Angina PDF

Angina KYCO Pharm I Amanda Blankenship, MS, PharmD, RPh Objectives: • Diagnose and recognize the three main types of angina • List targets for antianginal drugs • List main categories of antianginal drugs • Explain mechanism of action for antianginal drugs • List primary side effects for antianginal...

Angina KYCO Pharm I Amanda Blankenship, MS, PharmD, RPh Objectives: • Diagnose and recognize the three main types of angina • List targets for antianginal drugs • List main categories of antianginal drugs • Explain mechanism of action for antianginal drugs • List primary side effects for antianginal drugs • List comorbid conditions where antianginal drugs are commonly used • Describe contraindications or drug interactions for selected antianginal drugs • Describe mechanism of action for major drugs used for hyperlipidemia • Identify specific side effects of these drugs Angina Pectoris: • Severe pain, squeezing, or tightness in the chest, often spreading to the shoulders, arms, and neck • Pathophysiology: Caused by inadequate blood supply to the heart (tissue ischemia) Ischemic Heart Disease (IHD) • Acute Coronary Syndrome: any constellation of clinical signs or symptoms suggestive of MI, STEMI, NSTEMI, Angina • Can last from 15s to 15min • Often diaphoretic and nauseated • No myocyte necrosis • Classified by: symptom severity, • For example: specific activity • Treatment goals: • Reduce the frequency and intensity of anginal attacks • Increase the functional capacity of the patient • Decrease the overall progression of coronary artery disease (CAD) • #1 Primary treatment for ALL types of IHD is Lifestyle modifications What is Coronary Artery Disease (CAD) • AKA: Ischemic Heart Disease (IHD) • Coronary atherosclerotic plaque formation that leads to an imbalance between oxygen supply and demand resulting in myocardial ischemia • • Prime determinants: • Caliber of the resistance of vessels delivering blood (dilation, constriction, diameter, stenosis (narrowing), pressure changes) • Oxygen demand (heart rate, contractility, intramyocardial wall tension during systole) Silent ischemia: episodes of ischemia that do not cause angina Three types of Angina: 1. Stable Angina • Stable (Classic, angina of effort, exercise-induced)): Most common • Usually secondary to atherosclerosis (generally stenosis > 70%, coronary arteries cannot meet oxygen demand of the heart during exercise) • Exertional chest pain in classic distribution (diagnosis is with ECG in exercise) • Resolved with rest or nitroglycerin • Treatment: We will cover in more detail in later • Nitrates: vasodilator effect on the peripheral veins and arteries thereby decreasing N preload (left ventricular end diastolic pressure)and coronary artery dilation improves B collateral flow to ischemic regions C • Beta blockers: decrease the oxygen demands of the heart by slowing the HR and Newsworthy reducing the force of the heart muscle contraction (tell the doc) • Calcium channel blocker: cause vasodilation of smooth muscle in peripheral vasculature but not an to decease the oxygen demands of the heart; dilation of the coronary vessels to emergency: increase oxygen delivery; inhibition of myocardium contraction Stable • Anti-platelet agent 2. Unstable Angina • Thrombosis with incomplete coronary artery occlusion (May have ST depression (Not elevation) and/or T-wave inversion on ECG) • Cardiac biomarker will be normal (unlike NSTEMI: Non-ST elevation myocardial infarction) CK and Troponins • Pain at rest; increased during activity • If pain occurs at rest (diagnosis NOT with ECG in exercise: coronary angiography) • Thought to be induced by a ruptured atherosclerotic plaque that leads to a to thrombosis and embolization • More likely to lead to a MI than Stable • Treatment: Nickolas Cage • Nitrates Brittany Spears • Beta-blockers are Unstable • Statins for lipid management • Anticoagulants or platelet inhibitors are also used • Note: Unlike beta blockers, drugs like verapamil and diltiazem have not been proven to decrease the risk for heart attack and death in Unstable Angina 3. Variant (Prinzmetal) Angina Not triggered by • Also called vasospastic exertion or elevated by • Intermittent chest pain at rest rest • Not related to stress, activity, or BP • Oxygen delivery decreases as a result of reversible coronary vasospasm • Secondary to coronary artery spasm (Transient ST elevation on ECG) • Ischemia on ECG monitoring is more likely to be detected in the early morning hours • Often at night • Smoking is a risk factor (hypertension and hypercholesterolemia are not) • Triggers: Cocaine, stress, cold, alcohol, tobacco, and triptans (but cause is unknown) Variant • Treatment: (Beta Blockers NOT efficacious) New • Calcium channel blockers: Relaxation of coronary vessels and reducing spasm (vasodilatation) COVID • Nitrates: Relaxation of coronary vessels and reducing spasm (vasodilation) • Smoking cessation Medication used for Treatment of Angina: Nitrates: (Treats ALL three types of angina) • Oldest and most commonly prescribed antianginal agents • MOA: causes the