (p. 203) ARBs are more specific than ACEIs and may be expected to have fewer adverse reactions CNS: effects can include dizziness, fatigue, insomnia, and headache Upper respiratory infections occur more often in patients taking losartan GI: losartan can produce diarrhea Pain: both muscle cramps and leg and back pain have been reported with losartan Angioedema can occur, rarely Teratogenicity can occur if losartan is administered to pregnant women Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 98 Dental Drug Interactions of Angiotensin Receptor Blockers Haveles (p. 203) NSAIDs may antagonize the antihypertensive effect of losartan by inhibiting renal prostaglandin synthesis or causing sodium and fluid retention Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 99 Examples of Angiotensin Receptor Blockers Haveles (p. 196) (Box 15-4) candesartan (Atacand) eprosartan (Tevetan) irbesartan (Avapro) losartan (Cozaar) olmesartan (Benicar) telmisartan (Micardis) valsartan (Diovan) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 100 Renin Inhibitors Haveles (p. 203) aliskiren (Tekturna): the first of a new class of drugs approved by the U.S Food and Drug Administration for treatment of hypertension Works by binding to renin which then reduces the levels of angiotensin I, angiotensin II, and aldosterone Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 101 α1-Adrenergic Blocking Agents for Hypertension Haveles (p. 204) The adrenergic blockers include the αblockers and β-blockers previously described Two α-receptor subtypes have been identified, α1 and α2 Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 102 Mechanism of α1-Adrenergic Blocking Agents for Hypertension α1-Receptors, located on postsynaptic receptor tissues, produce vasoconstriction and increase peripheral resistance when stimulated α1-Blocking agents produce peripheral vasodilation in the arterioles and venules that decreases peripheral vascular resistance α1-Adrenergic blockers result in a reduction in urethral resistance and pressure, bladder outlet resistance, and urinary symptoms Used in management of older men who have an enlarged prostate gland Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 103 Adverse Reactions of α1-Adrenergic Blocking Agents for Hypertension Haveles (p. 204) Orthostatic hypotension: can result in dizziness or syncope CNS: α1-adrenergic blockers can cause CNS depression, producing either drowsiness or excitation and headache Cardiovascular: tachycardia, arrhythmias, and palpitations can occur Peripheral edema is another side effect Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 104 Dental Drug Interactions of α1Adrenergic Blocking Agents for Hypertension Haveles (p. 204) (Box 15-7) NSAIDs, especially indomethacin, can reduce antihypertensive effect of the α1-blockers Inhibit renal prostaglandin synthesis or cause sodium and fluid retention cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 105 Dental Drug Interactions of α1Adrenergic Blocking Agents for Hypertension Haveles (p. 204) (Box 15-7) Epinephrine: sympathomimetics can increase the antihypertensive effect of doxazosin α1-Blockers prevent α1-agonist effects (vasoconstriction) of epinephrine, leaving the β1agonist and β2-agonist effects (vasodilation) to predominate Can result in severe hypotension and reflex tachycardia Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 106 Uses of α1-Adrenergic Blocking Agents for Hypertension Haveles (p. 204) Both doxazosin and terazosin are indicated for the management of benign prostatic hypertrophy (BPH) in addition to the treatment of hypertension Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 107 Examples of α1-Receptor Antagonists (Blockers) for Hypertension Haveles (p. 196) (Box 15-4) doxazosin (Cardura) prazosin (Minipress) terazosin (Hytrin) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 108 Other Antihypertensive Agents Haveles (p. 204) These antihypertensive agents are used less often than those previously described because they generally have more or less tolerated adverse reactions Clonidine Other centrally acting antihypertensive agents • Guanethidine • Reserpine • Hydralazine Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 109 clonidine (Catapres) A CNS-mediated (centrally acting) antihypertensive drug that reduces peripheral resistance through a CNS-mediated action on the α-receptor Haveles (p. 204) Stimulation of presynaptic central α2-adrenergic receptors results in decreased sympathetic outflow Reduces heart rate, cardiac output, and total peripheral resistance May be administered orally or by transdermal patch Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 110 Adverse Reactions of Clonidine Include a high incidence of sedation and dizziness Haveles (p. 204) Rapid elevation of blood pressure has occurred with abrupt discontinuation CNS depressants employed in dental conscious-sedation techniques may contribute to postural hypotension when used in a patient taking clonidine Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 111 Oral Effects of Clonidine Haveles (p. 204) A high incidence of xerostomia (40%), parotid gland