DOSAGE FIBRINOLYTIC AGENTS

ALTEPLASE  ( Activase,t-PA )
Fibrinolytic Agent
Action And Clinical Pharmacology: Alteplase is a serine protease which has the property of fibrin-enhanced conversion of plasminogen to plasmin. It produces minimal conversion of plasminogen in the absence of fibrin; and when introduced into the systemic circulation, alteplase binds to fibrin in a thrombus and converts the entrapped plasminogen to plasmin. This initiates local fibrinolysis with minimal systemic effects. Following administration of alteplase there is a decrease (20 to 30%) in circulating fibrinogen. Decreases in plasminogen and a2-antiplasmin are also evident. Alteplase is cleared rapidly from circulating plasma with an initial half-life of less than 5 minutes. There is no difference in the dominant initial plasma half-life between the 3-hour and accelerated regimens for acute myocardial infarction (AMI). The plasma clearance of alteplase is approximately 500 mL/min. The clearance is mediated primarily by the liver. An occlusive thrombus is present in the infarct-related coronary artery in approximately 80% of patients experiencing a transmural myocardial infarction evaluated within 4 hours of onset of symptoms. Acute Myocardial Infarction Patients: Two alteplase dose regimens have been studied in patients experiencing AMI: accelerated infusion, and 3-hour infusion. The comparative efficacy of these 2 regimens has not been evaluated. 90-Minute Accelerated Infusion in Patients with Acute Myocardial Infarction: Accelerated infusion of alteplase was studied in an international, multicentre trial (GUSTO) where 41 021 patients with acute myocardial infarction were randomized to 4 thrombolytic regimens: accelerated infusion of alteplase (<100 mg over 90 minutes) plus i.v. heparin; streptokinase (1.5´10units over 60 minutes) plus i.v. heparin; streptokinase (1.5´10units over 60 minutes) plus s.c. heparin; or combined alteplase (1.0 mg/kg over 60 minutes) plus streptokinase (1.0´10units over 60 minutes). ASA was administered daily. The results are shown in Table I. The 30-day mortality for the accelerated infusion of alteplase was 1% lower (14% relative risk reduction) than for streptokinase (i.v. or s.c. heparin). In addition, the combined incidence of 30-day mortality or nonfatal stroke for accelerated alteplase was 1% lower (12% relative risk reduction) than for streptokinase (i.v. heparin) and 0.8% lower (10% relative risk reduction) than for streptokinase (s.c. heparin). Once a year follow-up data suggest a sustained mortality benefit. Subgroup analysis of patients by age, infarct location, and time from symptom onset to thrombolytic treatment showed consistently lower 30-day mortality for the group receiving the accelerated infusion of alteplase. For patients who were over 75 years of age, a predefined subgroup consisting of 12% of patients enrolled, the incidence of stroke was 4.0% for the group receiving the accelerated infusion of alteplase, 2.8% for streptokinase (i.v. heparin), and 3.2% for streptokinase (s.c. heparin); the incidence of combined 30-day mortality or nonfatal stroke was 20.6% for accelerated infusion of alteplase, 21.5% for streptokinase (i.v. heparin), and 22.0% for streptokinase (s.c. heparin). In-hospital events in the overall patient population, as well as events in patients who survived beyond 30 days are shown in Table II. An angiographic substudy of the GUSTO trial provided data on infarct-related artery patency. Results are shown in Table III. Reocclusion rates were similar for all 3 treatment regimens. 3-Hour Infusion in Patients with Acute Myocardial Infarction: In patients studied with coronary angiography prior to and following infusion of alteplase, the use of alteplase resulted in reperfusion of documented obstructed vessels within 90 minutes after the commencement of thrombolytic therapy in approximately 70% of patients. In 2 studies involving 145 patients, alteplase produced reperfusion in 73% of patients who received 70 to 100 mg (40.6 to 58´10IU) over 90 minutes. In 2 double blind randomized controlled trials in patients with AMI, the patients infused with 80 to 100 mg of alteplase experienced improved ventricular function and reduced incidence of clinical congestive heart failure compared to those treated with placebo. In a double-blind study involving 5 013 patients (ASSET Study) where patients were infused with either alteplase or placebo within 5 hours of onset of symptoms of AMI, improved 30-day survival was shown in patients receiving alteplase compared to placebo. At 1 month, the overall mortality rates were 7.2% for the alteplase-treated group and 9.8% for the placebo-treated group (p=0.001). This benefit was maintained at 6 months (10.4% and 13.1% for alteplase and placebo-treated patients respectively, p=0.008). In the LATE study involving 5 711 patients where patients were infused with either alteplase (100 mg over 3 hours) or placebo within 6 to 24 hours of onset of AMI symptoms, the 35-day mortality rates were 8.9% for Activase rt-PA treated patients and 10.3% for placebo-treated patients (p=not significant). Prespecified survival analysis according to treatment within 12 hours of symptom onset showed a significant reduction in mortality for the alteplase treated patients, 8.9% versus 12.0% for the placebo treated patients (p=0.0229). Indications And Clinical Uses: For i.v. use in adults for: the lysis of suspected occlusive coronary artery thrombi associated with evolving transmural myocardial infarction; and the reduction of mortality associated with AMI, the improvement of ventricular function following AMI and the reduction in the incidence of congestive heart failure. Treatment should be initiated as soon as possible after the onset of acute myocardial symptoms. Greater benefit appears to be associated with earlier treatment of alteplase, following the onset of symptoms. Alteplase is effective in patients in whom therapy is initiated within 6 hours of onset of symptoms for the accelerated infusion regimen or up to 12 hours after onset of symptoms for the 3-hour infusion regimen. The GUSTO study was designed to enrol patients within a 6-hour period following the onset of myocardial infarct symptoms. The data available from this trial are insufficient to support a recommendation for use of the accelerated infusion regimen in patients presenting more than 6 hours after the onset of symptoms. Contra-Indications: Because thrombolytic therapy increases the risk of bleeding, alteplase is contraindicated in the following situations: active internal bleeding; history of stroke; patients receiving other i.v. thrombolytic agents; recent (within 2 months) intracranial, or intraspinal surgery or trauma (see Warnings); intracranial neoplasm, arteriovenous malformation, or aneurysm; known bleeding diathesis; severe uncontrolled hypertension, i.e., diastolic BP³110 mm Hg and/or systolic BP³180 mm Hg; recent traumatic cardiopulmonary resuscitation; recent severe trauma. tag_WarningWarnings Manufacturers' Warnings In Clinical States: Bleeding: The most common complication encountered during therapy with alteplase is bleeding. The type of bleeding associated with thrombolytic therapy can be divided into 2 broad categories: internal bleeding involving the gastrointestinal tract, genitourinary tract, respiratory tract, retroperitoneal or intracranial sites; superficial or surface bleeding, observed mainly at invaded or disturbed sites (e.g., venous cutdowns, arterial punctures, sites of recent surgical intervention). The concomitant use of heparin anticoagulation contributes to the risk of bleeding. Fibrin will be lysed during the infusion of alteplase and bleeding from recent puncture sites may occur. Therefore, therapy with alteplase, as with other thrombolytic agents, requires careful attention to all potential bleeding sites (including catheter insertion sites, arterial and venous puncture sites, cutdown sites and needle punctures sites). I.M. injections and nonessential handling of the patient should be avoided during and immediately following treatment with alteplase. Venipunctures should be performed carefully and only as required. Should an arterial puncture be necessary during an infusion of alteplase, it is preferable to use an upper extremity vessel that is accessible to manual compression. Pressure should be applied for at least 30 minutes, a pressure dressing applied and the puncture site checked frequently for evidence of bleeding. Should serious bleeding in a critical location (not controllable by local pressure) occur, the infusion of alteplase and any other concomitant anticoagulant should be discontinued immediately and treatment initiated (see Overdose: Symptoms and Treatment). In the following conditions, the risks of alteplase therapy