Lowers the risk of coronary heart disease by 53% These patients can be allowed a year of lifestyle 2. No target damage

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1 This guideline is based on the National Heart, Blood and Lung Institute s Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (1997). Lowers the risk of stroke by 60% TARGET ORGAN DAMAGE of HTN APPROPRIATE TREATMENT OF HYPERTENSION (HTN) Lowers the risk of coronary heart disease by 53% Lowers the risk of renal failure MAJOR RISK FACTORS for HTN 1. Heart disease: Left ventricular hypertrophy Angina/prior myocardial infarction Heart fa ilure 2. Stroke or transient ischemic attack 3. Peripheral arterial disease 4. Nephropathy 5. Retinopathy TREATMENT DECISION Smoking Dyslipidemia Gender (men and menopausal women) Diabetes mellitus Age older than 60 years Family history of cardiovascular disease The decision to treat hypertension aggressively is based not only on the patient s level of blood pressure, but also on their placement in the following groups: Group A: Group A: 1. No clinical cardiovascular disease These patients can be allowed a year of lifestyle 2. No target damage intervention before prescribing medications. 3. No risk factors Group B: 1. No clinical cardiovascular disease 2. No target damage 3. One or more risk factors (excluding diabetes mellitus) Group C: 1. Clinical cardiovascular disease 2. Target damage 3. Diabetes mellitus or renal insufficiency Group B: Unless multiple risk factors are present, these patients can be given six months of lifestyle intervention before prescribing medications. Group C: These patients should be considered for prompt pharmacologic therapy. DETERMINING CATEGORY OF HYPERTENSION Category Systolic* Diastolic* Follow-up Group A Group B Group C Optimal < 120 < 80 Normal < 130 < 85 Check in 2 yrs High Normal Check in 1 yr Lifestyle Lifestyle Meds Hypertension Stage Check < 2 mos Lifestyle (12 mos) Lifestyle (6 mos) Meds Stage Eval < 1 mo Meds Meds Meds Stage 3 > 180 > 110 Eval < 1 wk Meds Meds Meds *The highest number, either systolic or diastolic, should be used to determine patients stages of hypertension. 1

2 APPROPRIATE WORK-UP FOR PATIENTS WITH HYPERTENSION History: Duration of hypertension Symptoms or history of coronary heart disease Congestive heart failure Cerebral vascular disease Peripheral vascular disease Renal disease Diabetes Dyslipidemia Family history of hypertension, coronary disease, stroke, diabetes, dyslipidemia, renal disease Change in weight Exercise level Diet history Medications including over-the-counter meds Effects of prior therapy for hypertension Physical Exam: >2 blood pressure (BP) measurements supine, seated, and standing after 2 minutes Confirmation of BP in contralateral arm Fundoscopic exam for retinopathy ENT neck bruits, neck vein distention, enlarged thyroid Heart rate and rhythm, size, heaves, clicks, murmurs, 3 rd and 4 th heart sounds Lungs bronchospasm and rales Abdomen bruits, kidney size, masses, abdominal pulsations Extremities edema and pulses Optional Laboratory: Creatinine clearance Complete blood count 24-hour urine for protein Calcium Uric acid Triglycerides, LDL Glycohemoglobin Thyroid stimulating hormone (TSH) Echocardiogram WHEN TO CONSIDER SECONDARY CAUSES OF HYPERTENSION Necessary Laboratory: Urinalysis Electrolytes, BUN, creatinine, glucose, cholesterol, HDL cholesterol Electrocardiogram (ECG) Initial work-up suggests a secondary