StudentShare
Contact Us
Sign In / Sign Up for FREE
Search
Go to advanced search...
Free

Pharmacology - Dose of Warfarin Schedule - Case Study Example

Cite this document
Summary
This paper under the headline 'Pharmacology - Dose of Warfarin Schedule" focuses on the fact that warfarin refers to an anticoagulant that is often used to prevent thrombosis and thromboembolism. Thrombosis is typically the development of blood clots in blood vessels. …
Download full paper File format: .doc, available for editing
GRAB THE BEST PAPER96.4% of users find it useful
Pharmacology - Dose of Warfarin Schedule
Read Text Preview

Extract of sample "Pharmacology - Dose of Warfarin Schedule"

Pharmacology study By Warfarin refers to an anticoagulant that is often used to prevent thrombosisand thromboembolism. Thrombosis is typically the development of blood clots in blood vessels while thromboembolism is the migration of such blood clots elsewhere within the body. Warfarin is much common, although it is inaccurately termed as blood thinner. Investigating possible interactions between JP234 and warfarin is the key idea behind this study. The administration of JP234, an oral antiarrhythmic agent, is utilized in heart rate control in atrial fibrillation. The administration of the drug among patients with cardiac arrhythmias has proved to be effective in prevention of arterial fibrillation. The effect of the new drug on the action of warfarin will be investigated in 12 healthy participants. The investigation is based on an open label study that would utilize a multiple dose design. To analyze the interaction between the two drugs in terms of the way JP234 would induce the metabolism of a single dose of warfarin, both R and S enantiomers were initiated through the CYP450 metabolic pathway. The study will be done based on the assumption that the new drug has been studied in vivo whereby in vitro metabolic studies will be consulted in determining whether JP234 is a substrate or an inhibitor the enzymes involved in the metabolism of warfarin. The study results will help in determining any possible interaction, such as whether PJ234 inhibits or induces the metabolism of warfarin. The mode of warfarin action in this case is based on its impact on the synthesis of vitamin K. The study will thus be able to portray the impact of drug interaction after eliminating warfarin. This will be considered from the results obtained from the group in which only the PJ234 is administered, as compared to the group whereby both the PJ234 and warfarin drugs are administered. 1.0 Background JP234 is well tolerated during clinical trials and there is no contradiction associated with it. The drug when administered is effective in doses of 50, 75 or 100mg once daily. The drug is metabolized in the liver and has a half life of about 24 hours. In vitro studies indicate that the drug can induce CYP2C9. Patients with chronic atrial fibrillation should be anticoagulated to hinder thromboembolism from taking place (Goodman, 2005). Patient taking JP234 are recommended to take warfarin that is partly metabolized by CYP2C9. JP234 is an antiarrhythmic drug and is usually excreted in the liver just the same as warfarin. The PJ234 drug is considered an inducer of CYP2C9 which takes part in the metabolism of warfarin. Before a drug is marketed to be utilized, its effectiveness should be outlined through well controlled and adequate clinical studies. A controlled study aims at exposing the population to the new agent with an intention of identifying the effects presented by the new agent such as concomitant therapy, placebo effect and spontaneous agent. The following parts of controls can be identified, historical control, dose-comparison concurrent control, placebo concurrent control and no treatment concurrent control (Doering et al, 1987). Drug interaction between the new drug and warfarin will also be tested. Testing for drug interaction is done with the efficacy and safety in mind. Investigation is done before marketing is done. The Warfarin is a widely utilized anticoagulant and is considered highly efficacious. Its metabolism however varies on various therapeutic responses. Both in vitro and in vivo studies show conflicting findings on clinical relevance of cytochrome P450. The enzyme metabolizes both R and S warfarin into 6, 7 and 8 hydroxywarfarin. The new drug induces the enzyme unlike other antiarrhythmic drugs such as amiodarone which inhibit the enzyme. This happens by binding to the active enzyme site, close to the heme group, and particularly to the opposite side of the