Antirheumatic drugs in pregnancy and lactation.

The natural inclination of patients with rheumatic diseases wishing to become pregnant or to breast feed will be to take as few medications as possible. The guidelines outlined above can be used to balance the risk of drug effect on the fetus or neonate with the risk of inducing a flare in disease activity by stopping the drug. Although there are situations where no information on drug behaviour during pregnancy or lactation exists, some guidelines can be developed from a knowledge of the drug's inherent metabolism. In the majority of the rheumatic diseases, disease activity can be reduced to a minimum using the smallest possible dose of drugs known to be safe in pregnancy and lactation, thus providing minimum risk to mother, fetus and neonate.

The use of antirheumatic medication during pregnancy and in the puerperium.

Patients with rheumatic diseases will want to take as few medications as possible while they are conceiving, pregnant, or breast feeding. The guidelines above can be used to balance the risk of a drug effect on the fetus or neonate with the effect of provoking a flare in disease activity by ceasing the drug. Where no information on drug concentration in pregnancy or lactation exists, guidelines can be developed from knowledge of the drug's inherent metabolism. In most of the rheumatic diseases, disease activity can be reduced to a minimum using the smallest possible dose of drugs with known behaviors in pregnancy and lactation and thus providing minimal risk to mother and fetus.

Comparison of methylprednisolone (1 g i.v.) with prednisolone (1 g orally) in rheumatoid arthritis: a pharmacokinetic and clinical study.

Methylprednisolone pulse therapy is often used in patients with severe rheumatoid arthritis (RA). To compare clinical and pharmacokinetic variables of methylprednisolone and oral prednisolone in patients with RA, a controlled crossover study was carried out. Pharmacokinetic variables for methylprednisolone were Vd of 69.9 l, t1/2 of 2.96 h, total plasma clearance of 17.5 l/h. Pharmacokinetic variables for prednisolone were Vd of 47.5 l, t1/2 of 3.08 h and total plasma clearance of 11.3 l/h. During the elimination phase, a secondary rise in methylprednisolone concentration occurred which may be related to enterohepatic circulation. Clinical response to both prednisolone and methylprednisolone was short-lived with neither lasting more than 6 weeks.

Streptococcus group G septic polyarthritis.

A case of streptococcus group G polyarthritis has been identified from blood and synovial fluid cultures and was sensitive to penicillin G. The clinical tendency to polyarticular infection by this organism and its discordant response to the antibiotics indicated by in vitro studies are discussed.

Antirheumatic medication in pregnancy.

Drug effects on fetal physiology as well as possible teratogenesis need to be considered before prescribing for women of child-bearing age. All nonsteroidal anti-inflammatory drugs (NSAIDs), because of their suppression of prostaglandin synthesis, may prolong gestation and labour. Aspirin is also associated with an increased risk of ante- and post-partum haemorrhage. Indomethacin may be teratogenic in humans and like aspirin may induce pulmonary hypertension in the neonate. To reduce the physiological alterations induced by NSAIDs, short-half-life drugs such as ibuprofen, flurbiprofen or ketoprofen should be used at the maximally tolerable dosage interval. Gold salts and corticosteroids show little human evidence of teratogenicity although the largest possible dosage interval of gold should be used. D-Penicillamine may be teratogenic thus it should not be commenced during pregnancy and if a patient becomes pregnant whilst receiving the drug, it should be slowly withdrawn or the dosage reduced. 4-Aminoquinoline compounds are contra-indicated in pregnancy.

Antirheumatic medication during lactation.

All nonsteroidal anti-inflammatory drugs (NSAIDs) and antirheumatic drugs are likely to be distributed into human milk to some extent; whether they are detected is a function of the assay sensitivity. For minimal infant exposure, the ideal drug for lactating women is one which has a short half-life, is found in minimal quantities in human milk and has inactive metabolites which also are present only in small amounts. In order to reduce the quantity of drug presented to the child, the drug should be taken by the mother at the time of breast-feeding with the next feed occurring after a time period equivalent to one half-life of the drug. Using the above-mentioned criteria, the choice of NSAIDs would be between a short half-life propionic acid derivative, with little biotransformation, such as ibuprofen or flurbiprofen. Diclofenac is also suitable. Gold salts and corticosteroids would seem safe to prescribe. However, the infant should be closely monitored if antimalarials are being used by lactating women.

Paralysis and unilateral arthritis: is the association established?

A patient with long-standing upper limb lower motor neurone paresis more recently developed homolateral upper motor neurone hemiplegia. Subsequent primary generalised osteoarthritis spared only the paralysed upper limb. Detailed review of reported cases suggest that the "protective" effect of paralysis against subsequent development of arthritis is not as clearly established as generally believed.

Clinical pharmacokinetics of the salicylates.

The use of salicylates in rheumatic diseases has been established for over 100 years. The more recent recognition of their modification of platelet and endothelial cell function has lead to their use in other areas of medicine. Aspirin (acetylsalicylic acid) is still the most commonly used salicylate. After oral administration as an aqueous solution aspirin is rapidly absorbed at the low pH of the stomach millieu. Less rapid absorption is observed with other formulations due to the rate limiting step of tablet disintegration - this latter factor being maximal in alkaline pH. The rate of aspirin absorption is dependent not only on the formulation but also on the rate of gastric emptying. Aspirin absorption follows first-order kinetics with an absorption half-life ranging from 5 to 16 minutes. Hydrolysis of aspirin to salicylic acid by nonspecific esterases occurs in the liver and, to a lesser extent, the stomach so that only 68% of the dose reaches the systemic circulation as aspirin. Both aspirin and salicylic acid are bound to serum albumin (aspirin being capable of irreversibly acetylating many proteins), and both are distributed in the synovial cavity, central nervous system, and saliva. The serum half-life of aspirin is approximately 20 minutes. The fall in aspirin concentration is associated with a rapid rise in salicylic acid concentration. Salicylic acid is renally excreted in part unchanged and the rate of elimination is influenced by urinary pH, the presence of organic acids, and the urinary flow rate. Metabolism of salicylic acid occurs through glucuronide formation (to produce salicyluric acid), and salicyl phenolic glucoronide), conjugation with glycine (to produce salicyluric acid), and oxidation to gentisic acid. The rate of formation of salicyl phenolic glucuronide and salicyluric acid are easily saturated at low salicylic acid concentrations and their formation is described by Michaelis-Menten kinetics. The other metabolic products follow first-order kinetics. The serum half-life of salicylic acid is dose-dependent; thus, the larger the dose employed, the longer it will take to reach steady-state. There is also evidence that enzyme induction of salicyluric acid formation occurs. No significant differences exist between the pharmacokinetics of the salicylates in the elderly or in children when compared with young adults. Apart from differences in free versus albumin-bound salicylate in various disease states and physiological conditions associated with low serum albumin, pharmacokinetic parameters in patients with rheumatoid arthritis, osteoarthritis, chronic renal failure or liver disease are essentially the same.(ABSTRACT TRUNCATED AT 400 WORDS)

Knee-joint rupture with giant antefemoral cyst formation.

A case of a patient with Reiter's disease, whose ruptured knee-joint effusion extended proximally along the femur to just below the inguinal ligament, and simulated an iliofemoral thrombosis, is reported. The mechanisms of joint rupture, and the need to differentiate it from thrombophlebitis, are discussed.