cause due to age of patient, history, exam, severity of HTN, or laboratory studies Blood pressure responds poorly to therapy Blood pressure changes after initially being controlled Stage-3 hypertension Sudden onset of hypertension associated with headache, pallor, palpitations, and/or diaphoresis suggestive of pheochromacytoma Abdominal bruit suggestive of renovascular disease Flank mass suggestive of polycystic kidneys Decreased femoral pulses or low BP in the lower extremities suggestive of aortic coarctation Truncal obesity suggestive of Cushing s syndrome and stria Low potassium suggestive of primary hyperaldosteronism Elevated calcium suggestive of hyperparathyroidism Elevated creatinine or abnormal urinalysis suggestive of renal disease LIFESTYLE MODIFICATION FOR HYPERTENSION PREVENTION AND MANAGEMENT Prescribe weight loss if patient is overweight. Limit alcohol intake to no more than 1 oz (30 ml) ethanol (e.g., 24 oz beer, 10 oz wine, or 2 oz 100-proof whiskey) per day or 0.5 oz (15 ml) ethanol per day for women and lighter weight people. Increase aerobic physical activity (30-45 minutes most days of the week). Reduce sodium intake to no more than 100 mmol per day (2.4 g sodium or 6 g sodium chloride). Maintain adequate intake of dietary potassium (approximately 90 mmol per day). Maintain adequate intake of dietary calcium and magnesium for general health. Prescribe smoking cessation, when appropriate. Reduce intake of dietary saturated fat and cholesterol for overall cardiovascular health. 2

3 CONSIDERATIONS FOR INDIVIDUALIZING ANTIHYPERTENSIVE DRUG THERAPY Indication Compelling Indications (unless contraindicated) Diabetes mellitus (type 1) with or without proteinuria.. Drug Therapy Angiotensin-Converting Enzyme (ACE) inhibitors, Angiotensin Receptor Blockers (ARBs) Heart failure ACE inhibitors, diuretics Isolated systolic hypertension (older patients)...diuretics (preferred), calcium antagonists Myocardial infarction.beta-blockers (non-intrinsic Sympathomimetic Activity [ISA]), ACE inhibitors (with systolic dysfunction), ARBs May Have Favorable Effects on Comorbid Conditions Angina Beta-blockers, calcium antagonists Atrial tachycardia and fibrillation...beta-blockers, some calcium antagonists Cyclosporine-induced hypertension (caution with the dose of cyclosporine) Calcium antagonists Diabetes mellitus (types 1 & 2 ) with proteinuria. Ace inhibitors (preferred), calcium antagonists Diabetes mellitus (type 2). Low-dose diuretics Dyslipidemia. Alpha-blockers Essential tremor. Beta-blockers (non-cardioselective) Heart failure Beta-blockers, ACE inhibitors, ARB Hyperthyroidism Beta-blockers Migraine Beta-blockers (non-cardioselective), (non-dihydropyridine) Myocardial infarction Diltiazem, Verapamil Osteoporosis.. Thiazides Preoperative hypertension. Beta-blockers Prostatism (BPH) Alpha-blockers Renal insufficiency (caution in renovascular hypertension and creatinine = mmol/l [3mg/dL]) ACE inhibitors May Have Unfavorable Effects on Comorbid Conditions+ Bronchospastic disease Beta-blockers* Depression Beta-blockers, central alpha-agonists, reserpine* Diabetes mellitus (types 1 & 2 ).. Beta-blockers, high-dose diuretic Dyslipidemia.Beta-blockers (non-isa), high-dose diuretics Gout Beta-blockers, some calcium antagonists* Second or third degree heart block.. Diuretics Heart failure. Beta-blockers (except carvedilol), calcium antagonists, (except amlodipine besylate, felodipine) Liver