Thromboembolism is a status which involves the dislodging of a blood coagulum which travels through the blood watercourse to barricade blood vass ( Neil and Randall, 2004 ) . Warfarin belongs to the category of drugs called unwritten decoagulants. It can be used in the intervention and prophylaxis of thromboembolism. The mark international normalised ratio ( INR ) for the intervention of pneumonic intercalation is 2.5 ( British National Formulary, 2010 ) . The INR is declarative of the prothrombin clip.
Warfarin exerts it anticoagulant activity by suppressing the enzyme vitamin K epoxide reductase.
This enzyme catalyses the transition of vitamin K epoxide to a decreased signifier of vitamin K. Warfarin is therefore a vitamin K adversary ( Grahame-Smith and Aronson,2002 ) . They besides suggest that the degree of suppression of vitamin K expoxide reductase enzyme is related to the concentration of Coumadin in the liver.
Harmonizing to ( Wright et al, 2006 ) the action of warfarin brings about a lessening in the hepatic synthesis of vitamin K dependent coagulating factors II, VII, IX and X in a dosage related mode.
This consequences in prolongation of the hemorrhage clip ( prothrombin clip ) and hence restricting the inclination of blood coagulum formation. Warfarin has no direct consequence on antecedently go arounding coagulating factors ( Dipiro et al, 2002 ) . Dollery ( 1999 ) besides explains that the oncoming of action of Coumadin is delayed until there is katabolism of bing coagulating factors.
The pharmacokinetic factor involves changing of the plasma degree of the drug whilst the pharmacodynamic factor is associated with the hazard of shed blooding without a alteration in warfarin plasma degree. Harmonizing to ( Jones, 2008 ) , a alteration in plasma degrees of Coumadin consequence in a alteration in ( INR ) . Jones ( 2008 ) besides explains that a drug that would impact thrombocyte collection will raise the hazard of shed blooding without a alteration in the INR.
Disease states viz. thyrotoxicosis, hypothyroidism, febrility, congestive bosom failure and liver disease can hold an consequence on the pharmacokinetics and pharmacodynamics warfarin. Hypermetabolic events such as thyrotoxicosis and febrility can ensue in addition katabolism of coagulating protein ( Regal and Tsui, 2007 ) . Jones ( 2008 ) besides explains that due to hyperthyroid activity and febrility, there is increase clearance of vitamin K coagulating factors and the sum of Coumadin required for anticoagulation will cut down. ( Stephens et al, 1989 ) states that hypothyroidism brings about a decrease in metamorphosis of curdling factors. These factors stay in circulation for a long clip and this consequence in an addition in the dosage of Coumadin for anticoagulant activity. Hyperthyrodism therefore brings about an addition in wafarin sensitiveness and hypothyroidism is besides associated with a lessening in warfarin sensitiveness.
Liver is the organ that is associated with the production of plasma proteins and coagulating factors ( Fox, 2004 ) . Demirkan et Al ( 2000 ) explains that liver disfunction is associated with an addition response to warfarin. Liver disfunction is besides linked to a reduced production of vitamin K coagulating factors and this history for a drawn-out factor II clip ( Lenham, 2008 ) . Harmonizing to Jones ( 2008 ) defects in the map of thrombocytes and factor I is found in many patients with liver disfunction. This as consequence can take to a higher hazard of bleed in such patients. Warfarin sensitiveness is increased in liver disfunction.
Grahame-Smith and Aronson ( 2002 ) states that hepatic congestion linked to bosom failure brings about an addition to warfarin sensitiveness. Congestive bosom failure reduces the metamorphosis of Coumadin which leads to an addition decoagulant activity and hence a high opportunity of shed blooding ( Jones, 2008 ) .
Jones ( 2008 ) besides suggests that Coumadin is metabolized by several cytochrome p450 ( CYP450 ) iso enzymes and drugs that affect the CYP2C9 enzyme system can hold an consequence on increasing or cut downing the INR. The more powerful signifier of Coumadin ( s-isomer ) is metabolized by CYP2C9 enzyme system ( Jones, 2008 ) . The other signifier the Coumadin ( r-enantiomer ) is metabolised by CYP1A2 and CYP3A4. ( www.medicines.org.uk ) . Drugs can interact with Coumadin through several mechanisms and this include impaired warfarin soaking up, supplanting of Coumadin from plasma protein-binding sites and change in warfarin metamorphosis ( www.parkinsons-information-exchange-network-online.com ) . Grahame-Smith and Aronson ( 2002 ) suggest that certain drugs induce the metamorphosis of Coumadin and this includes drugs like diphenylhydantoin, rifampicin and cabamazepine. Drugs that can suppress warfarin metamorphosis include Cordarone, fluconazole and Erythrocin. The reaction of Coumadin with these drugs demands to be monitored really closely if non avoided.
Drugs that displace warfarin from protein-binding sites, addition Coumadin ‘s anticoagulant consequence. Non steroidal anti-inflammatory drugs ( NSAIDs ) displace Coumadin from its adhering site and besides do stomachic ulceration as they erode the liner of the tummy. ( e.g Phenylbutazone ) . NSAIDs by and large inhibit platelet collection. However, the cyclogenase inhibitors ( cox 2 inhibitors ) have a somewhat different mechanism ( Grahame-Smith and Aronson, 2002 ) . Erythromycin which belongs to a category of drug called the macrolides, inhibits the metamorphosis and reduces the clearance of Coumadin from the organic structure. The activity of Coumadin may besides be lengthened due to alterations in the enteric vegetation and its synthesis of vitamin K for coagulating factor ( www.scoup.net ) . Rifampicin is a powerful inducer of the cytochrome CYP3A4. It increases the riddance of Coumadin and decreases its anticoagulant action ( Dollery, 1999 ) .
Cholestryamine is known to cut down the action of Coumadin by diminishing its soaking up and besides interfering with its enterohepatic recirculation ( Dollery, 1999 ) .
Harmonizing to research workers ( Daugherty and Smith, 2006 ) , anticoagulant consequence of Coumadin can be affected by certain nutrient merchandises. Jones ( 2008 ) besides explains that, nutrients rich in vitamin K tend to hold an consequence on the warfarin action and this include green leafy veggies ( Brassica oleracea italica, Bruxelless sprout, lettuce, spinach e.t.c ) . These nutrient merchandises can take down the prothrombin clip and hence a lessening in the INR. This action will diminish the action of Coumadin and it can ensue in addition incidence of blood coagulums ( www.uptodate.com ) . Harmonizing to some experts, cranberry juice can increase the anticoagulant consequence of Coumadin and this can take to a high hazard hemorrhage. However, a survey conducted revealed that a little part of canberry juice has no consequence on the INR. ( www.uptodate.com ) . Daugherty and Smith ( 2006 ) proposed that the presumed mechanism of action when Coumadin interacts with avocado involves debasement of Coumadin as a consequence of the action of microsomal liver enzymes. Intestinal soaking up of Coumadin is interrupted. Jones ( 2008 ) suggests that a patient on Coumadin demands to hold a balanced diet as major alterations in diet can hold consequence on warfarin action and hence eating high parts of these nutrient merchandises needs to be avoided. However, patients who need to alter their diet demand to seek advice from their physician or pattern nurse. Wright et Al, ( 2006 ) explains that patients should be good informed about the deductions hazards and benefits associated with the usage of Coumadin. Harmonizing to these research workers the xanthous anticoagulant book is good use for monitoring of the patient in footings of entering the INR, the dosing information for the patient, assignment day of the months for clinics and the safe usage of Coumadin.
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