Mirjana Huić

Pharmacokinetic Changes in Patients With Oedema

SummaryThe pharmacokinetics of furosemide (frusemide) in patients with oedema have been relatively well studied, but in many studies it is unclear whether the disease or the oedema per se has the major effect. The rate of absorption of oral furosemide in patients with oedema was decreased, but total bioavailability was almost unchanged. The peak serum concentration (Cmax) and time taken to achieve Cmax were either decreased or unchanged. Binding of furosemide to plasma proteins is lower in patients with congestive heart failure (CHF), decompensated liver cirrhosis (DLC) and nephrotic syndrome, probably as a result of hypoalbuminaemia. The elimination half-life (t½) can be unchanged (CHF, DLC) or prolonged (chronic renal failure: CRF). Plasma and renal clearance are reduced in patients with CRF and nephrotic syndrome, but are almost unchanged in CHF and DLC. Disease-induced disorders are mainly responsible for the alterations of furosemide pharmacokinetics in oedematous conditions, while the influence of oedema per se is probably not clinically relevant.The pharmacokinetics of digoxin have been studied in a small number of studies only. In patients with CHF, considerable interindividual differences have been found. Because digoxin has a narrow therapeutic window, this drug should be administered cautiously to oedematous patients.Theophylline has higher bioavailability in patients with oedema, with a significantly higher Cmax in patients with hepatic cirrhosis and CHF than in healthy volunteers (29 and 22%, respectively). Furthermore, clearance decreases and t½ increases in these patients.Angiotensin converting enzyme (ACE) inhibitors are often administered as prodrugs, and their pharmacokinetic profile could be influenced by the diseases that accompany oedematous states. However, the effect of oedema is difficult to discriminate from that of the disease. Individual ACE inhibitors are affected differently, but importantly the dosage of Perindopril should be reduced in patients with CHF, while for most other ACE inhibitors the changes in pharmacokinetic parameters are clinically irrelevant.In conclusion, studies on pharmacokinetic changes in oedema are limited. Besides affecting absorption (after oral administration) and conversion of the prodrug to the active form, probably as a result of the associated disease, oedema has not been proven to cause any clinically relevant changes in pharmacokinetic parameters for individual drugs. However, further studies of this aspect of pharmacokinetics are needed.

Inadequate Use of Preventive Strategies in Patients Receiving NSAIDs

AbstractObjective: Little is known about the factors that influence the decision to use NSAIDs in combination with gastroprotective drugs. The aims of this observational study were to evaluate the extent to which NSAID users are prescribed concomitant gastroprotective drug regimens (‘preventive strategies’), and to determine how patient risk factors for NSAID-associated gastrointestinal toxicity and physician prescribing preferences influenced the decision to prescribe a gastroprotective drug in combination with an NSAID. Design and patients: The study was conducted on 29 June 2004 and comprised 109 eligible adult patients hospitalised at the Clinical Hospital Center, Zagreb. Use of NSAIDs and gastroprotective drugs, risk factors for NSAID-associated gastrointestinal toxicity, and physician prescribing preferences were monitored throughout the study. Results: Sixty-six percent of patients receiving proton pump inhibitors or histamine H2-receptor antagonists with NSAIDs had no risk factors for gastrointestinal toxicity. Furthermore, 29% of patients who used NSAIDs had risk factors for gastrointestinal toxicity but were not receiving gastroprotective drugs. Even though patients at risk of NSAID-associated gastrointestinal complications had higher odds of receiving preventive strategies (odds ratio 1.25), the absolute rate of utilisation of these therapies in at-risk populations was unacceptably low (69%). However, the strongest independent correlation for gastroprotective drug use was the prescribing physician, with an odds ratio of 6.40. Conclusion: This study demonstrates that an individual physician’s prescribing style largely determines the odds of receiving preventive strategies with NSAID treatment and is more important than the patient’s risk factors for gastrointestinal toxicity.

Splenectomy? No, thank you!

Because of an extremely enlarged spleen, splenectomy was considered in a 60-year-old man with a 3-year history of osteomyelofibrosis and slightly depressed blood cell counts. Scintigraphic study with 99mTc-antigranulocyte antibodies (AGAb) was performed with a view to estimating the spread and activity of haematopoietically active bone marrow. Figure part a shows whole-body scans of the patient, without visible haematopoietic activity in the bones, and with prominent extramedullary haematopoiesis in the enlarged spleen. Figure part b shows normal bone marrow distribution in another patient. The accumulation of the AGAb in the spleen and liver is low and very variable: in normal patients 4 h after injection it amounts to about 6% of the injected activity in the spleen and up to 10% in the liver [1]. After the findings documented in a, splenectomy was cancelled. This case demonstrates all the benefits of AGAb. This method allows us to analyse the distribution and function of haematopoietically active bone marrow [2], the spread and activity of infection or inflammation [3] and, in addition, the status of the spleen [4]. References