peptide chain (Meunier, de Visser & Shaik, 2004). Generally, the metabolism of R-warfarin is found to be more efficient as compared to the metabolism of S-warfarin (Kim, et al., 2012). While warfarin has been depicted as important medication, it is known to show some common side effects with the main side effect being bleeding. The bleeding risk usually increases whenever the INR levels are out of range (Crowther, 2002). The INR levels could be influenced by overdose or drug interactions. Drug interactions could lead to overdose and the effect of warfarin. The need for vitamin K comes in in at this point. Vitamin K is very essential when it comes to the need for quick reversal of warfarin (Crowther, 2002). In this case, it has to be done with fresh frozen plasma or complex concentrate of prothrombin alongside intravenous vitamin K. For this study, vitamin K would be used to reverse warfarin instead of relying on blood products (Holbrook et al., 2005). 2.0 Method An open label study will be used, in which, both the participants and researchers will know the treatment being administered. The design will be very useful in this case whereby two treatments are being compared to determine the most effective. The clinical trial will be uncontrolled whereby all the participants will receive the same treatment. The open label study will make use of a multiple dose design for the interaction of drugs (as a single dose study will not reflect on the clinical settings in drug-drug interactions) in which 12 healthy individuals will participate. All participants will be given a dose of warfarin in various volumes including 2mg, 3mg or 10mg. The dose of warfarin administered will be adjusted to reach a stable International Normalized Ratio (INR) levels of between 2 and 3. Warfarin doses will be administered for 4 weeks until a steady state is reached and INR level stabilized. In the study, only subjects depicting the stable INR levels will receive a single dose of warfarin. From a clinical perspective, about 10% of patients require 1.5 mg for adjusting INR levels between 2 and 3 along with a 100mg of JP, which is the maximum tolerated dose and effective. JP is known to have a half-life of 23 hours, which in this study, will take it 5 days to reach a steady state. The two drugs will be administered for 2 weeks to measure the kinetics of this drug-drug interaction study. Two blood samples will be taken daily to measure the INR levels and analyzed. Taking the two blood samples will also be used for the determining the pharmacokinetic data. A dose of vitamin K may be given once a week to all subjects in case of fluctuating of INR levels and to avoid bleedings. 2.1 Sampling Schedule and Subject Selection The 12 subjects will include only the 18 to 50 years old healthy individuals selected keenly using a specified inclusion and exclusion criteria. The study findings will indicate which regimen is effective and will measure the drug interaction by utilizing the drug samples. In this regard, 8 blood samples will be obtained at 1, 2, 3, 4, 5, 6, 12, and 24 hours respectively. This will be done subsequent to every dose of JP234 administrations in order analyze for pharmacokinetics as well as blood samples to be taken for INR. Each of these will consist of 5ml making a total of 50ml, which should not exceed 0.5L within 9 days. Essentially, the participant selected will volunteer and give their consent to be used as study subjects. 2.2 Eligibility Participants selected will be between eighteen and fifty years of age. Both genders will be eligible for the study and volunteers who give their consent to the study will be selected. All the participants need to be healthy to take part in the study. 2.3 Inclusion criteria In this study, only healthy volunteers will be considered as the study participants. Patients may not be used for the study because they may develop complications associated with their previous health conditions, which will not be effective in determining the kinetics of the drug interactions. Besides, patients may not be in a position to understand whether they are getting a treatment or the experimental drugs. Thus, only healthy individuals, both female and male, who have to be nonsmoking subjects with body mass index of 18.0 to 32.0 kg/m2 and of age 18 to 50 years will be included in the study. Volunteers with hematocrit levels of around 36% and above will be selected. Hematocrit level of below 36% is of risk to the healthy volunteer as a result of the action of warfarin in cases of overdose. 