pharm 1 Exam 3.docx

HF 18 antiarrhythmic 16 antianginal 16 ACS 15 antiplatelets 10 bonus 3 (past disease states) *see page 37 for treatment of specific arrhythmias and STEMI/NSTEMI treatment HEART FAILURE: Indicate when medications are indicated in heart failure beta blockers (bisoprolol, metoprolol, carvedilol)...

HF 18 antiarrhythmic 16 antianginal 16 ACS 15 antiplatelets 10 bonus 3 (past disease states) *see page 37 for treatment of specific arrhythmias and STEMI/NSTEMI treatment HEART FAILURE: Indicate when medications are indicated in heart failure beta blockers (bisoprolol, metoprolol, carvedilol) Explain the rationale for using beta blockers (BB) in left ventricular (LV) systolic dysfunction based on the neurohormonal model of HF. BBs reverse hypertrophy and slow left ventricle dilation reduce circulating NA, AT2, and endothelin1 Abate further necrosis/apoptosis of cardiac cells State the types of HF patients that should not receive beta blockers (BB). Clinically unstable or hospitalized in ICU Require IV positive inotropic support Severe fluid overload or depletion Bradycardic or advanced heart block History of poorly controlled reactive airways disease indicated All HF patients should receive a BB as a part of their therapy First line if EF<40% Contraindicated Severe bradycardia 2nd or 3rd degree heart block Overt cardiac failure or cardiogenic shock Severe hepatic impairment (carvedilol) ACE inhibitors/ARBs State the MOA ACEi: Reduce synthesis of angiotensin II and block degradation of bradykinin (vasodilation, cough, angioedema) ARBs: block AT2 from binding ATR1 receptors Net result= reduction of RAAS activation and reduce preload and afterload Describe the mortality benefits Reduces cardiac remodeling, improves LV function, and reduces morbidity and mortality Explain the mechanism by which angiotensin converting-enzyme inhibitors (ACEI) interrupt the cycle of heart failure (HF). By blocking conversion of ATI to ATII, the ACEi interrupt the cycle of HF ATII vasoconstriction blocked= decreased TPR and decreased afterload ATII stimulatetion of aldosterone blocked= decreased preload indicated All patients with HF should receive regardless of symptoms Contraindicated Pregnancy (teratogenic) Bilateral renal artery stenosis ACEi: history of angioedema. Do not use within 36-hr of entresto (increases chances of angioedema related to bradykinin) sacubitril/valsartan= ENTRESTO [ARNi] Explain the use of ARNi vs ACE inhibitor use in HF Cannot use with ACEi/ARB within 36 hrs of an ACEi Explain the mechanism of action for each agent Sacubitril Neprilysin inhibitor. Valsartan ARB State the indication and which patients are candidates for its use NYHA class II-IV patients to reduce hospitalizations and cardiovascular death Class II-III patients who are symptomatic and tolerate ACEi or ARB, in pace of ACEi or ARB to further improve morbidity and survival (alternative first-line option) Contraindicated History of angioedema Do not use with ACEi/ARB within 36 hrs of an ACEi Teratogenic SGLT2 inhibitors Explain the MOA Inhibits Na-glucose cotransporter 2 in the proximal renal tubules reduces reabsorption of filtered glucose from the tubular lumen and lowers the renal threshold for glucose Also reduces Na reabsorption and increases the delivery of Na to the distal tubule, which may lower both preload and afterload of the heart and downregulate sympathetic activity benefits in patients with HF Patients stage II-IV or symptomatic chronic HFrEF Reduces hospitalization for HF and cardiovascular mortality Indicated In patients with NYHA II-IV (symptomatic chronic HFrEF) to reduce hospitalization for HF and cardiovascular mortality, irrespective of the presence of T2DM Contraindicated Severe renal impairment Type 1 DM Examples Dapagliflozin (farxiga), empagliflozin (jardiance) MRAs indicated Contraindicated Loop Diuretics MOA Block Na and Cl reabsorption in thick ascending loop of henle Decreases blood volume Describe the effects on mortality, relative potency and efficacy in renal disease, development of diuretic resistance and solutions No mortality benefit in HF patients relative potency and efficacy in renal disease development of diuretic resistance and solutions Indicated Relieve symptoms related to congestion and edema Contraindicated Anuria, sulfa allergy Hydral-nitrates Explain the mechanism of action of the isosorbide dinitrate/hydralazine combination in HF, the effects on preload and afterload, and whether a mortality benefit occurs. Hydralazine is a direct arterial vasodilator= decreased afterload Nitrates increase the availability of NO (venous vasodilator)= decreased preload Decreases mortality (not as much as ACEi/ARBs) Indicated For patients who cannot tolerate ACEi/ARB due to poor renal function, history of angioedema, or hyperkalemia African Americans with NYHA class III-IV HF who are still symptomatic despite optimal treatment with ACEi/ARBs/ARNi and BBs Contraindicated Hydralazine Mitral valve rheumatic heart disease CAD Isosorbide dinitrate Concurrent with PDE-5i Ivabradine Hyperpolarization-activated cyclic nucleotide-gated channel blocker (HCN-blocker) MOA Selectively inhibits the cardiac pacemaker current which is a mixed Na-K inward current that controls the spontaneous diastolic depolarization in the SA node and hence regulates the heart rate Prolongs diastolic depolarization by blocking the funny channels= lowering HR explain the indication and intended use in patients Reduces risk of hospitalizations for worsening HF NYHA II-III LVEF ≤ 35% Sinus rhythm with resting HR > 70bpm If on maximally tolerated BB or have contraindications to BB Contraindicated ADHF BP <90/50, SA irregularities, HR maintain by pacemaker, resting HR < 60, severe hepatic impairment, on a strong 3A4 inhibitor Teratogenic state the effects on HR and BP Decreases both. Contraindicated in BP <90/50 effect on mortality Decreases hospitalizations but does not reduce mortality Digoxin state the MOA and inotropic effects Inhibits Na-K-ATPase pump= increased CO (positive inotropy) Exerts parasympathetic effect at AV node= decreased HR (negative chronotropy) Identify the ADRs of digoxin and how ADRs are enhances Dizziness, mental disturbances, HA, N/V/D Factors enhancing Digoxin toxicity Electrolyte abnormalities (hypokalemia, hypomagnesemia, hypercalcemia, alkalosis) Drugs that decrease K and Mg can increase digoxin levels Decreased digoxin clearance (renal dysfunction, hypothyroidism, advanced age) Digoxin is a Pg-P and 3A4 substrate, watch for drugs that inhibit these Explain the rationale for the new target plasma level of digoxin (0.5-0.9, or <= 1.0 ng/mL) based on the neurohormonal model of HF. Toxicity at > 1 ng/mL State patients that receive the greatest benefits HFrEF? I have that and this…-Digoxin is effective to control resting HR in HF patients with reduced EF -Indicated for patients who remain symptomatic despite optimal treatment with ACEI/ARB and a BB (last-line add-on for patients with persistent HF symptoms)(last-line add-on for patients with persistent HF symptoms) I think newest