may be increased and should be weighed against the anticipated benefits: recent (within 10 days) major surgery, e.g., coronary artery bypass graft, obstetrical delivery, organ biopsy, previous puncture of noncompressible vessels; clinical evidence or history of transient ischemic attacks; recent gastrointestinal or genitourinary bleeding (with 10 days); recent trauma (within 10 days); a history or clinical evidence of hypertensive disease in a patient over 70 years old; advanced age, e.g., over 75 years old; high likelihood or known presence of left heart thrombus, e.g., mitral stenosis with atrial fibrillation; apical MI, with thrombus; acute pericarditis; subacute bacterial endocarditis; hemostatic defects including those secondary to severe hepatic or renal disease; significant liver dysfunction, e.g., prolonged prothrombin time; pregnancy; diabetic hemorrhagic retinopathy, or other hemorrhagic ophthalmic conditions; septic thrombophlebitis or occluded AV cannula at seriously infected site; patients currently receiving oral anticoagulants, e.g., warfarin sodium; any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location. Cholesterol Embolization: Cholesterol embolization has been reported rarely in patients treated with all types of thrombolytic agents; the true incidence is unknown. This serious condition, which can be lethal, is also associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy. Clinical features of cholesterol embolism include livedo reticularis, "purple toe" syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis, myocardial infarction, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, and rhabdomyolysis. Arrhythmias: Coronary thrombolysis may result in arrhythmias associated with reperfusion. These arrhythmias (such as sinus bradycardia, accelerated idioventricular rhythm, ventricular premature depolarizations, ventricular tachycardia) are not different from those often seen in the ordinary course of AMI and may be managed with standard antiarrhythmic measures. It is recommended that antiarrhythmic therapy for bradycardia and/or ventricular irritability be available when infusions of alteplase are administered. Use of Antithrombotics: ASA and heparin may be administered concomitantly with and following infusions of alteplase. Because either heparin, ASA or alteplase alone may cause bleeding complications, careful monitoring for bleeding is advised, especially at arterial puncture sites. Precautions: General: Alteplase should be administered in a hospital setting where the appropriate diagnostic and monitoring techniques are readily available. Routine management of myocardial infarction should not be deferred after evidence of successful thrombolysis is seen. Evaluation and management of underlying atherosclerotic heart disease should be carried out as clinically indicated. Noncompressible arterial puncture must be avoided. Arterial and venous punctures should be minimized. In the event of serious bleeding, alteplase and heparin should be discontinued immediately. Heparin effects can be reversed by protamine. Drug Interactions: The interaction of alteplase with other drugs has not been studied. In addition to bleeding associated with heparin and warfarin, drugs that alter platelet function (such as ASA) may increase the risk of bleeding if administered prior to, during or after alteplase infusion. Laboratory Tests: During alteplase infusion, coagulation tests and/or measures of fibrinolytic activity may be performed if desired. However, routine measurements of fibrinogen as well as fibrinogen degradation products are unreliable, and should not be undertaken unless specific precautions are taken to prevent in vitro artifacts. Alteplase is a serine protease that when present in blood in pharmacologic concentrations remains active under in vitro conditions. This can lead to degradation of fibrinogen in a blood sample removed for analysis. Collection of blood samples on aprotinin (150 to 200 units/mL) can to some extent mitigate this phenomenon. Geriatrics: The risks of therapy may be increased in the elderly (see Pharmacology, Warnings and Adverse Effects). Children: Safety and effectiveness of alteplase in children has not been established. Therefore treatment of such patients is not recommended. Pregnancy: Reproduction studies have not been conducted with alteplase. It is also not known whether alteplase can cause fetal harm when administered to a pregnant woman. Alteplase should be given to a pregnant woman only if clearly needed. Lactation: It is not known whether alteplase is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when alteplase is administered to a nursing woman. Readministration: There has been little documentation of readministration of alteplase. Readministration should be undertaken with caution. Less than 0.5% of patients receiving single courses of alteplase therapy have experienced transient antibody formation. Nevertheless, if an anaphylactoid reaction occurs, the infusion should be discontinued immediately and appropriate therapy initiated. Adverse Reactions: Bleeding: The most frequent adverse reaction associated with alteplase is bleeding. The type of bleeding associated with thrombolytic therapy can be divided into 2 broad categories: internal bleeding, involving the gastrointestinal tract, genitourinary tract, respiratory tract, retroperitoneal or intracranial sites; superficial or surface bleeding, observed mainly at invaded or disturbed sites (e.g., venous cutdowns, arterial punctures, sites of recent surgical intervention). The incidence of all strokes for the accelerated alteplase regimen in the GUSTO trial was 1.6%, while the incidence of nonfatal stroke was 0.9%. The incidence of hemorrhagic stroke was 0.7%, not all of which were fatal. Data from previous trials utilizing a 3-hour infusion indicates that the incidence of total stroke in 6 randomized double-blind placebo controlled trials was 1.2% (37/3 161) in alteplase-treated patients (£100 mg) compared with 0.9% (27/3 092) in placebo-treated patients. Although the incidence of all strokes, as well as that for hemorrhagic stroke, increased with increasing age, treatment with accelerated regimen of alteplase was still shown to reduce mortality in older patients. For patients who were over 75 years of age, a predefined subgroup consisting of 12% of patients enrolled, the incidence of stroke was 4.0% for the accelerated regimen of alteplase group, 2.8% for streptokinase (i.v. heparin), and 3.2% for streptokinase (s.c. heparin) (see Table IV). However, combined 30-day mortality or nonfatal stroke was 20.6% for accelerated regimen of alteplase, 21.5% for streptokinase (i.v. heparin) and 22.0% for streptokinase (s.c. heparin) in the GUSTO study. The following incidence of significant internal bleeding (estimated as ³250 mL blood loss) has been reported in studies involving over 1 300 patients treated at all doses of alteplase, administered as a 3-hour infusion regimen: gastrointestinal 5%, genitourinary 4%. The following incidence of moderate or severe bleeding was reported when £100 mg alteplase was administered by accelerated infusion to >10 000 patients [GUSTO study]: gastrointestinal 1.5%, genitourinary 0.5%. Incidence of £1% of ecchymosis, retroperitoneal bleeding, epistaxis and gingival bleeding has been reported in clinical studies involving alteplase. The incidence of intracranial bleeding in patients treated with up to 120 mg alteplase (3-hour infusion) has been 0.4%. At doses in excess of 120 mg (120 to 180 mg) the incidence of intracranial bleeding increased to 1.3%. The incidence of intracranial bleeding in patients treated £100 mg alteplase (accelerated infusion, weight adjusted) was 0.7%. The maximum total dose of alteplase should not exceed 100 mg. Death and permanent disability have been reported in patients who have experienced stroke and other serious bleeding episodes. Allergic Reactions: Allergic-type reactions, e.g., anaphylactoid reaction, laryngeal edema, rash and urticaria have been reported very rarely (<0.02%). A cause and effect relationship to alteplase therapy has not been established. Other Adverse Reactions: Patients with myocardial infarction can experience disease-related events such as cardiogenic shock, arrhythmias, pulmonary edema, heart failure, cardiac arrest, recurrent ischemia, reinfarction, myocardial rupture, mitral regurgitation, pericardial effusion, pericarditis, cardiac tamponade, venous thrombosis and embolism, and electromechanical dissociation. These events may lead to death. Other adverse reactions have been reported, principally nausea and/or vomiting, hypotension, and fever. These reactions are frequent sequelae of myocardial infarction and may or may not be attributable to alteplase therapy. Symptoms And Treatment Of Overdose: Symptoms and Treatment: Overdosage could lead to serious bleeding. Should serious bleeding occur in a critical location, the infusion of alteplase and any other concomitant anticoagulant should be discontinued immediately. If necessary, blood loss and reversal of the bleeding tendency can be managed with whole blood or packed red cells. In the event of clinically significant fibrinogen depletion, fresh frozen plasma or cryoprecipitate can be infused. tag_DosageDosage Dosage And Administration: Alteplase is intended for i.v. use only. It should be given via a dedicated i.v. line with an infusion pump. Extravasation of alteplase infusion can cause ecchymosis and/or inflammation. Management consists of terminating the infusion at the i.v. site and application of local therapy. Acute Myocardial Infarction: Administer alteplase as soon as possible after the onset of symptoms. There are 2 dose regimens for alteplase for use in the management of AMI. The comparative efficacy of these 2 regimens has not been evaluated. 