Drugs
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Dexrazoxane has been used successfully to reduce cardiac toxicity in patients receiving anthracycline-based chemotherapy for cancer (predominantly women with advanced breast cancer). The drug is thought to reduce the cardiotoxic effects of anthracyclines by binding to free and bound iron, thereby reducing the formation of anthracycline-iron complexes and the subsequent generation of reactive oxygen species which are toxic to surrounding cardiac tissue. Clinical trials in women with advanced breast cancer have found that patients given dexrazoxane (about 30 minutes prior to anthracycline therapy; dexrazoxane to doxorubicin dosage ratio 20:1 or 10:1) have a significantly lower overall incidence of cardiac events than placebo recipients (14 or 15% vs 31%) when the drug is initiated at the same time as doxorubicin. Cardiac events included congestive heart failure (CHF), a significant reduction in left ventricular ejection fraction and/or a > or = 2-point increase in the Billingham biopsy score. These results are supported by the findings of studies which used control groups (patients who received only chemotherapy) for comparison. The drug appears to offer cardiac protection irrespective of pre-existing cardiac risk factors. In addition, cardiac protection has been shown in patients given the drug after receiving a cumulative doxorubicin dose > or = 300 mg/m2. It remains to be confirmed that dexrazoxane does not affect the antitumour activity of doxorubicin: although most studies found that clinical end-points (including tumour response rates, time to disease progression and survival duration) did not differ significantly between treatment groups, the largest study did show a significant reduction in response rates in dexrazoxane versus placebo recipients. Dexrazoxane permits the administration of doxorubicin beyond standard cumulative doses; however, it is unclear whether this will translate into prolonged survival. Preliminary results (from small nonblind studies) indicate that dexrazoxane reduces cardiac toxicity in children and adolescents receiving anthracycline-based therapy for a range of malignancies. The long term benefits with regard to prevention of late-onset cardiac toxicity remain unclear. With the exception of severe leucopenia [Eastern Cooperative Oncology Group (ECOG) grade 3/4 toxicity], the incidence of haematological and nonhaematological adverse events appears similar in patients given dexrazoxane to that in placebo recipients undergoing anthracycline-based chemotherapy. Although preliminary pharmacoeconomic analyses have shown dexrazoxane to be a cost-effective agent in women with advanced breast cancer, they require confirmation. ⋯ Dexrazoxane is a valuable drug for protecting against cardiac toxicity in patients receiving anthracycline-based chemotherapy. Whether it offers protection against late-onset cardiac toxicity in patients who received anthracycline-based chemotherapy in childhood or adolescence remains to be determined. Further clinical experience is required to confirm that it does not adversely affect clinical outcome, that it is a cost-effective option, and to determine the optimal treatment regimen.
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Levobupivacaine is an enantiomer of the long-acting local anaesthetic bupivacaine, which, although currently the most widely used agent in surgery and obstetrics, is associated with potentially fatal cardiotoxicity. Levobupivacaine 75 to 122 mg was less arrhythmogenic than the same dose range of bupivacaine in healthy volunteers. Its effects on the corrected QT interval were significantly weaker than those of bupivacaine, and it tended to have a weaker effect on QRS duration. ⋯ Levobupivacaine 0.25% was as effective as bupivacaine 0.25% in women requiring epidural anaesthesia during labour with respect to time to onset of pain relief, overall quality of analgesia, extent of sensory blockade and number of patients reporting motor block. Levobupivacaine is as well tolerated as bupivacaine. In a clinical study involving 88 patients who received either drug, intraoperative hypotension was the most commonly reported adverse event with levobupivacaine and no serious arrhythmias occurred.
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Ankylosing spondylitis (AS) is a systemic inflammatory rheumatic disease involving spinal and sacroiliac joints. This condition is responsible for back pain, stiffness and discomfort. Several drugs are currently available in the management of AS, and may be divided into 3 groups. ⋯ Some specific clinical features are observed in AS: enthesopathy may be treated with local injection of corticosteroids; sacroiliac joint pain may be managed by corticosteroid injection performed under fluoroscopic control or guided by computed tomography. The management of patients with AS includes some other procedures such as patient education, rest, a programme of physical exercise and physiotherapy. In parallel with pharmacotherapy, these procedures are of great importance in reducing stiffness and spinal ankylosis, and thus improve the patient's quality of life.
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Review
Current drug treatment options in neonatal hyperbilirubinaemia and the prevention of kernicterus.
Neonatal jaundice is a frequent problem in neonatology, but the advent of phototherapy which has simplified its treatment, it no longer represents a major concern. Early hospital discharge of neonates has now resulted in a re-emergence of kernicterus. Neonatal jaundice is principally the result of a transient deficiency of bilirubin conjugation, of a partial deficiency of hepatic bilirubin uptake and intracellular transport and of an increased enterohepatic circulation of the pigment. ⋯ In preterm infants the typical clinical feature of kernicterus is seen very rarely, and kernicterus is now a very infrequent postmortem observation. Since it is very difficult to distinguish the effects of bilirubin from other potentially toxic factors, it is difficult to give guidelines for the treatment of jaundice in very low birthweight infants other than to keep the serum bilirubin levels to a lower level than in full term infant (e.g. 10 mg/dl lower than in full term babies). The intramuscular administration of a single dose of Sn-mesoporphyrin (6 mumol/kg bodyweight) in healthy term or near-term infants seems to be a promising treatment modality for controlling hyperbilirubinaemia.
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Several modes of reperfusion therapy for evolving myocardial infarction (MI) have been developed, which differ in terms of effectiveness, complexity and costs. Reperfusion resources are often restricted by budgetary or logistical circumstances. To arrive at an equitable distribution of treatment options, physicians should therefore consider which treatment to apply in which patient. ⋯ This 're-gain of lost years' is judged to be the ultimate treatment effect in an individual patient. An equitable treatment allocation should be such that patients who will benefit most will receive the most effective therapy, while patients with similar expected benefit will be offered the same mode of therapy. The conclusion is that treatment guidelines or protocols can be very useful in clinical practice, especially if rapid decision making is of vital importance.