Naloxone Drug Profile - Essay Example

Naloxone’s Drug Profile Section Part One Naloxone helps in reversing opioid effects like hypotension, depression,and respiratory sedation. It can also reverse constipation associated with opioids. When administered orally, Naloxone has a bioavailability ranging from 1.9 per cent to 2.2 per cent for the 20 milligram and 120 milligram oral doses. The bioavailability is low due the significant first-pass hepatic metabolism (O’Malley-Dafner 7; Davies 722-3). Part Two Orally administered, Naloxone undergoes a wide metabolism in normal subjects. It is minimally absorbed when given orally as it is quickly destroyed in the GI tract. Many greater doses are needed when using oral administration for any pharmacologic effect. Naloxone is absorbed in the liver, mainly through glucuronide conjugation, and eventually excreted from the body system in urine. Part Three Because of the penetrating biotransformation in the liver, Naloxone is ineffectual when taken orally, and because of this, it is dispensed exclusively for parenteral use (Robertson et al 512-5). Section 2 Part One Naloxone is available in both parenteral and oral formulations. In Australia, Naloxone comes as a sterilized solution for intramuscular, intravenous, and subcutaneous administration in three strengths (1milligram, 0.4milligram, and 0.02milligram) for every milliliter in the sterilized solution. Every milliliter of the one-milligram strength has 8.35 milligrams of NaCl. In Australia, Naloxone may be referred to by different brand names such as TARGIN or buprenorphine. They are offered in four strengths, which are 5/2.5 milligrams, 10/5 milligrams, 20/10milligrams 40/20 milligrams, and TARGIN tablets that come in boxes that have blister packs of 20 to 28 tablets. Packs of 20 tablets are only available until current stocks deplete (Kelly and Koutsogiannis 375) Part Two A Naloxone hydrochloride is injected either intravenously, intramuscularly, subcutaneously, or orally. Intravenous administration has proved to work faster than all the other forms of administration, hence its recommendation for use in emergency cases. As such, it is preferred in emergency circumstances. In intravenous infusion Naloxone, hydrochloride may be diluted in dextrose injection 5 per cent or sodium chloride injection 0.9 per cent (O’Malley-Dafner and Davies 212). Products from parenteral drugs ought to be examined visually for any complication such as discoloration prior to administration. Naloxone hydrochloride dose should not be mixed with any alkaline solution, preparations containing bisulfite, high-molecular-weight anions, metabisulfite, and long-chain. There should be no addition of chemical agents or drugs to this solution unless one knows its outcome on the solution’s chemical and physical and stability. Section 3 Part One After a parenteral administration, Naloxone quickly disperses in the body system, freely crossing the placenta. The binding of plasma protein follows, but has been reported to be rather weak. Although the principal binding component is plasma albumin, plasma constituents also undergo naloxone binding. Part Two The drug’s distribution volume in plasma, which is 3litres per kilogram (this is more or less equal to 210 litres for a 70kilogram person versus five to six liters of blood in the same person, which would seem rather large). However, to get transported, the drug is usually bound to plasma proteins for transport (Martin 415). Naloxone is 61.5 per cent in fetal plasma and 54 per cent protein bound in adults. Part Three The usual adult dose is 0.4 to 2 milligram per dose of intravenous, and intramuscular, or subcutaneously administration and it may sometimes be repeated at two or three-minute intervals. Therapy is done if there is no response after accumulative dose of 10 milligrams. Naloxone is given intracisternally in loading doses. 0.1 milligram/kg/dose is given to children and infants who are less than or equal to five years or less than or equal to 20 kg, and may be repeated after every two to three minutes if necessary (Burke and Dunwoody 319). Section 4 Part One The liver helps to clear Naloxone, as it conjugates it with substitutes of glucuronide. One notable attribute of Naloxone is its high hepatic clearance.?The drug’s hepatic extraction is significantly high since most of it gets converted to glucuronyl substrates although there is no data to point out that a dosage decrease is necessary during the typically short length of therapy. Clinical nursing of patient tolerance and response is suggested in patients with hepatic dysfunction. The total hepatic clearance of Naloxone in a healthy 70 kilogram male is 1.400 ml/min (Martin 416). The kidneys help in the excretion of Naloxone metabolites, although clearance by them (kidneys) is below 50 per cent. The clearance of the drug from the body may be hindered by acid-base imbalance, acute renal failure, and dehydration. The total renal clearance of Naloxone is negligible (Colleen, Dunwoody, and Arnold 39). With the magnitude of the elevated hepatic clearance of naloxone and moderately feeble agonist