study 2022 stated what is in () State the effects on mortality and QOL No mortality benefit but reduces hospitalizations Improves symptoms, exercise tolerance, and QOL indicated Last line. Indicated for patients who remain symptomatic despite optimal treatment with ACEI/ARB and a BB Contraindicated Ventricular fibrillation Identify which medications are indicated for HFrEF vs HFpEF Which medications have proven clinical benefits? HFrEF (LVEF <40%) ACEi/ARB (decrease symptoms and mortality) MI or angina-> BB DO NOT prescribe thiazolidinediones and non-DHP CCB in patients with LVEF<50% HFpEF Absolute for all patients: diuretics and SGLT2i. SGLT2i Reduces hospitalizations and CV mortality Diuretics for symptom reduction CAN USE but no mortality benefits: ARNi (further lowers BNP), MRA (improves diastolic function), ARB (can use if ARNi cannot) MRAs Describe the beneficial effects of aldosterone antagonists (AA) in HF and the NYHA stage patients who should be considered for AAs Aldosterone is a mineralocorticoid. Causes Na and water retention. Reduce cardiac remodeling and risk of sudden cardiac death Should be added to an ACEi/ARB/ARNi and BB in patients with NYHA III-IV State the common ADRs of MRAs Increased K, Serum Cr Spironolactone: gynecomastia, impotence, breast tenderness, irregular menses Eplerenone: increased TGs Explain the rationale for using aldosterone antagonists (AA) in severe HF. Reduces morbidity and mortality in HF patient Contraindicated Hyperkalemia, anuria, CrCl<30 Describe the properties of B-type natriuretic peptide (BNP) with regard to: endogenous source Synthesized and released from ventricular muscle cells in LV dysfunction of the early failing heart It is a marker for both the presence and severity of HF. levels > 200 indicate HF role as a “counterregulatory hormone” Physiological antagonist of AT2 that imposes an endogenous limit on activation of the RAAS effects on urine flow and sodium excretion Similar to ANP but with longer duration Causes 5-10x increase in sodium excretion net effects on pulmonary capillary wedge pressure (PCWP), TPR, plasma aldosterone levels, sodium and water retention, preload, and afterload Reduces PCWP, TPR, and plasma aldosterone= decreased Na and water retention Inhibits vasopressin secretion Decreases preload and afterload Describe the clinical uses of inotropic agents in the management of HF(dobutamine, dopamine, milrinone, epinephrine, norepinephrine) Palliative therapy for symptom control and awaiting transplantation State the preferred agent for preload reduction in severe HF and the vasodilator of choice for severe HF and acute MI. nitroglycerin Describe the hemodynamic and cardiac effects of angiotensin II (AT2) and state the neurotransmitters and hormones affected by AT2. •Activation of RAAS releases renin which converts angiotensinogen into angiotensin I (AT1) •ATI is then converted to AT2 by angiotensin converting enzyme (ACE) •AT2 at AT-type 1 receptors causes vasoconstriction and fluid retention •Also increases aldosterone release (Na and water retention) My next slide talks about the mechanism and place in therapy for ARBs and ACEI For all of the drugs used in management of HF, state which: are teratogenic ACEi/ARB Sacubitril/Valsartan (entresto) Ivabradine have demonstrated mortality benefits BB ACEi/ARB Aldosterone receptor antagonists (ARA) Hydralazine-nitrates SGLT2 are not associated with improved survival Digoxin Loop diuretics cause hyperkalemia ACEi/ARB Sacubitril/Valsartan (entresto) Aldosterone receptor antagonists (ARA) Digoxin toxicity cause hypokalemia Loop diuretics ANTIARRHYTHMICS: these meds work by affecting the electrical currents in the cells of the heart. Select drugs can reduce conduction velocity and/or automaticity, or prolong the refractory period Explain the Vaughan Williams Classification and the medications within those classes Classified based on dominant electrophysiological effect. This is most frequently used but controversial due to not classifying all antiarrhythmic drugs, some agents have mechanisms that overlap between classes, and does not incorporate use/indication State the MOA of the medications in Vaughan Williams Classifications Class 1 (Sodium channel blockers) Blockade of fast sodium channels= slowing the upstroke velocity of depolarization Decreases automaticity 1a Also block K-channels (ACh and alpha)= prolonging the action potential duration Moderate slowing of depolarization Moderate increase in action potential duration (APD) and Effective refractory period (ERP) 1b Bind and dissociate Na-channels rapidly: rapid on-off activity. Blocks depolarization= decreased conduction and decreased automaticity Little effect on ERP Decreases automaticity Effective for ventricular arrhythmias NOT EFFECTIVE for supraventricular arrhythmias like Afib 1c Bind and dissociate Na-channels slowly: slow on-off activity. Blocks depolarization significantly. Little to no effect on ERP Minimal effects on APD Widens QRS Class 2 (beta blockers) Blocks response of NE and EPI at beta receptors= indirectly blocking Ca-channels in SA and AV nodes Decreases automaticity and conduction velocity Increases refractory period *best potential to control ventricular rate in patients whose AF is caused by enhances sympathetic activity Class 3 (K-channel blockers) Delay phase 3 repolarization resulting in marked prolongation of APD and refractory period Most drugs in this class will have mixed mechanisms ibutilide (Na) Amiodarone Na channel blockade Decrease conduction velocity Increase APD K channel blockade Increase APD Increase ERP Ca channel blockade Decrease SA and AV node conduction Alpha and beta blockade Negative inotrope (decrease contractility) Reduces HR and TPR Peripheral and cardiac vasodilator Dronedarone (Na, Ca, beta, alpha, ACh) Sotalol (non-selective BB) Non selective BB= decreased HR and AV node conduction Blocks K channels Increase ERP, APD, and prolongs QT interval Dofetilide (K only) Class 4 (non-DHP CCB) Block L-type close calcium channels in cardiac tissue Slows AV and SA node conduction velocity Decrease automaticity Increase ERP Describe the effects/properties of the medications in the Vaughan Williams Classifications See above State the indications for the medications in the Vaughan Williams Classifications Quinidine (1a) Afib-prophylaxis of treatment for conversion to normal sinus rhythm (NSR) Conversion of premature ventricular contractions (PVCs) to NSR Life-threatening ventricular arrhythmias *** This drug requires therapeutic drug monitoring due to a narrow therapeutic index. Keep plasma levels 2-7 mcg/mL. Can have toxic reaction above 5 Describe the major contraindications to use quinidine and the ADR of cinchonism. Its effects enhanced by hyperkalemia and reduced in hypokalemia May cause hemolysis (avoid in patients with G6PD deficiency) May increase mortality in treatment of Afib or Aflutter. Control AV conduction before initiating Gi upset, DILE, low alpha 1 blockade= hypotension and syncope Cinchonism (overdose) Tinnitus, hearing loss, blurred