2.4 Exclusive criteria Individuals with any chronic or acute medical condition will be excluded from the study. Patients with a history of palpitations will be excluded from the study and those with cardiac diseases of clinical relevance. Participants with less than 18 years will be excluded from the study as well as those of the age above 50 years. The excluded, especially the elderly individuals, are more pronounced to risks due to the health instability. Young people of the age below 18 years on the other hand cannot give their personal consent due to their legal age. Patients with thromboembolic disorders will also be excluded from the study. Again, subjects who lack vitamin K epoxide reductase (VKOR1) enzyme will be excluded. The reason for this is that the activities of vitamin K reductase are highly associated with plasma concentration effect and that the warfarin inhibition of vitamin K reductase is irreversible (Fasco & Principe, 1982). Therefore, only normal volunteers are recommended. Carrying out the study design in patients who require the cardiovascular drugs would be risky since their clinical conditions would not allow it. Besides, there will be no meaningful reason for suspecting that atrial fibrillation would affect the drugs metabolism. 2.5 Dose and schedule of JP234 The drug is considered effective in the doses of 50, 75 and 100mg it is offered once in a day. It has a half life of 24 hours and is administered orally. The antiarrhythmic drug is administered once in a day (Harkness, 1984). The maximum dosage that can be taken is 100 mgs in a day. 2.6 Dose of warfarin schedule The control group will utilize 1.5 mg of warfarin while the other participants will be given JP234 and warfarin. Information and reactions should be taken before, during, and after the treatment. The dosage of warfarin will depend on INR values and the amount of vitamin K in the diets taken by the participants. The warfarin maintenance dose can actually fluctuate with respect to vitamin K amounts, usually in diets. The participants will be advised to maintain a stable level of vitamin K1. Vitamin K in this regard will be useful in controlling the fluctuation of INR levels as well as avoiding bleeding (Whitlon, Sadowski & Suttie, 1978). INR is one of the three key measures of coagulation extrinsic pathway. The other measure is the prothrombin time (PT), which is a derived measure of the prothrombin ratio (PR). The INR values are determined using the ProTime INR and it will be used to determine the clotting aspect of the blood sample obtained each day. Since measuring the INR level constitutes the end point of the study, the test will be the final task initiated in order to obtain the final study results. The status of vitamin K will be also analyzed at this point as an aspect of the drugs interactions. Overdosing and under dosing will have to be avoided because overdosing causes bleeding while under dosing results to thrombus formation (Serlin & Breckenridge, 2009). The maximum dose to be taken will be 100mgs in a day. In the study, warfarin 1.5 mg will be administered from day 7 to day 14 2.7 Procedure All the 12 subjects will receive a warfarin dose of 2mg, 3mg or 10mg that has to adjust to reach a stable INR levels of between 2 and 3. Warfarin drug will be dosed for 4 weeks to reach a steady state and attain a stabilized INR level. Only subjects with the stable INR levels will receive a single dose of warfarin, along with a 100mg of JP234. The two drugs will be given for 2 weeks. The kinetics of this drug-to-drug interaction study will then be determined. To go about this determination, 2 blood samples will be taken daily to measure the INR level, which will mark the study end point. Determination of the pharmacokinetic data will then be done. A dose of vitamin K may be given once each week to all the subjects in case of INR level fluctuations. The dose of vitamin K administered will also work the purpose of avoiding bleeding cases. 2.8 Investigations Investigations will focus on the interaction of the PJ234 drug on the metabolism of warfarin and the blood sample collected. Plasma concentrations of both warfarin and JP234 will be collected among the subjects and recorded for analysis of PK parameters, mainly Cmax, AUC and Tmax. Liver functional tests can also be performed to measure to measure the activities with regards to metabolism of both drugs among the subjects. This could be done as a way of monitoring liver function for safety. The main target will be INR, whose levels will be used to monitor the safety of warfarin as it is being administered with JP234 (Serlin & Breckenridge, 2009). The peak plasma concentration of both drugs will be calculated in both groups to identify any interaction among the drugs encountered during absorption. Tmax will represent the maximum concentration of the drug in blood plasma while Cmax will measure the concentration after intake at steady state (Serlin & Breckenridge, 2009). 