DRUGS USED IN CCU INCLUDING IONOTROPES

DRUGS USED IN CCU(INCLUDING IONOTROPES)11ANTICONVULSANT:

Barbiturates- PhenobarbitoneDeoxy Barbiturates-PrimidoneHydantoins- PhenytoinIminostilbens carbamazepine.Valproic Acid- Sodium ValproateSuccinamides-EthosuccinamideBenzodiazepine-Clonazepam-Carbamazepine2SEDATIVES AND ANXIOLYTICS:BenzodiazepinesNon Benzodiazepines - PhenobarbitonePhenothiazinesANTIARRHYTHMICS- Digoxin, Esmolol, Adenosine.

3ANTIHYPERTENSIVES-

Centrally Acting-ClonidinePeripherally Acting-PrazosinBeta Blockers-Atenolol and blockers-labetalolActing on smooth muscle- sodium nitroprussideCalcium channel blockers- amlodipineACE inhibitors EnalaprilAntiogentsin II receptor antagonist- valsartan.

4ANTI ANGINALSNitrates- isosorbide dinitrateBeta adrenergic and calcium channel blockers.Antiplatelets- aspirinVasodialtion- cinnirazineCOAGULANTSVitamin k analogues

5ANTICOAGULANTS, THROMBOLYTICS, ANTIPLATELETSParenteral- heparin, low molecular weight heparinOral- warfarinThrombolytics-streptokinaseAntiplatelets- aspirin.ANTIASTHAMTICSSympathomimetics- adrenaline, salbutamolXanthine derivatives- aminophyllineCorticosteroids- dexamethasoneAnticholinergics- ipratropiu bromideLeukotrine receptor antagonist- monteleukast

6DIURETICSThiazide- hydrochlorthiazideLoop- frusemidePotassium sparing- spirinolactoneCarbonc anhydrase inibitors- acetazolamideOsmotic diuretics- mannitolANAESTHETIC AGENTS:XylocainePropofolOTHERS;MorphinePethidineFentanyl.

7SEDATIVES AND ANXIOLYTICS:BenzodiazepinesNon Benzodiazepines - PhenobarbitonePhenothiazinesEMERGENCY DRUGS:AtropineAdrenalineNorepinephrineAdenojet8

(ADENOCARD), ADENOJET:PHARMACOLOGICAL NAME: adenosine

INDICATION:paroxysmal supraventricular tachycardia (PSVT).DOSAGE AND ADMINISTRATION:For rapid bolus intravenous use only.Adult Patients-Initial dose: 6 mg given as a rapid intravenous bolus (administered over a 1-2 second period).Repeat administration: If the first dose does not result in elimination of the supraventricular tachycardia within 1-2 minutes, 12 mg should be given as a rapid intravenous bolus. This 12 mg dose may be repeated a second time if required.

9DOSAGEPaediatric Patients-Initial dose: Give 0.05 to 0.1 mg/kg as a rapid IV bolus given either centrally or peripherally. A saline flush should follow.Repeat administration: If conversion of PSVT does not occur within 1-2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used.STORAGE:DO NOT REFRIGERATE as crystallization may occur.

10SIDE EFFECTS:Central Nervous System -Light headedness(2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).Gastrointestinal Nausea (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).Cardiovascular -Prolonged asystole, ventricular tachycardia, ventricular fibrillation, transient increase in blood pressure, bradycardia, atrial fibrillationRespiratory -BronchospasmCentral Nervous System -Seizure activity, including tonic clonic (grand mal) seizures, and loss of consciousness.

11DRUG INTERACTIONS:INHIBITED BY:caffeine and theophyllinePOTENTIATED BY: dipyridamole.OVERDOSE:The half-life of Adenocard (adenosine injection) is less than 10 seconds. Thus, adverse effects are generally rapidly self-limiting. CONTRAINDICATIONSSecond- or third-degree A-V block Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia Known hypersensitivity to adenosine.MECHANISM OF ACTIONHemodynamicsAdenosine decreases blood pressure by decreasing peripheral resistance.

12AMIODARONE:

GENERIC NAME: amiodarone BRAND NAME: CordaroneDRUG CLASS AND MECHANISM:a slowing of the speed of electrical conductiona reduction in the rapidity of firing (the heart's pacemaker); slowing of conduction through various specialized electrical pathways (called accessory pathways)amiodarone also causes blood vessels to dilate (enlarge). This effect can result in a drop in blood pressure. PREPARATIONS: Tablets (pink), round in shape: 200 mg. STORAGE: Tablets should be kept at room temperature, less than 30C (86F).

13INDICATIONS: ventricular fibrillation, ventricular tachycardia, atrial fibrillation, and atrial flutter. DRUG INTERACTIONS: Amiodarone may interact with beta-blockers or calcium channel blockers resulting in an excessively slow heart rate or a block in the conduction of the electrical impulse through the heart. Amiodarone increases the blood levels of digoxin, Procainamide and quinidine concentrations increase by 30%-50% during the first week of amiodarone therapy. SIDE EFFECTS14PRECAUTIONS:: liver disease, lung disease, thyroid problems.STORAGE: Store at room temperature between 68-77 degrees F (20-25 degrees C) away from light and moisture. ATROPINE SULFATE Injection 0.1 mg/mI (Adult) ,0.05 mg/mL (Pediatric) BRAND NAME: atropine.Atropine Sulfate Injection is a sterile, nonpyrogenic isotonic solution of atropine sulfate monohydrate in water.Atropine Sulfate Injection is a parenteral anticholinergic agent and muscarinic antagonist.

15INDICATIONS

1. As an antisialagogue 2. To blunt the increased vagal tone (decreased pulse and blood pressure) 3. To temporarily increase heart rate or decrease AV-block until definitive intervention can take place, 4. As an antidote for inadvertent overdose of cholinergic drugs or for cholinesterase poisoning such as from organophosphorus insecticides5. As an antidote for the "rapid type of mushroom poisoning due to the presence of the alkaloid muscarine 6. for reversal of neuromuscular blockade DOSAGE AND ADMINISTRATION:Adults 0.5 mg to 1 mg for antisialagogue and other antivagal effects, 2 to 3 mg as an antidote for organophosporous or muscarinic mushroom poisoning. Endotracheal administration of atropine -1 to 2 mg diluted to a total not to exceed 10 ml of sterile water or normal saline.

16Pediatricsrange of 0.01to 0.03 mg/kg body weight.Store at controlled room temperature 15 to 30C (59 to 86F). SIDE EFFECTS Dryness of the mouth, blurred vision, photophobia and tachycardia commonly occur with chronic administration of therapeutic doses. Constipation and difficulty in micturition may occur in elderly patients. Occasional hypersensitivity reactions.WARNINGSChildren are more susceptible than adults to the toxic effects of anticholinergic agents.Atropine is not removed by dialysis.PRECAUTIONSDo not administer unless solution is clear and seal is intact. Discard unused portion. acute glaucoma in susceptible patients

17CONTRAINDICATIONS:glaucoma, pyloric stenosis or prostatic hypertrophy, except in doses ordinarily used for preanesthetic medication.CLINICAL PHARMACOLOGYAtropine is commonly classified as an anticholinergic or ant parasympathetic drug. Atropine inhibits the muscarinic actions of acetylcholine on structures . the major action of atropine is a competitive or surmountable antagonism which can be overcome by increasing the concentration of acetylcholine at receptor sites of the effector organ (e.g., by using anticholinesterase agents which inhibit the enzymatic destruction of acetylcholine). 18CALCIUM CHLORIDE:

Calcium Chloride Injection 10%CALCIUMCHLORIDEInjection, 100 mg/mL(13.6 mEq Calcium/10 mL) INDICATIONShypocalcemic tetany.Insect bites or stings, such as Black Widow Spider bites.Sensitivity reactions, particularly when characterized by urticaria.treatment of depression due to over dosage of magnesium sulfate.In cardiac resuscitation, particularly after open heart surgery, DOSAGE AND ADMINISTRATIONThe usual adult dose of this preparation varies from 5 to 10 mL at intervals of 1 to 3 days.In cardiac resuscitation, the usual dose is 2 to 4 mL injected into the ventricular cavity.

19WARNINGSThis solution is suitable only for intravenous use. This product contains aluminum that may be toxic. PRECAUTIONSa digitalized patient should not receive an intravenous injection of a calcium compound unless the indications are clearly defined.OVERDOSE: The syndrome is characterized by weakness, lethargy, intractable nausea and vomiting, coma, and sudden death, and a markedly elevated plasma calcium level. STORAGE:Store at controlled room temperature 15-30C (59-86F)CONTRAINDICATIONSIn cardiac resuscitation, the use of calcium chloride is contraindicated in the presence of ventricular fibrillation.

20CLINICAL PHARMACOLOGY:Calcium is the fifth most abundant element in the body; the major fraction is in bone. It is essential for the functional integrity of the nervous and muscular systems, for normal cardiac contractility and the coagulation of blood. It also functions as an enzyme cofactor and affects the secretory activity of endocrine and exocrine glands.DOPAMINE (HYDROCHLORIDE) Injection.Dopamine HCl, a naturally occurring catecholamine, is an inotropic vasopressor agent.21

INDICATIONSDOPAMINE is indicated for the correction of hemodynamic imbalances present in the shock syndromerestoration of blood volumePoor Perfusion of Vital Organs:Low Cardiac Output:Hypotension: WARNING: This is a potent drug: It must be diluted before administration to patient.Suggested Dilution: Transfer contents of one or more ampules or vials by aseptic technique to either 250 mL or 500 mL of one of the following sterile intravenous solutions:Sodium Chloride Injection, USPDextrose (5%) Injection, USPDextrose (5%) and Sodium Chloride (0.9%) Injection, USP5% Dextrose in 0.45% Sodium Chloride SolutionLactated Ringer's SolutionSodium Lactate (1/6 Molar) Injection, USP22DOPAMINE has been found to be stable for a minimum of 24 hours after dilution in the sterile intravenousDo NOT add to Sodium Bicarbonate or other alkaline intravenous solutions, since the drug is inactivated in alkaline solution.Rate of Administration: Each patient must be individually titrated to the desired rate after the hemodynamic condition is stabilized. hemodynamic and/or renal response with DOPAMINE. Administration rates greater than 50 mcg/kg/minute have safely been used in advanced circulatory decompensation statesSTORAGE:Store at controlled room temperature 15-30C (59-86FWARNING: NOT FOR DIRECT INTRAVENOUS INJECTION, MUST BE DILUTED BEFORE USE.IV INFUSION ONLY.