vision, HA, delirium, thrombocytopenia, rash Contraindicated Prolonged QT Torsades de pointe Thrombocytopenia Taking quinolone ABX that prolong QT Procainamide PA (1a) Life-threatening ventricular arrhythmias **narrow therapeutic index, requires monitoring PA: 4-10 mcg/mL NAPA: 15-25 mcg/mL PA+NAPA: 10-30 mcg/mL Explain the total body clearance of procainamide and: Renal clearance (requires dose adjustment in renal impairment how the major metabolite NAPA is formed Procainamide Acetylation (metabolized) in liver into active metabolite N-acetylprocainamide (NAPA) the pharmacologic actions of NAPA Has antiarrhythmic activity (class III) Warnings Increased mortality is used in non-life threatening ventricular arrhythmias Disopyramide (1a) Life-threatening ventricular arrhythmias Renally cleared (requires renal dose adjustments) *hepatically metabolized. metabolite= mono-N-dealkylated mono-N-dealkylated has no antiarrhythmic activity and moderate anticholinergic activity State the warnings with disopyramide Increased mortality is used in non-life threatening ventricular arrhythmias Anticholinergic effects: caution in BPH/urinary retention, narrow-angle glaucoma, myasthenia gravis Negative inotropy: caution in hypotension, HF Contraindications Cardiogenic shock (negative inotropy) 2nd/3rd degree heart block without pacemaker Congenital QT prolongation Lidocaine (1b) Acute management of ventricular arrhythmias during myocardial infarction or digoxin toxicity Conversion of non-sustained V-tach to NSR **narrow TI, requires monitoring 1.5-6 mcg/mL Side effects CNS stimulation= dizziness, tremor, slurred speech, hallucinations, hearing disturbances Elderly more sensitive to CNS effects Renal impairment= accumulation of metabolites= CNS toxicity (seizures) Negative inotropic effects= caution in patients with HF/reduced cardiac output May promote more frequent and serious ventricular arrhythmias or complete heart block in sinus bradycardia or incomplete heart block control/increase HR prior to administration Contraindications Allergy to corn or amide-type anesthetics 2nd/3rd degree heart block without pacemaker WPW Adam-stokes syndrome Mexiletine (1b) Reserve use for life-threatening ventricular arrhythmias Orally active congener of lidocaine. Has antiarrhythmic actions and properties similar to lidocaine Metabolized in liver by CYP2D6 into inactive metabolites Renally excreted, half-life 10-12 hr (doubled in hepatic disease) Warnings DRESS (drug rash with eosinophilia and systemic symtpms) Type IV HSR Elevations of AST>3x upper limit Neurotoxicity Propafenone (1c) Life threatening ventricular arrhythmias Increased mortality is used in non-life threatening ventricular arrhythmias Paroxysmal SVT with disabling symptoms Conversion of paroxysmal Afib/flutter to NSR in symptomatic patients without structural heart disease Metabolized by 2D6, 3QA4, 1A2 Renally excreted with half-life 2-10 hr Side effects Metallic taste Dizziness, visual disturbances Contraindications SA/AV disorders and sinus bradycardia Structural heart disease Cardiogenic shock, hypotension Bronchospastic disorders Flecainide (1c) Life threatening ventricular arrhythmia Prevention of paroxysmal Afib/flutter with disabling symptoms Paroxysmal SVT with disabling symptoms in patients without structural heart disease Metabolized 2D6 Renally and fecally excreted with half life of 20 hr. Peaks 1-6 hr Side effects Dizziness, visual disturbances, dyspnea Contraindications Chronic Afib 2nd/3rd degree heart block without pacemaker Structural heart disease Cardiogenic shock Esmolol (2) Rapid control of ventricular rate in Afib or Aflutter in circumstances where short-term ventricular rate control is needed Noncompensatory sinus tachycardia where rapid HR requires intervention Amiodarone (3) Life-threatening recurrent ventricular fibrillation Life-threatening hemodynamically unstable ventricular tachycardia Also used for a wide variety of supraventricular and ventricular arrhythmias that is off-labeled IV dosage form available to use acutely until ventricular arrhythmias are stabilized Important 3A4 and 2C8 metabolized into an active metabolite Biliary excreted Extensively inhibits many CYP isoforms (many drug interactions) Drug accumulates in many tissues- organ toxicities Very long half-life IV 9-36 days Oral 40-60 days For the antiarrhythmic agents listed below, identify/describe/explain the associated topics. ADRs High incidence of QT prolongation (although it has a relatively low incidence of torsades de pointe) Pulmonary fibrosis- dose related >300mg/day Hepatotoxicity- asymptomatic elevations in liver enzymes Hypotension CNS- Dizziness, ataxia, NV, constipation, tremor DILE Contraindications HSR to iodine Sick sinus syndrome 2nd or 3rd degree AV block Bradycardia leading to syncope Evidence of hepatitis Thyroid dysfunction not controlled Warnings Hypothyroidism Drug inhibits conversion of T3 to T4; may also cause hyperthyroidism Neurotoxicity (peripheral neuropathy) Optic neuropathy Severe necrotizing skin reactions photosensitivity = blue-gray discoloration Monitoring ECG, BP, HR, electrolytes Pulmonary function with CXR annually Liver function test q 6 months Thyroid function q 3-6 months Regular ophthalmic exams Sotalol (3)- nonselective BB Life-threatening ventricular arrhythmias and Maintenance of NSR in Afib No metabolism, excreted renally unchanged Half-life 12 hrs For the antiarrhythmic agents listed below, identify/describe/explain the associated topics. Box warning Must be initiated (or initiated) in a setting with continuous EKG monitoring and ability to assess CrCl for 3 days ADR Bradycardia, hypotension, palpitations, chest pain, torsades de pointes, CHF, bronchoconstriction, dyspnea, depression proarrhythmic effects This drug is adjusted based on CrCl. QT prolongation is directly related to drug concentration and may lead to torsades Contraindications Bradycardia 2nd/3rd degree heart block Prolonged QT syndrome Ibutilide (3) Indication Indicated for recent onset Afib/flutter for rapid (IV inj) conversion to NSR. occurs 90 minutes or less after infusion Discontinue as soon as arrhythmia is terminated or prolonged QT interval occurs proarrhythmic effects (precautions: monitoring, serum potassium and magnesium) May cause polymorphic ventricular tachycardia requiring cardioversion. May or may not be in association with prolonged QT interval Must be in setting of continuous EKG monitoring for up to 8 hr post infusion or until QT returns to baseline Serum K and Mg must be normalized before dosing Dofetilide: (3) Indication Conversion of Afib to NSR Must be initiated in a setting with continuous EKG monitoring and ability to assess CrCl for 3 days Kinetics 3A4 metabolism- half-life 10 hrs 90-100% oral bioavailability Renally excreted proarrhythmic effects May cause prolonged QT. requires dose adjustment in renal impairment to prevent this Side effects Vtach (torsades de pointes), hypotension, QT prolongation Contraindications Congenital or aquired long QT syndrome Baseline QT>440 msec Severe renal impairment Concurrent use with: Cimetidine, Dolutegravir, HCTZ, Itraconazole, Ketoconazole, Megestrol, Prochlorperazine, Trimethoprim, verapamil Dronedarone: (3) Indication Paroxysmal or persistent Afib to reduce hospitalization Patients who are already in NSR 3A4 metabolized into less potent metabolite. Half life 13-19 hr (less than amiodarone due to decreased lipophilicity) Contraindicated with strong 3A4 inhibitors Bioavailability 4% without food and 15% with food Fecal excretion use in NYHA IV heart failure Increase risk of death, stroke, and HF in patients with decompensated HF (NYHA class IV or anyone with recent hospitalization with HF) or patient with permanent Afib (will not or cannot be cardioverted to NSR) Contraindicated for patient with recent decompensation or NYHA class IV HF AND patient in chronic Afib Warnings Hepatic failure- monitor liver function levels Lungs- pulmonary fibrosis, pneumonitis Renal- slight increase in SCr, acute renal failure in presence of HF or hypovolemia Prolongs QT (drug interactions) Decrease dose of digoxin by 50% when used together (interferes with Pgp transporter) Class 4 Rapid conversion of PSVT to SNR including those associated with accessory bypass tracts (WPW and LGL syndromes) Temporary control of rapid ventricular rate in Afib/flutter EXCEPT when these arrhythmias are associated with accessory bypass tracts (WPW) Contraindicated in presence of LV systolic dysfunction (HFrEF) decompensated HF due to negative inotropic effects Afib with WPW Verapamil: Indicated for supraventricular arrhythmias effects on AV nodal conduction velocity and time and the ERP markedly slows AV conduction by increasing ERP of the AV node; prolongs AV nodal time with no effects on P waves or QRS duration use in control of ventricular rate and exceptions to use Temporary control of rapid ventricular rate in Afib/flutter EXCEPT when these are associated with accessory bypass tracts (WPW) major contraindication contraindicated in WPW syndrome accompanied by AF or AFlutter Adenosine: effects on AV nodal conduction velocity, time, and ERP MOS: slows conduction through the AV node via activation of adenosine-1 receptors Decreases conduction velocity Increases conduction time and ERP Indication DOC for rapid conversion to NSR in paroxysmal supraventricular tachycardia Administered only by rapid IV because it has a half-life < 10 seconds ADR: heart block, transient asystole, effects in bronchospastic conditions Do not use in patients with 2nd/3rd degree heart block, SSS, symptomatic bradycardia, or bronchospastic lung disease Side effects: Transient, new arrhythmias and transient hypotension Dyspnea, chest pain/pressure Facial flushing, dizziness, neck discomfort, GI distress Digoxin: Mechanism Blocks Na-K-ATPase pump= blocked AV node= decreased conduction velocity and increased nodal ERP Reversal agent Antidote is digifab Therapeutic monitoring 3A4 metabolized with half-life 1-2 days. Renally excreted Caution with 3A4 inhibitors/inducers Narrow TI: Afib 0.8-2 ng/mL HF 0.5-0.8 ng/mL Indications Ventricular rate control in supraventricular arrhythmias (chronic Afib) Ineffective at controlling rate during exercise Not first line for rate-control and not usually used alone (combine with BB or CCB) Signs of severe toxicity Initial toxicity= N/V, loss of appetite, and bradycardia severe= blurred vision, diplopia, altered color perception, green/yellow halos around lights, abdominal pain, confusion, delirium, prolonged PR interval, arrhythmias Hypokalemia, hypomagnesemia, and hypercalcemia increases risk of toxicity Drug interactions Reduce when in use with amiodarone and dronedarone Caution with drugs that lower HR Hypothyroidism can increase digoxin levels State the drug which is the most frequent cause of drug-induced lupus. MAIN: PA long term use leads to positive antinuclear antibody (ANA) in 50% of patients More likely in slow acetylators Drugs that also cause DILE amiodarone State the medications at risk of causing blood dyscrasias Mexiletine (1b) Procainamide PA- mainly seen in first 3 months Describe the activity of lidocaine against: AF or atrial flutter Not indicated for Afib or flutter nonsustained VT Converts nonsustained ventricular tach to NSR Explain the dosage form of lidocaine Parenteral use only (extensive first pass metabolism) 2 active metabolites have both antiarrhythmic and convulsant properties State the major ADR of flecainide and the limitations on its clinical use. Dizziness Visual disturbance Dyspnea Pro-arrhythmic effect in patients with Afib. do not use in patients with chronic Afib= will worsen supraventricular or ventricular arrhythmias in all patients When treating Aflutter, it may cause rapid increase in ventricular rate and ventricular arrhythmias may occur. Pretreat with digoxin or BB (negative chronotropy) Explain why Class II antiarrhythmics are useful in thyrotoxicosis Beta blockers that can block sympathetic activity induced AF Explain the “Pill in the Pocket” Single oral loading dose of propafenone or flecainide Can terminate Afib in outpatients already taking BB or non-DHP CCB Has to be started in hospital setting before prescribed out of office Contraindications SA or AV node dysfunction BBB QT prolongation Structural heart disease State the indications for esmolol and describe its duration of action. Rapid control of ventricular rate in Afib or Aflutter in circumstances where short-term ventricular rate control is needed Noncompensatory sinus tachycardia where rapid HR requires intervention Duration of action: shorter duration of action which is why it is only used for HR control and is given IV. duration of 10-30 min Describe the effects of amiodarone on the APD, ERP, automaticity, conduction velocity, and AV nodal conduction time. Na channel blockade Decrease conduction velocity Increase APD K channel blockade Increase APD Increase ERP Ca channel blockade Decrease SA and AV node conduction Alpha and beta blockade Negative inotrope (decrease contractility) Reduces HR and TPR Peripheral and cardiac vasodilator Specific arrhythmias: Afib: Identify the listed complications of untreated atrial fibrillation (AF). Heart Failure 3x incidence, tachycardias induced cardiomyopathy, impaired diastolic filling, loss of atrial kick Thromboembolic risk Thrombi in left atrium from blood stasis 5x increase for stroke Increased with increased age Rapid ventricular response Potential lethal ventricular fib Can exacerbate ischemia, HF, or tach-induced cardiomyopathy Explain the selection for rate vs rhythm control Acute treatment: rate control Restore NSR: rhythm control (risk vs. benefit) Prevent recurrence (prophylaxis) Need for anticoagulation -paroxysmal AF is most often treated with rhythm control; if this fails, then rate control is tried. -permanent AF is most often treated with rate control; if the patient remains symptomatic, then rhythm control is tried -either approach may be tried for persistent AF -also depends on comorbidities and extent of symptoms State the drugs most commonly used for rate control in AF. Goal for chronic Afib: <110 bpm with chronic Afib and