2.9 Pharmacokinetic and pharmacodynamic parameters All pharmacological studies will be based on plasma concentration. The maximum plasma concentration will be determined by calculating the area under the concentration time curve. A curve of metabolism between both drugs will be drawn and used to calculate the concentration. Tmax is the time representing the maximum concentration of the drugs in plasma while Cmax will measure the concentration following the drug intake at steady state. Collection of other physical parameters and adverse events will be done assess the safety. The values will be measured from blood sample collected. The blood sample will also be used to monitor the action of both drugs (Harkness, 1984). 3.0 Discussions 3.1 Absorption Both warfarin and JP234 are oral drugs. R- Warfarin is less potent while S- warfarin is more potent and rapidly eliminated. Warfarin is absorbed well in the gut and has a hundred percent bioavailability. The half life of warfarin is 36- 42 hours and its metabolism takes place in the liver same to JP234 (Somberg, 2010). Both drugs will be administered orally and plasma concentration at steady state taken. The results will help determine any interaction that will influence the absorption of the drug. 3.2 Metabolism Warfarin is often administered as a mixture of both R- and S–warfarin. The enantiomers are metabolized by different CYP enzymes. S- Warfarin metabolism is mainly done by CYP2C9 enzyme with CYP2C18, CYP2C19, CYP2C8 and CYP3A4/5 considered as minor pathway in the metabolism process. CYP2C9 is an essential cytochrome P450 enzyme that has a key role in oxidizing endogenous and xenobiotic compounts. It makes around 18 per cent of the liver microsomes’ cytochrome P450 (Rettie & Jones, 2005). Regarding its pharmacogenomics, genetics polymorphosis is known to exist for the expression of CYP2C9 since CYP2C9 gene is very polymorphic. Over fifty single nucleotide polymorphisms (SNPs) are described within the regulaltory as well as the CYP2C9 gene’s codding regions. Some of these SNPs are attributed to reduced enzyme activiteis as compared to type in vitro (Sim, 2011). Various in vivo studies also depict that a number of CYP2C9 genotype mutants are responsible for the reduction of the in metabolism as well as the daily required doses of a given substrate of CYP2C9. Further, CYP2C9 has been found to metabolizes over 100 therapeutic drugs including warfarin (Sim, 2011). Both R- and S-warfarin enantiomers inhibit the functioning of vitamin K through an unambiguous mechanism. S-warfarin is between 2 and 5 times more active than R-warfarin (Fasco & Principe, 1982). The warfarin inhibition of vitamin K epoxide and vitamin K reductases is typically irreversible. S-warfarin has been found to inhibit the two reductases in vivo, but this does not happen on vitro (Fasco & Principe, 1982). The effect on S- warfarin metabolism may result in variability in the dosage requirement of the drug. The mode of action warfarin is based on its impact on the vitamin K synthesis. Interactions of JP234 on warfarin will the Vitamin K action since JP234 induces CYP2C9 enzyme that has a high S-warfarin metabolic efficiency thereby impacting on the metabolism of warfarin especially the S-enantiomers type. Vitamin K is also important in controlling the level of INR, which in turn determines maximum warfarin daily dose. The drug interaction taste can be determined based on Km Values. The bioavailability and plasma concentration of both warfarin and JP234 will also be considered (Serlin & Breckenridge, 2009). With respect to pharmacogenomics, genotyping for polymorphism within the CYP2C9 enzyme or the VKORC1 enzyme according to Maddison et al (2012) and Muskat et al. (2007) will not be used for predicting individual dosage of warfarin nor will it allow the predictions of INR. Nevertheless, the same aspect could be critical for further understanding of warfarin. In this regard, it is unworthy to initiate the screening of volunteers before the study enrollment. Warfarin by itself is a racemic mixture of the R and S enantiomers. In this case, analyses of population have depicted that warfarin’s biological effect that is clinically significant was mainly due to the S enantiomer. The R