C ALCIUM C HANNEL B LOCKERS (CCB) Maureen McGuinness, RN (Karch, 2013)

L EARNING O BJECTIVES Upon completion of this power-point presentation, the student will be able to: 1) Describe the three classifications of calcium channel blockers and their mode of action 2) Actively monitor patients for signs/symptoms and adverse reactions to calcium channel blockers, in order to respond and maintain patient safety. 3) Verbalize the differences between verapamil/diltiazem and amlodipine; describe their appropriate uses, in order to safely administer the medication.

T YPE /C LASS M ECHANISM OF A CTION I NDICATIONS CCB inhibit transport of calcium into myocardial and vascular smooth muscle cells, resulting in inhibition of excitation- contraction coupling and subsequent contraction. (Calcium channel blockers: classification, mechanism of action and indications, 2013)

CCB – C LASSIFICATION OF A GENTS V binding site D binding site N binding site (Calcium channel blockers: classification, mechanism of action and indications, 2013)

CCB - M ECHANISM OF A CTION (Calcium channel blockers: classification, mechanism of action and indications, 2013) CCB bind to specific receptor sites

CCB - M ECHANISM OF A CTION dihydropiridines Minimal effect on cardiac conduction or heart rate, Potent actions as arteriolar vasodilators verapamil and diltiazem Slow AV conduction Decrease SA node automaticity Decrease heart rate (Calcium channel blockers: classification, mechanism of action and indications, 2013)

M ECHANISM OF A CTION The mechanism of action of CCBs in hypertension is based on their vasodilator properties The effectiveness of all agents is similar, with no evidence to suggest that one drug is better than the other The use of the once-daily administered drug, e.g. amlodipine, felodipine and lercanidipine, is preferred to aid compliance Calcium channel blockers also have a role in isolated systolic hypertension in the elderly (Salama, 2008).

I NDICATIONS FOR U SE Tissue selectivities differ between agents Tissue selectivities differ between agents verapamil is more cardioselective verapamil is more cardioselective dihydropyridines are relatively smooth muscle selective dihydropyridines are relatively smooth muscle selective diltiazem has intermediate properties diltiazem has intermediate properties Clinical uses include hypertension, angina (by reducing cardiac work and antidysrhythmic action), and in the case or verapamil mainly in supraventricular arrhythmias. Clinical uses include hypertension, angina (by reducing cardiac work and antidysrhythmic action), and in the case or verapamil mainly in supraventricular arrhythmias. When prescribing refer to specific indication and license of the specific calcium channel blocker as differences exist When prescribing refer to specific indication and license of the specific calcium channel blocker as differences exist (Salama, 2008).

C OMMON T RADE N AMES Cardizem (diltiazem); Norvasc (amlodipine); Calan (Verapamil)

C ARDIZEM ( DILTIAZEM ) Therapeutic Class Antianginals, antiarrhythmics (class IV), antihypertensives Antianginals, antiarrhythmics (class IV), antihypertensivesIndications Hypertension, Angina pectoris and vasospastic (Prinzmetal's) angina, Supraventricular tachyarrhythmias and rapid ventricular rates in atrial flutter or fibrillation Hypertension, Angina pectoris and vasospastic (Prinzmetal's) angina, Supraventricular tachyarrhythmias and rapid ventricular rates in atrial flutter or fibrillation Evaluation/Desired Outcomes Decrease in BP, frequency and severity of anginal attacks Decrease in BP, frequency and severity of anginal attacks Suppression and prevention of tachyarrhythmias Suppression and prevention of tachyarrhythmias (Davis Drug Guide, 2013)

N ORVASC ( AMLODIPINE ) Therapeutic Class antihypertensives antihypertensivesIndications Alone or with other agents in the management of hypertension, angina pectoris, and vasospastic (Prinzmetal's) angina Alone or with other agents in the management of hypertension, angina pectoris, and vasospastic (Prinzmetal's) angina Evaluation/Desired Outcomes Decrease in BP, frequency and severity of anginal attacks Decrease in BP, frequency and severity of anginal attacks (Davis Drug Guide, 2013)

C ALAN (V ERAPAMIL ) Therapeutic Class Antianginals, antiarrhythmics (class IV), antihypertensives, vascular headache suppressants Antianginals, antiarrhythmics (class IV), antihypertensives, vascular headache suppressantsIndications Management of hypertension, angina pectoris, and/or vasospastic (Prinzmetal's) angina Management of hypertension, angina pectoris, and/or vasospastic (Prinzmetal's) angina Management of supraventricular arrhythmias and rapid ventricular rates in atrial flutter or fibrillation Management of supraventricular arrhythmias and rapid ventricular rates in atrial flutter or fibrillation Evaluation/Desired Outcomes Decrease in BP and severity of anginal attacks Decrease in BP and severity of anginal attacks Suppression and prevention of atrial tachyarrhythmias Suppression and prevention of atrial tachyarrhythmias (Davis Drug Guide, 2013)