stable LV function, OR asymptomatic/acceptable symptoms Drugs: BB non-DHP CCB Digoxin Amiodarone dronaderone For rhythm control in AF: prevention of Afib state the most commonly used agents Electrical Cardioversion (78% success rate) Class Ic= flecainide, propafenone Class III= ibutilide, sotalol, amiodarone, dofetilide(high risk of torsades), dronedarone state the restrictions placed on Class IC agents Avoid in patient with structural heart disease explain why amiodarone is the most commonly used agent from any class Amiodarone is more effective than other agents with a success rate of 61-86% BUT is used after other methods due to ADRs For pharmacologic cardioversion (conversion to NSR), state the : DOC amiodarone?? agents which are not recommended (digoxin, sotalol) Sotalol is not efficacious for conversion to sinus rhythm digoxin??? Explain the CHA2DS2VASC score and when anticoagulant therapy is recommended CHA2DS2-VASc quantifies ischemic stroke risk among patient with nonvalvular Afib and Aflutter Anticoagulation indicated when men 2 or over. Women 3 or over. If patient has Afib >48 hours or an unknown duration, needs anticoagulant for 3 weeks prior to and 4 weeks after cardioversion regardless of score and method of cardioversion If unable to have 3 weeks prior, transesophageal echocardiography (TEE) recommended If patient has Afib < 48 hours, start anticoagulation at time, perform cardioversion, and continue anticoag for 4 weeks Explain the HAS-BLED score and utilization in therapy HAS-BLED is the bleeding risk scores to quantify hemorrhage risk Score > 3 indicates potentially high risk Monitor INRs State the medications of choice for the following arrhythmias: Long QT syndrome BB to reduce frequency of premature ventricular contractions and shorten QT interval Torsades de Pointes Prompt defibrillation First line therapy: IV magnesium sulfate Wolff-parkinson-white syndrome Direct current cardioversion for life-threatening ventricular rate AAD that depress conduction and increase ERP of fast sodium channels Class IA and IC Procainamide may be drug of choice DO NOT USE: non-DHP CCB, digoxin, adenosine AV nodal reentrant tachycardias Vagal maneuvers Adenosine (DOC) IV non-DHP CCB or IV BB Cardioversion last line ANTIANGINAL DRUGS: Identify the which anginal situations NTG would be indicated (stable, unstable, prinzmetal, silent) All minus silent. Only take upon symptoms State which antianginal drugs are indicated and contraindicated in vasospastic (variant) angina. Indicated NTG?? Contraindicated BB Identify the clinical uses and mechanisms of primary drug therapies for angina (HR, BP, diastolic perfusion, contractility, oxygen demand/consumption, LV pressure) BACKGROUND: the overall goal of treatment is to improve functional capacity, reduce risk of CV death, antiplatelets/antianginal agents, and statin to reduce CV-related risks. (anginas typically caused by atherosclerosis) We want to: Restore balance between oxygen supply and demand (decrease workload of heart) Decrease VR= decrease LVEDV= decreased LV wall tension (decrease oxygen demand) Decrease HR and contractility (decrease oxygen demand) State the first, second, and third line therapies 1st: BB 2nd: CCB 3rd: Ronalazine Adjunctive: NTG State indications for antianginal therapies See in specific drug classes below NTG: Explain the mechanism of action of nitrates in producing vascular smooth muscle relaxation and vasodilation. It's a prodrug that serves as a source of nitric oxide. NO activates guanyl cyclase to increase intracellular levels of cyclic GMP. cGMP activates cGMP-dependent protein kinase= phosphorylates various proteins in smooth muscle= phosphorylates myosin light chain= inhibition of contraction= vasodilation= decreased myocardial oxygen demand Describe the first-pass metabolism of nitroglycerin (NTG) and organic nitrates and how bioavailability by the oral and sublingual routes is affected. Sublingual allows if to avoid first-pass metabolism= therapeutic blood level rapidly Onset 1-3 minutes with duration of 10-30 minutes State the three major effects of nitrates on the venous smooth muscle and preload, and the major ADR that may occur. Effects Dilation of collateral vessels= blood flow to subendocardial region of heart Dilation of epicardial coronary arteries Contraindications: PDE5-inhibitors (vasodilators) Sildenafil, tadalafil, vardenafil, avanafil warnings/side effects hypotension= syncope, flushing, dizziness, HA Tolerance (tachyphylaxis) Monitoring: BP, HR, chest pain Explain the reflex tachycardia that occurs with nitrates and the effects on oxygen demand. How it occurs??? Maybe vasodilation= increases VR= increases HR to keep up with supply? Check notes-baroreceptor response: reflex tachycardia, increased contractility; may cause paradoxical increase in oxygen demand BB used in combo with nitrates help prevent/lower reflex tachycardia Differentiate between short acting and long acting NTG State the major uses for both rapid onset, short duration and slower onset, long duration dosage forms of nitrates, and be able to identify which dosage forms belong in these categories. Short-acting Recommended for all symptomatic anginas for immediate relief of symptoms SL tablet (nitrostat), TL spray (nitromist), SL powder (GoNitro) Avoids first pass metabolism Used prophylactically before exercise if necessary Long-acting Topical. Still faster than oral due to avoiding first pass Ointment (nitro-BID), patch (nitro-Dur) Also oral options Isosorbide mononitrate IR/ER Isosorbide dinitrate Indicated for angina relief when BB contraindicated or as add-on therapy Explain the effects of NTG on: coronary vascular resistance NTG= vasodilation= decrease in TPR redistribution of coronary flow caused by NTG and its beneficial effects. ???•Dilation of collateral vessels: produces a redistribution of coronary blood flow through collateral vessels in favor of the subendocardial regions of the heart that have undergone the greatest reduction in blood flow due to atherosclerosis •Dilation of epicardial coronary arteries (this was in notes and is for both of the above) State the types of angina for which nitrates are indicated. Chronic stable angina Variant angina Unstable angina Describe the indication for using sublingual NTG for relief of anginal pain, the accompanying side effects, and the proper use and storage of NTG sublingual tablets. ????