enantiomer was found to give insignificant contributions (Hamberg et al., 2007). S-warfarin is seen to be 3 to 5 times more potent at inhibiting the VKORC1 complex than the R enantiomer (Choonara et al., 1986). Due to the complexity of the enantiomers, the changes in the warfarin INR values arising from JP234 is likely to result from the S enantiomer. Nevertheless, this assertion requires further analysis. The S enantiomer is typically metabolized by the CYP2C9 enzyme, but the R enantiomer is specifically metabolized by the CYP3A4 enzyme and the CYP2C19 enzyme among other enzymes (Naganuma et al., 2001). Generally, in-vitro metabolic studies will be done only to establish whether JP234 is an inhibitor or a substrate of the enzymes involved in the metabolism of warfarin. Conversely, only live animal studies can be used to detect if JP234 is actually an enzyme inducer. Given a situation whereby CYP2C9 is inhibited by JP234 antiarrhythmic, much care need to be taken regarding the drug-drug interactions. This is necessary especially given that warfarin is a low therapeutic index drug (Van Booven et al., 2010). If the metabolism of warfarin is inhibited, there will be a decrease in the prevailing total body clearance. If CYP2C9 is induced by CYP2C9, this could result to twice the clearance of the S-warfarin and in turn lead to the loss of the associated coagulation actions (Rang and Dale, 2007). Analysis of whether JP234 is a substrate, an inducer, or an inhibitor of the CYP enzymes that are involved in the metabolism of warfarin is therefore essential with regard to the understanding of the drug-drug interactions. Pre-clinical animal data with toxicokinetic included can provide adequate data for leading the path for meaningful drug-drug interaction studies. The pharmacokinetics studies are however done on humans in vivo to prevent issues associated with extrapolating data. In vitro studies need to use human hepatocytes. 3.3 Elimination Terminal half-life of warfarin after a single dose is usually one week while the half life of JP234 is twenty fur hours (Langier et al, 2009). The effective warfarin half-life range is however 20-60 hours with an average of 40 hours. S-warfarin clearance is twice compared to R- warfarin. The half –life of S-warfarin is shorter than that of R-warfarin. Most of the oral warfarin drugs is recovered in Urine with less eliminated unchanged (Serlin & Breckenridge, 2009). Both JP234 and warfarin are metabolized in the liver and excreted in urine. The study will be able to identify the effect of drug interaction on elimination of warfarin. 3.4 Distribution Warfarin distribution phase occurs within 6- 12 hours with 0.14L/kg as an appropriate volume of distribution. The drug will be administered orally in the study. In vitro and in vivo studies have indicated that warfarin binds to blood plasma proteins. Small fraction of it is however unbound and non available for therapeutic use (Serlin & Breckenridge, 2009). The narrow therapeutic window of warfarin and its ability to cause bleeding if overdosed and thrombus if under dozed calls for regular monitoring. 3.5 International normalized ration (IRN) Usually, the results for a PT that is performed on normal individuals vary in accordance with the employed type of analytical system. In this study, INR will be employed to standardize the study results. An international Sensitivity Index (ISI) is expected to be assigned on each of the drug samples to be used. The ISI mainly ranges between 1 and 2 and indicates the way a given batch of tissue factors is comparable to the international reference tissue factors. INR on the other hand refers to the ratio of prothrombin time of a patient to a control/normal sample, usually raised to the ISI value power, for the used analytical system (Fritsma, 2000). Thus: Effective use of warfarin can be able to control coagulation problems experienced by patient with arterial fibrillation. Warfarin treatment can be effectively monitored by checking the IRN levels. International normalized ration (IRN) testing plays an important role in warfarin treatment. IRN help in prevention of warfarin overdose and underdose. IRN result in addition to result interpretation can help manage the patient on the drug. Warfarin IRN normal range is between 2.0 to 3.0. Above 3.0 bleeding may occur while less than 2.0 thromboembolic state occurs. Patient taking warfarin should be tested regularly for IRN levels (Serlin & Breckenridge, 2009). Participants will be informed of the warning signs of bleeding or thrombus formation and should be able to report it