Cardiac Medications

Drug Category: Antithrombotic Agents

These agents prevent the formation of thrombus associated with myocardial infarction and inhibit platelet function by blocking cyclooxygenase and subsequent aggregation. Antiplatelet therapy has been shown to reduce mortality by reducing the risk of fatal myocardial infarctions, fatal strokes, and vascular death.

Aspirin (Anacin, Bayer Buffered Aspirin, Ecotrin)
Administer as soon as possible. Inhibits cyclooxygenase, which produces thromboxane A2, a potent platelet activator. Early administration has been shown to reduce 35-day mortality rate by 23% compared to placebo. There is an added mortality benefit when used in combination with thrombolytics.
Adult Dose 160-324 mg PO (chewed)
Pediatric dose not established
Contraindications
Documented hypersensitivity; vitamin K deficiency; liver damage, hypoprothrombinemia, bleeding disorders, asthma; because of association of aspirin with Reye syndrome, do not use in children (<16 y) with influenza
Interactions
Effects may decrease with antacids and urinary alkalinizing agents; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses >2 g/d may potentiate glucose lowering effect of sulfonylurea drugs
Pregnancy D - Unsafe in pregnancy
Precautions May cause transient decrease in renal function and aggravate chronic kidney disease; caution in patients with severe anemia, history of blood coagulation defects, or are taking anticoagulants

Heparin
Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse preformed clot, but it is able to inhibit further thrombogenesis after thrombolysis. Prevents reaccumulation of clot after spontaneous fibrinolysis. Benefit as adjunctive therapy for SK not clear. Associated with an increased risk of hemorrhage when used with APSAC.
Adult Dose 60 U/kg (max 4000 U) IV bolus; followed by a 12 U/kg/h (max 1000 U/h) maintenance infusion
Pediatric Dose Not established
Contraindications
Documented hypersensitivity; subacute bacterial endocarditis, active bleeding; history of heparin-induced thrombocytopenia Interactions Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, aspirin, dextran, dipyridamole, and hydroxychloroquine may increase heparin toxicity
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions
Caution in severe hypotension and shock

Drug Category: Vasodilators

Opposes coronary artery spasm, which augments coronary blood flow and reduces cardiac work by decreasing preload and afterload. It is effective in the management of symptoms in AMI but may reduce the mortality rate only slightly. Nitroglycerin can be administered sublingually by tablet or spray, topically, or IV. In the setting of AMI, topical administration is a less desirable route because of unpredictable absorption and onset of clinical effects.

Nitroglycerin (Minitran, Nitrogard, Nitrol, Nitrolingual, Nitrostat, Nitro-Dur)
Causes relaxation of vascular smooth muscle by stimulating intracellular cyclic guanosine monophosphate production. Result is decrease in blood pressure.
Adult Dose 400 mcg SL tab or spray q5min, repeated up to 3 times; if symptoms persist, infuse IV at a rate of 5-10 mcg/min; titrate dose to a 10% reduction in MAP or limiting side effects of hypotension (>30% reduction in MAP or systolic BP <90), or severe headache
Pediatric Dose Not established
Contraindications
Documented hypersensitivity; severe anemia, shock, postural hypotension, head trauma, closed-angle glaucoma, cerebral hemorrhage, known right ventricular infarct
Interactions
Aspirin may increase nitrate serum concentrations; marked symptomatic orthostatic hypotension may occur with coadministration of calcium channel blockers (dose adjustment of either agent may be necessary)
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Caution in coronary artery disease and low systolic blood pressure

Drug Category: Beta-adrenergic blockers

Inhibit chronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation and reduce blood pressure, which decreases myocardial oxygen demand. Short-term and long-term mortality rates are reduced in patients with AMI. Greatest benefit is achieved when given within 8 h of symptom onset. Aim for a target heart rate of 60-90 beats per minute (bpm).