•Topical: much faster absorption than oral due to extensive first pass effect of NTG •Indication for angina relief: used when BBs are contraindicated or as add-on therapy Describe the proper use and storage of NTG sublingual tablets: -place under tongue while sitting (may cause burning or stinging) -keep tablets in original container; no child resistant cap required -store in a dry place at room temp -do not eat, drink or smoke for at least 5-10 min after using the product or while experiencing chest pain Side effects = •Dizziness/lightheadedness •Flushing •Syncope Warnings = •Hypotension •Headache •Tolerance (tachyphylaxis) à long-acting formulation Explain the consequence of continuous nitrate use and the methods for preventing tolerance. Continuous nitrate use leads to tolerance of antianginal effects Therapy should be interrupted every day to prevent tolerance Timing of interruption based on patient’s angina pattern Patch and ointment: 12 hr on 12 hr off IV infusion can create tolerance if infused beyond 12 hours Beta Blockers: 1st line Explain the mechanisms by which beta blockers relieve anginal pain, and state which types of angina have beta blocker indications. BB slow HR = increased diastolic perfusion time= reduced myocardial oxygen demand Improves symptoms for 80% of stable angina patients Improves exercise duration Delays appearance of ST changes (which are indicative of ischemia) Indications First line for prophylaxis and daily maintenance monotherapy for chronic stable angina Can also be used in unstable angina but NOT variant angina More effective in reducing episodes of silent ischemia, early AM ischemia, and mortality after Q-wave/transmural MI Cardioselective BB preferred Bisoprolol, betaxolol, atenolol, metoprolol, acebutolol ADR Bradycardia, hypotension, fatigue, dizziness, depression Do not d/c abruptly State the precautions for beta blocker use with concomitant asthma, diabetes, and peripheral vascular disease. Asthma Blocks beta 2= blocking bronchodilation Diabetes Blocks beta 2= blocks glycogenolysis= decreases blood glucose (hypoglycemia) PVD Blocks beta 2= blocks peripheral vasodilation CCBs: 2nd line or adjunctive Explain the mechanism of antianginal action for calcium channel blockers (CCB). Inhibits calcium entry into myocardial cells= limits contraction of cardiac muscle (neg. inotropic) and vascular smooth muscle (vasodilation) Peripheral vasodilation= decreased TPR which can trigger baroreceptors= reflex tachycardia. If this happens, can worsen angina and patient may require a BB Indicated when BB are contraindicated Non DHP- works more on AV node Verapamil Highest risk of depressed contractility (caution with BB) Diltiazem Has some vasodilation and no reflex tachycardia Indicated for unstable (verapamil), stable, and variant Potent coronary artery vasodilation DHP- works more peripherally Nifedipine, amlodipine, felodipine Long-acting option of nifedipine to cause less reflex tachycardia Indicated for variant (DOC) and stable DHP + BB counteract each others tachycardia and bradycardia, respectively State which of the calcium channel blockers (nifedipine, verapamil, diltiazem) causes: (repeat objective) the greatest amount of reflex tachycardia nifedipine the most potent peripheral vasodilation DHP CCB (nifedipine) the greatest amount of flushing, headache, hypotension DHP CCB- nifedipine the most constipation Verapamil Explain why the chronotropic and inotropic effects of verapamil and diltiazem may be highly variable. Verapamil depresses contractility more than diltiazem Check notes for anything more Ranolazine: 3rd line or adjunctive MOA Decreases late phase Na current which facilitates calcium entry via Na-Ca-exchanger= decreased myocardial O2 demand Decreases ventricle tension and contractility Improves blood flow No effect on HR, BP, or mortality 3A4 metabolized (avoid with 3A4 inhibitors) Indications Option for patients who are intolerant to BB or need additional symptom relief ADRs Constipation, nausea, dizziness, HA Warnings QT prolongation= torsade de pointes and Vtach Acute renal failure in patients with CrCl<30 Monitor EKG, K, renal function Acute Coronary Syndrome: Explain the difference between unstable angina, NSTEMI, and STEMI Symptoms, cardiac enzymes, ECG changes, Blockage Define troponin levels Identify which parenteral anticoagulants are indicated with PCI PCI=percutaneous coronary intervention (reperfusion therapy). Should be done within 90 or 120 minutes of STEMI Coronary angiography of infarcted artery with: Balloon angioplasty= percutaneous transluminal (PTCA) Stenting with bare metal (BMS) or drug-eluting (DES) Aspirin 162-325 given before PCI and continued 81 after P2Y12i at time of PCI and continues for year after stent Gp2b/3a IV if no P2Y12 pretreatment Heparin (UFH) and bivalirudin can also be used at time of PCI Bivalirudin monotherapy preferred over Gp2b/3a+UFH due to higher risk of bleeding STEMI: = ST elevation MI State the treatments (with relation to short term or long term goals) for treatment of STEMI Short-term Early restoration of blood- prevent further infarct expansion Prevent death Prevent re-occlusion Relief of chest pain Resolution of ST and Twave changes Long-term Control CV risk factors Prevent reinfarction, stroke, HF Improve quality of life (QOL) State prehospital management for patients with STEMI Aspirin 162-325 mg(by patient or EMS) By EMS Establish venous access Review reperfusion checklist 12-lead EKG Relay info to facility State the essential pharmacological components of ER management of STEMI and explain the reasons for using each of these therapies. Continuous 12 lead EKG Physical exam, lab tests, thrombolytic checklist MONA-GAP-BA Provides immediate relief of ischemia and preventing MI expansion or death MONA Morphine Does not reduce mortality, decreases BP & HR Treat chest symptoms if can;t have nitrates Blocks SNS= vasodilation= decreased TPR and preload= decreased O2 demand Decreases catecholamines= decreases tendency of arrhythmias Antidote: naloxone O2 Via NC For O2 sat <90 or those in respiratory distress Mechanical ventilation if severe CHF/pulmonary embolism Nitrates Causes vasodilation= increase blood flow, decreased preload/afterload, decreases ventricular tension=decrease O2 demand SL q5min x3 followed by IV Controls hypertension, chest pain, and pulmonary congestion ASA Irreversible COX-1 and COX-2 inhibition= inhibition of TXA2 production= inhibition of platelet aggregation 25% reduction in death, reinfarction, and stroke Crush or chew noneneteric coated 162-325 mg then maintain by taking 81-162 daily forever Alternative: P2Y12 inhibitors GAP Gp2b/3a antagonists Blocks the platelet receptors= prevents platelet aggregation Medical management (eptifibatide or tirofiban) or for all PCI patients +/- stent If used for PCI, add unfractionated heparin Anticoagulants Inhibits clotting Low molecular weight heparin, unfractionated heparin, or bivalirudin P2Y12 inhibitors Inhibits the receptor on platelets= inhibiting platelet aggregation Medical management (clopidogrel or ticagrelor) and PCI (same as med management + plasugrel) Loading dose before maintenance dosing Not for patient undergoing CABG BA BB Decreased HR, BP, contractility= decrease O2 demand Decreases mortality, ischemia, reinfarction, and arrhythmias Prevent cardiac remodeling Initiate within first 24 hrs except in signs of HF, in low-output state, or at increased risk of cardiogenic shock can be given in IV at time of STEMI and hypertensive Move to nonDHP-CCB if BB+NTG not effective ACEi Inhibits ACE= blocks ATII production= inhibition of RAAS= decreased preload/afterload Decreases mortality and prevent cardiac remodeling Initiate within 1st 24 hrs and continue indefinitely If intolerant