Chapter 16 Coronary Artery Disease and Antianginal Medications

Chapter 16 Coronary Artery Disease and Antianginal Medications Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 1

Drug Overview Sublingual Tablet Ø nitroglycerin (key drug), isosorbide dinitrate Translingual Spray Transdermal Patch Topical Ointment Oral Ø nitroglycerin, isosorbide dinitrate, isosorbide mononitrate Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 2

Indications Labeled Uses Ø Acute angina, angina prophylaxis Unlabeled Uses Ø CHF, AMI, Raynaud’s phenomenon, PVD Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 3

Pathophysiology Lesions Ø Ø Increased Myocardial Oxygen Demand Ø Ø Atherosclerotic process Total occlusion by thrombus Exercise, stress, fluctuations in BP and HR Vasospasm, platelet plugging, partial occlusion by thrombus Catecholamine Release Ø Ø Response to exertional and emotional stress or activity Produces increased oxygen demand ischemia Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 4

Disease Process Risk Factors Framingham study • NCEP Expert Panel Ø Traditional factors Ø Inflammatory markers • CRP: Highly sensitive but lacks specificity Ø Associated with prevalence of atherosclerosis, risk of recurrent cardiovascular events, metabolic syndrome, smoking, type 2 DM, dyslipidemias • Homocysteine Associated with poor dietary folate, vitamins B 6 and B 12 deficiency, and renal insufficiency Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 5

Disease Process Risk Factors (cont’d) Lp(a): Lipoprotein (a) • Possesses an atherogenic effect • Associated with diabetes or elevated LDL Ø Fibrinogen: Plasma protein • Important role in thrombosis • Measurement is not reliable Ø Collagen vascular disease • Recently identified: Lupus and rheumatoid Ø Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 6

Mechanism of Action Angina Pectoris Antianginal drug classes • Nitrates • β-Blockers (see Chapter 18) • Calcium channel blockers (see Chapter 19) Ø Nitrates • Relax vascular smooth muscle via stimulation of Ø intracellular cyclic GMP • Reduce myocardial oxygen demand Decreasing preload primarily (some afterload decrease) Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 7

Mechanism of Action Ø Nitrates (cont’d) • Major dilation of venous bed • Minor effects Reduction in afterload through arterial relaxation Decrease in myocardial work and oxygen consumption Improvement in myocardial oxygen supply – Dilation of coronary arteries – Increased use of coronary collaterals Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 8

Treatment Principles Standardized Guidelines Management of Patients with Chronic Stable Angina (American College of Cardiology, 2002) Ø ACC/AHA Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction, 2004 Ø Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 9

Treatment Principles Evidence-Based Recommendations Ø Stable angina • β-Blockers • Calcium channel blockers • Nitrates • Potassium channel openers Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 10

Treatment Principles Cardinal Points of Treatment Control of acute attack of angina • Nitrates Ø Long-term management • Long-acting nitrate • β-Blocker • ACE inhibitor • Calcium channel blocker • Aspirin • Consideration of revascularization Ø Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 11

Treatment Principles Risk Reduction—Key Component Ø Ø Ø Hypertension Cigarette smoking Lipid abnormalities Diabetes mellitus Obesity Physical inactivity Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 12

Treatment Principles Acute Anginal Attack NTG sublingually at 3 - to 5 -minute intervals for three doses Ø If worse or unimproved: 911 Ø Oxygen 2 L/min via cannula Ø ASA 325 mg (chew) Ø Transport Ø Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 13

Treatment Principles Chronic Stable Angina/Prevention/ Post–Myocardial Infarction Management Ø Ø See Tables 16 -1 and 16 -2 Prophylaxis • Long-acting transdermal patch • Oral sustained-release tablet • Topical ointment Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 14

How to Monitor Record of PRN Use Review Record at Follow-up Visits Evaluate Ø Ø Ø Increased frequency Multiple dosing to eliminate symptoms Changes in activity that produce angina Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 15

Patient Variables Geriatrics Ø Ø Ø Pediatrics Ø Risk of syncope Administer while seated or lying down Usually require lower doses of nitrates Safety and efficacy have not been established Pregnancy and Lactation Ø Category C: Safety has not been established Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 16

Patient Education NTG Is Very Unstable Ø Ø Heat and sunlight accelerate loss in potency Storage considerations • Container • Temperature • Expiration date Side Effects: Natural and Predictable Ø Flushing, headache, increased heart rate, and dizziness/light-headedness when changing position Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 17

Patient Education Notify Provider Ø Blurring of vision, persistent headache, dry mouth Take As Directed: May Prevent Damage to the Myocardium Tolerance May Occur Record Frequency, Number of Pills Taken, and Side Effects Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 18