90-Minute Accelerated Infusion: See Table V. The recommended total dose is based upon patient weight, not to exceed 100 mg. For patients weighing >67 kg, the recommended dose is 100 mg, administered as a 15 mg i.v. bolus, followed by 50 mg infused over 30 minutes and then 35 mg infused over the next 60 minutes. For patients weighing <67 kg, the recommended dose is 15 mg administered as an i.v. bolus, followed by 0.75 mg/kg to a maximum of 50 mg, infused over the next 30 minutes, and then 0.50 mg/kg to a maximum of 35 mg infused over the next 60 minutes. Preparation and Administration: The alteplase dose administered by accelerated infusion may be prepared and administered as follows: A. The bolus dose may be prepared in one of the following ways: 1. By removing 15 mL from the vial of reconstituted (1 mg/mL) alteplase using a syringe and needle. For 50 mg vials, the syringe should not be primed with air and the needle should be inserted into the alteplase vial stopper. If the 100 mg vial is used, the needle should be inserted away from the puncture mark made by the transfer device. 2. By removing 15 mL from a port (second injection site) on the infusion line after the infusion set is primed. 3. By programming an infusion pump to deliver a 15 mL (1 mg/mL) bolus at the initiation of the infusion. B. The remainder of the alteplase dose may be administered as follows: 50 mg vials: Administer using either a polyvinyl chloride bag or glass vial and infusion set. 100 mg vials: Insert the spike end of an infusion set through the same puncture site created by the transfer device in the stopper of the vial of reconstituted alteplase. Hang the vial of alteplase from the plastic molded capping attached to the bottom of the vial. 3-Hour Infusion: The recommended dose is 100 mg administered as 60 mg (34.8´10IU) in the first hour, of which 6 to 7 mg is administered as a bolus over the first 1 to 2 minutes and the remainder is administered by continuous infusion, 20 mg (11.6´10IU) by continuous infusion during the second hour, and 20 mg (11.6´10IU) by continuous infusion over the following 1 to 4 hours. For smaller patients (<65 kg), a dose of 1.25 mg/kg may be warranted. The alteplase dose administered by 3-hour infusion may be prepared and administered as follows: A. The bolus dose may be prepared in one of the following ways: 1. By removing 6 to 10 mL from the vial of reconstituted (1 mg/mL) alteplase using a syringe and needle. For 50 mg vials, the syringe should not be primed with air and the needle should be inserted into the alteplase vial stopper. If the 100 mg vial is used, the needle should be inserted away from the puncture mark made by the transfer device. 2. By removing 6 to 10 mL from a port (second injection site) on the infusion line after the infusion set is primed. 3. By programming an infusion pump to deliver a 6 to 10 mL (1 mg/mL) bolus at the initiation of the infusion. B. The remainder of the alteplase dose may be administered as follows: 50 mg vials: Administer using either a polyvinyl chloride bag or glass vial and infusion set. 100 mg vials: Insert the spike end of an infusion set through the same puncture site created by the transfer device in the stopper of the vial of reconstituted alteplase. Hang the vial of alteplase from the plastic molded capping attached to the bottom of the vial. Anticoagulation During and After Treatment with Alteplase: To date, heparin has been administered concomitantly in more than 90% of patients given alteplase. Adjunctive i.v. heparin administration is recommended to obtain a therapeutic partial thromboplastin time (PTT). The infusion of heparin should be initiated prior to the termination of the infusion of alteplase. Reconstitution and Dilution: Alteplase should be reconstituted by aseptically adding to the vial, the appropriate volume of Sterile Water for Injection, USP (50 mL for 50 mg vials, 100 mL for 100 mg vials). It is important that alteplase be reconstituted only with Sterile Water for Injection, USP, without preservatives. Do not use Bacteriostatic Water for Injection. The reconstituted preparation results in a colorless to pale yellow transparent solution containing alteplase 1 mg/mL at a pH of 7.3. The osmolality of this solution is approximately 215 mOsm/kg. Before further dilution or administration, parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration whenever solution and container permit. Because alteplase contains no preservatives, it should be reconstituted immediately before use (see Stability and Storage). The reconstituted solution may be diluted further immediately before administration to yield concentrations as low as 0.5 mg/mL in 0.9% Sodium Chloride for Injection, USP or 5% Dextrose for Injection, USP. Excessive agitation during dilution should be avoided; mixing should be accomplished with gentle swirling and/or slow inversion. Do not use other infusion solutions e.g., Sterile Water for Injection, USP, or preservative containing solutions for further dilution. No other medication should be added to alteplase solution. Solutions should be administered as described above. Unused infusion solution should be immediately discarded. 50 mg vials: Using a large bore needle (e.g., 18 gauge), and the accompanying 50 mL Sterile Water for Injection, USP, direct the stream of Sterile Water for Injection, USP into the lyophilized cake. Do not use if vacuum is not present. Slight foaming upon reconstitution is not unusual; standing undisturbed for several minutes is usually sufficient to allow dissipation of any large bubbles. Excessive or vigorous shaking should be avoided. 100 mg vials: Using the transfer device provided, the contents of the accompanying 100 mL vial of Sterile Water for Injection, USP should be added to the contents of the 100 mg vial of alteplase powder. Slight foaming upon reconstitution is not unusual; standing undisturbed for several minutes is usually sufficient to allow dissipation of any large bubbles. No vacuum is present in 100 mg vials. Please refer to the accompanying instructions for Reconstitution and Administration of the 100 mg vials: 1. Use aseptic technique throughout. 2. Remove the protection flip-caps from 1 vial of alteplase and 1 vial of Sterile Water for Injection, USP. 3. Open the package containing the transfer device by peeling the paper label off the package. 4. Remove the protective cap from one end of the transfer device and keeping the vial of Sterile Water for Injection upright, insert the piercing pin vertically into the centre of the stopper of the vial of Sterile Water for Injection. 5. Remove the protective cap from the other end of the transfer device. Do not invert the vial of Sterile Water for Injection. 6. Holding the vial of alteplase upside-down, position it so that the centre of the stopper is directly over the exposed piercing pin of the transfer device. 7. Push the vial of alteplase down so that the piercing pin is inserted through the centre of the alteplase stopper. 8. Invert the 2 vials so that the vial of alteplase is on the bottom (upright) and the vial of Sterile Water for Injection is upside-down, allowing the Sterile Water for Injection to flow down through the transfer device. Allow the entire contents of the vial of Sterile Water for Injection to flow into the alteplase vial (approximately 0.5 mL of Sterile Water for Injection will remain in the diluent vial). Approximately 2 minutes are required for this procedure. 9. Remove the transfer device and the empty Sterile Water for Injection vial from the alteplase vial. Safely discard both the transfer device and the empty diluent vial according to institutional procedures. 