move to ARB Avoid IV in first 24 hr due to risk of hypotension STATIN Initiate or continue high intensity statin (atorvastain or rosuvastatin) State the alternatives to PCI for patients that do not qualify (identify when a patient would not qualify) If patient unable to get to PCI-capable facility within 120 minutes they should receive fibrinolytic therapy within 30 minutes of arriving to hospital for STEMI med= alteplase (tPA), reteplase, tenecteplase Contraindications Internal bleeding Recent stroke Intracranial hemorrhage Severe uncontrolled HTN ASA and clopidogrel can be used before or with this therapy. Following my continued ASA (indefinitely) and clopidogrel for 14 days- 1 year Describe the benefits of using thrombolytic reperfusion therapy in specific time intervals Greatest benefit occurs when thrombolysis is initiated within 6 hr of symptom onset Definite benefit occurs when therapy is begun within 12 hrs State the recommendations for avoidance of use of nitroglycerin (NTG). Vasodilator resulting in lowered BP. avoid if SBP<90, HR< 50, RV infarct, or patient taking PDE-5i in last 24 hr (48 hr for tadalafil) What if you do not know this about the patient Compare on the use of NTG to control ischemia post-STEMI during the first 24-48 hr period Causes vasodilation= increase blood flow, decreased preload/afterload, decreases ventricular tension=decrease O2 demand after 48 hr. Loses its effects after 48 hrs due to tachyphylaxis State the recommended antiplatelet therapy for post-STEMI patients regardless of whether they received reperfusion therapy. ASA given to all patient with suspected ACS as soon as possible If allergic, clopidogrel State the approved antiplatelet therapies ASA, clopidogrel, P2Y12i (dependent upon PCI) State the contraindications for beta blocker use in STEMI patients HF, low-output state, increased risk of cardiogenic shock Describe the recommendations for use of beta blockers: for STEMI patients who did not receive BBs in the first 24 hr Still start if they do not have any contraindications. Still has reinfarction and death protection for patients who received thrombolytic therapy or PCI BB administered to patients with contraindications, irrespective of concomitant fibrinolytic therapy, or performance of primary PCI Use BB in patients with no contraindications regardless of concurrent thrombolytic therapy or whether a patient has received primary angioplasty What does this mean? in patients with early contraindications in the first 24 hr of STEMI. If BB contraindicated, administer nonDHP CCB from notes i have to re-evaluate patient for BB administration. I do see “NonDHP-CCB if BBs and nitrates ineffective” on her slide Explain the goals of late BB therapy and how long BBs should be given. Late BB therapy is started between 24 hr- 28 days post MI Goal is to prevent reinfarction (32% decrease) and death (23% decrease) Describe the use of angiotensin converting-enzyme inhibitors in STEMI patients, when they should be started, and how long they should be continued. Start within first 24 hours and continue indefinitely Describe the use of aldosterone antagonists in post-STEMI patients: Use indefinitely in all patients on ACEi, on BB Contraindications Renal dysfunction (SCr<2.5 (men) or 2 (women)) Hyperkalemic (SK<5) concurrent conditions Symptomatic HF and DM EF<40% Explain the role of calcium channel blockers in the management of STEMI. AVOID DHP-CCB= can increase mortality Can use non-DHP CCB if BBs and nitrates ineffective Describe the use of aspirin (dosage, how long) in post-discharge therapy of STEMI patients: after stent placement with no stent Take 162-325 before PCI and continue 81 qd indefinitely regardless of stent or not Describe the use of clopidogrel (75 mg/day) in post-discharge therapy of STEMI patients for: after stent placement Start at PCI and continue for year following no stent Take at start of PCI for patients at low CV risk for both types of stents Take clopidogrel for 1 year regardless State the medications to avoid in an acute setting and why DHP-CCB Increases mortality in patients with CAD Not recommended for ACS NSAIDS Increases mortality risk, reinfarction, HTN, cardiac rupture, renal insufficiency, and HF Explain the use of statin therapy and indication Indicated for all post STEMI indefinitely Initiate or continue high intensity statin (atorvastain or rosuvastatin) NSTEMI/UA: =non-ST elevation MI State the initial medication (anti-ischemic and analgesic therapy) for NSTEMI and when each is indicated Initial: MONA P2Y12i If increased troponin or EKG changes: prasugrel or ticagrelor Anticoagulant LMWH, UFH (heparin) If PCI, bivalirudin may be used Early PCI Gp2b/3a inhibitor Only if P2Y12i wasn’t used prior to PCI Secondary BB No proof of efficacy for NSTEMI but not harmful. Still given ACEi/ARB Statin (high intensity) State the use of antithrombotic therapy (antiplatelet and anticoagulation) in patients with NSTEMI Primary P2Y12i, heparin, bivalirudin, Gp2b/3a (see above) Secondary Antithrombotic Antiplatelet: DAPT 12 months AVOID NSAIDS Proton pump inhibitors (PPI) Highest risk for GI bleeding from DAPT Hx of GI bleeding Triple therapy with DAPT Oral anticoagulant with or without hx of GI bleeding Describe the use of the TIMI risk score and purpose in therapy TIMI is a risk calculator: thrombolysis in myocardial infarction Identify when standard medical therapies are recommended in NSTEMI Antithrombotic, beta blocker, ACEi/ARB, CCBs, statins, NSAIDs, PPIs These are discussed above Identify when GPIs are indicated in NSTEMI therapy Discussed above ANTIPLATELETS: Explain the physiologic actions of COX-1 and COX-2 Aspirin: Describe the mechanism of the antiplatelet actions of aspirin. How long do these actions affect the platelet? Irreversible binds to and inhibits COX-1 and COX-2. Inhibition lasts the lifetime of the platelet (10 days) Also antipyretic (fever reducer), analgesic, and anti-inflammatory properties Explain the dose-dependent effect of aspirin Low dose (75-81mg/day) COX 1 inhibition (antiplatelet) Cardioprotection Best for adults 40-59 with 10% 10-year CVD Not recommended for adults 60 and older as a CVD prevention Medium dose (650mg-4g/day) COX 1&2 inhibition Blocks Prostaglandin production= analgesic and antipyretic High dose (4-8g/day) Anti-inflammatory for rheumatic disorders Toxicities at dose limit= tinnitus and GI intolerance State indications of aspirin therapy Acute coronary syndrome STEMI or NSTEMI: avoid enteric coated Chew low-medium dose post-ACS Secondary prevention of CV death, MI, and stroke TIA or minor noncardioembolic stroke Reduces risk of stroke, MI, vascular death, or death Post stent Prevents stent thrombosis analgesic/antipyretic 325-1g q4-6 hrs Anti Inflammatory for arthritis 4-8g total a day Compare formulations and clinical uses (I will talk about the specifics for this objective during lecture and it will be on a slide) EC-ASA does not cause less GI bleeding, but may lessen dyspepsia Uncoated ASA is not less efficacious than EC-ASA (based on incidence of CV events) Chew plain ASA