Metoprolol (Lopressor)
Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor blood pressure, heart rate, and ECG. Goal of treatment is to reduce heart rate to 60-90 bpm.
Adult Dose 5 mg IV q5min 3 times; titrate to heart rate and SBP
Pediatric Dose Not established
Contraindications Documented hypersensitivity; uncompensated congestive heart failure, bradycardia, asthma, cardiogenic shock, AV conduction abnormalities
Interactions Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels of metoprolol, possibly resulting in decreased pharmacologic effects; toxicity of metoprolol may increase with coadministration of sparfloxacin, phenothiazines, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives; metoprolol may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor patient closely and withdraw the drug slowly; during IV administration, carefully monitor blood pressure, heart rate, and ECG

Esmolol
Used in patients at risk for experiencing complications from beta-blockade, particularly those with reactive airway disease, mild-to-moderate LV dysfunction, and/or peripheral vascular disease. Short half-life of 8 min allows for titration to desired effect and quick discontinuation if needed.
Adult Dose Loading dose: 500 mcg/kg/min IV over 1 min
Optional loading dose: 0.5 mg/kg slow IV infusion
Maintenance dose: 0.1 mg/kg/min IV initially; titrate in increments of 0.05mg/kg/min q10-15min to a total dose of 0.2 mg/kg/min
Average maintenance dose: 50 mcg/kg/min over 4 min
Pediatric Dose Not established
Contraindications
Documented hypersensitivity; uncompensated congestive heart failure, bradycardia, cardiogenic shock, AV conduction abnormalities, cocaine-related ischemia
Interactions
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels of esmolol, possibly resulting in decreased pharmacologic effect; cardiotoxicity of esmolol may increase when administered concurrently with sparfloxacin, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives; toxicity of esmolol increases when administered concurrently with digoxin, flecainide, acetaminophen, clonidine, epinephrine, nifedipine, prazosin, haloperidol, phenothiazines, and catecholamine-depleting agents
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions
Beta-adrenergic blockers may mask signs and symptoms of acute hypoglycemia and clinical signs of hyperthyroidism; symptoms of hyperthyroidism, including thyroid storm may worsen when medication is abruptly withdrawn; withdraw drug slowly and monitor patient closely; caution in patients on other negative inotropes, such as verapamil

Drug Category: Thrombolytic agents

These agents prevent recurrent thrombus formation and rapid restoration of hemodynamic disturbances. In addition, they remove pathologic intraluminal thrombus or embolus not yet dissolved by the endogenous fibrinolytic system. When given within 12 h of symptom onset, they restore patency of occluded arteries, salvage myocardium, and reduce morbidity and mortality of AMI. Thrombolytic treatment should be started within 30 min of arrival (door-drug time). Maximum benefit occurs when administered within 1-3 h of symptom onset.

Alteplase (Activase) or Reteplase (Retavase)
Alteplase: Fibrin-specific agent with a brief half-life of 5 min. Adjunctive therapy with IV heparin is necessary to maintain patency of arteries recanalized by t-PA, especially during the first 24-48 h. Heparin may be administered during t-PA infusion.
Reteplase: Recombinant plasminogen activator that forms plasmin after facilitating cleavage of endogenous plasminogen. In clinical trials, reteplase has been shown to be comparable to t-PA in achieving TIMI 2 or 3 patency at 90 min.
Adult Dose Alteplase: 15 mg IV bolus; 0.75 mg/kg IV over 30 min; not to exceed 50 mg; followed by 0.5 mg/kg over 60 min, up to 35 mg; not to exceed 100 mg
Reteplase: 10.8 U IV over 2 min; repeat in 30 min
Pediatric Dose not established
Contraindications
Documented hypersensitivity; stroke within last 2 mo; intracranial or intraspinal surgery or trauma; intracranial hemorrhage on pretreatment evaluation, active internal bleeding, intracranial neoplasm, arteriovenous malformation or aneurysm, bleeding diathesis, severe uncontrolled hypertension, suspicion of subarachnoid hemorrhage Interactions Drugs that alter platelet function (aspirin, dipyridamole, abciximab) may increase risk of bleeding prior to, during, or after therapy; may give heparin with, and after, alteplase infusions to reduce risk of rethrombosis; either heparin or alteplase may cause bleeding complications
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions
Monitor for bleeding, especially at arterial puncture sites, with coadministration of vitamin K antagonists; control and monitor blood pressure frequently during and following therapy (when managing acute ischemic stroke); caution in cardiovascular arrhythmias, hypotension, and perfusion arrhythmias
Do not use >0.9 mg/kg alteplase to manage acute ischemic stroke; doses >0.9 mg/kg may cause ICH