10. Swirl gently to dissolve the alteplase powder. Do not shake. Stability and Storage: Lyophilized alteplase is stable up to the expiration date stamped on the vial when stored at controlled temperatures between 2 and 30°C. Protect the lyophilized material during extended storage from excessive exposure to light. Unused reconstituted alteplase (in the vial) may be stored at 2 to 30°C for up to 8 hours. After that time, any unused portion of the reconstituted material should be discarded. During the period of reconstitution and infusion, protection from light is not necessary. Availability And Storage: 50 mg: Each vial of sterile, lyophilized powder contains: alteplase 50 mg. Nonmedicinal ingredients: L-arginine, phosphoric acid, polysorbate 80. Phosphoric acid and/or sodium hydroxide may be used prior to lyophilization for pH adjustment. Vials of 50 mg with vacuum present. Boxes of 1 vial of Activase rt-PA 50 mg (29´10IU), and 1 vial of Sterile Water for Injection, USP 50 mL, for preparing a sterile solution of Activase rt-PA. 100 mg: Each vial of sterile, lyophilized powder contains: alteplase 100 mg. Nonmedicinal ingredients: L-arginine, phosphoric acid, polysorbate 80. Phosphoric acid and/or sodium hydroxide may be used prior to lyophilization for pH adjustment. Vials of 100 mg with no vacuum present. Boxes of 1 vial of Activase rt-PA 100 mg (58 ´ 10IU) and 1 vial of Sterile Water for Injection, USP 100 mL, and 1 transfer device for preparing a sterile solution of Activase rt-PA. Biological potency is determined by an in vitro clot lysis assay and is expressed in International Units (58´10IU/mg alteplase). ANISTREPLASE Anistreplase (Eminase) Anistreplase Classification: Thrombolytic enzyme Action/Kinetics: Prepared by acylating human plasma derived from lys-plasminogen and purified streptokinase derived from group C beta-hemolytic streptococci. When prepared, anistreplase is an inactive derivative of a fibrinolytic enzyme although the compound can still bind to fibrin. Anistreplase is activated by deacylation and subsequent release of the anisoyl group in the blood stream. The production of plasmin from plasminogen occurs in both the blood stream and the thrombus leading to thrombolysis. Lyses thrombi obstructing coronary arteries and reduces the size of infarcts. t 1/2: 70-120 min. Uses: Management of AMI in adults, resulting in improvement of ventricular function and reduction of mortality. Treatment should be initiated as soon as possible after the onset of symptoms of AMI. Contraindications: Use in active internal bleeding; within 2 months of intracranial or intraspinal surgery; recent trauma, including cardiopulmonary resuscitation; history of CVA; intracranial neoplasm; arteriovenous malformation or aneurysm; known bleeding diathesis; severe, uncontrolled hypertension; severe allergic reactions to streptokinase. Special Concerns: Use with caution in nursing mothers. Safety and effectiveness have not been determined in children. NOTE: The risks of anistreplase therapy may be increased in the following conditions; thus, benefit versus risk must be assessed prior to use. Within 10 days of major surgery (e.g., CABG, obstetric delivery, organ biopsy, previous puncture of noncompressible vessels); cerebrovascular disease; within 10 days of GI or GU bleeding; within 10 days of trauma including cardiopulmonary resuscitation; SBP > 180 mm Hg or DBP > 110 mm Hg; likelihood of left heart thrombus (e.g., mitral stenosis with atrial fibrillation); SBE; acute pericarditis; hemostatic defects including those secondary to severe hepatic or renal disease; pregnancy; clients older than 75 years of age; diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions; septic thrombophlebitis or occluded arteriovenous cannula at seriously infected site; clients on oral anticoagulant therapy; any condition in which bleeding constitutes a significant hazard or would be difficult to manage due to its location. Side Effects: Bleeding: Including at the puncture site (most common), nonpuncture site hematoma, hematuria, hemoptysis, GI hemorrhage, intracranial bleeding gum/mouth hemorrhage, epistaxis, anemia, eye hemorrhage. CV: Arrhythmias conduction disorders, hypotension; cardiac rupture chest pain, emboli (causal relationship to use of anistreplase unknown). Allergic: Anaphylaxis, bronchospasm angioedema, urticaria, itching, flushing, rashes, eosinophilia, delayed purpuric rash which may be associated with arthralgia, ankle edema, mild hematuria, GI symptoms, and proteinuria. GI: N&V. Hematologic: Thrombocytopenia. CNS: Agitation, dizziness, paresthesia, tremor, vertigo. Respiratory: Dyspnea, lung edema. Miscellaneous: Chills, fever, headache, shock. Laboratory Test Alterations: Transaminase levels, thrombin time, activated PTT, and PT. Plasminogen and fibrinogen. Drug Interactions: Increased risk of bleeding or hemorrhage if used with heparin, oral anticoagulants, vitamin K antagonists, aspirin, or dipyridamole. How Supplied: Powder for injection: 30 U Dosage IV only: 30 units over 2-5 min into an IV line or vein as soon as possible after onset of symptoms. STREPTASE (streptokinase) DESCRIPTION Streptase®, Streptokinase, is a sterile, purified preparation of a bacterial protein elaborated by group C (beta) -hemolytic streptococci. It is supplied as a lyophilized white powder containing 25 mg cross-linked gelatin polypeptides, 25 mg sodium L-glutamate, sodium hydroxide to adjust pH, and 100 mg Albumin (Human) per vial or infusion bottle as stabilizers. The preparation contains no preservatives and is intended for intrvenous and intracoronary administration Streptase Indications & Dosage INDICATIONS  Acute Evolving Transmural Myocardial Infarction: Streptase, Streptokinase, is indicated for use in the management of AMI in adults, for the lysis of intracoronary thrombus , the improvement of ventricular function, and the reduction of mortality associated with AMI, when administered by either the intrvenous or the intracoronary route, as well as for the reduction of infarc size and CHF associated with AMI when administered by the intravenous route. Earlier administration of Streptokinase is correlated with greater clinical benefit. Pulmonary Embolism:   Streptase, Streptokinase, is indicated for the lysis of objectively diagnosed (angiography or lung scan) pulmonary emboli, involving obstruction of blood flow to a lobe or multiple segments, with or without unstable hemodynamics. Deep Vein Thrombosis:   Streptase, Streptokinase, is indicated for the lysis of objectively diagnosed (preferably ascending venography), acute, extensive thrombi of the deep veins such as those involving the popliteal and more proximal vessels. Arterial Thrombosis or Embolism:   Streptase, Streptokinase, is indicated for the lysis of acute arterial thrombi and emboli. Streptokinase is not indicated for arterial emboli originating from the left side of the heart due to the risk of new embolic phenomena such as cerebral embolism. Occlusion of Arteriovenous Cannulae:   Streptase, Streptokinase, is indicated as an alternative to surgical revision for clearing totally or partially occluded arteriovenous cannulae when acceptable flow cannot be achieved. DOSAGE AND ADMINISTRATION Acute Evolving Transmural Myocardial Infarction:   Administer Streptokinase as soon as possible after onset of symptoms. The greatest benefit in mortality reduction was observed when Streptokinase was administered within four hours, but statistically significant benefit has been reported up to 24 hours. Route Total Dose Dosage/Duration Intravenous infusion 1,500,000 IU 1,500,000 IU within 60 min. Intracoronary infusion 140,000 IU 20,000 IU by bolus followed by 2,000 IU/min. for 60 min. Pulmonary Embolism, Deep Vein Thrombosis, Arterial Thrombosis or Embolism:   Streptase, Streptokinase, treatment should be instituted as soon as possible after onset of the thrombotic event, preferably within 7 days. Any delay in instituting lytic therapy to evaluate the effect of heparin therapy decreases the potential for optimal efficacy. Since human exposure to streptococci is common, antibodies to Streptokinase are prevalent. Thus, a loading dose of Streptokinase sufficient to neutralize these antibodies is required. A dose of 250,000 IU of Streptokinase infused into a peripheral vein over 30 minutes has been found appropriate in over 90% of patients. Furthermore, if the thrombin time or any other parameter of lysis after 4 hours of therapy is not significantly different from the normal control level, discontinue Streptokinase because excessive resistance is present. Indication Loading Dose IV Infusion Dosage/Duration Pulmonary Embolism 250,000 IU/30 min. 100,000 IU/hr for 24 hr (72 hrs if concurrent DVT is suspected). Deep Vein Thrombosis 250,000 IU/30 min. 100,000 IU/hr for 72 hr Arterial Thrombosis or Embolism 250,000 IU/30min. 100,000 IU/hr for 24-72 hr