disease Labetolol Hcl, methyldopa* Peripheral vascular disease.. Beta-blockers Pregnancy. Ace inhibitors, angiotensin II receptor blockers* Renal insufficiency...potassium-sparing agents Renovascular disease Ace inhibitors, angiotensin II receptor blockers +These drugs may be used with special monitoring unless *Contraindicated contraindicated. If there is no compelling indication, consider a diuretic or a beta-blocker as a first-line agent. If response to the first medication is inadequate after titrating to the full dose, add a drug from a different class, or, if the first medication is not well tolerated, substitute a medication from a different class. In general, if a diuretic is not selected as the first-line agent, it should be considered second. 3

4 ALGORITHM FOR THE TREATMENT OF HYPERTENSION Begin or Continue Lifestyle Modifications Not at Goal Blood Pressure (<140/90mmHg) Lower goals for patients with diabetes or renal disease Initial Drug Choices (unless contraindicated) UNCOMPLICATED HYPERTENSION: Diuretics Beta-blockers COMPELLING INDICATIONS: Heart Failure: ACE Inhibitors Diuretics COMPELLING INDICATIONS: Diabetes mellitus (type 1) with or without proteinuria:* ACE Inhibitors Isolated Systolic Hypertension (older persons) Diuretics (preferred) Long-acting Dihydropyridine Calcium Antagonists COMPELLING INDICATIONS: Myocardial Infarction: Beta-blockers (non-isa) ACE Inhibitors Not at Goal Blood Pressure No Response or Troublesome Side Effects Inadequate Response but Well-Tolerated Substitute Another Drug from a Different Class Add a Second Agent from a Different Class Not at Goal Blood Pressure Continue Adding Agents from Other Classes Consider Referral to a Hypertension Expert * Recent studies have shown that the use of ACE inhibitors can be beneficial in preventing onset of proteinuria. 4

5 FOLLOW- UP FOR PATIENTS WITH HYPERTENSION 1. Patients should be seen within 1-2 months after starting therapy or sooner if there are associated medical problems. 2. Once stabilized, subsequent visits can be scheduled at 3-6 month intervals. POTENTIAL CAUSES OF INADEQUATE RESPONSE TO THERAPY RESISTA NT HYPERTENSION OCCURS WHEN BLOOD PRESSURE CANNOT BE CONTROLLED on a THREE-DRUG REGIMEN Drug-Related Causes: Doses too low Inappropriate combinations Rapid inactivation (e.g., hydralazine) Drug actions and interactions including: Sympathomimetics Nasal decongestants Appetite suppressants Cocaine and other illicit drugs Caffeine Oral contraceptives Adrenal steroids Licorice (as may be found in chewing tobacco) Cyclosporine, tacrolimus Erythropoietin Antidepressants Non-steroidal anti-inflammatory drugs Non-adherence to therapy (see below) Pseudoresistance: White coat hypertension or office elevations Pseudohypertension in older adults Use of regular cuff on very obese arm Volume Overload: Excess salt intake Progressive renal damage (nephrosclerosis) Fluid retention from reduction of blood pressure Inadequate diuretic therapy Associated Conditions: Smoking Increasing obesity Sleep apnea Insulin resistance/hyperinsulinemia Ethanol intake of more than 1 oz (30 ml) per day Anxiety-induced hyperventilation or panic attacks Chronic pain Intense vasoconstriction (arteritis) Organic brain syndrome (e.g., memory deficit) GUIDELINES TO IMPROVE PATIENT ADHERENCE TO ANTIHYPERTENSIVE THERAPY Be aware of signs of patient non-adherence to antihypertensive therapy. Clearly communicate the goal of therapy: to reduce