23SIDE EFFECTSCardiovascular Systemventricular arrhythmia (at very high doses ,ectopic beats ,tachycardia, anginal pain ,palpitation, cardiac conduction abnormalities, widened QRS complex,bradycardia,hypotension,hypertensionvasoconstrictionRespiratory System -dyspneaGastrointestinal System-nausea ,vomiting, metabolic/Nutritional System, azotemiaCentral Nervous System-headache, anxietyDermatological System- piloerectionOtherGangrene of the extremitiesA few cases of peripheral cyanosis have been reported.24DRUG INTERACTIONSTherefore, EXTREME CAUTION should be exercised when administering dopamine HCl to patients receiving cyclopropane or halogenated hydrocarbon anaesthetics.WARNINGSDo NOT add DOPAMINE to any alkaline diluent solution, since the drug is inactivated in alkaline solution. IMPORTANT - Antidote for Peripheral Ischemia - To prevent sloughing and necrosis in ischemic areas, the area should be infiltrated as soon as possible with 10 to 15 mL of saline solution containing 5 to 10 mg of Regitine (brand of phentolamine), an adrenergic blocking agent.

25PRECAUTIONS:Careful monitoring required Hypoxia, Hypercapnia, Acidosis Ventricular Arrhythmias Decreased Pulse Pressure Hypotension Extravasation Occlusive vascular disease Weaning -Labor and Delivery:

26Nursing Mothers:Paediatric Use: Peripheral gangrene has been reported in neonates and children.OVERDOSE Since the duration of action of DOPAMINE is quite short, no additional remedial measures are usually necessary. CONTRAINDICATIONS:pheochromocytoma.uncorrected tachyarrhythmia or ventricular fibrillation.

27CLINICAL PHARMACOLOGY

Dopamine is a natural catecholamine .Dopamine produces positive chronotropic and inotropic effects on the myocardium, resulting in increased heart rate and cardiac contractility. This is accomplished directly by exerting an agonist action on beta-adrenoceptors and indirectly by causing release of norepinephrine from storage sites in sympathetic nerve endings.Dopamine's onset of action occurs within five minutes of intravenous administration.

28ADRENALINE:

Adrenalin Chloride Solution (epinephrine) Injection, 1:1000 DRUG DESCRIPTIONsubcutaneous or intramuscular injection. When diluted, it may also be administered intracardially or intravenously. It may also be administered intraspinally by adding to anesthetic spinal fluid mixture. INDICATIONS:to relieve respiratory distress due to bronchospasm, to provide rapid relief of hypersensitivity reactions to drugs and other allergens, andto prolong the action of infiltration anesthetics.restoring cardiac rhythm in cardiac arrest due to various causes.29Indications contdas a hemostatic agent. treating mucosal congestion of hay fever, rhinitis, and acute sinusitis;to relieve bronchial asthmatic paroxysms; in syncope due to complete heart block or carotid sinus hypersensitivity; for symptomatic relief of serum sickness, urticaria, angioneurotic edemafor resuscitation in cardiac arrest following anesthetic accidents; in simple (open angle) glaucoma; for relaxation of uterine musculature and to inhibit uterine contractions. Epinephrine injection can be utilized to prolong the action of intraspinal and local anesthetics

30DOSAGE AND ADMINISTRATION

0.2 to 1 mL (mg). Start with a small dose and increase if required For cardiac resuscitation.STORAGE:Store between 15 and 25C (59 and 77F),Protect from light and freezing.SIDE EFFECTS:Transient and minor side effects of anxiety, headache, fear, and palpitations often occur with therapeutic doses, especially in hyperthyroid individuals. Repeated local injections can result in necrosis at sites of injection from vascular constriction. Epinephrine-fastness can occur with prolonged useDRUG INTERACTIONSUse of epinephrine with excessive doses of digitalis, diuretics, or other drugs that sensitize the heart to arrhythmias is not recommended.The effects of epinephrine may be potentiated by tricyclic antidepressants; certain antihistamines, e.g., diphenhydramine31WARNINGS:Administer with caution to elderly people; to those with cardiovascular disease, hypertension, diabetes, or hyperthyroidism; in psychoneurotic individuals; and in pregnancy. Overdosage or inadvertent intravenous injection of epinephrine may cause cerebrovascular hemorrhage resulting from the sharp rise in blood pressure.PRECAUTIONSAdrenalin (epinephrine injection,) should be protected from exposure to light. The solution should not be used if it is pinkish or darker than slightly yellow or if it contains a precipitate.Epinephrine is readily destroyed by alkalies and oxidizing agents.

32CONTRAINDICATIONSnarrow angle (congestive) glaucoma, shock, during general anaesthesia with halogenated hydrocarbons or cyclopropane and in individuals with organic brain damage. local anesthesia of certain areas, e.g., fingers, toes, because of the danger of vasoconstriction producing sloughing of tissue; in labour because it may delay the second stage; in cardiac dilatation and coronary insufficiency.CLINICAL PHARMACOLOGYAdrenaline (epinephrine) is a sympathomimetic drug. It activates an adrenergic receptive mechanism on effector cells and imitates all actions of the sympathetic nervous system except those on the arteries of the face and sweat glands. Epinephrine acts on both alpha and beta receptors and is the most potent alpha receptor activator.

33DOBUTAMINE:

INDICATIONSDepressed contractility resulting either from organic heart disease or from cardiac surgical procedures.Congestive heart failure. DOSAGE AND ADMINISTRATIONNoteDo not add dobutamine to 5% Sodium Bicarbonate Injection or to any other strongly alkaline solution. Preparation and Stability At the time of administration, dobutamine must be further diluted in an IV container to at least a 50 mL solution using one of the following intravenous solutions as a diluent: 5% Dextrose Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 10% Dextrose Injection, IsolyteM with 5% Dextrose Injection, Lactated Ringer's Injection, 5% Dextrose in Lactated Ringer's Injection.

34SIDE EFFECTSIncreased Heart Rate, Blood Pressure, and Ventricular Ectopic Activity Hypotension Reactions at Sites of Intravenous Infusion Miscellaneous Uncommon Effects DRUG INTERACTIONS:Preliminary studies indicate that the concomitant use of dobutamine and nitroprusside results in a higher cardiac output and, usually, a lower pulmonary wedge pressure than when either drug is used alone.WARNINGSIncrease in Heart Rate or Blood PressureEctopic ActivityHypersensitivityPRECAUTIONSDuring the administration of dobutamine, as with any adrenergic agent, ECG and blood pressure should be continuously monitored. In addition, pulmonary wedge pressure and cardiac output should be monitored .Usage Following Acute Myocardial Infarction

35OVERDOSESigns and Symptoms Toxicity from dobutamine is usually due to excessive cardiac -receptor stimulation. Treatment The initial actions to be taken in a dobutamine overdose are discontinuing administration, establishing an airway, and ensuring oxygenation and ventilation. Resuscitative measures.CONTRAINDICATIONSidiopathic hypertrophic subaortic stenosis and in patients who have shown previous manifestations of hypersensitivity to dobutamine.CLINICAL PHARMACOLOGYDobutamine is a direct-acting inotropic agent whose primary activity results from stimulation of the receptors of the heart while producing comparatively mild chronotropic, hypertensive, arrhythmogenic, and vasodilative effects. It does not cause the release of endogenous norepinephrine, as does dopamineSystemic vascular resistance is usually decreased with administration of dobutamine. Occasionally, minimum vasoconstriction has been observed.

36ESMOLOL

100 mg, 10 mL Single Dose Vial - Each mL contains 10 mg Esmolol Hydrochloride, 5.9 mg Sodium Chloride, 100 mg, 5 mL DOUBLE STRENGTH Single Dose Vial - Each mL contains 20 mg Esmolol Hydrochloride, 4.1 mg Sodium ChlorideINDICATIONSSupraventricular Tachycardia,Intraoperative and Postoperative Tachycardia and/or HypertensionDOSAGE AND ADMINISTRATIONSUPRAVENTRICULAR TACHYCARDIAAn initial loading dose of 0.5 milligrams/kg (500 micrograms/kg) infused over a minute duration followed by a maintenance infusion of 0.05 milligrams/kg/min (50 micrograms/kg/min) for the next 4 minutes is recommended. After the 4 minutes of initial maintenance infusion (total treatment duration being 5 minutes), depending upon the desired ventricular response, the maintenance infusion may be continued at 0.05 mg/kg/min or increased step-wise (e.g. 0.1 mg/kg/min, 0.15 mg/kg/min to a maximum of 0.2 mg/kg/min) with each step being maintained for 4 or more minutes.

37Stable for 24 hours at controlled room temperature or under refrigeration:BREVIBLOC is NOT compatible with Sodium Bicarbonate (5%) Injection, DRUG INTERACTIONSCatecholamine-depleting drugs, e.g., reserpineAdditionally, BREVIBLOC should not be used to control supraventricular tachycardia in the presence of agents which are vasoconstrictive and inotropic such as dopamine, epinephrine, and norepinephrine because of the danger of blocking cardiac contractility when systemic vascular resistance is high.PRECAUTIONS:HypotensionCardiac FailureIntraoperative and Postoperative Tachycardia and/or HypertensionBronchospastic DiseasesDiabetes Mellitus and Hypoglycemia

38SIDE EFFECTSsupraventricular tachycardia hypotension Cardiovascular -Symptomatic hypotension (diaphoresis, dizziness) Central Nervous System -Dizziness; somnolence ,confusion, headache, and agitation and fatigue .Paresthesia, asthenia, depression, abnormal thinking, anxiety, anorexia, and lightheadedness were reported in less than 1% of patients. Respiratory -Bronchospasm, wheezing, dyspnea, nasal congestion, rhonchi, and rales have each been reported in less than 1% of patients.Gastrointestinal -Nausea. Vomiting, Dyspepsia, constipation, dry mouth, and abdominal discomfort Skin (Infusion Site)-Infusion site reactions including inflammation and induration Edema, erythema, skin discoloration, burning at the infusion site, thrombophlebitis, and local skin necrosis from extravasation.39OVERDOSEAcute ToxicityCardiac arrest. Bradycardia, hypotension.BronchospasmCardiac FailureCONTRAINDICATIONSSinus bradycardia, heart block greater than first degree, cardiogenic shock or overt heart failure CLINICAL PHARMACOLOGYBREVIBLOC inhibits the beta1 receptors located chiefly in cardiac muscle, but this preferential effect is not absolute and at higher doses it begins to inhibit beta2 receptors located chiefly in the bronchial and vascular musculature.

