Case warfarin

Fig. 3.4 Permeability profiles for (a) warfarin (acid), (b) propranolol (base) and (c) morphine (ampholyte) based on a BBB PAMPA model (plON) composed of animal brain extract of lipids. The data (unpublished) were analyzed with the pCEL-X program (plON), with the refined parameters indicated in the three frames. In all three cases, there was evidence for the permeation of charged...

Azathioprine, mycophenolate mofetil, and enteric-coated MPA are not metabolized through the CYP isozyme system therefore, they do not experience the same DDI profiles as cyclosporine, tacrolimus, and sirolimus. Azathioprine s major DDIs involve allopurinol, angiotensin-converting enzyme (ACE) inhibitors, aminosalicylates (e.g., mesalamine and sulfasalazine), and warfarin.11 The interaction with allopurinol is seen frequently and has clinical significance. Allopurinol inhibits xanthine oxidase, the enzyme responsible for metabolizing azathioprine. Combination of azathioprine and allopurinol has resulted in severe toxicities, particularly myelosuppression. It is recommended that concomitant therapy with azathioprine and allopurinol be avoided, but if combination therapy is necessary, the azathioprine doses must be reduced to one-third or one-fourth of the current dose. Use of azathioprine with the ACE inhibitors or aminosalicylates also can result in enhanced myelosuppression.11 Some case reports exist demonstrating that warfarin s therapeutic effects may be decreased by azathioprine.43-45... 

In the case of thrombosis-related SVCS, anticoagulation is controversial because there is a lack of survival benefit. However, thrombolytics (e.g., alteplase) and anti coagulation with heparin and warfarin may be beneficial in patients with thrombosis owing to indwelling catheters if it is used within 7 days of onset of symptoms, although catheter removal maybe required. 

Good manufacturing practices (GMPs) ensure that products meet specific quality standards, are not adulterated or misbranded, and contain the correct ingredients and doses stated on the label. GMPs specifically for dietary supplements are being proposed from the FDA. Cases of adulteration have been reported to the FDA, and examples include a plantain product adulterated with digitalis and hibiscus tea adulterated with warfarin [29]. 

Two case reports describe symptoms such as insomnia, headache, tremulousness, irritability, and visual hallucinations when taking phenelzine concurrently with ginseng [43,44]. Reduction of the international normalized ratio (INR) may be observed when ginseng and warfarin are taken together [45]. 

Aldehydes and ketones are readily reduced back to primary and secondary alcohols, respectively. In the case of ketones, although the reduction is reversible, ketoreductase utilizes NADPH, the concentration of which is higher than NADP+, and this drives the reaction toward the secondary alcohol. A good example is warfarin as shown in Figure 5.3 (19). However, aldehydes are further oxidized to carboxylic acids and carboxylic acids are not reduced back to aldehydes thus eliminating the aldehyde. Reductive metabolism of esters and amides also does not generally occur. 

Pharmacokinetic interactions Preliminary evidence suggests that Saint-John s-wort induces the cytochrome oxidase enzyme isoform CYP3A4 (Ernst 1999). This raises the potential for pharmacokinetic interactions with drugs metabolized by the same enzyme. A few cases have been reported of reduced warfarin levels (Yue et al. 2000). Similar interactions have also been reported for concurrent use with digoxin, theophylline, and cyclosporin (Nebel et al. 1999 Ruschitzka et al. 2000 Johne et al. 1999). As with any other medication, potential interactions should be considered when taking a combination of drugs. 

Very rapidly, a number of other anticoagulants, including the indanediones (4), (Structure 2), were developed as rodenticides. Warfarin first came into wide usage as a rodenticide in 1950 and virtually supplanted all other materials then in use. In the case of all these early materials, multiple bait applications were needed to control rodent populations which, while making the materials safer to use than the available acute poisons, curtailed their use in underdeveloped and less affluent countries because of the large quantities of bait that must be placed to destroy the populations of rodents. 

Treatment for warfarin poisoning includes vitamin K administration and, in severe cases, transfusions of whole blood... 

WARNING Cases of fulminant liver failure resulting in death have occurred Uses Adjunct to carbidopa/levodopa in Parkinson Dz Action COMT inhibitor slows levodopa metabolism Dose 100 mg PO tid w/ 1st daily levodopa/carbidopa dose, then dose 6 12 h later -1- w/ renal impair Caution [C, ] Contra Hqjatic impair, w/ nonselective MAOI Disp Tabs SE Constipation, XCTOstomia, vivid dreams, hallucinations, anorexia, N/D, orthostasis, liver failure, Rhabdomyolysis Interactions T Effects OF CNS dqjressants, SSRIs, TCAs, warfarin, EtOH t risk of hypotensive crisis W/ nonselective MAOIs (phenelzine, tranylc5 promine) EMS Has been associated w/ liver failure and death may experience hallucinations concurrent EtOH use can T CNS dqjression T effects of warfarin severe D is common sevoal wks afto starting OD May cause NA and dizziness... 

Case Study How Long Until My Warfarin Dose Stabilizes ... 

Zafirlukast and montelukast are well tolerated. Zafirlukast increases plasma concentrations of warfarin and decreases the concentrations of theophylline and erythromycin. In rare cases, treatment of patients with CysLT receptor antagonists is associated with the development of Churg-Strauss syndrome, a condition marked by acute vasculitis, eosinophilia, and a worsening of pulmonary symptoms. Because these symptoms often appear when patients are given the leukotriene receptor antagonists when they are being weaned from oral corticosteroid therapy, it is not clear whether they are related to the action of the antagonists or are due to a sudden reduction in corticosteroid therapy. 

Warfarin with reduced effects of phenprocoumonf and warfarin lethargy and grogginess were reported in a patient taking St. lohn s wort and paroxetinef, and the serotonin syndrome has been reported in users of nefazodonef or sertraline (case reports) St. John s wort alone has been associated with serotonin syndrome-like events (case reports). 

Warfarin A brief case report described an increased clotting time in two patients taking warfarin and garlic garlic alone has also been associated with bleeding (case reports). 

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