to the medical practitioners in charge. The target of warfarin is 2.5 with a target range of between 2.0 TO 3.0. Utilization of warfarin in the treatment of arterial fibrillation should be conducted for indefinite period of time. Dosing calendars are of essence in the stipulated treatment. The participant should adhere to treatment regimen and avoid alcohol intake during the study period (Vann, 2011). The IRN level can be monitored to help identify any influence of JP234 on warfarin since IRN can be affected by drug interaction. When the IRN value is above 5, warfarin administration should be stopped and should be restarted when the level goes below five. 3.6 Collection of blood sample Blood sample can be collected from the participants to test for plasma and blood level after administration (Hayakawa, 2011). The peak plasma levels can also be identified, measured, and recorded. The collection of the samples and tests will be conducted by trained practitioners. Both in vitro and in vivo studies will be conducted after administration of the drug and warfarin. Liver enzyme test will be conducted and the drug interaction between the two drugs identified and recorded. A blood sample will measure the half life of the drugs at a given time. Blood test is considered to be an accurate way of determining whether the person has been intoxicated. Such tests are to be conducted by qualified personnel (Hay, 2009). The blood sample collected from the participants will be utilizing in confirming the half life of the new drug. Identifying the drug interaction is essential approach toward determining the safety of the drug. 3.7 Washout period The participants taking part in the study will be followed for twenty days. The half life of JP234 is twenty four hours while that one of warfarin has an average of fourty hours. The drugs will be administered in the first fourteen days with the rest six days utilized as washout period. Washout period is 5 times the half-life of the drug. Various tests including the INR will be conducted after the washout period to ensure the participants are safe. Fig. 1: The study design 4.0 Conclusion Warfarin has been known to interact with various drugs that are commonly used. Its metabolism varies significantly between patients, which is likely to happen between participants in the case of the proposed study. Other than metabolic interactions, warfarin can be displaced serum albumin by bound drugs that are highly protein. This can lead to an INR increase making it difficult to find the correct dosage thereby accentuating the need for close monitoring when medications known to interact with warfarin are being initiated. In this regard, checks on INR are enhanced or the doses could be adjusted up to a point where an idea dosage is obtained. The need for significant amounts of vitamin K has been specified as an effective way of reducing any adverse effects of warfarin instead of relying on blood products for any needed reversals (Crowther, 2002). Several other mechanisms can be utilized for the same effect such adjustments in the rate of clotting factors breakdown as well as changes in warfarin metabolism. Through the induction of the CYP2C9 enzyme by JP234 as the new drug, the INR levels may decrease thereby making patients become more prone to creating clots as well as thrombus. Warfarin affect vitamin K synthesis mainly by inhibiting the 279 and 10 clotting factors (Aiste Baltramaityte and David Anderton Derby Hospitals NHS Foundation Trust, n.d.). This study has been considered as being highly useful in determining the feasibility of the proposed drug, by considering its interaction with warfarin. In this regard, the study findings will provide a clear ground after investigating the drug interactions between JP234 and warfarin by considering the effect of JP234 on the metabolism of warfarin. The result obtained will help determined the effectiveness and pharmacokinetics of the proposed drugs when administered alongside the warfarin drug (Harkness, 1984). The tests targeting the participant will help identify the safety of the drug when it is administered together with anticoagulant drugs such as warfarin. Patients with abnormal electrical conductivity of the heart often suffer from thromboembolic event, hence the need to utilize both the anticoagulant and antiarrhythmic drug in the management of the condition. Drug interactions can worsen the possible side effects and the health providers are requested to monitor the heart activity after such drugs have been administered especially with others. Therefore, the actual study will provide a medical insight into which of the two regimen would be effective by measuring the drug interactions through the utilization of the drug samples. The aspect of JP234 to inhibit the metabolism as well as the ability of CYP2C9 to induce the metabolism will be fully considered and analyzed for effective medical decisions. 