40KETAMINE HYDROCHLORIDE:INDICATIONSAnesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation. To supplement low-potency agents, such as nitrous oxide.PREOPERATIVE PREPARATIONSKetamine is recommended for use in the patient whose stomach is not empty when, in the judgement of the practitioner, the benefits of the drug outweigh the possible risks.Atropine, scopolamine, or another drying agent should be given at an appropriate interval prior to induction.

41DOSAGE AND ADMINISTRATIONParenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.If the ketamine dose is augmented with diazepam, the two drugs must be given separately. Do not mix ketamine hydrochloride and diazepam in syringe or infusion flask. DOSAGE:As with other general anesthetic agents, the individual response to ketamine is somewhat varied depending on the dose, route of administration, and age of patient, so that dosage recommendation cannot be absolutely fixed. The drug should be titrated against the patient's requirements.

42Intravenous Route: The initial dose of ketamine administered intravenously may range from 1 mg/kg to 4.5 mg/kg (0.5 to 2 mg/lb). Rate of Administration: It is recommended that ketamine be administered slowly (over a period of 60 seconds). Intramuscular Route: The initial dose of ketamine administered intramuscularly may range from 6.5 to 13 mg/kg (3 to 6 mg/lb). Dilution: To prepare a dilute solution containing 1 mg of ketamine per mL, aseptically transfer 10 mL (50 mg per mL vial) to 500 mL of Dextrose Injection, 5% or Sodium Chloride Injection, 0.9% and mix well. The resultant solution will contain 1 mg of ketamine per mL.43HOW SUPPLIEDEach 10 mL vial contains 50 mg/mL, Protect from light.SIDE EFFECTSCardiovascular- Blood pressure and pulse rate are frequently elevated following administration of ketamine alone. Respiration -depression of respiration or apnea may occur following rapid intravenous administration of high doses of ketamine. LaryngospasmsEye -Diplopia and nystagmus have been noted following ketamine administration. Neurological -In some patients, enhanced skeletal muscle tone may be manifested by tonic and clonic movements sometimes resembling seizures Gastrointestinal -Anorexia, nausea and vomiting have been observed; however, this is not usually severe and allows the great majority of patients to take liquids by mouth shortly after regaining consciousness General -Anaphylaxis. Drug Abuse And DependenceKetamine has been reported being used as a drug of abuse.44DRUG INTERACTIONSProlonged recovery time may occur if barbiturates and/or narcotics are used concurrently with ketamine.PRECAUTIONSKetamine should be used by or under the direction of physicians experienced in administering general anesthetics and in maintenance of an airway and in the control of respiration.Because pharyngeal and laryngeal reflexes are usually active, ketamine should not be used alone in surgery or diagnostic procedures of the pharynx, larynx, or bronchial tree. Mechanical stimulation of the pharynx should be avoided, whenever possible, if ketamine is used alone. Muscle relaxants, with proper attention to respiration, may be required in both of these instances.Resuscitative equipment should be ready for use.45OVERDOSERespiratory depression may occur with over dosage or too rapid a rate of administration of ketamine, WARNINGSCardiac function ,hypertension or cardiac decompensation.Postoperative confusional states Respiratory depression may occur

46CONTRAINDICATIONSelevation of blood pressure ,hypersensitivity to the drug.CLINICAL PHARMACOLOGYKetamine is a rapid-acting general anesthetic producing an anesthetic state characterized by profound analgesia, normal pharyngeal-laryngeal reflexes, normal or slightly enhanced skeletal muscle tone, cardiovascular and respiratory stimulation, and occasionally a transient and minimal respiratory depression.

47XYLOCAINE:

Xylocaine (lidocaine HCl) Injection, USP Xylocaine (lidocaine HCl and epinephrine) Injection, For Infiltration and Nerve BlockDRUG DESCRIPTIONXylocaine (lidocaine HCl) Injections are sterile, nonpyrogenic, aqueous solutions that contain a local anesthetic agent with or without epinephrine and are administered parenterally by injection.INDICATIONSlocal or regional anesthesiaDOSAGE AND ADMINISTRATIONThe actual volumes and concentrations to be used depend on a number of factors such as type and extent of surgical procedure, depth of anesthesia and degree of muscular relaxation required, duration of anesthesia required, and the physical condition of the patient. For intravenous regional anesthesia, only the 50 mL single dose vial containing Xylocaine (lidocaine HCl) 0.5% Injection should be used.

48Epidural AnesthesiaFor epidural anesthesia, only the following dosage forms Xylocaine Injection are recommended:1% without epinephrine1% with epinephrineCaudal and Lumbar Epidural BlockAs a precaution against the adverse experience sometimes observed following unintentional penetration of the subarachnoid space, a test dose such as 2 to 3 mL of 1.5% lidocaine HCl should be administered at least 5 minutes prior to injecting the total volume required for a lumbar or caudal epidural block. The test dose should be repeated if the patient is moved in a manner that may have displaced the catheter

49SIDE EFFECTSCentral Nervous System -CNS manifestations are excitatory and/or depressant and may be characterized by lightheadedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred or double vision, vomiting, sensations of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, respiratory depression and arrest. Cardiovascular System -Cardiovascular manifestations are usually depressant and are characterized by bradycardia, hypotension, and cardiovascular collapse, which may lead to cardiac arrest.Allergic -Allergic reactions are characterized by cutaneous lesions, urticaria, edema or anaphylactoid reactions. Neurologic-positional headaches, hypotension and backache; 2 percent for shivering; and less than 1 percent each for peripheral nerve symptoms, nausea, respiratory inadequacy and double vision. Many of these observations may be related to local anesthetic techniques, with or without a contribution from the local anesthetic.50DRUG INTERACTIONSClinically Significant Drug InteractionsThe administration of local anesthetic solutions containing epinephrine or norepinephrine to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension.Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine. Drug/Laboratory Test InteractionsThe intramuscular injection of lidocaine HCl may result in an increase in creatine phosphokinase levels.

51WARNINGSimmediate availability of oxygen, other resuscitative drugs, cardiopulmonary equipment and the personnel needed for proper management of toxic reactions and related emergencies. delay in proper management of dose-related toxicity, underventilation from any cause and/or altered sensitivity may lead to the development of acidosis, cardiac arrest and, possibly, death. PRECAUTIONSResuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use52CONTRAINDICATIONSknown history of hypersensitivity to local anesthetics of the amide type.CLINICAL PHARMACOLOGYMechanism of ActionLidocaine HCl stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses thereby effecting local anesthetic action.PRIMACOR IVPRIMACOR (milrinone lactate 5% Dextrose InjectionINDICATIONSpatients with acute decompensated heart failure53DOSAGE AND ADMINISTRATIONLOADING DOSE50 mcg/kg: Administer slowly over 10 minutes WARNING- DO NOT USE IN SERIES CONNECTIONS. HOW SUPPLIEDPRIMACOR Flexible Containers (200 mcg/mL in 5% Dextrose Injection) are supplied:100 mL (200 mcg/mL) in 5% Dextrose Injection single units. 200 mL (200 mcg/mL) in 5% Dextrose Injection single units.Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing.

54SIDE EFFECTSCardiovascular Effects: ventricular arrhythmias ,Ventricular ectopic activity, nonsustained ventricular tachycardia, sustained ventricular tachycardia, 1% and ventricular fibrillation, Other cardiovascular adverse reactions include hypotension, 2.9% and angina/chest pain, 1.2%.CNS Effects -Headaches, usually mild to moderate in severity, have been reported in 2.9% of patients receiving PRIMACOR.Other Effects -Other adverse reactions reported, but not definitely related to the administration of PRIMACOR include hypokalemia, 0.6%; tremor, 0.4%; and thrombocytopenia, 0.4%.Post-Marketing Adverse Event ReportsIsolated spontaneous reports of bronchospasm and anaphylactic shock.Liver function test abnormalities and skin reactions such as rash.Administration site conditions: Infusion site reaction.

55PRECAUTIONSsevere obstructive aortic or pulmonic valvular diseaseSupraventricular and ventricular arrhythmiasIf prior vigorous diuretic therapy is suspected to have caused significant decreases in cardiac filling pressure, OVERDOSEproduce hypotension because of its vasodilator effect. If this occurs, administration of PRIMACOR should be reduced or temporarily discontinued until the patient's condition stabilizes. No specific antidote is known.CONTRAINDICATIONSPRIMACOR is contraindicated in patients who are hypersensitive to it.

56CLINICAL PHARMACOLOGYPRIMACOR is a positive inotrope and vasodilator, with little chronotropic activity different in structure and mode of action from either the digitalis glycosides or catecholamines.PRIMACOR, at relevant inotropic and vasorelaxant concentrations, is a selective inhibitor of peak III cAMP phosphodiesterase isozyme in cardiac and vascular muscle. This inhibitory action is consistent with cAMP mediated increases in intracellular ionized calcium and contractile force in cardiac muscle, as well as with cAMP dependent contractile protein phosphorylation and relaxation in vascular muscle. 57NALAXONE

NARCAN (naloxone hydrochloride) Injection, Opioid AntagonistINDICATIONScomplete or partial reversal of opioid depression, including respiratory depression, diagnosis of suspected or known acute opioid over dosage.NARCAN may be useful as an adjunctive agent to increase blood pressure in the management of septic shock.DOSAGE AND ADMINISTRATION:NARCAN may be administered intravenously, intramuscularly, or subcutaneously. NARCAN may be diluted for intravenous infusion in normal saline or 5% dextrose solutions. The addition of 2 mg of NARCAN in 500 mL of either solution provides a concentration of 0.004 mg/mL. Mixtures should be used within 24 hours. After 24 hours, the remaining unused mixture must be discarded. The rate of administration should be titrated in accordance with the patient's response.

58hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnea, pulmonary edema, and cardiac arrest. Death, coma, and encephalopathy have been reported as sequelae of these events. Opioid DependenceCardiac Disorders: pulmonary edema, cardiac arrest or failure, tachycardia, ventricular fibrillation, and ventricular tachycardia. Gastrointestinal Disorders: vomiting, nauseaNervous System Disorders: convulsions, paresthesia, grand mal convulsionPsychiatric Disorders: agitation, hallucination, tremulousnessRespiratory Thoracic and Mediastinal Disorders: dyspnea, respiratory depression, hypoxiaSkin and Subcutaneous Tissue Disorders: nonspecific injection site reactions, sweating

59DRUG INTERACTIONSLarge doses of naloxone are required to antagonize buprenorphine since the latter has a long duration of action due to its slow rate of binding and subsequent slow dissociation from the opioid receptor. WARNINGSDrug DependenceRespiratory Depression due to Other DrugsRenal Insufficiency/FailureThe safety and effectiveness of NARCAN in patients with renal insufficiency/failure have not been established in well-controlled clinical trialsLiver Diseaseliver diseaseCONTRAINDICATIONShypersensitive to naloxone hydrochloride

60CLINICAL PHARMACOLOGYComplete or Partial Reversal of OpioidWhile the mechanism of action of NARCAN is not fully understood, in vitro evidence suggests that NARCAN antagonizes opioid effects by competing for the , and opiate receptor sites in the CNS, with the greatest affinity for the receptor.Adjunctive Use in Septic ShockNARCAN has been shown in some cases of septic shock to produce a rise in blood pressure that may last up to several hours; however, this pressor response has not been demonstrated to improve patient survival

61NICARDIPINE:

Cardene (nicardipine hydrochloride) is a calcium ion influx inhibitor (slow channel blocker or calcium channel blocker). Cardene I.V. Premixed Injection for intravenous administration contains 20 mg of nicardipine hydrochloride per 200 mL (0.1 mg/mL) in either dextrose or sodium chloride.INDICATIONS Hypertension DOSAGE AND ADMINISTRATIONRecommended DosingCardene I.V. is intended for intravenous use. Titrate dose to achieve the desired blood pressure reduction. Individualize dosage depending on the blood pressure to be obtained and the response of the patient.Dosage as a Substitute for Oral Nicardipine TherapyThe intravenous infusion rate required to produce an average plasma concentration equivalent to a given oral dose 62HOW SUPPLIEDDosage Forms And StrengthsCardene I.V. Premixed Injection is supplied as a single-use, ready-to-use, iso-osmotic solution for intravenous administration in a 200 mL GALAXY container with 20 mg (0.1 mg/mL) nicardipine hydrochloride in either dextrose or sodium chloride.SIDE EFFECTSAdverse Reactions Observed in Clinical TrialsBody as a Whole: fever, neck pain Cardiovascular: angina pectoris, atrioventricular block, ST segment depression, inverted T wave, deep-vein thrombophlebitisDigestive: dyspepsiaHemic and Lymphatic: thrombocytopeniaMetabolic and Nutritional: hypophosphatemia, peripheral edemaNervous: confusion, hypertoniaRespiratory: respiratory disorderSpecial Senses: conjunctivitis, ear disorder, tinnitusUrogenital: urinary frequencyDRUG INTERACTIONSBeta-Blockers, Cimetidine, Cyclosporine

63PRECAUTIONSExcessive Pharmacodynamic EffectsUse in Patients with AnginaUse in Patients with Heart FailureUse in Patients with Impaired Hepatic FunctionUse in Patients with Impaired Renal FunctionIntravenous Infusion SiteCONTRAINDICATIONS -Advanced Aortic StenosisMechanism of ActionNicardipine inhibits the transmembrane influx of calcium ions into cardiac muscle and smooth muscle without changing serum calcium concentrations.

64NITROSTAT DRUGNitrostat is a stabilized sublingual compressed nitroglycerin tablet that contains 0.3 mg (1/200 grain), 0.4 mg (1/150 grain), or 0.6 mg (1/100 grain) nitroglycerin; INDICATIONSacute relief of an attack or acute prophylaxis of angina pectoris due to coronary artery disease.DOSAGE AND ADMINISTRATIONOne tablet should be dissolved under the tongue or in the buccal pouch at the first sign of an acute anginal attack. The dose may be repeated approximately every 5minutes, until relief is obtained. If the pain persists after a total of3 tablets in a15-minute period, prompt medical attention is recommended. Nitrostat may be used prophylactically5 to 10 minutes prior to engaging in activities which might precipitate an acute attack.During administration the patient should rest, preferably in the sitting position. No dosage adjustmentis required in patients with renal failure.

65HOW SUPPLIEDNitrostat is supplied as white, round, flat-faced tablets in 3 strengths (0.3 mg, 0.4 mg, and 0.6 mg) in bottles containing 100 tablets each, with color-coded labels, and in color-coded Patient0.3 mg, 0.4 mg, 0.6 mg Store at Controlled Room Temperature 20-25C (68-77F)SIDE EFFECTSHeadache which may be severe and persistent may occur immediately after use. Vertigo, dizziness, weakness, palpitation, and other manifestations of postural hypotension may develop occasionally, particularly in erect, immobile patients.

66DRUG INTERACTIONSPatients receiving antihypertensive drugs, beta-adrenergic blockers, or phenothiazines and nitrates should be observed for possible additive hypotensive effects. The vasodilatory and hemodynamic effects of nitroglycerin maybe enhanced by concomitant administration of aspirinTricyclic antidepressants (amitriptyline, desipramine, doxepin, others) and anticholinergic drugs may cause dry mouth and diminished salivary secretions. patients receiving sublingual nitroglycerin should avoid ergotamine and related drugs or be monitored for symptoms of ergotism if this is not possibleDrug/Laboratory Test Interactionsfalse report of decreased serum cholesterol.

67PRECAUTIONS:GeneralOnly the smallest dose required for effective relief of the acute anginal attack should be used. Excessive use may lead to the development of tolerance. OVERDOSE:Hemodynamic EffectsThe effects of nitroglycerin overdose are generally the results of nitroglycerin's capacity to induce vasodi-latation, venous pooling, reduced cardiac output, and hypotension. including increased intracranial pressure, with any or all of persistent throbbing headache, confusion, and moderate fever; vertigo; palpitations; tachycardia; visual disturbances; nausea and vomiting (possibly with colic and even bloody diarrhea); syncope (especially in the upright posture); dyspnea, later followed by reduced ventilatory effort, diaphoresis, with the skin either flushed or cold and clammy; heartblock and bradycardia; paralysis; coma; seizures; and death.Methemoglobinemia -rarely reported

68CONTRAINDICATIONSearly myocardial infarction, severe anemia, increased intracranial pressure, and those with a known hypersensitivity to nitroglycerin.CLINICAL PHARMACOLOGYThe principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle. Although venous effects predominate, nitroglycerin produces, in a dose-related manner, dilation of both arterial and venous beds. Dilation of postcapillary vessels, including large veins, promotes peripheral pooling of blood, decreases venous return to the heart, and reduces left ventricular end-diastolic pressure (preload). Nitroglycerin also produces arteriolar relaxation, thereby reducing peripheral vascular resistance and arterial pressure (afterload), and dilates large epicardial coronary arteries; 69NITROPRESS

for(sodium nitroprusside) Injection.an inorganic hypotensive agent.INDICATIONSfor the immediate reduction of blood pressure of patients in hypertensive crises. Concomitant longer-acting antihypertensive medication should be administered so that the duration of treatment with sodium nitroprusside can be minimized.treatment of acute congestive heart failure.DOSAGE AND ADMINISTRATIONDilution to proper strength infusion: Depending on the desired concentration, the solution containing 50 mg of NITROPRESS must be further diluted in 250-1000 mL of sterile 5% dextrose injection. The diluted solution should be protected from light, using the supplied opaque sleeve, aluminum foil, or other opaque material. It is not necessary to cover the infusion drip chamber or the tubing.

70WARNING: Do not use flexible container in series connections.To protect NITROPRESS from light, it should be stored in its carton until it is used.SIDE EFFECTSexcessive hypotension and cyanide toxicity. Methemoglobinemia: Thiocyanate Toxicity: Thiocyanate interferes with iodine uptake by the thyroid.Abdominal pain, apprehension, diaphoresis, dizziness, headache.Cardiovascular: Bradycardia, electrocardiographic changes, tachycardia.Dermatologic: Rash.Endocrine: Hypothyroidism.Gastrointestinal: Ileus.Hematologic: Decreased platelet aggregation.Neurologic: Increased intracranial pressure.Miscellaneous: Flushing, venous streaking, irritation at the infusion site.

71WARNINGSThe principal hazards of NITROPRESS administration are excessive hypotension and excessive accumulation of cyanide Excessive HypotensionPRECAUTIONSGeneral -Like other vasodilators, sodium nitroprusside can cause increases in intracranial pressure..Hepatic -Use caution when administering nitroprusside to patients with hepatic insufficiency.Use in Anesthesia -When sodium nitroprusside (or any other vasodilator) is used for controlled hypotension during anesthesia, the patient's capacity to compensate for anemia and hypovolemia may be diminished. 72OVERDOSEOverdosage of nitroprusside can be manifested as excessive hypotension or cyanide toxicity .Treatment of cyanide toxicity:Treatment of cyanide toxicity consists ofdiscontinuing the administration of sodium nitroprusside;providing a buffer for cyanide by using sodium nitrite to convert as much haemoglobin into methemoglobin as the patient can safely tolerate; and theninfusing sodium thiosulfate in sufficient quantity to convert the cyanide into thiocyanate.

73CONTRAINDICATIONStreatment of compensatory hypertension,to produce hypotension during surgery in patients with known inadequate cerebral circulation, for the treatment of acute congestive heart failureCLINICAL PHARMACOLOGYThe principal pharmacological action of sodium nitroprusside is relaxation of vascular smooth muscle and consequent dilatation of peripheral arteries and veins. Other smooth muscle (e.g. , uterus, duodenum) is not affected. 74NOREPINEPHRINE:

Norepinephrine is a sympathomimetic amine which differs from epinephrine by the absence of a methyl group on the nitrogen atomINDICATIONSFor blood pressure control in certain acute hypotensive states As an adjunct in the treatment of cardiac arrest and profound hypotension.DOSAGE AND ADMINISTRATIONDiluent: LEVOPHED should be diluted in 5 percent dextrose injection or 5 percent dextrose and sodium chloride injections. These dextrose containing fluids are protection against significant loss of potency due to oxidation. Administration in saline solution alone is not recommended. Whole blood or plasma, if indicated to increase blood volume, should be administered separately (for example, by use of a Y-tube and individual containers if given simultaneously).Average Dosage: Add the content of the vial (4 mg/4 mL) of LEVOPHED to 1,000 mL of a 5 percent dextrose containing solution. Duration of Therapy: The infusion should be continued until adequate blood pressure and tissue perfusion are maintained without therapy.