Tenecteplase
Modified version of alteplase (t-PA) made by substituting 3 amino acids of alteplase. Can be given as single bolus over 5-second infusion instead of 90 min with alteplase. Appears to cause less nonintracranial bleeding but has similar risk of intracranial bleeding and stroke as alteplase. Base the dose using patient weight. Initiate treatment as soon as possible after onset of AMI symptoms. Because tenecteplase contains no antibacterial preservatives, reconstitute immediately before use.
Adult Dose Give IV bolus over 5 seconds using body weight; not to exceed 50 mg
<60 kg: 30 mg (6 mL)
60-70 kg: 35 mg (7 mL)
70-80 kg: 40 mg (8 mL)
80-90 kg: 45 mg (9 mL)
>90 kg: 50 mg (10 mL)
Pediatric Dose not established
Contraindications
Documented hypersensitivity; active internal bleeding, intracranial neoplasm, known bleeding diathesis, severe uncontrolled hypertension, arteriovenous malformation or aneurysm; history of stroke; intracranial or intraspinal surgery or trauma within 2 mo Interactions Heparin and vitamin K antagonists, acetylsalicylic acid, dipyridamole, and GP IIb/IIIa inhibitors may increase risk of bleeding if coadministered with tenecteplase therapy
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions
Caution if readministering to patients who have received prior plasminogen activator therapy (may develop immunity); coronary thrombolysis may result in arrhythmias associated with reperfusion but not different from those often observed in ordinary course of AMI (may be managed with standard antiarrhythmic measures); in elderly patients, weigh benefits of tenecteplase on mortality against risk of increased adverse events, including bleeding; cholesterol embolism is associated with all types of thrombolytic agents but true incidence is unknown

Anistreplase (Eminase)
Recently approved for use in AMI. Non–fibrin-specific agent with a half-life of 90 min. Activates the conversion of plasminogen to plasmin, which is capable of degrading fibrin, fibrinogen, and other procoagulant proteins into soluble fragments. These effects result in thrombolysis. Has no survival benefit over SK and higher rate of allergic and bleeding complications. Easier to administer than t-PA, has a lower cost ($1500), and does not require heparinization.
Adult Dose 30 U IV over 2-5 min
Pediatric Dose not established
Contraindications Documented hypersensitivity; history of stroke, intracranial neoplasm, active internal bleeding, recent intracranial surgery, severe uncontrolled hypertension, arteriovenous malformation or aneurysm
Interactions Increases bleeding potential of heparin, warfarin, and aspirin
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions
Caution in cardiovascular arrhythmias, hypotension, and perfusion arrhythmias

Streptokinase (Kabikinase, Streptase)
Non–fibrin-specific agent with a half-life of 23 min. Need for adjunctive therapy with heparin is controversial. Acts with plasminogen to convert plasminogen to plasmin. Plasmin degrades fibrin clots as well as fibrinogen and other plasma proteins. An increase in fibrinolytic activity that degrades fibrinogen levels for 24-36 h takes place with intravenous infusion of streptokinase. Adult Dose 1.5 million U in 50 cc D5W IV over 60 min
Pediatric Dose not established
Contraindications Documented hypersensitivity; active internal bleeding, intracranial neoplasm, aneurysm, diathesis, severe uncontrolled arterial hypertension
Interactions
Antifibrinolytic agents may decrease effects of streptokinase; heparin, warfarin, and aspirin may increase risk of bleeding
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions
Caution in severe hypertension, intramuscular administration of medications, and trauma or surgery in previous 10 d; measure hematocrit, platelet count, aPTT, TT, PT, or fibrinogen levels before therapy is implemented; either TT or aPTT should be less than twice the reference range control value following infusion of streptokinase and before (re)instituting heparin; PT, aPTT, TT or fibrinogen should be monitored 4 h after initiation of therapy

Drug Category: Platelet aggregation inhibitors

These agents inhibit platelet aggregation and reduce mortality.