action of its metabolites, it is doubtful that dose modifications would be essential in cases of renal failure. However, there is no material to demonstrate that a dosage decline is necessary during the typically short time of therapy. Renal dysfunctional patients should be clinically monitored on their response and tolerance. Part Two Naloxone inhibits neutrophil superoxide release, alters transmembrane calcium flux, affects lipid peroxidation, has antioxidant actions, stabilizes lysosome membranes, inhibits proteolysis and may have several platelet anti-aggregators effects. Naloxone also blocks the cerebral arterial vasoconstrictive effects of norepinephrine and in high concentrations, produces vasodilation and cerebral blood flow. Finally, naloxone may attenuate cerebral edema (Stephens 391). Naloxone should administered carefully among patients who have had a history with a cardiac illness or patients who have been prescribed for possible serious cardiovascular conditions like pulmonary edema, fibrillation, and tachycardia hypotension. Naloxone increases the syndromes of these diseases, and thus naloxone should be adjusted when dealing with such patients. Pharmacodynamics actions of Naloxone last for a shorter period, although, the removal half-life of naloxone is 1.5 hours. When administered IV, naloxone has an exceptionally fast onset of action (usually 1-2 minutes) (Burke and Dunwoody 45). If administered IM, naloxone has an onset of action within 5 minutes of administration. The period of action frequently continues from 45-90 minutes, although it may sometimes work for up to three hours. Section 5: Half-life The half-life of Naloxone ranges between one hour and 1.5 hours in adults, while in neonates it is up to three hours. Its drug action duration is approximately 0.75 of an hour (Arcangelo and Peterson 74). In a majority of cases, this duration is less than the action of the offending narcotic. The offending narcotic’s overdose effect usually returns, making it necessary for the re-administration of Naloxone. When taken orally naloxone is ineffective due to its short acting drug characteristics. With oral administration, the drug’s effect occurs within one to two hours and stay on for twenty-four to forty-eight hours. The drug’s half-life is dozens of minutes and has a strong biotransformation, an attribute that limits its use only for parenteral cases (Arcangelo and Peterson 76). Section 6: Therapeutic Drug Monitoring Naloxone is a semi-synthetic opioid antagonist, with the sign for the partial or complete reversal of life-threatening central nervous system caused by opioids. Naloxone is habitually improperly used in the hospital setting. It is given as a full ampule in reaction to physiological normal opioid to decrease in the respiratory rate. This undoubtedly comes from the application of ideologies of use in the Emergency Department to other settings (Belz and Lieb 468). It is normal to have a lower respiratory rate in the course of sleeping particularly on opioids. Mild bradypnea, which is not linked with physiological consequences like hypoxemia, should be monitored closely Depending on the dose given, naloxone administration to a patient physically depends on the opioids that will cause the sudden return of pain and can precipitate a withdrawal syndrome, with symptoms ranging from minor anxiety, muscle aches and irritability to life-threatening hypertension and tachycardia. Naloxone can cause pulmonary edema and cardiovascular failure. Most likely, through, an unexpected increase in the sympathetic nervous system activity is allied to opioid reversal (Belz and Lieb 470). Works Cited Arcangelo, Virginia Poole & Peterson, Andrew. Pharmacotherapeutics for Advanced Practice: A Practical Approach. New York: Lippincott Williams & Wilkins. 2005. Print Belz, D., & Lieb, J. Naloxone use in a tiered response alternative health services System. PrehospEmerg Care 10.4(2006): 468-71. Burke, D.F and Dunwoody CJ. A Word of Caution. Orthopaedic Nursing. 23.6(1990): 44-46 Colleen J., Dunwoody M.S., & Robert A. Using Naloxone, 2nd ed.End of Life/palliative. New York: Education Resource Center. 2005. Print Stephens, Everett. Opioid Toxicity Treatment & Management Updated: Jul 5, 2012. Retrieved from emedicine.meds.com. Web September 17, 2012 Kelly A. M. and Koutsogiannis. Intranasal naloxone for life threatening opioid toxicity. EmergMed J. 19.375(2002): doi: 10.1136/em. Martin, T. G. Take naloxone home: feasability, safety and probability. J ToxicolClinToxicol 41.4 (2003): 415-416. O’Malley-Dafner, L & Davies P. Naloxone-Induced Pulmonary Edema. AJN. 100.11(2000):24AA-JJ. Parkin, J. M. & Murphy, M. Admissibility, side-effects of post-exposure And prophylaxis for HIV contagion. Lancet. 