blood pressure to non-hypertensive levels with minimal or no adverse effects. Educate patients about the disease, and involve them and their families in its treatment. Maintain contact with patients; consider telecommunication or nurse follow-up by phone. Keep care inexpensive and simple. Encourage lifestyle modifications. Integrate pill-taking into routine activities of daily living. Prescribe medications according to pharmacologic principles favoring formulations. Be willing to stop unsuccessful therapy and try a different approach. Anticipate adverse effects, and adjust therapy to prevent, minimize, or ameliorate side effects. Continue to add effective and tolerated drugs, stepwise in sufficient doses to achieve the goal of therapy. Encourage a positive attitude about achieving therapeutic goals. Consider using nurse case management. 5

6 HYPERTENSIVE CRISIS Hypertensive crisis occurs when immediate blood pressure reduction is required to limit target organ damage. The goal is to lower mean arterial blood pressure by 25% within 2 hours, then to 160/100 within 6 hours. The following conditions constitute a hypertensive crisis: Hypertensive encephalopathy Intracranial hemorrhage Unstable angina pectoris Acute myocardial infarction Acute left ventricular failure with pulmonary edema Dissecting aneurysm Eclampsia HYPERTENSION IN PREGNANCY Optic disc edema Progressive target organ complications Perioperative hypertension Chronic hypertension in pregnancy (as opposed to blood pressure elevation in preeclampsia and eclampsia) is defined as hypertension present prior to pregnancy or up to the 20 th week. The Report of the NHBPEP Working Group on High Blood Pressure in Pregnancy permits continuation of drug therapy in women with chronic hypertension (except ACE inhibitors or angiotensin II receptor blockers). In women with chronic hypertension with diastolic levels of 100 mmhg or greater (lower when end organ damage or underlying renal disease is present) and in women with acute hypertension when levels are 105 mmhg or greater, the following agents are suggested. Suggested Drug Central alpha-agonists Beta-blockers Calcium antagonists ACE inhibitors, angiotensin II receptor blockers Diuretics Direct vasodilators Comments Methyldopa is the drug of choice recommended by the NHBPEP Working Group. Atenolol and metopropolol appear to be safe and effective in late pregnancy. Labetolol also appears to be effective (alpha and beta-blockers). Beta-blockers in early pregnancy may cause fetal growth retardation. Potential synergism with magnesium sulfate may lead to precipitous hypotension. Fetal abnormalities, including death, can be caused, and these drugs should not be used in pregnancy. Diuretics are recommended for chronic hypertension if prescribed before gestation or if patients appear to be saltsensitive. They are not recommended in preeclampsia. Hydralazine is the parenteral drug of choice, based on its long history of safety and efficacy. 6