swelling, and pain Another side effect is dysgeusia Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 112 Other Centrally Acting Antihypertensive Agents Two other centrally acting antihypertensive agents are also available Haveles (pp. 204-205) methyldopa (Aldomet) and guanabenz (Wytensin) Adverse effects and indications are similar to clonidine May be combined with diuretics in essential hypertension management Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 113 guanethidine (Ismelin) Severe adverse reactions severely limits its use Blocks the release of norepinephrine from the sympathetic nerve endings Haveles (pp. 198, 204-205) (Fig. 15-5) Also depletes the amount of norepinephrine stored in synaptic vesicles Reduces sympathetic nervous system tone and decreases blood pressure Causes severe postural and exertional hypotension Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 114 Reserpine Haveles (p. 205) Depletes norepinephrine from the sympathetic nerve endings Adverse effects include diarrhea, bad dreams, sedation, and even psychic depression leading to suicide Aggravates peptic ulcers Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 115 hydralazine (Apresoline) Acts directly on arterioles to reduce peripheral resistance (vasodilation) At the same time a rise in heart rate and output occurs Haveles (p. 205) Propranolol is often administered concurrently to reduce the tachycardia and increased cardiac output Side effects include cardiac arrhythmias, angina, headache, and dizziness The drug of choice for treatment of a pregnant hypertensive woman Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 116 Management of the Dental Patient Taking Antihypertensive Agents Haveles (p. 205) (Box 15-8) Check for xerostomia and its management If taking a CCB, check for gingival enlargement Check blood pressure before each appointment Avoid dental agents that add to side effects such as opioids If on diuretics, check for symptoms of hypokalemia, which may exacerbate arrhythmias from epinephrine If taking an ACEI, check for symptoms of neutropenia cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 117 Management of the Dental Patient Taking Antihypertensive Agents Haveles (p. 205) Adverse reactions Xerostomia Dysgeusia Gingival enlargement Orthostatic hypotension Constipation Central nervous system sedation Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 118 Antihyperlipidemic Agents Haveles (pp. 205-207) 3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors Niacin Cholestyramine Gemfibrozil Dental Implications cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 119 Antihyperlipidemic Agents Haveles (p. 205) Hyperlipidemia and hyperlipoproteinemia are elevations of plasma lipid concentrations above accepted normal values These metabolic distortions include elevations in cholesterol and/or triglycerides and are associated with the development of arteriosclerosis Many different types of hyperlipoproteinemias may result in elevations of chylomicrons, very-low-density lipoproteins (VLDLs), low-density lipoproteins (LDLs), or combinations of these cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 120 Antihyperlipidemic Agents Foam cells, more prevalent in uncontrolled diabetes, become filled with cholesterol esters Accumulation of esters leads to deposition of lipids in arteries Collagen and fibrin also accumulate, occluding the vessels Atherosclerosis can lead to coronary artery disease, myocardial infarction, and cerebral artery disease Endothelium over the plaques activates platelets leading to formation of thrombi and clinical symptoms cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 121 Antihyperlipidemic Agents Haveles (p. 205) Cholesterol and other plasma lipids are carried in the blood as protein complexes to make them more soluble in plasma LDLs carry the greatest concentration of cholesterol and are considered to be the most dangerous High-density lipoproteins (HDLs) carry the least cholesterol and are considered to be beneficial cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 122 Antihyperlipidemic Agents The first line of treatment is increasing exercise and decreasing saturated fat and cholesterol from the diet Haveles (pp. 205-206) (Table 15-12) Drug therapy of hyperlipoproteinemia is directed at lowering the level of LDL cholesterol Some are more specific for cholesterol and some are more specific for triglycerides Drugs include bile acid-binding resins, niacin, gemfibrozil, and HMG CoA reductase inhibitors Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 123 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Often called “statins” because generic names end in that suffix Haveles (p. 206) lovastatin (Mevacor) is an example They lower cholesterol levels by inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 124 Adverse Effects of 3-Hydroxy-3Methylglutaryl Coenzyme A Reductase Inhibitors Haveles (p. 206) GI complaints, myositis, skin rash, impotence, hepatotoxicity, blurred vision, and lens opacities Myositis results in complaints of muscle pain Can increase anticoagulant effect of warfarin Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 