C ONTRAINDICATIONS P RECAUTIONS A DVERSE E VENTS D IETARY AND H ERBAL C ONSIDERATIONS

C ONTRAINDICATIONS Cardizem (diltiazem)Norvasc (amlodipine)Calan (Verapamil) Hypersensitivity Sick sinus syndrome 2nd- or 3rd-degree AV block (unless an artificial pacemaker is in place) Systolic BP <90 mm Hg Recent MI or pulmonary congestion Concurrent use of rifampin. Hypersensitivity; Systolic BP <90 mm Hg. Hypersensitivity Sick sinus syndrome 2nd- or 3rd-degree AV block (unless an artificial pacemaker is in place) Systolic BP <90 mm Hg HF, severe ventricular dysfunction, or cardiogenic shock, unless associated with supraventricular tachyarrhythmias; Concurrent IV beta blocker therapy (Davis Drug Guide, 2013)

P RECAUTIONS Cardizem (diltiazem)Norvasc (amlodipine)Calan (Verapamil) Severe hepatic impairment (↓ dose recommended) Geri: ↓ dose; slower IV infusion rate recommended; ↑ risk of hypotension; consider age-related decrease in body mass, ↓ hepatic/renal/cardiac function, concurrent drug therapy and other disease states Severe renal impairment Serious ventricular arrhythmias or HF OB: Lactation: Pedi: Safety not established. Severe hepatic impairment (↓ dose recommended) Aortic stenosis; History of HF; OB: Lactation: Pedi: Safety not established; Geri: (↓ dose recommended) ↑ risk of hypotension. Severe hepatic impairment (↓ dose recommended) History of serious ventricular arrhythmias or HF; Geri: Dose ↓/slower IV infusion rates recommended (↑ risk of hypotension); OB: Lactation: Safety not established. (Davis Drug Guide, 2013)

C OMMON S IDE E FFECTS & A DVERSE E VENTS SystemCardizem (diltiazem) Norvasc (amlodipine) Calan (Verapamil) CV ARRHYTHMIAS, HF, peripheral edema, bradycardia, chest pain, hypotension, palpitations, syncope, tachycardia peripheral edema, angina, bradycardia, hypotension, palpitations ARRHYTHMIAS, HF, bradycardia, chest pain, hypotension, palpitations, peripheral edema, syncope, tachycardia GI ↑ liver enzymes, anorexia, constipation, diarrhea, dry mouth, dysgeusia, dyspepsia, nausea, vomiting gingival hyperplasia, nausea ↑ liver enzymes, anorexia, constipation, diarrhea, dry mouth, dysgeusia, dyspepsia, nausea, vomiting GU dysuria, nocturia, polyuria, sexual dysfunction, urinary frequency * CAPITALS indicate life-threatening. Italics indicate most frequent (Davis Drug Guide, 2013)

C OMMON S IDE E FFECTS & A DVERSE E VENTS SystemCardizem (diltiazem) Norvasc (amlodipine) Calan (Verapamil) DERM STEVENS-JOHNSON SYNDROME, dermatitis, erythema multiforme, flushing, sweating, photosensitivity, pruritus/urticaria, rash flushing dermatitis, erythema multiforme, flushing, photosensitivity, pruritus/urticaria, rash, sweating ENDO gynecomastia, hyperglycemia HEMAT anemia, leukopenia, thrombocytopenia METABweight gain MS joint stiffness, muscle cramps * CAPITALS indicate life-threatening. Italics indicate most frequent (Davis Drug Guide, 2013)

C OMMON S IDE E FFECTS & A DVERSE E VENTS SystemCardizem (diltiazem) Norvasc (amlodipine) Calan (Verapamil) NEUROparesthesia, tremor MISCgingival hyperplasia STEVENS-JOHNSON SYNDROME, gingival hyperplasia (Davis Drug Guide, 2013)

C OMMON D IETARY C ONSIDERATIONS Cardizem (diltiazem) Norvasc (amlodipine) Calan (Verapamil) DIETARY Grapefruit juice ↑ levels and effect. Grapefruit juice ↑ serum levels and effect. ↑ caffeine levels with caffeine-containing herbs (cola nut, guarana, mate, tea, coffee). (Davis Drug Guide, 2013)

C OMMON H ERBAL C ONSIDERATIONS Herbs Cardizem (diltiazem) Norvasc (amlodipine) Calan (Verapamil) Arnica May  effectiveness of antihypertensives Astragalus, BarberryMay ↑effectiveness of antihypertensives BayberryMay block effects of antihypertensives Black cohosh rootMay lower blood pressure Cats claw, parsley seeds, Increased hypotension when taken with antihypertensives Chinese angelicaMonitor patients on antihypertensives for toxic effects Coleus forskolin Use caution when taking with antihypertensives, severe additive effects can occur DHEARisk of interactions with calcium channel blockers (Karch, 2013)

C OMMON H ERBAL C ONSIDERATIONS Herbs Cardizem (diltiazem) Norvasc (amlodipine) Calan (Verapamil) DHEARisk of interactions with calcium channel blockers GoldensealMay interfere with antihypertensives Guayusa, melatonin, mistletoe leaves, rue extract Advise caution with antihypertensives Mau huangWarn against use with antihypertensives (Karch, 2013)