75Adjunctive Treatment in Cardiac ArrestInfusions of LEVOPHED are usually administered intravenously during cardiac resuscitation to restore and maintain an adequate blood pressure after an effective heartbeat and ventilation have been established by other means. SIDE EFFECTSBody As A Whole: Ischemic injury due to potent vasoconstrictor action and tissue hypoxia.Cardiovascular System: Bradycardia, probably as a reflex result of a rise in blood pressure, arrhythmias.Nervous System: Anxiety, transient headache.Respiratory System: Respiratory difficulty.Skin and Appendages: Extravasation necrosis at injection site.Prolonged administration of any potent vasopressor may result in plasma volume depletion which should be continuously corrected by appropriate fluid and electrolyte replacement therapy

76DRUG INTERACTIONSCyclopropane and halothane anesthetics increase cardiac autonomic irritability and therefore seem to sensitize the myocardium to the action of intravenously administered epinephrine or norepinephrine. DRUG INTERACTIONSCyclopropane and halothane anesthetics increase cardiac autonomic irritability and therefore seem to sensitize the myocardium to the action of intravenously administered epinephrine or norepinephrine.

77OVERDOSEOverdosage with LEVOPHED may result in headache, severe hypertension, reflex bradycardia, marked increase in peripheral resistance, and decreased cardiac output. In case of accidental overdosage, as evidenced by excessive blood pressure elevation, discontinue LEVOPHED until the condition of the patient stabilizes.CONTRAINDICATIONSLEVOPHED should not be given to patients who are hypotensive from blood volume deficits except as an emergency measure to maintain coronary and cerebral artery perfusion until blood volume replacement therapy can be completed. CLINICAL PHARMACOLOGYLEVOPHED functions as a peripheral vasoconstrictor (alpha-adrenergic action) and as an inotropic stimulator of the heart and dilator of coronary arteries (beta-adrenergic action).

78

PENTOBARBITOL:

NEMBUTAL Sodium Solution(pentobarbital sodium) Injection, USPBarbiturates are nonselective central nervous system depressants which are primarily used as sedative hypnotics and also anticonvulsants in subhypnotic doses. The barbiturates and their sodium salts are subject to control under the Federal Controlled Substances Act.INDICATIONSParenteral Sedatives.Hypnotics, Anticonvulsant, in anesthetic doses, in the emergency control of certain acute convulsive episodes,

79DOSAGE AND ADMINISTRATIONDosages of barbiturates must be individualized with full knowledge of their particular characteristics and recommended rate of administration. Intramuscular Administration: The usual adult dosage of NEMBUTAL Sodium Solution is 150 to 200 mg as a single IM injection; Intravenous AdministrationA commonly used initial dose for the 70 kg adult is 100 mg. Proportional reduction in dosage should be made for pediatric or debilitated patients. Anticonvulsant use: In convulsive states, dosage of NEMBUTAL Sodium Solution should be kept to a minimum to avoid compounding the depression which may follow convulsions. Special patient population: Dosage should be reduced in the elderly or debilitated.Inspection: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution containers permit. Solutions for injection showing evidence of precipitation should not be used.

80HOW SUPPLIEDNEMBUTAL Sodium Solution (pentobarbital sodium injection, USP) is available in the following sizes:20-mL multiple-dose vial, 1 g per vial and 50-mL multiple-dose vial, 2.5 g per vial Each mL contains:Pentobarbital Sodium, derivative of barbituric acid.......................................50 mgPropylene glycol........................................................................................40% v/vAlcohol ............................................................................................................10%Water for Injection..............................................................................................qs (pH adjusted to approximately 9.5 with hydrochloric acid and/or sodium hydroxide.)81Nervous system: Agitation, confusion, hyperkinesia, ataxia, CNS depression, nightmares, nervousness, psychiatric disturbance, hallucinations, insomnia, anxiety, dizziness, thinking abnormality.Respiratory system: Hypoventilation, apnea.Cardiovascular system: Bradycardia, hypotension, syncope.Digestive system: Nausea, vomiting, constipation.Other reported reactions: Headache, injection site reactions, hypersensitivity reactions (angioedema, skin rashes, exfoliative dermatitis), fever, liver damage, megaloblastic anemia following chronic phenobarbital use.

82DRUG INTERACTIONSAnticoagulantsCorticosteroids:Doxycycline:Phenytoin, sodium valproate, valproic acid:Central nervous system depressants:Monoamine oxidase inhibitors (MAOI):Estradiol, estrone, progesterone and other steroidal hormones:Habit forming:Acute or chronic pain:PRECAUTIONSBarbiturates may be habit forming. In patients with hepatic damage, barbiturates should be administered with caution and initially in reduced doses.Barbiturates should not be administered to patients showing the premonitory signs of hepatic coma.

83PRECAUTIONSBarbiturates may be habit forming. In patients with hepatic damagesigns of hepatic coma.OVERDOSEThe toxic dose of barbiturates varies considerably. In general, an oral dose of 1 gram of most barbiturates produces serious poisoning in an adult. Death commonly occurs after 2 to 10 grams of ingested barbiturate. CONTRAINDICATIONSBarbiturates are contraindicated in patients with known barbiturate sensitivity. Barbiturates are also contraindicated in patients with a history of manifest or latent porphyria.

84CLINICAL PHARMACOLOGYBarbiturates are capable of producing all levels of CNS mood alteration from excitation to mild sedation, to hypnosis, and deep coma. Overdosage can produce death. In high enough therapeutic doses, barbiturates induce anesthesia.Barbiturates depress the sensory cortex, decrease motor activity, alter cerebellar function, and produce drowsiness, sedation, and hypnosis.Barbiturate-induced sleep differs from physiological sleep. 85(Potassium chloride) K-LOR 20 MEQEach packet of K-LOR 20 mEq powder contains potassium 20 mEq and chloride 20 mEq provided by potassium chloride 1.5 g.INDICATIONSFor the treatment of patients with hypokalemia with or without metabolic alkalosis, in digitalis intoxication, and in patients with hypokalemic familial periodic paralysis. DOSAGE AND ADMINISTRATIONThe usual dietary potassium intake by the average adult is 50 to 100 mEq per day. Potassium depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of potassium from the total body store.Dosage must be adjusted to the individual needs of each patient. 86SIDE EFFECTSThe most common adverse reactions to oral potassium salts are nausea, vomiting, flatulence, abdominal pain/discomfort, and diarrhea. DRUG INTERACTIONS-Potassium-sparing diuretics, angiotensin converting enzyme inhibitors .HyperkalemiaIn patients with impaired mechanisms for excreting potassium, the administration of potassium salts can produce hyperkalemia and cardiac arrest. Hypokalemia should not be treated by the concomitant administration of potassium salts and a potassium-sparing diuretic, e.g., spironolactoneAngiotensin converting enzyme (ACE) inhibitors (e.g., captopril, enalapril) will produce some potassium retention by inhibiting aldosterone production. 87LABORATORY TESTSOVERDOSEThe administration of oral potassium salts to persons with normal excretory mechanisms for potassium rarely causes serious hyperkalemia. Intravenous administration of 300 to 500 ml/hr of 10% dextrose solution containing 10-20 units of crystalline insulin per 1,000 ml;Correction of acidosis, if present, with intravenous sodium bicarbonate;

88CONTRAINDICATIONSchronic renal failure, systemic acidosis such as diabetic acidosis, acute dehydration, extensive tissue breakdown as in severe burns, adrenal insufficiency, or the administration of a potassium-sparing diuretic.CLINICAL PHARMACOLOGYPotassium ion is the principal intracellular cation of most body tissues. Potassium ions participate in a number of essential physiological processes including the maintenance of intracellular tonicity, the transmission of nerve impulses, the contraction of cardiac, skeletal and smooth muscle, and the maintenance of normal renal function.

89PROCAINAMIDE:INDICATIONSventricular arrhythmias, ventricular tachycardia.DOSAGE AND ADMINISTRATIONTo provide approximately 50 mg per kg of body weight per day*SIDE EFFECTSCardiovascularHypotension and serious disturbances of cardiorhythm such as ventricular asystole or fibrillation are more common after Second degree heart block has been reported in 2 of almost 500 patients taking PA orally.MultisystemA lupus erythematosus-like syndrome of arthralgia, pleural or abdominal pain, HematologicNeutropenia, thrombocytopenia, or hemolytic anaemia

90SkinAngioneurotic oedema, urticaria, pruritus, flushing, and maculopapular rash have also occurred occasionally.GastrointestinalAnorexia, nausea, vomiting, abdominal pain, bitter taste, or diarrheaElevated Liver EnzymesElevations of transaminase with and without elevations of alkaline phosphatase and bilirubin have been reported. Nervous SystemDizziness or giddiness, weakness, mental depression, and psychosis with hallucinationsDRUG INTERACTIONSIf other antiarrhythmic drugs are being used, additive effects on the heart may occur with PA administration, and dosage reduction may be necessary.Anticholinergic drugs administered concurrently with PA may produce additive antivagal effects on A-V nodal conduction, although this is not as well documented for PA as for quinidine.

91Patients weighing lbkg 88-11040-50250 mg q3h to 500 mg q6h132-15460-70375 mg q3h to 750 mg q6h176-19880-90500 mg q3 hr to 1 g q6h> 220> 100625 mg q3h to 1.25 g q6h*Initial dosage schedule guide only, to be adjusted for each patient individually, based on age, cardiorenal function, blood level (if available), and clinical response.92WARNINGSBlood DyscrasiasDigitalis IntoxicationFirst Degree Heart BlockPredigitalization for Atrial Flutter or FibrillationPatients with atrial flutter or fibrillationCongestive Heart FailureConcurrent Other Antiarrhythmic AgentsRenal insufficiencyMyasthenia Gravis

93PRECAUTIONS:Immediately after initiation of PA therapy, patients should be closely observed for possible hypersensitivity reactions, especially if procaine or local anaesthetic sensitivity is suspected, and for muscular weakness if myasthenia gravis is a possibility.Laboratory TestsLaboratory tests such as complete blood count (CBC), electrocardiogram, and serum creatinine or urea nitrogen may be indicated, depending on the clinical situation, and periodic rechecking of the CBC and ANA may be helpful in early detection of untoward reactions.