EMERGENCY MEDICATIONS

1. ACE INHIBITORS ( ANGIOTENSIN-CONVERTING ENZYME INHIBITORS )

     Anti hypertensive

    Common Agents : Captopril,enalapril,lisinopril,ramipril.
    Indications          : MI ,Hypertension,CHF,Heart failure w/o hypotension,ST Segment elevation,
                                left ventricular dysfunction after MI.
    Dose                  : see individual order and dosage
                                Usually not started in emergency department,but within 24 hrs after fibrinolitic
                                therapy has been completed and blood pressure has stabilized.
    Contraindication : Lactation,pregnancy,angioedema,hypersensitivity to ACE inhibitors,serum
                               serum potassium   >5 mEq/L.
    Side Effects        : Tachycardia,dizzines,headache,fatigue,hypotension,hyperkalemia.
    Precautions        : Reduce dose in renal failure.

2. ADENOSINE  (  Adenocard,adenosan ) Anti arrhythmic.
    Indication           : Narrow complex tachycardia and PSVT.
    Dose                  : 6 mg rapid intravenous push ( IVP )over 1-3 second followed by a 20 ml bolus of
                                normal saline. Give 12 mg by IVP in 1-2 minute if needed. A third dose of
                               12 mg IVP may be given in 1-2 minute,max 30 mg.
    Contraindication : Hypersensitivity,sick sinus syndrome,2nd or 3rd degree AV block (unless a
                                functional artificial pacemaker is present,drug or poison-induced tachycardia.
    Side Effects        : Flushing,dizzines,bronchospasm,chest pain or tightness,bradycardia,AV block,
                                asystole,ventricular ectopic beats,VF.
    Precautions        : Ineffective in treating Atrial fibrilation,atrial flutter,or VT. Avoid in patients with
                               receiving dipyridamole and in patients with ashtma or unstable angina.

3. AMIODARONE  (Cordorane,Pacerone ) Anti Arrhythmic
    Indications         :Wide and narrow complex tachycardia,polymorphic VT,shock refractory VF
                               or pulseless VT,SVT,PSVT.
    Dose                 : Cardiac arrest 300 mg (diluted in 20-30 mL D5W ) IVP,
                               Consider additional 150 mg IVP  in 3-5 min.Wide narrow complex tachycardia
                               (stable) 150 mg IVP over first  10 min ( 15 mg/min )-may repeat infusion
                               of 150 mg IVP every 10 min as needed. Slow infusion of 360 mg IV over
                               next 6 hr ( 1 mg /min ).Max.cumulative dose 2.2 g IV in 24 hr.
  Contraindications: Bradycardia,hypersensitivity,cardiogenic shock,2nd or 3rd degree AV Block.
  Side Effects        : Vasodilation,hypotension,visual impairment,hepatotoxicity,pulmonary toxicity,
                              CHF;may prolonge QT Interval.
  Precautions        : Avoid concurrent use with procainamide.Correct hypokalemia and
                             hypomagnesemia if possible before use. Draw up amiodarone through a large
                             gauge needle to reduce foaming.For slow or maintenance IV infusion,mix
                             medication only in glass bottle containing D5W and administer through an in-
                             line filter.          
                              
4. ASPIRIN   ( Acetylsalicylic Acid ) Antiplatelet.
   Indications       :  Acute coronary syndrome,symptoms suggestive or cardiac ischemia.
   Dose               :  162-325 mg PO non-enteric coated for antiplatelet effect.
                             Give within minutes of onset.
  Contraindications: Known allergy to aspirin,pregnancy.
  Side effects      : Anorexia,nausea,epigastric pain,anaphylaxis.
  Precautions      : Active ulcers and asthma,bleeding disorders or thrombocytopenia.