5.0 Bibliography Aiste Baltramaityte and David Anderton Derby Hospitals NHS Foundation Trust, n.d. WARFARIN DRUG INTERACTIONS. Crowther MA, Douketis JD, Schnurr T, Steidl L, Mera V, Ultori C, Venco A, Ageno W., 2002. Oral vitamin K lowers the international normalized ratio more rapidly than subcutaneous vitamin K in the treatment of warfarin-associated coagulopathy. A randomized, controlled trial. Ann. Intern. Med. 137 (4): 251–4. Doering, W., Maass, L., Irmisch, R., & Konig, E. 1987. Pharmacokinetic interaction study with ramipril and digoxin in healthy volunteers. The American journal of cardiology, 59(10), D60-D64. Fasco, M. J. & Principe, L. M., 1982. R- and S-Warfarin Inhibitiono f Vitamin K and Vitamin K 2,3-Epoxide Reductase Activities in the Rat*. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 257(9), pp. 4894-4901. Fritsma, George A., 2002. Evaluation of Hemostasis. Hematology: Clinical Principles and Applications. Ed. Bernadette Rodak. W.B. Saunders Company: Philadelphia, 2002. 719- 53. Goodman, S. 2005. Ethics and evidence in clinical trials. Clinical Trials, 195-196. Harkness, R. 1984. Drug interactions handbook. Englewood Cliffs, N.J.: Prentice-Hall. Hay, G. 2009. Drug interactions with warfarin. Reactions, 11-12. Hayakawa, K. 2011. Evaluation of drug effect of antiarrhythmic agents. a. Guideline of evaluation of effect of antiarrhythmic agents. Rinsho Yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics, 413-414. Holbrook AM, Pereira JA, Labiris R, McDonald H, Douketis JD, Crowther M, Wells PS., 2005. Systematic overview of warfarin and its drug and food interactions. Arch. Intern. Med. 165 (10): 1095–106. Jolobe, O. 2006. A perspective on antiarrhythmic drug therapy. American Heart Journal, E17-E17. Karl, J. 1996. The antiarrhythmic treatment of atrial fibrillation. Drug and Therapeutics Bulletin, 41-45. Kim, S.-Y.et al., 2012. Metabolism of R- and S-Warfarin by CYP2C19 into Four Hydroxywarfarins. Drug Metab Lett., 6(3), p. 157–164. Langier, G., Marinchak, R., Rials, S., & Kowey, P. 2009. Antiarrhythmic drug interactions. Current Opinion in Cardiology, 26-28. Meunier B, de Visser SP, Shaik S., 2004. Mechanism of oxidation reactions catalyzed by cytochrome p450 enzymes. Chem. Rev. 104 (9): 3947–80. Morselli, P. 1974. Drug interactions. New York: Raven Press. Obach, R. 2010. Drug-drug interactions: An important negative attribute in drugs. Drugs of Today, 301-301. Rettie AE, Jones JP, 2005. Clinical and toxicological relevance of CYP2C9: drug-drug interactions and pharmacogenetics". Annu. Rev. Pharmacol. Toxicol. 45: 477–94. ReisI, A. M. M. & CassianiII, S. H. D. B., 2011. Prevalence of potential drug interactions in patients in an intensive care unit of a university hospital in Brazil. Clinics (Sao Paulo) , 66(1), p. 9–15. Serlin, M., & Breckenridge, A. 2009. Drug Interactions with Warfarin. Drugs, 610-620. Sim, Sarah C., 2011. CYP2C9 allele nomenclature. Cytochrome P450 (CYP) Allele Nomenclature Committee. Simon, R. 2007. New challenges for 21st century clinical trials. Clinical Trials, 167-169. Somberg, J. 2010. Antiarrhythmic Drug Therapy. Cardiology, 329-348. Stockley, I. 1999. Drug interactions: A source book of adverse interactions, their mechanisms, clinical importance and management (5th ed.). London: Pharmaceutical Press. Vann, A. 2011. Clinical trials ... A caregivers recommendations. Clinical Trials, 679-679. Verma, K. 2010. Base of a Research: Good Clinical Practice in Clinical Trials. Journal of Clinical Trials. Whitlon DS, Sadowski JA, Suttie JW 1978. Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition. Biochemistry 17 (8): 1371–7. Read More
Cite this document
  • APA
  • MLA
  • CHICAGO
(Pharmacology - Dose of Warfarin Schedule Case Study, n.d.)
Pharmacology - Dose of Warfarin Schedule Case Study. Retrieved from https://studentshare.org/health-sciences-medicine/1673216-pharmacology-assignment
(Pharmacology - Dose of Warfarin Schedule Case Study)
Pharmacology - Dose of Warfarin Schedule Case Study. https://studentshare.org/health-sciences-medicine/1673216-pharmacology-assignment.
“Pharmacology - Dose of Warfarin Schedule Case Study”, n.d. https://studentshare.org/health-sciences-medicine/1673216-pharmacology-assignment.
  • Cited: 0 times