formation of Nitric oxide (NO) → leading to activation of guanylate cyclase→ increasing cGMP→ relaxation via dephosphorylation of myosin light chains (Vasodilator {↓ preload (mostly) and afterload}, ↓ workload, ↓ Oxygen demands of heart, ↑oxygen delivery to heart) • Selective direct-acting smooth muscle relaxant • • • • • • • • • • • • • Highly lipid soluble and crosses membranes with ease, thus, can be administered via many routes (pill, spray, ointment, patch, IV) Mechanism of action is the same with all delivery routes (pharmacokinetics is the only difference) Contraindication: Phosphodiesterase-5 (PDE-5) inhibitors (sildenafil, tadalafil, vardenafil): can cause extreme hypotension and death Adverse Effect: Headache, hypotension, reflex tachycardia, intracranial pressure increase Use caution in patients ≥ 65 and a history of syncope (due to nitrates potential to exacerbate episodes of syncope) NTG SL: DOC for prompt relief DOC for prophylaxis of stable or vasospastic angina Dinitrate & Mononitrate slower onset of action NOT for acute attack (prevention) Do not crush or chew formulations Tachyphylaxis: rapidly diminishing response to successive doses of a drug, making it less effective (dose escalation does not overcome this, only nitrate absence) “Nitrate free interval”: 6-8 hours at night when there is deceased demand on the heart Ex: Nitro patches are worn 12 hours on and 12 hours off in variant angina Their angina worsens early in the mornings perhaps due to circadian catecholamine surges, so nitrate-free interval should be late in the afternoon Nitrates Dosage Form Onset Duration NTG: nitroglycerin IV SL Spray Topical Patch ER Immediate 1-3 minutes 1-3 minutes 15-30 minutes 30 minutes 60 minutes 3-5 minutes 25 minutes 25 minutes 7 hours 12 hours 4-8 hours Isosorbide Dinitrate SL IR SR and ER 2-5 minutes 20-40 minutes 1 hour 1-2 hours Up to 8 hours (2-3 times a day dosing) Isosorbide Mononitrate Oral (IR and ER) 30-40 minutes IR: ≥ 6 hours ER: ≥ 24 hours (Daily to BID dosing) Beta Blockers: (Stable and Unstable) Atenolol, Metoprolol, Propranolol • MOA: Inhibition of the beta receptors on the myocardium ↓ both the heart rate and the force of contraction, leading to a ↓ of myocardial oxygen demand, ↓afterload • As the HR slows, the diastolic period is prolonged, enabling increased oxygen delivery by improving myocardial perfusion • Not used for vasospastic angina • May worsen such attacks by blocking some β2 receptors that produce vasodilator effects, leaving α-mediated effects unopposed • Side Effects: Sexual Dysfunction: #1 cause of noncompliance in men, Lethargy which usually goes away over time, Bradycardia • *Beta blocker therapy must be discontinued gradually over 5-10 days to avoid rebound angina or hypertension* • Contraindicated: Brittle diabetics and Heart block • Use Caution in Asthma patients • Note: do not us BB that has intrinsic sympathomimetic activity (IPA): are less effective (ex: pindolol) Calcium Channel Blockers (CCB): Variant and Stable (Can use in Unstable but not first line) • MOA: Block Calcium entry into the myocardial and smooth muscle cells, causing muscular relaxation and vascular dilation (primarily in the arterioles and coronary arteries) ↓oxygen demands of heart, ↑ oxygen delivery, ↓ afterload *have little effect on venous beds so not affect preload • Uses: All types of angina (including vasospastic) • SE: Edema, Flushing, Headache, Constipation • Not use in HF (edema), Bradycardia (esp. Non-DHP), caution adding beta blocker (cause heart block) Types of CCB: 1. Dihydropyridines: (Higher affinity for the peripheral vessels) • Nifedipine (Procardia, Adalat CC) Note: can cause gingival hyperplasia and hypotension • Amlodipine (Norvasc): also used to treat Raynaud phenomenon • Side effect: edema, reflex tachycardia (may worsen ischemia) 2. Non-Dihydropyridines: Higher affinity for the heart. Also cause negative inotropy due to slowing of SA and AV node conduction. CYP 3A4 Inhibitors • Papaverine derivatives (Higher affinity for the heart): • Verapamil (Calan) (Non-DHP) • CYP 3A4 Inhibitor • Benzothiazapine derivatives (More divided, but still more affinity for the heart) • Diltiazem (Cardizem) (Non-DHP) • Verapamil and Diltiazem also classified and non-dihydropyridines • Adverse Effects: Constipation and gingival hyperplasia • Non-DHPs contraindicated in Atrioventricular Block (AV Block): slow the HR through the AV node • Vascular smooth muscle: amlodipine = nifedipine > diltiazem > verapamil • Heart: verapamil > diltiazem > amlodipine = nifedipine Ranolazine (Ranexa): Late sodium current blocker • MOA: prevents late inward sodium (late INa channel) entry into cells, which prevents Calcium overload and diastolic depoloriaztion • Calcium overload causes electrical instability, contractile dysfunction, and consumption of ATP • Decreases work load of the heart and ischemia Exerts antianginal and anti-ischemic effects without changing hemodynamic parameters (heart rate or blood pressure) • Use as adjunct (not first line) • Adverse Effect: May prolong QT interval (may cause Torsade's)