N URSING C ONSIDERATIONS

N URSING C ONSIDERATIONS VERAPAMIL AND DILTIAZEM Monitor BP and pulse before, during titration and periodically during therapy. Monitor BP and pulse before, during titration and periodically during therapy. Monitor ECG periodically during prolonged therapy. Monitor ECG periodically during prolonged therapy. Monitor intake and output ratios and daily weight. Monitor intake and output ratios and daily weight. Assess for rash and signs of HF. Assess for rash and signs of HF. Monitor patient compliance with medication regimen. Monitor patient compliance with medication regimen. Monitor routine serum digoxin levels for signs and symptoms of digoxin toxicity. Monitor routine serum digoxin levels for signs and symptoms of digoxin toxicity. For treatment of Angina monitor for location, duration, intensity, and precipitating factors of patient's anginal pain For treatment of Angina monitor for location, duration, intensity, and precipitating factors of patient's anginal pain For treatment of Arrhythmias monitor EKG report bradycardia or prolonged hypotension promptly For treatment of Arrhythmias monitor EKG report bradycardia or prolonged hypotension promptly (Davis Drug Guide, 2013)

L AB C ONSIDERATIONS : VERAPAMIL AND DILTIAZEM Total serum calcium concentrations are not affected by calcium channel blockers. Total serum calcium concentrations are not affected by calcium channel blockers. Monitor serum potassium periodically. Hypokalemia ↑ risk of arrhythmias and should be corrected. Monitor serum potassium periodically. Hypokalemia ↑ risk of arrhythmias and should be corrected. Monitor renal and hepatic functions periodically during long-term therapy. May cause ↑ hepatic enzymes after several days of therapy, which return to normal on discontinuation of therapy. Monitor renal and hepatic functions periodically during long-term therapy. May cause ↑ hepatic enzymes after several days of therapy, which return to normal on discontinuation of therapy. (Davis Drug Guide, 2013)

N URSING C ONSIDERATIONS : AMLODIPINE Monitor BP and pulse before therapy, during dose titration, and periodically during therapy. Monitor ECG periodically during prolonged therapy. Monitor BP and pulse before therapy, during dose titration, and periodically during therapy. Monitor ECG periodically during prolonged therapy. Monitor intake and output ratios and daily weight. Assess for signs of HF (peripheral edema, rales/crackles, dyspnea, weight gain, jugular venous distention). Monitor intake and output ratios and daily weight. Assess for signs of HF (peripheral edema, rales/crackles, dyspnea, weight gain, jugular venous distention). Angina: Assess location, duration, intensity, and precipitating factors of patient's anginal pain. Angina: Assess location, duration, intensity, and precipitating factors of patient's anginal pain. Lab Test Considerations: Total serum calcium concentrations are not affected by calcium channel blockers. Total serum calcium concentrations are not affected by calcium channel blockers. (Davis Drug Guide, 2013)

Q UESTIONS

Q UESTION # 1 1) Mr. Jones is being discharged from the hospital with a new prescription for Norvasc (amlodipine) for hypertension. He is concerned about the side effects. The nurse explains common side effects include: (Choose the best answer). a) ARRHYTHMIAS, HF, peripheral edema, bradycardia, chest pain, hypotension, palpitations, syncope, tachycardia b) Peripheral edema, angina, bradycardia, hypotension, palpitations, gingival hyperplasia, nausea, flushing c) Dermatitis, erythema multiforme, flushing, photosensitivity, pruritus/urticaria, rash, sweating d) ↑ liver enzymes, anorexia, constipation, diarrhea, dry mouth, dysgeusia, dyspepsia, nausea, vomiting Answer B Rationale: Norvasc (Amlodipine) is a third generation dihydropiridines which has minimal effect on cardiac conduction or heart rate, while having potent actions as arteriolar vasodilators.

Q UESTION # 2 2) Mrs. Francis is currently receiving calcium channel blockers for angina. The nurse understands that she must: (Select all that apply). a) Perform a physical assessment to establish baseline status before beginning therapy and during therapy b) Inspect skin color and integrity c) Monitor laboratory test results, including liver and renal function tests d) All of the above Answer: D a) Rationale: Establish baseline to determine the effectiveness and evaluate for any potential adverse events. Inspect skin color and integrity to identify possible adverse skin reactions. Monitor lab results to determine the need for possible dose adjustments.

Q UESTION # 3 3) After teaching a patient who is receiving verapamil for long-term treatment of angina, the nurse determines that the patient has understood the teaching when the patient identifies what potential adverse effect? (Select all that apply) a) a) Hypotension b) b) Palpitations c) c) Anorexia d) d) Increased exercise tolerance Answer: A, B, C Rationale: Hypotension, palpations and anorexia are all symptoms of adverse reactions, increased exercise tolerance is not.

R EFERENCES Calcium channel blockers: classification, mechanism of action and indications. (2013). Retrieved November 21, 2013, from Pharmacology Corner: Davis Drug Guide. (2013, August 20). Retrieved from Nursing Central: Karch, A. M. (2013). Focus on nursing pharmacology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkin. Salama, R. (2008). Calcium channel blockers: uses and prescribing rationale. Nurse Prescribing, 6(4),