7 Drug Dose Onset of Action VASODILATORS Sodium nitroprusside µg/kg per minute as IV infusion (maximal dose for 10 min only) 2002 Clinical Practice Guidelines PARENTAL DRUGS FOR TREATMENT OF HYPERTENSIVE EMERGENCIES Duration of Action Adverse Effects may occur with all agents Immediate 1-2 min Nausea, vomiting, muscle twitching, sweating, thiocynate and cyanide intoxication Special Indications Most hypertensive emergencies; caution with high intracranial pressure or azotemia Nicardipine hydrochloride 5-15 mg/h IV 5-10 min 1-4 hr Tachycardia, headache, flushing, local phlebitis Most hypertensive emergencies except acute heart failure; caution with coronary ischemia Fenoldopam mesylate µg/kg per min IV infusion < 5 min 30 min Tachycardia, headache, nausea, flushing Most hypertensive emergencies; caution with glaucoma Nitroglycerin 5-100µg/min as IV infusion 2-5 min 3-5 min Headache, vomiting, methemoglobinemia, tolerance with prolonged use Enalaprilat mg every 6 hr IV min 6 hr Precipitous fall in pressure in high-renin states; response variable Coronary ischemia Acute left ventricular failure; avoid in acute myocardial infarction Hydralazine hydrochloride mg IV; mg IM min; min 3-8 hr Tachycardia, flushing, headache, vomiting, aggravation of angina Eclampsia Diazoxide mg IV bolus repeated; or mg/min infusion 2-4 min 6-12 hr Nausea, flushing, tachycardia, chest pain Now obsolete, when intensive monitoring available ADRENERGIC INHIBITORS Labetalol hydrochloride Esmolol hydrochloride mg IV bolus every 10 min mg/min IV infusion µg/kg/min for 1 min, then µg/kg/min for 4 min; may repeat sequence -2 min 5-10 min 3-6 hr Vomiting, scalp tingling, burning in throat, dizziness, nausea, heart block, orthostatic hypotension Most hypertensive emergencies except acute heart failure 1-2 min min Hypotension, nausea Aortic dissection, perioperative Phentolamine 5-15 mg IV 1-2 min 3-10 min Tachycardia, flushing, headache Catecholamine excess 7

8 O RAL ANTIHYPERTENSIVE DRUGS: DIURETICS (partial list) GENERAL SIDE EFFECTS Short-term: increases cholesterol and glucose levels. Biochemical abnormalities: decreases potassium, sodium and magnesium levels, increases uric acid and calcium levels. Rare: blood dyscrasias, photosensitivity, pancreatitis, hyponatremia. Drug Trade Name Dose Range/mg Selected Side Effects and Comments (frequency/day) Chlorthalidone Hygroton (1) Hydrochlorothiazide Hydrodiuril, Microzide, (1) Esidrix Indapamide Lozol (1) Less or no hypercholesterolemia Metolazone Mykrox; Zaroxolyn (1) (1) LOOP DIURETICS Bumetanide Bumex (2-3) Short duration of action; no hypercalcemia Ethacrynic acid Edecrin (2-3) Only non-sulfonamide diuretic; ototoxicity Furosimide Lasix (2-3) Short duration of action; no hypercalcemia Torsemide Demadex (1-2) POTASSIUM-SPARING AGENTS Hyperkalemia Amiloride hydrochloride Midamor 5-10 (1) Spironalactone Aldactone (1) Gynecomastia Triamterene Dyrenium ORAL ANTIHYPERTENSIVE DRUGS: CALCIUM ANTAGONISTS NONHYDROPYRADINES Conduction defects, worsening of systolic dysfunction, gingival hyperplasia Diltiazem hydrochloride Cardizem SR, Cardizem CD, (1-2) Nausea, headache Dilacor XR, Tiazac Verapamil hydrochloride Isoptin SR, Calan SR, (2) Constipation Verelan, Covera HS (2) DIHYDROPYRIDINES Edema of the ankle, flushing, headache, gingival hypertrophy Amlodipine besylate Norvasc (1) Felodipine Plendil (1) Isradipine DynaCirc 5-20 (1-2) Nicardipine Cardene SR (2) Nifedipine Procardia XL; Adalat CC (1) Nisoldipine Sular (1) 8