94CONTRAINDICATIONSComplete Heart BlockIdiosyncratic HypersensitivityLupus ErythematosusTorsades de PointesCLINICAL PHARMACOLOGYProcainamide (PA) increases the effective refractory period of the atria, and to a lesser extent the bundle of His-Purkinje system and ventricles of the heart. It reduces impulse conduction velocity in the atria, His-Purkinje fibers, and ventricular muscle, but has variable effects on the atrioventricular (A-V) node, a direct slowing action and a weaker vagolytic effect which may speed A-V conduction slightly. Myocardial excitability is reduced in the atria. 95DIPRIVAN(PROPOFOL) INJECTABLE EMULSIONFOR IV ADMINISTRATION:INDICATIONSDIPRIVAN Injectable Emulsion is an IV sedative-hypnotic agent that can be used as described in the table below.Table 3. Indications for DIPRIVAN Injectable Emulsion IndicationApproved Patient PopulationInitiation and maintenance of Monitored Anesthesia Care (MAC) sedationAdults onlyCombined sedation and regional anesthesiaAdults only Induction of General AnesthesiaPatients 3 years of ageMainenance of General AnesthesiaPatients 2 months of ageIntensive Care Unit (ICU) sedation of intubated, mechanically ventilated patientsAdults onlyDIPRIVAN Injectable Emulsion is not indicated for use in Pediatric ICU sedation since the safety of this regimen has not been established96DOSAGE AND ADMINISTRATIONPropofol blood concentrations at steady state are generally proportional to infusion rates, especially in individual patients. Undesirable effects such as cardiorespiratory depression are likely to occur at higher blood concentrations which result from bolus dosing or rapid increases in the infusion rate. Administration with Lidocaine: If lidocaine is to be administered to minimize pain on injection of DIPRIVAN, it is recommended that it be administered prior to DIPRIVAN administrationDilution Prior to Administration: DIPRIVAN Injectable Emulsion is provided as a ready- to-use formulation. However, should dilution be necessary, it should only be diluted with 5% Dextrose Injection, USP, and it should not be diluted to a concentration less than 2 mg/mL because it is an emulsionAdministration with Other Fluids5% Dextrose Injection, USPLactated Ringers Injection, USPLactated Ringers and 5% Dextrose Injection5% Dextrose and 0.45% Sodium Chloride Injection, USP5% Dextrose and 0.2% Sodium Chloride Injection, USP

97HANDLING PROCEDURESParenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.Do not use if there is evidence of separation of the phases of the emulsion. There have been reports in which failure to use aseptic technique when handling Diprivan Injectable Emulsion was associated with microbial contamination of the product and with fever, infection/sepsis, other life-threatening illness, and/or death. Diprivan, with EDTA, inhibits microbial growth for up to 12 hours, as demonstrated by test data for representative USP microorganisms.HOW SUPPLIEDDIPRIVAN Injectable Emulsion is available as follows:Propofol undergoes oxidative degradation, in the presence of oxygen, and is therefore packaged under nitrogen to eliminate this degradation path.Store between 4-22C (40-72F). Do not freeze. Shake well before use.

98DRUG INTERACTIONSThe induction dose requirements of DIPRIVAN Injectable Emulsion may be reduced in patients with intramuscular or intravenous premedication, particularly with narcotics (e.g., morphine, meperidine, and fentanyl, etc.) and combinations of opioids and sedatives.WARNINGSUse of DIPRIVAN Injectable Emulsion has been associated with both fatal and life- threatening anaphylactic and anaphylactoid reactions.Sedated patients should be continuously monitored, and facilities for maintenance of a patent airway, providing artificial ventilation, administering supplemental oxygen, and instituting cardiovascular resuscitation must be immediately available. Patients should be continuously monitored for early signs of hypotension, apnea, airway obstruction, and/or oxygen desaturation.

99OVERDOSEIf overdosage occurs, DIPRIVAN Injectable Emulsion administration should be discontinued immediately. Overdosage is likely to cause cardiorespiratory depression. Respiratory depression should be treated by artificial ventilation with oxygen. Cardiovascular depression may require repositioning of the patient by raising the patient's legs, increasing the flow rate of intravenous fluids, and administering pressor agents and/or anticholinergic agents.PRECAUTIONSGeneralAdult and Pediatric Patients: A lower induction dose and a slower maintenance rate of administration should be used in elderly, debilitated, patients. Patients should be continuously monitored for early signs of hypotension and/or bradycardia. Apnea requiring ventilatory support often occurs during induction and may persist for more than 60 seconds. Very rarely the use of DIPRIVAN Injectable Emulsion may be associated with the development of a period of postoperative unconsciousness which may be accompanied by an increase in muscle tone. This may or may not be preceded by a brief period of wakefulness.Recovery is spontaneous.

100CONTRAINDICATIONSHypersensitivity Allergies to eggs, egg products, soybeans or soy productsCLINICAL PHARMACOLOGYDIPRIVAN Injectable Emulsion is an intravenous sedative-hypnotic agent for use in the induction and maintenance of anaesthesia or sedation. Intravenous injection of a therapeutic dose of propofol induces hypnosis, with minimal excitation, usually within 40 seconds from the start of injection (the time for one arm-brain circulation). As with other rapidly acting intravenous anaesthetic agents, the half-time of the blood-brain equilibration is approximately 1 to 3 minutes, accounting for the rate of induction of anaesthesia.

1015% SODIUM BICARBONATE INJECTIONINDICATIONStreatment of metabolic acidosisDOSAGE AND ADMINISTRATIONFor mild acidosis, the usual dosage is 1 to 2 mEq per kg of body weight, administered slowly.For more severe acidosis, 2 to 5 mEq per kg of body weight may be administered over a 4 to 8 hour period. In emergencies, 300 to 500 mL of the 5% Sodium Bicarbonate Injection should or administered as rapidly as is possible without over alkalinizing the patient.

102SIDE EFFECTSAlkalosisHyperirritability or tetanyFebrile response,Infection at the site of injection, Venous thrombosis or phlebitis extending from the site of injection,Extravasation, and hypervolemia. nate, USP in Water for Injection, USP.103WARNINGSRapid administration of sodium salts may precipitate volume overload and acute pulmonary edema. Rapid or excessive administration of Sodium Bicarbonate Injection may produce tetany due to a decrease in ionized calcium and hypokalemia as potassium reenters the cells.Sodium containing solutions should be used with great care, if at all, in patients with congestive heart failure, severe renal insufficiency and in clinical states in which there exists edema with sodium retention.Excessive or too rapid administration of Sodium Bicarbonate Injection may produce alkalosis. PRECAUTIONSCorrection of acidosis without correction of a potassium deficit may lead to severe hypokalemia. Coexistent hypocalcemia may be associated with carpopedal spasm as the plasma pH rises.

104CONTRAINDICATIONSSodium Bicarbonate Injection is contraindicated in patients with metabolic and respiratory alkalosis and in patients with hypocalcemia in which alkalosis may produce tetany.CLINICAL PHARMACOLOGYThe bicarbonate-carbonic acid system constitutes the principal extracellular buffer. Increasing the bicarbonate concentration buffers excess hydrogen ion concentration, raises blood pH and reverses the clinical manifestations of acidosis. HOW SUPPLIEDExposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. It is recommended the product be stored at room temperature (25C): brief exposure up to 40C does not adversely affect the product.

105VECURONIUM BROMIDE:

ZEMURON (rocuronium bromide) injection is a nondepolarizing neuromuscular blocking agentINDICATIONSadjunct to general anaesthesia to facilitate both rapid sequence and routine tracheal intubation, and to provide skeletal muscle relaxation during surgery or mechanical ventilation.DOSAGE AND ADMINISTRATIONThe recommended initial dose of ZEMURON, regardless of anesthetic technique, is 0.6 mg/kg. HOW SUPPLIEDZEMURON (rocuronium bromide) injection is available as5 mL multiple dose vials containing 50 mg rocuronium bromide injection (10 mg/mL) 10 mL multiple dose vials containing 100 mg rocuronium bromide injection (10 mg/mL)

106SIDE EFFECTSIn clinical trials, the most common adverse reactions (2%) are transient hypotension and hypertension.The following adverse reactions are described, or described in greater detail, in other sections:Anaphylaxis Residual paralysis Myopathy Increased pulmonary vascular resistance Cardiovascular: arrhythmia, abnormal electrocardiogram, tachycardia Digestive: nausea, vomiting Respiratory: asthma (bronchospasm, wheezing, or rhonchi), hiccup Skin and Appendages: rash, injection site edema, pruritus107DRUG INTERACTIONSAntibioticsDrugs which may enhance the neuromuscular blocking action of nondepolarizing agents such as ZEMURON include certain antibiotics (e.g., aminoglycosides; vancomycin; tetracyclines; bacitracin; polymyxins; colistin; and sodium colistimethate). If these antibiotics are used in conjunction with ZEMURON, prolongation of neuromuscular block may occur.AnticonvulsantsIn 2 of 4 patients receiving chronic anticonvulsant therapy, apparent resistance to the effects of ZEMURON was observed in the form of diminished magnitude of neuromuscular block, or shortened clinical duration. Lithium CarbonateLithium has been shown to increase the duration of neuromuscular block and decrease infusion requirements of neuromuscular blocking agents

108SUCCINYLCHOLINE:If ZEMURON is administered following administration of succinylcholine, it should not be given until recovery from succinylcholine has been observed. PRECAUTIONSThe drug should not be administered unless facilities for intubation, mechanical ventilation, oxygen therapy, and an antagonist are immediately available. It is recommended that clinicians administering neuromuscular blocking agents such as ZEMURON employ a peripheral nerve stimulator to monitor drug effect, need for additional doses, adequacy of spontaneous recovery or antagonism, and to decrease the complications of overdosage if additional doses are administered. AnaphylaxisExtravasation

109OVERDOSEOverdosage with neuromuscular blocking agents may result in neuromuscular block beyond the time needed for surgery and anesthesia. The primary treatment is maintenance of a patent airway, controlled ventilation and adequate sedation until recovery of normal neuromuscular function is assured. Once evidence of recovery from neuromuscular block is observed, further recovery may be facilitated by administration of an anticholinesterase agent in conjunction with an appropriate anticholinergic agent.CONTRAINDICATIONShypersensitivity CLINICAL PHARMACOLOGYZEMURON is a nondepolarizing neuromuscular blocking agent with a rapid to intermediate onset depending on dose and intermediate duration. It acts by competing for cholinergic receptors at the motor end-plate. This action is antagonized by acetylcholinesterase inhibitors, such as neostigmine and edrophonium.