during a MI; however, any formulation of ASA is OK if available State the major side effects, contraindications, and drug interactions with aspirin therapy Side effects Bleeding Administered with proton-pump inhibitor can reduce GI bleeding in patients with peptic ulcer disease. omeprazole+ASA GI: dyspepsia, heartburn, nausea Tinnitus Severe skin rash Contraindications NSAID or salicylate allergy Syndrome rhinitis, nsala polyps, asthma Increases risk of urticaria, angioedema, or bronchospasms Children with viral infections Risk of reyes syndrome= rapidly progressive encephalopathy with hepatitis dysfunction. symptoms= vomiting, confusion, fatigue, seizures/coma Drug interactions Excess alcohol, NSAIDs, anticoagulants, other antiplatelets, SSRIs, SNRIs Dipyridamole: State the antiplatelet mechanism of action and approved indications for oral dipyridamole. Blocks reuptake of adenosine and inhibits phosphodiesterase(PDE)-mediated cAMP degradation= increased levels of cAMP cAMP promotes Ca uptake= less Ca in cell= inhibiting platelet activation and aggregation Vasodilator Oral- see below Identify when dipyridamole is indicated in therapy Heart valve replacement ORAL Prevent post-op thrombus Use as adjunct with warfarin Radionuclide myocardial perfusion IV Imaging to evaluate extent of CAD When indicated to use + ASA. (relatively weak antiplatelet on its own) Secondary stroke prevention: Reduce risk of stroke in patients who have already had a complete ischemic stroke or TIA Used for thromboprophylaxis in patients undergoing hemodialysis Side effects GI upset HA, facial flushing, dizziness, hypotension (vasodilation) Bleeding (aggrenox) P2Y12 inhibitors: not first line agents State the MOA of P2Y12 inhibitors Binds to ADP P2Y12 platelet receptor= inhibition of ADP-induced platelet aggregation Inhibits ADP activation of Gp2b/3a receptors Thienopyridines: irreversible inhibition Ticlopidine, clopidogrel, prasugrel Require hepatic CYP enzyme activation Non Thienopyridines: reversible inhibition Ticagrelor, cangrelor Not prodrugs so they have faster onset State the indications of ticlopidine, clopidogrel, prasugrel, ticagrelor, and cangrelor Ticlopidine Secondary prevention of stroke after thrombotic stroke/TIA Only if patients intolerant of ASA or failed ASA therapy Reduces stroke, MI, and vascular death Stent thrombus prevention with ASA Clopidogrel ACS and secondary prevention of MI, stroke, and PAD Prasugrel ACS in patients being managed with PCI *10x more potent than clopidogrel (higher risk of bleeding) Ticagrelor ACS Greater efficacy in reducing rate of CV death and MI than cangrelor Cangrelor PCI to reduce risk of periprocedural MI in patients who have not been pre-treated with any other ADP antagonist and not receiving Gp2b/3a inhibitor Injectable only Compare ticlopidine and clopidogrel with regard to: cross-reactivity with aspirin Ticlopidine has no cross-reactivity with aspirin mechanism of antiplatelet action Both are thienopyridines incidence of severe hematological ADR Ticlopidine has life-threatening ADRs= neutropenia/agranulocytosis, thrombotic thrombocytopenic purpura (TTP) and aplastic anemia Highest risk first 3 months efficacy of antiplatelet actions compared to aspirin Clopidogrel more effective than ASA but more expensive Ticlopidine and ASA equally effective Explain the potential problems for patients taking clopidogrel if they are: deficient in the normal amount of CYP2C19 Clopidogrel is a thienopyridine that requires CYP to be metabolized to be active. Poor metabolizers have increased risk of CV events 2C19 inhibitors=omeprazole, esomeprazole taking PPIs (know specific PPI interactions) 30% increased number of poor CV outcomes PPI should only be added in high-risk patient (gastritis, rent GI bleed) For each indication of P2Y12 inhibitor therapy, state the duration of use. In conjunction with ASA for ACS Post PCI with stent= 12 month duration Stable ischemic heart disease DAPT with ASA + clopidogrel after stent placement or CABG BMS: 1 month or more DES: 6 months or more CABG: 12 months Check this the above is for dual antiplatelet therapy and this is for monotherapy in ACS…(just my understanding) •Given loading dose (LD): rapid antiplatelet effect •Maintenance dose (MD): take daily up to 12 months •Exception is cangrelor, only given IV for procedure (PCI); LD followed by IV infusion What are the class ADRs for P2Y12 inhibitors Additive bleeding risks with NSAIDs, warfarin, SSRIs, SNRIs Bleeding, hematoma, pruritus Identify specific scenarios where aspirin, P2Y12 inhibitors, or antithrombotics may be chosen over the other. Come back to this Describe the two indications for which combined aspirin-clopidogrel therapy has been proven beneficial. After stent placement or CABG Explain DAPT Combination of 2 types of meds like ASA and P2Y12 inhibitors to prevent blood clots GIIb/IIIa: Describe the MOA Block Gp2b/3a receptor= inhibits cross-binding of fibrinogen across platelets= inhibits platelet aggregation Reversible: tirofiban, eptifibatide Platelet function returns 4-8 hr after d/c Irreversible: abciximab List the indications for eptifibatide and tirofiban ACS- UA/STEMI only Undergoing PCI +/- stent with heparin Reduces risk of death, new MI, refractory ischemia, or repeat cardiac procedures State the class and specific side effects for eptifibatide and tirofiban ALL: bleeding, thrombocytopenia (duh) Contraindicated if platelets<100,000, active internal bleeding, severe uncontrolled HTN Eptifibatide Hypotension, not immunogenic Contraindicated if recent trauma within 6 weeks Contraindicated if Hx of stroke within 30 days or Hx of hemorrhagic stroke Tirofiban Edema, leg or pelvic pain, vasovagal reactions, bradycardia, CA dissection, dizziness, sweating; not immunogenic Contraindicated is recent trauma within 4 weeks Identify when GIIb/IIIa antagonists are indicated in therapy Answered above PAR1 antagonist MOA Inhibits PAR1 receptor (thrombin receptor)= inhibits most potent platelet activator= removing pathway of platelet activation half-life= 4 weeks (duration of platelet inhibition) High risk of bleeding Can combine with low-dose ASA and/or clopidogrel Indication Patient with very high VC risk When needed to reduce risk of thrombotic and CV events (MI, stroke, CV death, procedures to restore blood flow to heart) Patients with history of MI or PAD Contraindicated Combined therapy with prasugrel or ticagrelor Treatment of specific arrhythmias: SVT (supraventricular controlled) Goal is to cardiovert 1A (Na blocker) 1C (Na blocker) III (K blocker) IV (CCB) PSVT (supraventricular) Can use meds for SVT but these have lower ADR: IV (CCB) adenosine Vtach (ventricular) IA IB IC Do not use if hemodynamically unstable or structural heart dx (MI, HF, CAAD, valve dx) BBW: 1:1 conduction= increased HR Pretreat with BB, CCB, or digoxin III ACS Treatment: STEMI MONA Morphine only if unresponsive to nitrates Nitrates short acting Aspirin 162-325mg PCI<90min (<120 if at location without and have to travel) Need antiplatelet & anticoag (plavix and heparin) PCI performed +/- stent