5. ATROPINE ( Antiarrhythmic,Anticholinergic )
    Indications     : Symptomatic sinus bradycardia,asystole,PEA with rate <60bpm,cholinergic
                           drug toxicity and mushroom poisoning ( Antidote )
    Dose             : Cardiac arrest 1mg IVP every 3-5 min (may give trough ET/endotracheal
                           tube ) at 2.0-3.0 mg diluted in 10 mL normal saline,max 0.03-0.04 mg/kg.
                           Bradycardia 0.5-1.0 mg IVP every 3-5 min,max 0.03-0.04mg/kg.

  Contraindications: A-fib,A-flutter (see Reading ECG),glaucoma,asthma.
  Side efffects    :Tachycardia,headache,dry mouth,dilated pupil,VF or VT.
  Precautions     : Use caution in myocardial ischemia and hypoxia.
                          Avoid in hypothermic bradycardia and in 2nd degree or 3rd degree AV Block.

 6. BETA BLOCKERS  ( Antihypertensive )
    Common agents: Atenolol,esmolol,labetalol,metoprolol,propanolol.
    Indications    : MI ,unstable angina,PSVT ,A-fb,A-flutter,HTN.
    Dose            : See individual order or dose
    Contraindications: HR < 60 bpm systolic BP <100 mmHg,2nd-3rd dgree AV Block,
                         Left ventricle failure.
    Side effects   : Hypotension,dizzzines,bradycardia,headache,nausea and vomiting.
    Precautions   : Concurrent use with calcium channel blockers,such as verapamil or
                          diltiazem can cause hypotension. Use cautions in patients with a history
                          of bronchospasm or cardiac failure.

7. CALCIUM CHLORIDE (Mineral/Electrolytes/calcium salt.
    Indications   : Hyperkalemia ,hypcalcemia,hypermagnesemia,
                         Antidote to calcium channel blockers and beta blockers,given prophylactically
                         with calcium channel blockers to prevent hypotension.
   Dose            : Hyperkalemia and antidote to calcium channel blockers 8-16 mg/kg
                         ( usually 5-10 mL ) slow IVP.May be repeated as needed.
                         Given prophylactically prior to IV calcium channel blockers 2-4 mg/kg
                         ( usually 2 mL ) slow IVP.
   Contraindications : Hypercalcemia,VF ,digoxin toxicity,renal calculi.
   Sise effects     : Bradycardia,asystole,hypotension,VF,nausea and vomiting.
   Precautions    : Incompatible with sodium bicarbonat.

 8.DIGOXIN IMMUNE FAB (Fragment Antigen Binding ) DIGIBIND=Antidote to

                      digoxin,digitoxin.

   Indications   : Symptomatic digoxin toxicity or acute ingestion of unknown amount of digoxin.
   Dose           : Dependent on serum digoxin level. one 40 mg vials binds to approximately 0.6
                        of digoxin,dose tipically administered over 30 min.
  Contraindications : Allergy only,otherwise none known.
  Side effects   ; Worsening of CHF ,A-fib ,hypokalemia,increased serum digoxin level.
  Precautions   : Allergy to sheep proteins or other sheep products.

9. DIGOXIN ( Lanoxin ) ( Inotropic,Antiarrhythmic)
    Indications  : To slow ventricular response in A-fib or A-flutter,as a positive inotrope
                         in CHF,pulmonary edema.May be used as an alternative drug for PSVT.
    Dose          :  loading dose of 10-15 microgram/kg.administer over 5 min.
                         Maintenence dose determined by body size and renal function.
    Contraindications : hypersensitivity,uncontrolled ventricular arrhythmia,AV Block,idiopatic
                         hypertrophic subaortic stenosis ( IHSS ),constrictive pericarditis.
    Side effects : Arrhythmias,particularly VF and AV Block,bradycardia,fatigue,nausea,
                        vomiting,blurred or yellow vision,headache,hypokalemia.
    Precautions : Avoid electrical cardioversion of stable patients.If the patients condition
                         is unstable use lower current settings such as 10-12 J. Use cautiously in
                         elderly patients. Monitor digoxin level,moniotor clinical sign of toxicity.

10. DILTIAZEM ( Cardizem ) Calcium Channel B locker )
      Indications : A-fib,A-flutter,PSVT refractory to adenosine with narrow QRS complex
                         and adequate BP.
      Dose         : 15-20 mg ( 0.25 mg/kg) IVP over 2 min. May repeat in 15 min at
                         20-25 mg ( 0.35mg/kg ) IVP over 2 min. Start maintenence drip
                         at 5-15 mg/hr and titrate to HR.
     Contraindications: Drug or poison induced tachycardia,wide complex tachycardia
                         of uncertain origin,rapid A-fib and A-flutter with Wolf- Parkinson-
                         White syndrome,sick sinus syndrome,2nd-3rd degree AV block.
     Side effects : Hypotension,bradycardia,chest pain,ventricular arrhythmias.
     Precautions : Severe hypotension,in patients receiving beta blockers,hepatic injury,
                         renal disease.

11. DOPAMINE ( INTROPIN )  Vasopressor,Inotropic.
     Indications : Symptomatic bradycardia and hypotension,cardiogenic shock.
     Dose         : Continuous infusion ( tritate to patient response):
                        Low dose 1-5 microgram/kg/min
                        Moderate dose 5-10 microgram/kg/min. ( cardiac dose )
                        High dose 10-20microgram/kg/min ( vasopressor dose )
                        Mix 400 mg/250 mL in normal saline,lactated Ringers solutions
                        or D5W (1600 microgram/mL ).
    Contraindications :Pheochromocytoma,uncorrected tachycardia,cardiogenic shock
                        with CHF.
    Side effects : Tachyarrhythmias,angina,hypotension,palpitations,vasoconstriction,
                        dyspnea,nausea and vomiting.
    Precautions : Hypovolemia,MI. Adjust dosage in elderly patients and in those with occlusive
                        vascular disease.Ensure adequate hydration prior to infusion. Taper slowly.
                        Do not mix with sodium bicarbonate.Use care with peripheral administration,
                        infiltration can cause tissue necrosis. Central line is prefered.


 12. EPINEPHRINE ( Adrenalin ) ( Adrenergic  Agonist )
      Indications : Cardiac arrest: PEA,asystole,pulseless VT,VF,severe hypotension,symptomatic
                          bradycardia,anaphylaxis,severe allergic reactions.
     Dose         : Cardiac arrest 1mg IVP ( 10 mL of 1:10.000 solution ) every 3-5 min,
                         follow each dose with 20 mL IV flush,higher dose up to 0.2 mg/kg may be
                         used if 1 mg dose fails. Give 2.0-2.5 mg diluted in 10 mL normal saline
                         if administering by ET Tube. For continuous infusion add 30 mg ( mL of
                        1 : 1000 solution ) to 250 mL normal saline or D5W,run at 100 mL/hr,
                        and tritate to response.
                        Profound Bradycardia or hypotension 2-10 microgram/min IV
                        ( add 1 mg of 1 : 1000 solution to 500 mL normal saline or D5W and infuse
                        at 1-5 mL/min.
                        Anaphylaxis/asthma  0.1-0.5 mg SC or IM   of 1 : 1000 solution every
                        5-15 min,may be followed by 1-4 micogram/min continuous infusion.
    Contraindications : Hypersensitivity to adrenergic amines,hypovolemic shock,coronary
                        insufficiency.
    Side effects : Angina,HTN,tachycardia,VT,VF,nervousness,restlessness,tremors,weakness,
                        headache,nausea.
    Precautions : Use caution in HTN and increasing heart rate ( may cause increased
                        myocardial oxyggen demand ).Higher doses can contribute to post arrest
                        cardiac impairment,but they may be requaired to treat poison or drug
                        induced shock.

