Principles and practice of infectious diseases, 3rd ed. Churchill Livingston, New York, 1990 Halsted Cc. Rapid tests for group A streptococcus: unsettled issued. Infectious Diseases Newsletter 5: 83-84, 1986 Idsoe 0 , Guthe T, Wilcox RR, et al. Nature and extent of penicillin side reactions with particular reference to fatalities from anaphylactic shock. Bulletin of the World Health Organization 38: 159-188, 1968 Kaplan EL. The rapid identification of group A beta-hemolytic streptococci in the upper respiratory tract: current status. New
Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) advocated for use in painful and inflammatory rheumatic and certain nonrheumatic conditions. It may be administered orally or rectally using a convenient once or twice daily regimen. Dosage adjustments are not usually required in the elderly or those with mild renal or hepatic impairment although it is probably prudent to start treatment at a low dosage and titrate upwards in such groups of patients. Numerous clinical trials have confirmed that the analgesic and anti-inflammatory efficacy of naproxen is equivalent to that of the many newer and established NSAIDs with which it has been compared. The drug is effective in many rheumatic diseases such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and nonarticular rheumatism, in acute traumatic injury, and in the treatment of and prophylaxis against acute pain such as migraine, tension headache, postoperative pain, postpartum pain and pain associated with a variety of gynaecological procedures. Naproxen is also effective in treating the pain and associated symptoms of primary or secondary dysmenorrhoea, and decreases excessive blood loss in patients with menorrhagia. The adverse effect profile of naproxen is well established, particularly compared with that of many newer NSAIDs, and the drug is well tolerated. Thus, the efficacy and tolerability of naproxen have been clearly established over many years of clinical use, and it can therefore be considered as a first-line treatment for rheumatic diseases and various pain states.
Since their synthesis in the late l800s paracetamol (acetaminophen) and phenacetin have followed divergent pathways with regard to their popularity as mild analgesic/antipyretic drugs. Initially, paracetamol was discarded in favour of phenacetin because the latter drug was supposedly less toxic. Today the opposite is true. and paracetamol. along with aspirin. has become one of the two most popular 'over-the-counter' non-narcotic analgesic agents. This marked increase in the wide approval attained by paracetamol has been accompanied by the virtual commercial demise of phenacetin because of its role, albeit somewhat circumstantial. in causing analgesic nephropathy.Both paracetamol and phenacetin are effective mild analgesics, suitable for treating mild to moderate pain. and their actions are broadly comparable with those of aspirin and related salicylates. although they do not appear to possess significant anti-inflammatory activity. Since a major portion of a dose of phenacetin is rapidly metabolised to paracetamol. it seems possible that phenacetin owes some of its therapeutic activity to its main metabolite. paracetamol. whereas its most troublesome side effect (methaemoglobinaemia) is due to another metabolite. p-phenetidine. The mechanism of action of paracetamol is poorly defined. although it has been speculated that it may selectively inhibit prostaglandin production in the central nervous system. which would account for its analgesic/antipyretic properties. The lack of any significant influence on peripheral cyclooxygenase would explain the absence of anti-inflammatory activity.At therapeutic doses paracetamol is well tolerated and produces fewer side effects than aspirin. The most frequently reported adverse effect associated with paracetamol is hepatotoxicity. which occurs after acute overdosage (usually doses greater than 10 to 15g are needed) and. very rarely. during long term treatment with doses at the higher levels of the therapeutic range. Paracetamol damages the liver through the formation of a highly reactive metabolite which is normally inactivated by conjugation with glutathione. Overdoses of par aceta mol exhaust glutathione stores. thus allowing the accumulation of this toxic metabolite which covalently binds with vital cell elements and can result in liver necrosis. Glutathione precursors (notably intravenous N-acetylcysteine) have proved remarkably successful in treating paracetamol overdose, as long as treatment is initiated within 10 hours.Apart from pharmacokinetic drug interactions resulting from changes in gastric emptying rate. there have been very few reports of clinically important drug-drug interactions involving paracetamol or phenacetin.The pre-eminent position of paracetamol and aspirin as the non-narcotic analgesic agents of choice for mild to moderate pain is being seriously challenged by 'newer' nonsteroidal anti-inflammatory drugs. Some of these newer agents have been found to have significantly superior analgesic activity and. in some cases. longer durations of action.
Pentoxifylline (oxpentifylline) is an orally active haemorheological agent for the treatment of peripheral vascular disease, cerebrovascular disease and a number of other conditions involving a defective regional microcirculation. Pentoxifylline acts primarily by increasing red blood cell deformability, by reducing blood viscosity and by decreasing the potential for platelet aggregation and thrombus formation. Extensive open and placebo-controlled studies have shown that pentoxifylline 600 to 1200 mg/day for at least 6 weeks is associated with subjective and objective improvements in 60 to 100% of patients with peripheral vascular disease. The most commonly assessed clinical parameter, walking distance, is usually improved by about 100%, although much greater improvements have also been documented. Other parameters which have been clearly improved include lower limb rest pain, paraesthesia, muscle blood flow, cramps and leg ulcers. Pentoxifylline has produced consistently better results than placebo, and in those studies using comparative drugs, better results than nylidrin, adenosine and naftidrofuryl. In patients with cerebrovascular disorders, open studies with pentoxifylline, usually at a dosage of 600 to 1200 mg/day (300 to 600 mg/day in Japan), have shown marked overall clinical improvements in about 85% of patients. Symptomatic improvements in rehabilitation psychometric tests, neuromotor and speech deficits and other subjective symptoms have accompanied increased cerebral blood flow, particularly to ischaemic areas. Pentoxifylline would appear to be useful in most types of cerebrovascular disease including transient ischaemic attacks, sequelae of cerebral thrombosis and haemorrhage, and chronic ischaemic disorders. In patients with chronic cerebrovascular disease pentoxifylline 600 to 1200 mg/day conferred significant clinical benefit compared with placebo and in isolated studies proved to be superior to drugs such as co-dergocrine mesylate, adenosine and pyrithioxine. Preliminary studies indicate that pentoxifylline may also prove useful in vaso-occlusive crises of sickle cell disease, some hearing disorders, disorders of eye circulation, high altitude sickness and asthenozoospermia. Pentoxifylline is usually well tolerated when administered as the conventional controlled release formulation, gastrointestinal symptoms (about 3%) being the most common complaint, although these and other adverse effects have not occurred to a significantly greater extent than with placebo. Thus, pentoxifylline offers a well-tolerated and effective alternative to the treatment options available for patients with peripheral vascular disease.(ABSTRACT TRUNCATED AT 400 WORDS)
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