Patient Education Use NTG in Anticipation of Situations Where They Can Predict Anginal Attacks Will Occur Do Not Change NTG Products Without Notifying the Provider Avoid ETOH Do Not Stop Taking NTG Abruptly Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 19

Patient Education Sublingual Tablets Let medication dissolve; do not chew or swallow Ø If pain is worse or unimproved, call EMS Ø May repeat after 3 to 5 minutes for a maximum of three doses Ø Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 20

Patient Education Translingual Spray Metered dose: Dispenses 200 doses of 0. 4 mg of nitroglycerin Ø Shelf-life: 2 to 3 years Ø No refrigeration Ø Highly flammable Ø Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 21

Patient Education Transdermal Patch Apply to a hairless spot May wash, bathe, or swim Do not cut or tear patch If patch comes off, discard and replace at a new site with a new patch Ø Keep out of reach of children Ø Ø Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 22

Patient Education Topical Ointment Ø Ø Apply thin layer to skin with applicator and ruler Do not rub or massage into the skin Wash off medication that may be on hands Discard used paste in a safe place out of reach of children Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 23

Patient Education Oral Medication Take on an empty stomach and follow with a glass of water Ø Isosorbide dinitrate: Take 30 minutes to 1 hour before meals; allow 12 -hour nitrate-free period to prevent tolerance Ø Isosorbide mononitrate: Take on waking, then 7 hours later; with sustained-release products, do not crush or chew Ø Dosing schedule: 8 AM, 1 PM, 6 PM Ø Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 24

Sublingual Nitroglycerin (Nitrostat) Contraindications Ø Hypersensitivity, severe anemia, closed-angle glaucoma, postural hypotension, early MI, head trauma, cerebral hemorrhage Warnings/Precautions Use with caution in AMI; avoid use of longacting nitrates Ø Postural hypotension may occur Ø May aggravate angina caused by idiopathic hypertrophic cardiomyopathy Ø Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 25

Sublingual Nitroglycerin (Nitrostat) Warnings/Precautions (cont’d) Ø Ø Ø Tolerance Caution in patients with open-angle glaucoma Excessive dosage side effects Volume depleted or hypotensive patients Withdrawal reactions Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 26

Sublingual Nitroglycerin (Nitrostat) Pharmacokinetics (see Table 16 -3) isosorbide mononitrate • Metabolized by liver • Not subject to first-pass effect • Nearly 100% bioavailability Ø isosorbide dinitrate • Metabolized by liver • Subject to first-pass effect • 40% to 50% bioavailability Ø Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 27

Sublingual Nitroglycerin (Nitrostat) Adverse Effects CNS: HA, light-headedness, syncope, anxiety, weakness Ø GI: N/V/D, dyspepsia, abdominal pain Ø CV: Tachycardia, hypotension, crescendo angina, rebound hypertension, arrhythmias, PVCs, postural hypotension Ø Dermatologic: Rash, exfoliative dermatitis, cutaneous vasodilation Ø Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 28

Sublingual Nitroglycerin (Nitrostat) Adverse Effects (cont’d) Miscellaneous: Perspiration, blurred vision, diplopia, edema Ø Transdermal patch: Skin reaction caused by NTG system, not the NTG molecule Ø Do not use defibrillator over NTG patch Ø Ointment may cause topical skin reactions, anaphylactoid swelling of oral mucosa, and edema of conjunctiva Ø Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 29

Sublingual Nitroglycerin (Nitrostat) Drug Interactions Ø See Table 16 -4 Dosage and Administration SL tablets: 0. 3 mg, 0. 4 mg (most common dosage), 0. 6 mg; under tongue Ø Translingual spray: 0. 4 mg metered dose; spray onto or under tongue Ø Topical 2% ointment (15 mg/inch): ½ inch to 2 inches; first dose on awakening, second dose 6 hours later Ø Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 30

Sublingual Nitroglycerin (Nitrostat) Dosage and Administration (cont’d) Isosorbide dinitrate, oral: 5, 10, 20, 30, and 40 mg scored oral tablets; 40 mg sustainedrelease tablets Ø Isosorbide dinitrate, sublingual • Prophylaxis: 2. 5 to 5 mg 2 to 3 hours before Ø anticipated angina; do not crush/chew Ø Isosorbide dinitrate, extended release: Take on an empty stomach Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 31

Sublingual Nitroglycerin (Nitrostat) Dosage and Administration (cont’d) Ø Isosorbide mononitrate, oral: 10 and 20 mg tablets; 60 mg extended-release tablets • Tablets: 20 mg bid (on awakening and 7 hours later) • Extended-release tablets: 30 mg (½ tablet) to 60 mg in AM; may be increased to 120 to 240 mg Ø Isosorbide mononitrate, extended release: Take with fluid, do not crush/chew Mosby items and derived items © 2009, 2004 by Mosby, Inc. , an affiliate of Elsevier Inc. 32