 13. FIBRINOLYTIC AGENTS  (Thrombolytic,Fibrinolytic )
     Common agents :Alteplase (Activase,t-PA ),anistreplase (Eminase ),reteplase ( Revatase )
                        streptokinase (Streptase ),tenecteplase (TNKase ).
     Indications :Within  < 12 hr from onset of symptoms of acute MI
                        Alteplase is the only Fibrinolytic agent approved for acute ischemic stroke
                        and must be started < 3 hr from onset of symptoms.
     Dose         : See Dosage Fibrinoytic Agents
     Contraindications :Active internal bleeding within 21 days ( except menses ),
                       neuorvascular event within 3 month ,major surgery or trauma within 2 weeks,
                       aortic dissection,severe HTN,bleeding disorder,prolonged CPR,
                       lumbar punctur within 1 week.
    Side effects : Hypotension,reperfusion,arrhythmias,heart failure,headache,increased bleeding
                      time,deep or superficial hemorrhage,flushing,urticaria,anaphylaxis.
    Precautions : Use cautiously in patients with severe renal or hepatic disease.

14.FUROSEMIDE ( LASIX ) Diuretic,loop diuretic.
     Indications : CHF with acute pulmonary edema,hypertensive crisis,post arrest cerebral edema,
                        hepatic or renal disease.
     Dose         : 0.5-1.0 mg /kg slow IVP over 1-2 min,may repeat at 2 mg/kg slow IVP over
                        1-2 min.
    Contrindications : Hypersensitivity,uncontrolled electrolyte imbalance,hepatic coma,anuria,
                       hypovolemia.
    Precautions : Use cautiously in severe liver disease,accompanied by cirrhosis or ascites,
                        electrolyte depletion,diabetes mellitus,pregnancy,lactation,risk for ototoxicity,
                        with increased dose or rapid injection,Monitor electrolytes closely.

15. IBUTILIDE ( Corvert ) (AntiArrhythmic )
      Indications : SVT including A-fib and A- flutter,most effective for conversion of  A-fib or
                         A-flutter or short duration.
     Dose          : Patient more than 60 kg 1mg IVP over 10 min, may repeat same dose in 10 min.
                        Patient less than 60 kg  0.01 mg/kg IVP over 10 min,may repeat same dose  in
                        10 min.
     Contraindications : Known hypersensitivity,history of ventricular arrhythmias including
                        torsade de pointes.
     Side effects : Headache,nausea and vomiting.
     Precautions : Monitir ECG for 4-6 hr after administration,with defibrillator nearby.
                         Correct  electrolyte abnormalities prior to used.If A-fib > 48 hr,anticoagulation
                         is requaired before cardioversion with ibutilide.

16. ISOPROTERENOL ( Isuprel ) Sympathomimetic,Beta Adrenergic Agonist.
       Indications : Symptomatic bradycardia,refractory torsade de pointes unresponsive to
                          magnesium,bradycardia in heart transplant patients,bete blocker poisoning.
       Dose         : IV infusion : mix 1 mg /250 mL in normal saline,Lactate Ringer solution,or D5W,
                          run at 2-10 microgram/min,and tritate to patient response.
      Contraindications : Cardiac arrest,concurrent use with epinephrine ( can cause VF or VT ),
                         poison or drug induced shock ( exception : beta blocker poisoning ).
      Side effects : Anxiety,tachycardia,palpitations,skin flushing.
      Precautions : May increase myocardial ischemia,tachycardia,restlessness
                          High dose are harmfull except in beta blocker overdose.

17. LIDOCAINE ( Xylocaine ) Antiarrhytmic,Anesthetic.
      Indications : VF or pulseless VT,STABLE vt,wide complex tachycardia or uncertaine origin,
                          wide complex PSVT.
      Dose          : Cardiac arrest from VF or VT 1.0-1.5 mg/kg IVP or 2-4 mg/kg via ET tube.
                          may repeat 0,5-0.75 mg/kg IVP every 5-10 min. Max 3mg/kg.
                          Stable VT,Wide complex tachycardia of uncertaine origin use 0.5-0.75 mg/kg
                          and up to 1.0-1.5 mg/kg. May repeate 0.5-0.75 mg/kg every 5-10 min.
                          Max total dose 3.0 mg/kg. If conversion is succesfull,start an IV infusion of
                          1-4 mg/min in normal saline or D5W.
    Contraindications : Prophylactic use in acute MI,andvanced AV Block,hypotension,
                          Wolf-Parkinson-White Syndrome,hypersensitivity to amide-type local
                          anesthetics.
    Side effects   : Confusion,seizures,hypotension,bradycardia,cardiovascular collapse,
                           respiratory arrest.
    Precautions   : CHF,repiratory depression,shock. Reduce maintenence dose ( not loading dose )
                           in presence of impaired liver function or left ventricular dysfunction or in the elderly.
                           Stop infusion if sign of toxicity ( prolonge PR interval,QRS widening,or CNS
                           changes) develop.

18. MAGNESIUM SULFATE ( Electrolyte,Antiarrhythmic )
      Indications : Torsade de pointes,VF refractory to lidocaine,digoxin induced VT/VF.
      Dose         :  Cardiac arrest ( in hypomagnesemia or torsade de pointes )
                         1-2 g ( 2-4 mL of 50% solution ) diluted in 10 mL of D5W IVP.
                         Digoxin-induced VT or VF 1-2 g IVP.
                         Torsade de pointes ( non-cardiac arrest )load with 1-2 mixed in 50-100 mL
                         of D5W infused over 5-60 min IV,then infuse 0.5-1.0 g/hr IV ( titrate to control
                         torsade ).
                         Acute MI load with 1-2 g mixed in 50-100 mL of D5W over 5-60 min IV,
                         then infuse 0.5-1.0 g/hr IV for up to 24 hr.
     Contraindications : Hypermagnesemia,hypocalcemia,renal disease,AV block,toxemia of
                        pregnancy 2 hr prior to delivery.
     Side effects : Hypotension,bradycardia,cardiac arrest,respiratory depression,altered level of
                         consciousness ( LOC ),flushed skin,diaphoresis.
     Precautions : Renal insufficiency,occasional fall in BP with rapid administration.
                         Monitor serum magnesium level.