Clopidogrel (Plavix)
Selectively inhibits adenosine diphosphate (ADP) binding to platelet receptor and subsequent ADP-mediated activation of glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation.
Adult Dose 75 mg PO qd
Pediatric Dose not established
Contraindications
Documented hypersensitivity; active pathological bleeding, such as peptic ulcer, or intracranial hemorrhage Interactions Coadministration with naproxen, associated with increased occult GI blood loss; clopidogrel prolongs bleeding time; safety of coadministration with warfarin not established
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions
Caution in patients at increased risk of bleeding from trauma, surgery or other pathological conditions; caution in patients with lesions with propensity to bleed (eg, ulcers)

Eptifibatide (Integrilin)
Antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor, which reversibly prevents von Willebrand factor, fibrinogen, and other adhesion ligands from binding to the GP IIb/IIIa receptor. End effect is the inhibition of platelet aggregation. Effects persist over duration of maintenance infusion and are reversed when infusion ends.
Adult Dose 180 mcg/kg IV load; followed by 2 mcg/kg/min IV for 72 h PTCA: 135 mcg/kg IV bolus before procedure; followed by 0.5 mcg/kg/min IV for 20-24 h
Pediatric Dose not established
Contraindications
Documented hypersensitivity; severe hypertension (SBP >200 mm Hg), active internal bleeding, history of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation or aneurysm, acute pericarditis or bleeding diathesis; trauma or stroke within previous 30 d; platelet count <100,000/mm3; history of thrombocytopenia following prior exposure to this product; serum creatinine >2 mg/dL (for the 180 mcg/kg bolus and 2 mcg/kg/min infusion) or >4 mg/dL (for the 135 mcg/kg bolus and 0.5 mcg/kg/min infusion)
Interactions
Coadministration with heparin, warfarin, or aspirin may increase risk of bleeding; monitor closely when using other drugs that affect hemostasis
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions
Caution in platelet count <150,000/mm3 and hemorrhagic retinopathy; caution with concurrent use of drugs that affect hemostasis, such as thrombolytics, ticlopidine, NSAIDs, warfarin, dipyridamole, and clopidogrel; measure activated clotting time (ACT) and maintain aPTT between 50-70 s unless a PCI needs to be performed; maintain ACT between 300-350 s during a PCI; if platelets decrease to <100,000/mm3, perform additional platelet counts to exclude possibility of pseudothrombocytopenia; if thrombocytopenia is confirmed, discontinue GP IIb/IIIa inhibitors and heparin and appropriately monitor and treat the condition; monitor aPTT 6 h after start of heparin infusion and adjust to maintain aPTT higher than twice the baseline level