9 ORAL ANTIHYPERTENSIVE DRUGS: ADRENERGIC INHIBITORS GENERAL SIDE EFFECTS Alpha blockers: postural hypotension. Beta-blockers: bronchospasm, bradycardia, heart failure, may mask insulin-induced hypoglycemia. Less serious: impaired peripheral circulation, insomnia, fatigue, decreased exercise tolerance, hypertriglyceridemia except agents with intrinsic sympathomimetic activity. Drug Trade Name Dose Range/mg Selected Side Effects and Comments (frequency/day) PERIPHERAL AGENTS Guanadrel Hylorel (2) Postural hypotension, diarrhea Guanethidine monosulfate Ismelin (1) Postural hypotension, diarrhea Reserpine Serpasil (1) Nasal congestion, sedation, depression, activation of peptic ulcer Central alpha-agonists Sedation, dry mouth, depression, activation of peptic ulcer Clonidine hydrochloride Catapres (2-3) More withdrawal Guanabenz acetate Wytensin 8-32 (2) Guanfacine hydrochloride Tenex 1-3 (1) Less withdrawal Methyldopa Aldomet 500-3,000 (2) Hepatic and autoimmune disorders ALPHA-BLOCKERS Doxazosin mesylate Cardura 1-16 (1) Prazosin hydrochloride Minipress 2-30 (2-3) Terazosin hydrochloride Hytrin 1-20 (1) BETA-BLOCKERS Acebuterolol Sevtral (1) Atenolol Tenormin (1-2) Betaxolol Kerlone 5-20 (1) Bisoprolol fumarate Zebeta (1) Carteolol hydrochloride Cartrol (1) Metoprolol tartrate Lopressor (2) Metoprolol succinate Toprol-XL (1) Nadolol Corgard (1) Penbutolol sulfate Levatol (1) Pindolol Vishken (2) Propranolol hydrochloride Inderal (1-2) Timolol maleate Blocadren (2) COMBINED ALPHA- AND BETA-BLOCKERS Carvedilol Coreg (2) Labetalol hydrochloride Normodyne, Trandate 200-1,200 (2) 9

10 Drug Trade Name Dose Range/mg (frequency/day) ANGIOTENSIN II CONVERTING ENZYME (ACE) Inhibitors Benazepril hydrochloride Lotensin 5-40 (1-2) Captopril Capoten (2-3) Enalapril maleate Vasotec 5-40 (1-2) Fosinopril sodium Monopril (1) Lisinopril Prinivil, Zestril 5-40 (1) Moexipril Univasc (2) Quinapril hydrochloride Accupril 5-80 (1-2) Ramipril Altace (1-2) Trandolapril Mavik 1-4 (1) ANGIOTENSIN II RECEPTOR BLOCKERS Losartan potassium Cozaar (1-2) Valsartan Diovan (1) Irbesartan Avapro (1) GENERAL SIDE EFFECTS Headache, fluid retention, tachycardia 2002 Clinical Practice Guidelines ORAL ANTIHYPERTENSIVE DRUGS: ANGIOTENSIN II AGENTS Selected Side Effects and Comments Common: cough Rare: angioedema, hyperkalemia, rash, loss of taste, leukopenia Angioedema (very rare), hyperkalemia ORAL ANTIHYPERTENSIVE DRUGS: DIRECT VASODILATORS Drug Trade Name Dose Range/mg Selected Side Effects and Comments (frequency/day) Hydralazine hydrochloride Apresoline (2) Lupus syndrome Minoxidil Loniten (1) Hirsutism 10

11 Drug BETA-ADRENERGIC BLOCKERS AND DIURETICS Atenolol, 50 or 100mg/Chlorthalidone, 25mg Bisoprolol fumigate, 2.5, 5, or 10mg/hydrochlorothiazide, 25mg Metoprolol tartrate, 50 or 100mg/hydrochloroth iazide, 6.25mg Nadolol, 40 or 80mg/bendroflumethiazide, 5mg Propranolol hydrochloride, 40 or 80mg/hydrochlorothiazide, 25mg Propranolol hydrochloride (extended release), 80, 120, or 160mg/hydrochlorothiazide, 50mg Timolol maleate, 10mg/hydrochlorothiazide, 25mg ACE INHIBITORS AND DIURETICS Benazepril hydrochloride, 5, 10, or 20mg/hydrochlorothiazide 6.25, 12.5, or 25mg Captopril, 25 or 50mg/hydrochlorothiazide 15 or 25mg Enalapril maleate, 5 or 10mg/hydrochlorothiazide 12.5 or 25mg Lisinopril, 10 or 20mg/hydrochlorothiazide 12.5 or 25mg ANGIOTENSIN II RECEPTOR ANTAGONISTS AND DIURETICS Losartan potassium, 50mg/hydrochlorothiazide 12.5mg CALCIUM ANTAGONISTS AND ACE INHIBITORS Amlodipine besylate, 2.5 or 5mg/benazepril hydrochloride, 10 or 20mg Diltiazem hydrochloride, 180mg/enalapril maleate, 5mg Verapamil hydrochloride (extended release), 180 or 240mg/trandolapril, 1, 2, or 4mg Felodipine, 5mg/Enalapril maleate, 5mg OTHER COMBINATIONS Triamterene, 37.5, 50, or 75mg/hydrochlorothiazide 25 or 50mg Spironolactone, 25 or 50mg/hydrochlorothiazide 25 or 50mg Amiloride hydrochloride, 5mg/hydrochlorothiazide 50mg Guanethidine monosulfate, 10mg/hydrochlorothiazide, 25mg Hydralazine hydrochloride, 25, 50 or 100mg/hydrochlorothiazide 25 or 50mg Methyldopa, 250 or 500mg/hydrochlorothiazide 15, 25, 30 or 50mg Reserpine, 0.125mg/hydrochlorothiazide 25 or 50mg Reserpine, 0.10mg/hydralazine hydrochloride, 25mg/hydrochlorothiazide 15mg Clonidine hydrochloride, 0.1, 0.2, or 0.3mg/chlorthalidone 15mg Methyldopa, 250mg/chlorothiazid,. 