125 Inhibitors of Intestinal Absorption of Cholesterol Haveles (pp. 206-207) ezetimibe (Zetia): works by inhibiting intestinal absorption of cholesterol Currently comes in combination with simsvastin to treat cholesterol from two different mechanisms of action Side effects include fatigue, abdominal pain, and diarrhea Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 126 Niacin Haveles (p. 207) Overview A B vitamin: in large doses, lowers cholesterol levels by inhibiting the secretion of VLDLs without accumulation of triglycerides in the liver At larger doses, commonly produces cutaneous flushing and a sensation of warmth after each dose • This is blocked by pretreatment with aspirin or ibuprofen Hyperuricemia, allergic reactions, cholestasis, and hepatotoxicity have been reported Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 127 Dental Implications of Niacin Haveles (p. 207) Hypotension may occur as a result of vasodilation Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 128 Cholestyramine Haveles (p. 207) Bile acid–binding resins lower cholesterol because cholesterol is a precursor required for the synthesis of new bile acids When the resins bind with bile acids, they produce an insoluble product lost through the GI tract Bile acids use up cholesterol, thereby reducing cholesterol levels cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 129 Cholestyramine Adverse reactions relate to the GI tract and include constipation and bloating Patients often abandon their use Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 130 gemfibrozil (Lopid) Haveles (p. 207) Used to treat hyperlipidemias, especially when triglycerides are elevated Increases lipolysis of triglycerides, decreasing lipolysis in adipose tissue, and inhibiting secretion of VLDLs from the liver cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 131 Gemfibrozil Adverse reactions Can promote gallstone formation (cholelithiasis) Taste perversion and hyperglycemia have been reported Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 132 Dental Implications of Antihyperlipidemic Agents Haveles (p. 207) Patients who take antihyperlipidemic agents have a higher risk of atherosclerosis and are at increased risk for cardiovascular emergencies (not because of the drug but because of the condition for which the drug is prescribed) GI and liver abnormalities are side effects associated with many of these drugs Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 133 Examples of Antihyperlipidemic Agents HMG-CoA reductase inhibitors (statins) Haveles (p. 206) (Table 15-10) atorvastatin (Lipitor) fluvastatin (Lescol) lovastatin (Mevacor) pravastatin (Pravachol) simvastatin (Zocor) Bile acid sequestrants cholestyramine (Questran, Prevalite) colestipol (Colestid) cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 134 Examples of Antihyperlipidemic Agents Miscellaneous Haveles (p. 206) (Table 15-10) clofibrate (Atromid-S) ezetimibe (Zetia) ezetimibe/simvastin (Vytorin) nicotinic acid (Niacin) fibrates fenofibrate (Lipidil-DSC, Tricor) gemfibrozil (Lopid) Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 135 Drugs that Affect Blood Coagulation Anticoagulants Haveles (pp. 207-211) Hemostasis Warfarin Heparin Clopidogrel Ticlopidine Streptokinase and alteplase Dipyridamole Pentoxifylline Drugs that increase blood clotting Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 136 Anticoagulants Haveles (p. 207) Drugs that interfere with coagulation Administered in an attempt to prevent clotting Examples of indications for warfarin (Coumadin) are after a MI or thrombophlebitis Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 137 Hemostasis Haveles (pp. 207-208) (Fig. 15-8) Designed to prevent loss of blood after injury to a blood vessel Thromboplastin; factors V, VII, and X; and calcium ions form prothrombin, thrombin, and finally fibrinogen and fibrin Fibrin, along with vascular spasms, platelets, and red blood cells quickly forms the clot cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 138 Hemostasis If the blood vessel’s interior remains smooth, circulating blood does not clot If internal injury to the vessel occurs and a roughened surface develops, intravascular clotting will take place Many factors required in the clotting process are synthesized in the liver Prothrombin (II) and factors VII, IX, and X require vitamin K for synthesis Warfarin antagonizes vitamin K and interferes with the synthesis of four clotting factors to produce an anticoagulant effect cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 139 Hemostasis Intravascular clots can form in certain diseases Clots or thrombi may break off, forming emboli that lodge in the smaller vessels of major organs such as the heart, brain, and lungs Anticoagulant therapy attempts to reduce intravascular clotting If the dose is too large, hemorrhage may occur If the dose is too small, the danger of embolism remains Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 140 Warfarin (Coumadin) An oral anticoagulant that blocks the γcarboxylation of glutamate residues in the synthesis of factors VII, IX, and X, prothrombin (II), and endogenous anticoagulant protein C Haveles (pp. 208-209) Prevents the metabolism of the inactive vitamin K epoxide back to its active form The pharmacologic effect is delayed when therapy begins and ends cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 141 Warfarin (Coumadin) Haveles (p. 208) (Fig. 15-9) Monitoring: the effect of warfarin is monitored using the INR A function of the prothrombin time (PT) of the patient, PT of control, and the international sensitivity index (ISI) The target INR for most indications is between 2 and 3, it can range from 1 to 4 cont’d… Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 142 Warfarin (Coumadin) Haveles (p. 208) Adverse reactions: the most common adverse effects are various forms of bleeding Look for petechial hemorrhages on the hard palate Ecchymoses can occur, even without trauma Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 143 Warfarin-Aspirin Interaction Haveles (p. 208) (Table 15-11) Patients taking warfarin should not be given aspirin or aspirin-containing products, bleeding episodes or fatal hemorrhages can result Aspirin causes hypoprothrombinemia and alters platelet adhesiveness • Can irritate the gastrointestinal tract Aspirin and warfarin compete for the same plasma protein-binding site • Increases the proportion of free (unbound) warfarin in the blood Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 144 Warfarin-Acetaminophen Interaction Haveles (p. 209) A statistically significant association was found between acetaminophen use and the abnormal elevation of the INR Toxicity has not been proved Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 145 Warfarin-Antibiotics Interaction Haveles (p. 209) (Table 15-12) Antibiotics can potentiate the effect of warfarin Antibiotics reduce the bacterial flora in the GI tract that normally synthesize vitamin K This results in a decrease in vitamin K absorbed Because warfarin also inhibits vitamin K–dependent factors, an added anticoagulant effect occurs This interaction does not have a chance to develop when antibiotics are used before a dental procedure Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 146 Management of the Dental Patient Taking Warfarin Haveles (p. 209) (Box 15-9) Bleeding: consult with physician regarding PT or INR Analgesics: aspirin is contraindicated unless the patient is taking one aspirin daily for its anticoagulant effect Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 147 Heparin One of the most commonly used anticoagulant agents for hospitalized patients Haveles (pp. 209-210) Administered by injection; not used orally Used after MI, stroke (embolism), or thrombophlebitis When heparin is started, warfarin is also begun An overdose of heparin is antagonized by protamine sulfate Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 148 clopidogrel (Plavix) Haveles (p. 210) An inhibitor of adenosine diphosphate (ADP)induced platelet aggregation Indicated for patients with recent history of MI or stroke, established peripheral arterial disease, and for patients with acute coronary artery syndrome Side effects include thrombotic thrombocytopenia purpura (TTP) and increased bleeding Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 149 ticlopidine (Ticlid) Haveles (p. 211) An irreversible inhibitor of ADP-induced platelet aggregation, which results in increased bleeding time Indicated to decrease thrombotic stroke in patients with previous stroke Used in patients who are intolerant of aspirin Major side effect is neutropenia Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 150 streptokinase (Streptase, Kabikinase) and alteplase (tPA, Activase) Haveles (p. 211) Enzymes, called “clotbusters” are sometimes used in the therapy of deep vein thrombosis, arterial thrombosis, pulmonary embolism, and acute coronary artery thrombosis associated with myocardial infarction Called thrombolytic drugs because they promote conversion of plasminogen to plasmin, the natural clot-resolving enzyme Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 151 dipyridamole (Persantine) Haveles (p. 211) Used to prolong the life of platelets in patients with prosthetic heart valves Artificial valves cause premature death of platelets due to their mechanical effect (trauma) on blood cells passing through the valves Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 152 pentoxifylline (Trental) Haveles (p. 211) Improves blood flow by its hemorheologic effect Lowers blood viscosity and improves flexibility of red blood cells Indicated for claudication (limping) produced by chronic occlusive artery disease of the limbs Side effects include cardiovascular and gastric symptoms Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 153 Drugs that Increase Blood Clotting Haveles (p. 211) Hemostatic Agents (fibrinolytic inhibitors) Aminocaproic acid (EACA) and tranexamic acid (Cyklokapron) are similar to the amino acid lysine, and they inhibit plasminogen activation Adverse effects include intravascular thrombosis, hypotension, and abdominal discomfort • Used in the treatment of hemorrhage after surgery Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 154