110THIOPENTAL: -PENTOTHAL(thiopental sodium) for InjectionDRUG DESCRIPTIONThe drug is prepared as a sterile powder and after reconstitution with an appropriate diluent is administered by the intravenous route. The following diluents in various container, syringe and vial sizes are provided in Pentothal Kits, Pentothal Ready-to-Mix Syringes and Vials for preparing solutions of Pentothal (Thiopental Sodium for Injection, USP) for clinical use.

111INDICATIONS (1) as the sole anaesthetic agent for brief (15 minute) procedures, (2) for induction of anesthesia prior to administration of other anesthetic agents, (3) to supplement regional anesthesia, (4) to provide hypnosis during balanced anesthesia with other agents for analgesia or muscle relaxation, (5) for the control of convulsive states during or following inhalation anesthesia, local anesthesia, or other causes, (6) in neurosurgical patients with increased intracranial pressure, if adequate ventilation is provided, and (7) for narcoanalysis and narcosynthesis in psychiatric disorders. DOSAGE AND ADMINISTRATIONPentothal is administered by the intravenous route onlyPremedication Premedication usually consists of atropine or scopolamine to suppress vagal reflexes and inhibit secretions. 112Test Dose It is advisable to inject a small "test" dose of 25 to 75 mg (1 to 3 mL of a 2.5% solution) of Pentothal to assess tolerance or unusual sensitivity to Pentothal, COMPLICATIONS Respiratory depression Laryngospasm Myocardial depression, Extra vascular infiltration Shivering 113WARNING: The 2.5 g and larger sizes contain adequate medication for several patients. HOW SUPPLIEDStorage: Store at controlled room temperature 15 to 30C( 59 to 86F).Keep reconstituted solution in a cool place. SIDE EFFECTSPentothalAdverse reactions include respiratory depression, myocardial depression, cardiac arrhythmias, prolonged somnolence and recovery, sneezing, coughing, bronchospasm, laryngospasm and shivering. Anaphylactic and anaphylactoid reactions to Pentothal (Thiopental Sodium for Injection, USP) have been reported. Symptoms, e.g., urticaria, bronchospasm, vasodilation and edema should be managed by conventional means. Rarely, immune hemolytic anemia with renal failure and radial nerve palsy have been reported. DRUG ABUSE AND DEPENDENCE

114DRUG INTERACTIONSThe following drug interactions have been reported with thiopental.

115DrugEffectProbenecidProlonged action of thiopentalDiazoxideHypotensionZimelidineThiopental antagonismOpioid analgesicsDecreased antinociceptive actionAminophyllineThiopental antagonismMidazolamSynergismWARNINGSPentothalKEEP RESUSCITATIVE AND ENDOTRACHEAL INTUBATION EQUIPMENT AND OXYGEN READILY AVAILABLE. MAINTAIN PATENCY OF THE AIRWAY AT ALL TIMES. This drug should be administered only by persons qualified in the use of intravenous anesthetics. Avoid extravasation or intra-arterial injection.

116PRECAUTIONSObserve aseptic precautions Care should be taken in administering the drug to patients with advanced cardiac disease, increased intracranial pressure, ophthalmoplegia plus, asthma, myasthenia gravis and endocrine insufficiency (pituitary, thyroid, adrenal, pancreas). PentothalOverdosage: may occur from too rapid or repeated injections. Too rapid injection may be followed by an alarming fall in blood pressure even to shock levels. Apnea, occasional laryngospasm, coughing and other respiratory difficulties with excessive or too rapid injections may occur. In the event of suspected or apparent overdosage, the drug should be discontinued, a patent airway established (intubate if necessary) or maintained, and oxygen should be administered, with assisted ventilation if necessary. 117

MANAGEMENT OF 0VERDOSAGE

It is generally agreed that respiratory depression or arrest due to unusual sensitivity to thiopental sodium or overdosage is easily managed if there is no concomitant respiratory obstruction. If the airway is patent, any method of ventilating the lungs (that prevents hypoxia) should be successful in maintaining other vital functions. CONTRAINDICATIONSAbsence of suitable veins for intravenous administration, hypersensitivity (allergy) to barbiturates and variegate porphyria (South African) or acute intermittent porphyria. Relative ContraindicationsSevere cardiovascular disease, hypotension or shock, conditions in which the hypnotic effect may be prolonged or potentiated - excessive premedication, Addison's disease, hepatic or renal dysfunction, myxedema, increased blood urea, severe anemia, asthma, myasthenia gravis, and status asthmaticus. 118CLINICAL PHARMACOLOGY

Pentothal (Thiopental Sodium for Injection, USP) is an ultrashort-acting depressant of the central nervous system which induces hypnosis and anesthesia, but not analgesia. It produces hypnosis within 30 to 40 seconds of intravenous injection. Recovery after a small dose is rapid, with some somnolence and retrograde amnesia. Repeated intravenous doses lead to prolonged anesthesia because fatty tissues act as a reservoir; they accumulate Pentothal in concentrations 6 to 12 times greater than the plasma concentration, and then release the drug slowly to cause prolonged anesthesia.

119PHENYTOIN:

DILANTIN(PHENYTOIN SODIUM) 100 MG EXTENDED ORAL CAPSULEPhenytoin sodium is an antiepileptic drug.INDICATIONSDilantin is indicated for the control of generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery.DOSAGE AND ADMINISTRATIONDosage should be individualized to provide maximum benefit. In some cases, serum blood level determinations may be necessary for optimal dosage adjustmentsthe clinically effective serum level is usually 10-20 mcg/mL.

120Adult DosagePatients who have received no previous treatment may be started on one 100-mg Dilantin (Phenytoin sodium) Extended Oral Capsule three times daily and the dosage then adjusted to suit individual requirements.SIDE EFFECTSCentral Nervous System: nystagmus, ataxia, slurred speech, decreased coordination, and mental confusion. Dizziness, insomnia, Gastrointestinal System: Nausea, vomiting, constipation, toxic hepatitis, and liver damage.Integumentary System: Dermatological manifestations sometimes accompanied by fever have included scarlatiniform or morbilliform rashes. A morbilliform rash (measles-like) is the most common; 121Hemopoietic System: Hemopoietic complications, some fatal, have occasionally been reported in association with administration of phenytoin. These have included thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, and pancytopenia with or without bone marrow suppression. Connective Tissue System: Coarsening of the facial features, enlargement of the lips, gingival hyperplasia, hypertrichosis, and Peyronie's disease.Immunologic: Hypersensitivity syndrome (which may include, but is not limited to, symptoms such as arthralgias, eosinophilia, fever, liver dysfunction, lymphadenopathy, or rash), systemic lupus erythematosus, periarteritis nodosa and immunoglobulin abnormalities.

122DRUG INTERACTIONSDrugs which may increase phenytoin serum levels include: acute alcohol intake, amiodarone, chloramphenicol, chlordiazepoxide, cimetidine, diazepam, dicumarol, disulfiram, estrogens, ethosuximide, fluoxetine, H2-antagonists, halothane, isoniazid, methylphenidate, phenothiazines, phenylbutazone, salicylates, succinimides, sulfonamides, ticlopidine, tolbutamide, trazodone.Drugs which may decrease phenytoin levels include: carbamazepine, chronic alcohol abuse, reserpine, and sucralfate. Moban brand of molindone hydrochloride contains calcium ions which interfere with the absorption of phenytoin. Ingestion times of phenytoin and antacid preparations containing calcium should be staggered in patients with low serum phenytoin levels to prevent absorption problems.Phenytoin may decrease serum concentrations of T4

123WARNINGSAbrupt withdrawal of phenytoin in epileptic patients may precipitate status epilepticus. PRECAUTIONSThe liver is the chief site of biotransformation of phenytoin; patients with impaired liver function, elderly patients, or those who are gravely ill may show early signs of toxicity.A small percentage of individuals who have been treated with phenytoin have been shown to metabolize the drug slowly. Slow metabolism may be due to limited enzyme availability and lack of induction; it appears to be genetically determined.Phenytoin should be discontinued if a skin rash appears Laboratory TestsPhenytoin serum level determinations may be necessary to achieve optimal dosage adjustments.TreatmentTreatment is nonspecific since there is no known antidote.

124CONTRAINDICATIONS hypersensitive to phenytoin or other hydantoins.CLINICAL PHARMACOLOGYPhenytoin is an antiepileptic drug which can be used in the treatment of epilepsy. The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. Possibly by promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of posttetanic potentiation at synapses. Loss of posttetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas. Phenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of tonic-clonic (grand mal) seizures.