150 or 250mg Reserpine, or 0.25mg/chlorthalidone, 25 or 50mg Reserpine, or 0.25mg/chlorothiazide, 250 or 500mg Prazosin hydrochloride, 1,2, or 5mg/polythiazide, 0.5mg 2002 Clinical Practice Guidelines ORAL ANTIHYPERTENSIVE DRUGS: COMBINATION DRUGS FOR HYPERTENSION Trade Name Tenoretic Ziac Lopressor HCT Corzide Inderide Inderide LA Timolide Lotensin HCT Capozide Vaseratic Prinzide, Zestoretic Hyzaar Lotrel Teczem Tarka Lexxel Dyazide, Maxzide Aldactazide Moduretic Esimil Apresazide Aldoril Hydropres Ser-Ap-Es Combipres Aldochlor Demi-Regroton Diupres Minizide 11

12 SELECTED DRUG INTERACTIONS WITH ANTIHYPERTENSIVE THERAPY Class of Agent Increase Efficacy Decrease Efficacy Effect on Other Drugs Diuretics Diuretics that act at different sites in the nephron (e.g., furosemide + thiazides) Resin-binding agents NSAIDs Steroids Diuretics raise serum lithium levels Potassium-sparing agents may exacerbate hyperkalemia due to ACE inhibitors Beta-blockers ACE inhibitors Calcium antagonists Alpha-blockers Central alpha 2 - agonists and peripheral neuronal blockers Cimetidine (hepatically metabolized beta-blockers) Quinidine (hepaticallymetabolized beta-blockers) Food (hepaticallymetabolized beta-blockers) Chlorpromazine or clozapine Grapefruit juice (some dihydropyridines) Cimetidine or ranitidine (hepatically-metabolized calcium antagonists) NSAIDs Withdrawal of clonidine Agents that induce hepatic enzymes, including rifampin and phenobarbital NSAIDs Antacids Food decreases absorption (moexipril) Agents that induce hepatic enzymes, including rifampin and phenobarbital Tricyclic antidepressants (and probably phenothiazines) Monamine oxidase inhibitors Sympathomimetics or phenothiazines antagonize guanethidine monosulfate or guanadrel sulfate Iron salts may reduce methyldopa absorption Propranolol hydrochloride induces hepatic enzymes to increase clearance of drugs with similar metabolic pathways Beta-blockers may mask and prolong insulin-induced hypoglycemia Heart block may occur with nondihydropyridine calcium antagonists Sympathomimetics cause unopposed alpha-adrenoceptor-mediated vasoconstriction Beta-blockers increase angina-inducing potential of cocaine ACE inhibitors may raise serum lithium levels ACE inhibitors may exacerbate hyperkalemia effect of potassiumsparing diuretics Cyclosporine levels increase with diltiazem hydrochloride, verapamil hydrochloride, mibefradil dihydrochloride, or nicardipine hydrochloride (but not felodipine, isradipine, or nifedipine) Nondihydropyridines increase levels of other drugs metabolized by the same hepatic enzyme system, including digoxin, quinidine sulfonylureas, and theophylline Verapamil hydrochloride may lower serum lithium levels Prazosin may decrease clearance of verapamil hydrochloride Methyldopa may increase serum lithium levels Severity of clonidine hydrochloride withdrawal may be increased by beta-blockers Many agents used in anesthesia are potentiated by clonidine hydrochloride MS