Norkenz

Norepinephrine bitartrate.

Each mL contains: Norepinephrine (as bitartrate) USP 2 mg (1 mg as Norepinephrine base).

Pharmacotherapeutic group: Adrenergic and Dopaminergic Agonist. ATC Code: C01CA03 (C: Cardiovascular system).
Pharmacology: Pharmacodynamics: Norepinephrine has a very potent action on alpha receptors and moderate effect on beta-1 receptors. Norepinephrine causes generalized vasoconstriction, except for the coronary vessels which it dilates indirectly by increasing the oxygen consumption. This results in an increase in the force (and in the absence of vagal inhibition) in the rate of myocardial contraction. Peripheral resistance increases and diastolic and systolic pressures are raised.
Pharmacokinetics: Two stereoisomers of Norepinephrine exist, the biologically active L-isomer is the one present in Norepinephrine 1 mg/mL concentrate for solution for infusion.
Absorption: Subcutaneous: Poor.
Oral: Norepinephrine is rapidly inactivated in the gastrointestinal tract following oral administration.
After intravenous administration Norepinephrine has a plasmatic half-life of about 1 to 2 minutes.
Distribution: Norepinephrine is rapidly cleared from plasma by a combination of cellular reuptake and metabolism. It does not readily cross the blood-brain barrier.
Biotransformation (Metabolism): Methylation by catechol-o-methyltransferase.
Deamination by monoamine oxydase (MAO).
Ultimate metabolites from both 4-hydroxy-3-methoxymandlic acid.
Intermediate metabolites include normetanephrine and 3,4-dihydroxymandelic acid.
Excretion: Norepinephrine is mainly eliminated as glucuronide or sulphate conjugates of the metabolites in the urine.

Secondary treatment of acute hypotension or shock according to different diseases (shock due to myocardial infarction, and septicemia caused by shock, anaphylactic shock, hypotension or shock, according to the decreased circulating blood volume, acute hypotension during anesthesia, etc.).
Secondary treatment for cardiac arrest.

Acute hypotension or shock: Properly increase or decrease by diluting Norepinephrine bitartrate 8 mg (norepinephrine as 4 mg) to 5% glucose injection liquid or 1000 mL of 5% glucose saline injection while observing the reaction by intravenous infusion at a rate per minute of 2 ~ 3 mL.
Individual differences may exist but the requirement for maintenance is 0.5 mL to 1 mL per minute.
Cardiac Arrest: After retaining valid heart rate and ventilation while cardiac resuscitation, inject intravenously for case of acute hypotension or shock.

Symptoms of severe hypertension, reduced cardiac output, peripheral resistance increases, reflective bradycardia, photophobia, posterior sternal pain, pallor, intense sweating, vomiting, cerebral hemorrhage, and headache, edema may appear. In this case, stop the administration until the patient is stabilized and handle appropriately.

Norepinephrine is contraindicated to: Patients with low blood pressure due to lack of blood volume (except for emergency situations to maintain cerebral perfusion until blood volume replacement therapy is completed).
Patients with high blood pressure (rapid increase may occur due to vasoconstriction).
Patients with hyperthyroidism (significant increase in blood pressure may appear accompanying with severe headache and photophobia).
Patients with pheochromocytoma.
Patients with renal dysfunction.
Patients with pulmonary heart disease.
Patients with severe arrhythmia.
Patients with fingers, toes, nose anesthetized.
Pregnant Women or possibly pregnant women.

Emergency treatment of shock is procuring ventilation, raising the blood pressure of the fluid and increasing cardiac output.
The circulation dynamics of the shock varies depending on the state of the disease and cause of shock so, careful about selecting and using the time of blood pressure medication. It is emergency drug for antihypertensive agent, but not a substitute for blood or fluids.
May cause an excessive increase in blood pressure and acute pulmonary edema action, arrhythmia, cardiac arrest may occur, so this may not be excessively administered.
Frequently check the blood pressure and the administration rate when injecting the drug to prevent high blood pressure.
Continuation of this drug without replacement for maintaining of blood pressure may cause remarkable peripheral and internal vasoconstriction, decrease in renal perfusion and urea emission, decrease in blood volume despite normal blood pressure, tissue hypoxia, metabolic acidosis may occur so, using with blood volume replacement should be considered.
Use alpha blocker (phentolamine) if excessive rise in blood pressure.