CHECK THESE SAMPLES OF Pharmacology - Dose of Warfarin Schedule

Pharmacokinetics and Pharmacodynamics of Warfarin

The author of this paper "Pharmacokinetics and Pharmacodynamics of warfarin " aims to analyze the stereoselective metabolism of warfarin, its relations, impact, genotyping and possible chemical interactions with other drugs.... hellip; warfarin is a racemic mixture consisting of equal amounts of R- and S- warfarin, and its metabolism is stereoselective.... R-warfarin is converted mainly to R-6-hydroxywarfarin and some 7-hydroxywarfarin....
4 Pages (1000 words) Essay

The investment demand schedule

Investment demand schedule is a decision… Interest rates are changeable and cannot be easily forecast.... The economic crisis has played a great role on interest rates needed to make an investment demand schedule.... An investment demand schedule is needed by the government for public expenditures....
4 Pages (1000 words) Essay

Pharmacology and Coumadin dosing

Pharmacists must be very careful in their knowledge of their patient, and not dose too much or too littl.... The concept of pharmacogenomics is based on “therapy with the right drug at the right dose in the right patient” (Mancinelli 84).... One of the most important and most influential fields in biology is pharmacogenomics, which is a recent revolutionary area that integrates the genomic information generated from DNA analysis and the pathophysiology of preventive medicine (Bhagat and Nhachi 9)....
5 Pages (1250 words) Research Paper

The GH Inhibitory Effects

Suppression of hormone is reached pharmacology pharmacology Somatostatin derived from a native a native inhibitory hormone, this of agents represent a physiologically approach in the treatment of GH excess.... Somatostatin derived from a native a native inhibitory hormone, this class of agents represent a physiologically approach in the treatment of GH excess....
2 Pages (500 words) Coursework

The Relationship of Pathophysiology and Pharmacology

Heart failure is a disease characterized by the inability of the heart to pump enough blood in the vascular system leading to hypoperfusion of different organs and systems in the body.... Whenever a person suffers from heart failure, there is a decrease in the cardiac output.... This… Accumulation of blood in the ventricles leads to the accumulation of blood in the atria and the venous channels....
8 Pages (2000 words) Essay

Medications in Work Environment

I should ensure that drugs that appear in single dose are sealed as required without tempering and not to store excess medications from single doses.... Its key principle is the drug clearance which is the elimination of drugs from the body, analogous to the principle of creatinine clearance (Crisp & Taylor, 2009). Pharmacodynamics… It entails both study of physiological effects of drugs as well as the mechanisms of such action incorporating the correlation between the actions and effects within their chemical structures. Should not be taken er pregnancy unless the doctor measures Prothrombin frequently, ask if patient is under other drugs for treatment of TB, prevent blood clots, supplements containing vitamin K and antidepressant Binding to insulin receptors on cells in the body by making cells in liver, muscles and fat tissues to raise the uptake of glucose from the bloodstream and reduce the production of glucose by the liver hence controlling the glucose level Hypoglycaemia (common), skin thickening or pitting, redness, swelling at injection site, Excessive fluid retention (oedema), visual challenges and skin reactions such as itching, hives or rash....
8 Pages (2000 words) Assignment

Ethics and Evidence in Clinical Trials

The effect of the new drug on the action of warfarin will be investigated in 20 healthy volunteers.... mg of warfarin from day 3 to 10 and then 50mgs once a day from day 7 to 14.... The result of the finding will be utilized in identifying the action of the new drug on the metabolism of warfarin.... The study aims at finding out the effect of JP234 on the action of warfarin.... The study “Ethics and Evidence in Clinical Trials” aims at investigating possible interactions between the new drug (JP234) and warfarin when they are administered in the treatment of patients with arterial fibrillation....
10 Pages (2500 words) Assignment

Traditional Salary Schedules versus Diversified Salary Schedules

hellip; The traditional salary scheme has been marred by a number of inefficient with regard to the ramification in the current situation in the education sector thus it needs to be revamped or rather be replaced with the diversified salary schedule technique since it tends to address the pertinent issues more robustly that the former....
8 Pages (2000 words) Essay
sponsored ads
We use cookies to create the best experience for you. Keep on browsing if you are OK with that, or find out how to manage cookies.
Contact Us