Tirofiban (Aggrastat)
Antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor that reversibly prevents von Willebrand factor, fibrinogen, and other adhesion ligands from binding to the GP IIb/IIIa receptor, thereby inhibiting platelet aggregation. Effects persist over the duration of maintenance infusion and are reversed after stopping the infusion.
Adult Dose 0.4 mcg/kg/min IV for 30 min; followed by 0.1 mcg/kg/min Pediatric Dose not established
Contraindications Documented hypersensitivity; history of intracranial hemorrhage; severe hypertension (SBP >200 mm Hg), active internal bleeding, intracranial neoplasm, arteriovenous malformation or aneurysm, acute pericarditis and bleeding diathesis; trauma or stroke within previous 30 d; platelet count <100,000/mm3, history of thrombocytopenia following prior exposure to this product; serum creatinine >2 mg/dL (for the 180 mcg/kg bolus and 2 mcg/kg/min infusion) or >4 mg/dL for the 135 mcg/kg bolus and the 0.5 mcg/kg/min infusion
Interactions Coadministration with heparin, warfarin, and aspirin may increase risk of bleeding
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions
Caution in platelet count <150,000/mm3 and hemorrhagic retinopathy; caution with concurrent use of drugs that affect hemostasis, such as thrombolytics, ticlopidine, NSAIDs, warfarin, dipyridamole, and clopidogrel; measure activated clotting time (ACT) and maintain aPTT between 50-70 s unless a PCI needs to be performed; maintain ACT between 300-350 s during a PCI; if platelets decrease to <100,000/mm3, perform additional platelet counts to exclude possibility of pseudothrombocytopenia; if thrombocytopenia is confirmed, discontinue GP IIb/IIIa inhibitors and heparin, and appropriately monitor and treat condition; monitor aPTT 6 h after start of heparin infusion and adjust to maintain aPTT higher than twice baseline level

Abciximab (ReoPro)
Chimeric human-murine monoclonal antibody approved for use in elective/urgent/emergent percutaneous coronary intervention. Binds to receptor with high affinity and reduces platelet aggregation by 80% for as long as 48 h following infusion. Prevents acute cardiac ischemic complications in unstable angina unresponsive to conventional therapy.
Adult Dose 0.25 mg/kg IV bolus; followed by 10 mcg/min IV for 12 h
Pediatric Dose not established
Contraindications
Documented hypersensitivity; bleeding diathesis, thrombocytopenia (<100,000 cells/mcL), recent trauma, intracranial tumor, severe uncontrolled hypertension, history of vasculitis, stroke within 2 y Interactions Toxicity increases with coadministration of anticoagulants, antiplatelets, and thrombolytics
Pregnancy D - Unsafe in pregnancy
Precautions Bleeding complications may occur in patients <75 kg body weight, >65 years, with history of GI disease, or who recently received thrombolytic therapy; severe thrombocytopenia may occur within first 24 h of use

Drug Category: Analgesics

Reduce pain, which decreases sympathetic stress. May provide some preload reduction. Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients who experience chest discomfort resulting from a myocardial infarction.

Morphine sulfate (Duramorph, Astramorph, MS Contin)
DOC for analgesia because of reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Various IV doses are used; commonly titrated until desired effect obtained.
Adult Dose 1-3 mg IV; repeat and titrate to pain
Pediatric Dose not established
Contraindications
Documented hypersensitivity; hypotension; potentially compromised airway where establishing rapid airway control would be difficult
Interactions
Phenothiazines may antagonize analgesic effects of opiate agonists; tricyclic antidepressants, MAOIs, and other CNS depressants may potentiate adverse effects of morphine
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions
Caution in severe hypotension, respiratory depression, nausea, emesis, constipation, urinary retention, atrial flutter, and other supraventricular tachycardias; has vagolytic action and may increase ventricular response rate

Drug Category: Anxiolytics

For those who experience significant anxiety. Anxiolytics allow the clinician to administer a smaller analgesic dose to achieve the same effect.

Alprazolam (Xanax)
For anxiety and management of panic attacks. Binds receptors at several sites within CNS, including the limbic system and reticular formation. Effects may be mediated through GABA receptor system.
Adult Dose 0.5-1 mg IV/SL
Pediatric Dose not established
Contraindications
Documented hypersensitivity; severe respiratory depression, narrow-angle glaucoma, preexisting hypotension Interactions Carbamazepine and disulfiram decrease effects; toxicity increases with cimetidine, lithium, contraceptives, and CNS depressants (including alcohol)
Pregnancy D - Unsafe in pregnancy
Precautions Withdrawal symptoms, including seizures, may occur upon abrupt discontinuation of drug