Not administering as a rule, but in particular necessity, administer carefully for following patients: Patients with cocaine poisoning (use of cocaine can enhance the central action and sympathetic stimulation and weakened the symptoms).
Patients with ventricular tachycardia (the symptoms may be exacerbated by the reduction of cardiac output and the cerebral blood flow.
Patients with atherosclerosis (Elevate blood pressure and reduce peripheral blood flow).
Patients with heart disease (may affect cardiac function).
Patients with bradycardia (may cause arrhythmia).
Patients of coronary, mesenteric, peripheral vascular thrombosis patients (there is a risk of ischemia and increase area of infarction).
Patients with hypotension due to myocardial infarction.
Patients with Prinzmetal angina.
Elders.
Allergies such as anaphylaxis can be appeared since it contains sodium sulfite, and some sensitive patients may represent a much weaker or even in life-threatening asthma. Overall incidence of sulfite sensitivity is unknown but low in general people and sulphite sensitivity is frequent in patients with asthma than non-asthmatics.
Use in the Elderly: Carefully administer due to the possibility of excessive increase in blood pressure.

Avoid administering for pregnant or possibly pregnant women since fetus could be in suspended animation due to the contraction of the uterine blood vessels.
Whether this drug is expressed into breast milk is unknown, but carefully administer during lactation.

Body As A Whole: Ischemic injury due to potent vasoconstrictor action and tissue hypoxia.
Cardiovascular System: Cardiogenic shock, arrhythmia, bradycardia, probably as a reflex result of a rise in blood pressure, stress cardiomyopathy.
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. If plasma volumes are not corrected, hypotension may recur when Norepinephrine is discontinued, or blood pressure may be maintained at the risk of severe peripheral and visceral vasoconstriction (e.g., decreased renal perfusion) with diminution in blood flow and tissue perfusion with subsequent tissue hypoxia and lactic acidosis and possible ischemic injury. Gangrene of extremities has been rarely reported.
Overdoses or conventional doses in hypersensitive persons (eg. hyperthyroid patients) cause severe hypertension with violent headache, photophobia, stabbing retrosternal pain, pallor, intense sweating and vomiting.

Cyclopropane and halothane anesthetics increase cardiac autonomic irritability and therefore seem to sensitize the myocardium to the action of intravenously administered epinephrine or levarterenol. Hence, the use of Norepinephrine during cyclopropane and halothane anesthesia is generally considered contraindicated because of the risk of producing ventricular tachycardia or fibrillation. The same type of cardiac arrhythmias may result from the use of Norepinephrine in patients with profound hypoxia or hypercarbia. Norepinephrine should be used with extreme caution in patients receiving monoamine oxidase (MAO) inhibitors or antidepressants of the triptyline or imipramine types, because severe, prolonged hypertension may result.

Instructions and special precautions for handling and disposal: 1. Precaution: Cut with extreme caution especially for the elderly and children to minimize mixing of glass shards which can cause side effects.
2. Administer intravenous carefully to prevent unstable rise of blood pressure.
3. The infusion site should be checked frequently for free flow. Care should be taken to avoid extravasation of Norepinephrine into the tissues, as local necrosis might ensue due to the vasoconstrictive action of the drug that's why whenever possible, Norepinephrine should be given into a large vein to lower the risk of prolonged vasoconstriction and necrosis. After extravasation is noted, phentolamine should be given as soon as possible to prevent sloughing and necrosis in areas in which extravasation has taken place.
4. This drug is used to dilute to 5% glucose injection solution or physiological saline glucose injection solution (glucose can give to suppress the reduction of the potency due to oxidation).
5. Infusion containing the drug should not used in combination with alkali agent, oxidizing agent, barbiturate based drug, chlorophenylamine, chlorothiazide, nitrofurantoin, novobiocin, phenytoin, sodium bicarbonate, sodium iodide, and the drug streptomycin.

Store at temperatures not exceeding 30°C.

Vasoconstrictors

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