19.MORPHINE ( Opioid Agonist Analgesic )
     Indications : Chest pain unrelieved by nittroglicerin,CHF and dyspnea associated with
                        pulmonary edema.
     Dose         : 2-4 mg IVP over 1-5 min every 5-30 min.
     Contraindications : Hypersensitivity,heart failure due to chronic lung disease,respiratory
                        depression,hypotension.
    Side effects : Respiratory depression,hypotension,nausea and vomiting,bradycardia,
                        altered LOC,seizures.
    Precautions : Administer slowly and tritate to effect. Reverse with naloxone (0.4-2.0 mg IVP).
                        Use caution in cerebral edema and pulmonary edema with compromised respiration.
                       
20. NITROGLYCERINE ( Nitrostat,Nitrolingual Pumpspray )

                       Antianginal,Nitrate.

     Indications : Angina,CHF associated with acute MI,hypertensive crisis.
     Dose         : Sublingual route,0.3-0.4 mg ( 1 tablet ),repeat every 5 min,max 3 doses/15 min.
                        Aerosol, spray for 0.5-1.0 sec at 5 min interval ( provides 0.4 mg/dose ),
                        max 3 sprays/15 min.
                        If no sublingual or spray used ( IVP at 12.5-25.0 microgram )
                        IV infusion ; mix 25 mg/250 mL (100 microgram/mL) in D5W,run at 5-20
                        microgram/min and tritate to desired response.
    Contraindications : Hypersensitivity,systolic BP < 90 mmHg,severe bradycardia,or severe
                       tachycardia,sildenafil ( viagra ),tadalafil ( cialis ),vardenafil (levitra )
                       within 24hr,right ventricular infarction.
    Side effects : Hypotension with secondary tachycardia,syncope,headache,flushed skin.
    Precautions : Do not mix with other medications,tritate IV to maintain systolic BP >90 mmHg.
                        Mix only in glass IV bottles and infuse only through tubing provided by manufacturer,
                        standard polyvinyl chloride tubing can bind up to 80% of the medication,
                        making it necessary to infuse higher doses.

21. OXYGEN ( Gas )
      Indications : Cardiopulmonary  emergencies with shortness of breath and chest pain,cardiac
                         or respiratory arrest.
      Dose         : Nasal cannula 1-6 L/min ( 24%-44% oxygen )
                         Venturi mask  4-8 L/min ( 24%-40% oxygen )
                         Simple mask   5-8 L/min ( 40%-60% oxygen )
                         Partial rebreathing mask 6-15 L/min ( 35%- 60% oxygen )
                         Non rebreathing mask    6-15L/min  ( 60%-90% oxygen )
                         Bag valve mask                  15L//min ( up to 100% oxygen ) 
     Contraindications : Emphysema ( deliver < 35% oxygen unless severely hypoxic,hyperventilation.
     Side effects : Drying of respiratory mucosa,possible bronchospasm if oxygen is extremly
                         cold and dry.Oxygen supports combustion and can cause fuel a fire.
    Precautions : Respiratory arrest in patients with hypoxic drive. Patient needs an airway
                        and adequate ventilation before oxygen is effective.
 
22. PROCAINAMIDE ( Pronestyl ) Antiarrhythmic
      Indications : Reccurent VT or VF,PSVT,refractory to adenosine and vagal stimulation,
                         rapid A-fib with Wolf-Parkinson-White syndrome,stable wide complex
                         tachycardia of uncertaine origin,maintenance after conversion.
      Dose         : 20 mg/min IV infusion or up to 50 mg/min under urgent conditions,
                         max. 17mg/kg loading dose.
                         Maintenance IV infusion : mix 1 g/250 mL in normal saline or D5W,
                         run at 1-4 mg/min.
     Contraindications : 2nd and 3rd degree AV Block ( unless a functioning artificial pacemaker
                         is in place ),torsade de pointes,hypersensitivity.
     Side effects : Hypotension,widening QRS Complex,headache,nausea and vomiting,flushed skin
                         seizures,ventricular arrhythmias,AV block,cardiovascular collapse,arrest.
     Precautions : Monitor BP every 2-3min while administering procainamide.
                         If QRS width increase by 50% or more or of BP decreases to <90 systolic,
                         stop drug.
                         Reduce total dose to 12 mg/kg and maintenance infusion to 1-2 mg/min if cardiac
                         or renal dysfunction is present. Use cautiously in myasthenia gravis and in hepatic
                         or renal disease.

23. SODIUM BICARBONAT ( Alkalizing Agent,Buffer )
      Indications : Prolonged resuscitation with effective ventilation,hyperkalemia,diabetic ketoacidosis
                         cocaine toxicity,tricyclic anti depressan.diphenhydramine or acetylsalicylic acid
                         overdose,hypercarbic acidosis.
     Side effects : Hypokalemia,metabolic alkalosis,seizures,tetany.
     Precautioans : CHF,renal disease,cirrhosis,toxemia,concurrent corticosteroid therapy.
                         Not recommended for routine use in cardiac arrest patients because adequate
                         ventilation and CPR are the major "buffer agents'' in cardiac arrest.
                         Incompatible with many drugs,flush line before and after administration.

24. VASOPRESSIN ( Pitressin Synthetic ) Vasopressor,Hormone )
      Indications : Vasodilatory septic shock,an alternative to epinephrine in shock-refractory
                         VF and pulseless VT.
      Dose         : Cardiac arrest 40 units IVP single dose.
      Contraindications : Seizures,heart failure,asthma,coronary artery disease ( CAD ),migraine,
                         allergy to beef or pork protein,chronic renal failure with increased blood urea 
                         nitrogen (BUN )
     Side effects: Dizziness,headache,nausea and vomiting ,MI, chest pain,abdominal cramps,
                        diaphoresis,bronchocostriction,anaphylaxis,coma,convulsions.
     Precautions : CAD (may precipitate angina or MI ),renal impairment,potent peripheral
                         vasoconstrictor.

25. VERAPAMIL ( Calan ,Isoptin ) Calcium Channel Blocker,Antiarrhythmic,Antihypertensive.
      Indications : PSVT ( with narrow QRS and adequate BP ) refractory to adenosine,
                         rapid ventricular rates in A-fib,A-fultter,or MAT.
      Dose         : 2.5-5.0 mg slow IVP over 2 min,may give second dose if needed,of 5-10 mg IVP
                         in 15-30 min,max.dose 20 mg.
                         An alternativec second dose is 5 mg IVP every 15 min,max dose 30 mg.
     Contraindications :A-fb with Wolf-Parkinson-White syndrome,wide complex tachycardia of
                         uncertaine origin,2nd or 3rd degree AV Block,sick sinus syndrome,hypotension,
                         severe CHF,cardiogenic shock.
     Side effects : Hypotension,exacerbation of CHF with left ventricular dysfunction,bradycardia,
                         AV Block.
     Precautions : Concurrent beta blockers,CHF,impaired hepatic or renal function.
                          In geriatric patients administer dose slowly over 3 min.                           

                                          EMERGENCY SKILL


 DEFIBRILLATION

  MANUAL DEFIBRILLATION

AUTOMATIC EXTERNAL DEFIBRILLATION ( AED )

CARDIOVERSION

TRANSCUTANEOUS PACING.