125HYDROCORTISONE:

CORTEF (HYDROCORTISONE) TABLETCORTEF Tablets contain hydrocortisone which is a glucocorticoid. Glucocorticoids are adrenocortical steroids, both naturally occurring and synthetic, which are readily absorbed from the gastrointestinal tract. Hydrocortisone USP is white to practically white, odorless, crystalline powder with a melting point of about 215 C. It is very slightly soluble in water and in ether; sparingly soluble in acetone and in alcohol; slightly soluble in chloroform.INDICATIONSEndocrine DisordersPrimary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the first choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy mineralocorticoid supplementation is of particular importance)Congenital adrenal hyperplasiaNon suppurative thyroiditisHypercalcemia associated with cancer126Rheumatic DisordersAs adjunctive therapy for short-term administration (Psoriatic arthritisRheumatoid arthritis, including juvenile rheumatoid arthritis Ankylosing spondylitisAcute and subacute bursitisAcute nonspecific tenosynovitisAcute gouty arthritis

127Post-traumatic osteoarthritisSynovitis of osteoarthritisEpicondylitisCollagen DiseasesDuring an exacerbation or as maintenance therapy in selected cases of:Systemic lupus erythematosusSystemic dermatomyositis (polymyositis)Acute rheumatic carditisDermatologic DiseasesPemphigusSevere psoriasisSevere seborrheic dermatitis Allergic States

128DOSAGE AND ADMINISTRATIONThe initial dosage of CORTEF Tablets may vary from 20 mg to 240 mg of hydrocortisone per day depending on the specific disease entity being treated. IT SHOULD BE EMPHASIZED THAT DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE UNDER TREATMENT AND THE RESPONSE OF THE PATIENT. HOW SUPPLIEDCORTEF Tablets are available in the following strengths and package sizes:5 mg (white, round, scored, imprinted CORTEF 5)10 mg (white, round, scored, imprinted CORTEF 10)20 mg (white, round, scored, imprinted CORTEF 20)Store at controlled room temperature 20 to 25C (68 to 77F)

129SIDE EFFECTS

Fluid and Electrolyte DisturbancesSodium retentionFluid retentionCongestive heart failure in susceptible patientsPotassium lossHypokalemic alkalosisHypertensionMusculoskeletalMuscle weaknessSteroid myopathyLoss of muscle massOsteoporosisTendon rupture, particularly of the Achilles tendonVertebral compression fracturesAseptic necrosis of femoral and humeral headsPathologic fracture of long bones 130

DRUG INTERACTIONS

Drugs that induce hepatic enzymes such as phenobarbital, phenytoin and rifampin may increase the clearance of corticosteroids and may require increases in corticosteroid dose to achieve the desired response. Drugs such as troleandomycin and ketoconazole may inhibit the metabolism of corticosteroids and thus decrease their clearance.131WARNINGS

In patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting corticosteroids before, during, and after the stressful situation is indicated.Corticosteroids may mask some signs of infection, and new infections may appear during their use.

132PRECAUTIONS

Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. There is an enhanced effect of corticosteroids on patients with hypothyroidism and in those with cirrhosis.Corticosteroids should be used cautiously in patients with ocular herpes simplex because of possible corneal perforation.the reduction should be gradual.Psychic derangements may appear when corticosteroids are used.133CONTRAINDICATIONS

Systemic fungal infections and known hypersensitivity to componentsCLINICAL PHARMACOLOGYNaturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs are primarily used for their potent anti-inflammatory effects in disorders of many organ systems. Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli.

134VITAMIN K1 DRUG DESCRIPTION

Vitamin K1 InjectionINDICATIONScoagulation disorders which are due to faulty formation of factors II, VII, IX and X when caused by vitamin K deficiency or interference with vitamin K activity.anticoagulant-induced prothrombin deficiencyprophylaxis and therapy of hemorrhagic disease of the newborn;hypoprothrombinemia due to antibacterial therapy;hypoprothrombinemia secondary to factors limiting absorption or synthesis of vitamin K, e.g., obstructive jaundice.other drug-induced hypoprothrombinemia e.g., salicylates.

135DOSAGE AND ADMINISTRATIONWhenever possible, Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP) should be given by the subcutaneous route. When intravenous administration is considered unavoidable, the drug should be injected very slowly, not exceeding 1 mg per minute.Protect from light at all times.Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.DIRECTIONS FOR DILUTION136Vitamin K1 Injection

Newborns DosageDosageHemorrhagic Disease of the Newborn Prophylaxis0.5 to 1 mg IM within 1 hour of birth Treatment1 mg SC or IM (Higher doses may be necessary if the mother has been receiving oral anticoagulants)AdultsInitial DosageAnticoagulant-Induced Prothrombin Deficiency (caused by coumarin or indanedione derivatives)2.5 mg to 10 mg or up to 25 mg indanedione derivatives)Hypoprothrombinemia Due to other causes (Antibiotics; Salicylates)2.5 mg to 25 mg or more (rarely up to 50 mg)137SIDE EFFECTSDeaths have occurred after intravenous and intramuscular administration. Transient "flushing sensations" and "peculiar" sensations of taste have been observed, as well as rare instances of dizziness, rapid and weak pulse, profuse sweating, brief hypotension, dyspnea, and cyanosis.Pain, swelling, and tenderness at the injection site may occur.The possibility of allergic sensitivityInfrequently, usually after repeated injection, erythematous, indurated, pruritic plaques have occurred; Hyperbilirubinemia138DRUG INTERACTIONSTemporary resistance to prothrombin-depressing anticoagulants may result, especially when larger doses of phytonadione are used. If relatively large doses have been employed, it may be necessary when reinstituting anticoagulant therapy WARNINGSBenzyl alcohol as a preservative in Bacteriostatic Sodium Chloride Injection has been associated with toxicity in newborns. An immediate coagulant effect should not be expected after administration of phytonadione. It takes a minimum of 1 to 2 hours for measurable improvement in the prothrombin time. Whole blood or component therapy may also be necessary if bleeding is severe.

139PRECAUTIONSLaboratory TestsProthrombin time should be checked regularly

CONTRAINDICATIONSHypersensitivity to any component of this medication.

140CLINICAL PHARMACOLOGY

Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP) aqueous dispersion of vitamin K1 for parenteral injection, possesses the same type and degree of activity as does naturally-occurring vitamin K, which is necessary for the production via the liver of active prothrombin (factor II), proconvertin (factor VII), plasma thromboplastin component (factor IX), and Stuart factor (factor X). The prothrombin test is sensitive to the levels of three of these four factors-II, VII, and X. 141II.CARE OF DRUGS:

1. Moisture:Deliquescent preparations like zinc chloride,ephedrine, digitalis preparations, ergot preparations must be preserved from moisture in air tight containers with dehydrating agents. Nurse must take proper care of them in their stores during rainy season by keeping them in dry places.2. Light:Direct sun light destroys the activity of drugs. Bismuth subcarbonate and ephedrine decomposes slowly in light. Tannic acid, bismuth salts, quinine and aminopyrine, change their colour with light. These drugs should be stored in amber or dark colour bottles. Drugs contained in the colour bottles must be protected from light by keeping them in dark place.1423. Temperature:Biological drugs are damaged even at room temperature. They must be stored at a temperature between 2-10C. Small pox vaccine should be kept even below OC, because of their losing of potency very rapidly in room temperature. Biological products, antibiotics, ethyl nitrite and insulin must be kept in refrigerators (2 15C) in the Drug Stores and Pharmacies and maintenance of constant low temperature should be checked.4.Air:Air due to 02, CO2, and moisture may cause deterioration of the drugs. Arsphenamine, chloral hydrate, calcium lactate, codeine sulphate, ferrous sulphate, hydantoin sodium, etc. will be damaged when exposed to air. Thyroid and other glandular products will be damaged by air also due to the growth of bacteria, mold and fungus. Containers of these drugs should be repeatedly checked against leakages.

1435. Age:Arsenic preparations like neoarsphnamine, procaine solutions, many tinctures, fluid extracts deteriorate with age in spite of best preservations. Biological drugs and antibiotics also lose their potency with time. These drugs should not be sold after the expiration date. These drugs should be stored separately and constant watch on the expiry dates of these drugs should be made6. Bacterial and Fungal growth:The growth of these plants commonly occur in carbohydrate containing drugs like syrups and mucilage and also in plant and animal extracts, and other pharmaceutical preparations like mixtures, emulsions, ointments, creams,sterile solutions, injections and biological products.These preparations may be protected against these growth by adding 0.2% of benzoic acid Or sodium benzoate and 0.5 % of chlorbutol, cresol, phenol, sodium bisulphite, etc. 1446. Chemical Stabilizers:Many drugs which are highly oxidizable such as vitamin C, adrenaline, phenylephrene, fats and oils are protected by the use of chemical stabilizers like anti-oxidants such as sodium bisulphite, sodium meta-bi sulphite maleic acid, or sulphur di-oxide. pH sensitive drugs are stabilized by using buffer solutions. Acetanilide acts as a negative catalyst in hydrogen peroxide. Sugars are used to prevent decomposition of ferrous iron in solution.7. Glass containers:Glass may also cause deterioration of some drugs.The hard glass containers contain silicon dioxide which is more resistant but the soft glass contains sodium and calcium oxides.The soft glass containers containing solution under high temperature dissolves the oxides and produces alkaline hydroxides and increase the pH of the solution and may affect the stability of the pH sensitive substances.

145For patients:It is important to store medicines properly. Guidelines for proper storage include:Keep out of the reach of children. Keep medicines in their original containers. Store away from heat and direct light. Do not store capsules or tablets near the kitchen sink, or in other damp places. Heat or moisture may cause the medicine to break down. Also, do not leave the cotton plug in a medicine container that has been opened, since it may draw moisture into the container. Keep liquid medicines from freezing. Do not store medicines in the refrigerator unless directed to do so. Do not leave your medicines in an automobile for long periods of time. Do not keep outdated medicine or medicine that is no longer needed. Be sure that any discarded medicine is out of the reach of children.

146III. PRINCIPLES OF DRUG ADMINISTRATION, ROLE OF NURSE:I. The Five Plus Five Rights of Drug Administration 5 Traditional Rights 1. right client2. right drug3. right dose4. right time5. right route5 Additional Rights 1. right assessment 2. right documentation 3. clients right to education 4. right evaluation 5. clients right to refuse

147Nurse must do: check medication order is complete & legible.know general purpose or action, dosage & route of drugcompare drug card with drug label three times.1. at time of contact with drug bottle/ container2. before pouring drug3. after pouring drug

1484 Categories of Drug Orders: Standing Order / Routine Order ongoing order may have special instructions to base administrationinclude PRN ordersex. digoxin 0.2 mg PO q.d., maintain blood level at 0.5 2.0 ng/ml 2.One-time (single) order given only once, at a specific time ex. Cefixime 2mg IM at 7 AM on 12-1-05 3. PRN order given at clients request & nurses judgement for need & safety ex Mefenamic Acid 500mg q 4h PRN for pain 4. STAT order given once, immediately ex. Morphine 2mg IV STAT

149C. Right Dose Nurse must do: Calculate and check drug dose accurately. Check PDR, drug package insert or drug handbook for recommended range of specific drugs. D. Right Time Nurse must do: Administer drugs at specified times. Administer drugs that are affected by foods, before meals. Administer drugs that can irritate stomach, with food. Drug administration may be adjusted to fit schedule of clients lifestyle, & activities. & diagnostic procedures. Check expiration date. Antibiotics should be administered at even intervals.

150E. Right Route Nurse must do: assess ability to swallow before giving oral meds. Do not crush or mix meds