355.9205. (2000): 722-3. Robertson, T. M., & Hendey, G. W. Intranasal naloxone is a reasonablesubstitute to intravenous naloxone narcotic overdose. PrehospEmerg Care. 13.4(2009): 512-5. Drug Profile activities for Module 5: Naloxone Section 1: Life stages as a factor in variability Part 1 Although, age plays a role in naloxone administration, there are no hard facts to support this, and previous research has failed to come up with strong facts. Mostly, administration bases on body weight (0.01 per kilogram) and may be adjusted when need arises in most hepatic and pediatric patients. For instance, a dosage of 0.1milligram per kilogram for infants and children from aged between zero and five years is sufficient. In adults, an initial dosage of 0.4 milligram to 2 milligrams is administered repeatedly. If the results are negative, then the dosage can be administered in increments of 0.1milligram to 0.2milligram. Intramuscular administration might be needed if the arterial method is not obtainable (MangoldD and McCaul 310). Part 2 These adjustments are due to pharmacokinetics; the onset of action is mostly within two minutes of naloxone administration intravenously. The onset of action is less rapid in subcutaneous and intramuscular administration. Action duration is dependent on dosage and method of administration of naloxone. For instance, intravenous administration is faster compared to intramuscular administration. Dosage repeat is dependent on the amounts, type, and route of administration of the antagonized narcotic (Wand and Weerts 1453). Section 2: Impact of disease states Part 1 Naloxone is processed in the liver; hence any disease complication in the liver that suppresses the naloxone effect means there should be some adjustments in the dosage. For example, pruritus is a distressing and common complication of cholestasis and non-cholestasis chronic liver diseases. It varies from trivial to severe, and limits regular activities, causes suicidal ideation and sleep deprivation. The pathogenesis of the disease is unknown but numerous proposals have been built, such as the bile acid accretion, and an increase in the buildup of endogenous opioids. Pruritus treatment associated with cholestasis is the rectification of the fundamental illness. Various measures can be tried for pruritus relieve if definitive therapy is not possible. In minor conditions of pruritus, generalprocedures can be employed to regulateindications such as ointmentsplus warm baths. In addition, in severe conditions these measures often fail. One option for moderate to severe cases is the opioid adversaries such as blood naloxone (0.2 µg/kg/ min per day) or oral naltrexone (50 mg per day) (Bergasa, 505). Part 2 Pharmacodynamics factors lead to dosage adjustments in treatment of hepatic diseases. Naloxone action as well as tranquility, hypertension, and depression converse opioids effects. Additionally, it mightconverse the psychotomimetic effect of agonist-antagonists e.g. Pentazocine Naloxone is clean opioid antagonist, i.e., It does not hold the morphine-like possessions distinctive of other opioid antagonists. It indicates that no pharmacologic action when managed in customaryamounts, in the absenteeism of agonistic effects of supplementary opioid adversaries (Mangold & McCaul 311). Section 3: Drug dependence, misuse, and abuse Part 1 Patients who areoversensitive to naloxone or whicheverconstituents contained in the making may contraindicate when vaccinated by naloxone hydrochloride. There is no clinical experience with naloxone hydrochloride over dosage in humans hence reduced chances of overdose due to its high therapeutic index. Instances where the patient is a drug addicts it intensifies withdrawal signs, and this is also evident when it is in excess. Withdrawal should not halt the use of the drug for this can lead to the patient reversing the side effects of opiates. In cases of pulmonary edema and arrhythmias, cardio respiratory support may be highly recommended (Lewanowitsch, 303). Part 2 Naloxone is used to treat opiate overdose. In children, I would ensure accuracy in measurements of the drug amount. Secondly accurately determine the age or weight of the kid before administering any dosage. In adults, I would ensure to give the right dosage amounts and keep a close eye to check whether the patient responds positively or negatively. If negative feedback I would change mode of administering or increase dosage. Procedural mistakes may lead to death among others (Adinoff 5289). Works Cited Adinoff, B., Krebaum S.R., Chandler PA., Ye W., Brown M.B, & Williams, M.J. Dissection of hypothalamic-pituitary-adrenal pathology in one-month abstinent alcohol-dependent me: response to CRH and Naloxone. Alcohol ClinExp Res. 29.2(2005):528–537. Bergasa, N.V. Treatment of the Cholestasis. Gastroenterol. 7.6(2004):501-508. Lewanowitsch, T. & Irvine R.J. Naloxone and its quaternary derivative. Res 964 (2007):302–305. Mangold D,. McCaul, M, & Ali, M. Generating a dose response curve to naloxone in a Single session. Biol Psychiatry. 48.2 (2009):310–314. Wand G,. Weerts, E., Xu, X,. McCaul, M.E., Kuwabara, H & Frost J. Naloxone-induced cortisol predictsmu opioid receptor binding potential in specific brain regions. Psychoneuroendocrinology. 36.2 (2011):1453–1459. Watson, S.J., Coy, D.H., Khachaturian, H., Goldstein, A. & Akil, H. Comparison of the delivery of dynorphin systems and enkephalin systems in brain. Science. 21.8 (2006):1134–1136. Read More