Treatment of Rheumatoid Arthritis with Chloroquine

Abstract

Nov. 15, 1958 TEMPERATURE AFTER BIRTH ASPHYXIA BLRNL 1199Group C comprised 18 babies who received N-allyl morphine, and 17 who breathed in three minutes without it. These subgroups were analysed separately, and as there was very little difference between them they have been taken together to give the total 35 group C babies. The failure of N-allyl morphine, used as an antidote to pethidine apnoea, to influence the later temperature is the subject of comment below.There was no clinical disorder in any of the babies, apart from the need for brief resuscitative measures at birth in a minority of the apnoeic ones, as has already been noted. Cyanosis both of the lips and of the extremities occurred to a varying degree, as did variations in respiratory rate. DiscussionThe fact that there is a significant difference in temperature over several hours between group A and group D suggests that asphyxia causes a fall in oxygen consumption and energy production as in the experiments on pure anoxia (15% oxygen) already quoted. It is worth speculating on the degree of anoxia our subjects had met, as Brodie et al. noted no fall in rectal temperature in infants breathing 15% oxygen for 50 minutes. The pronounded fall in heat production suggested by the low rectal temperature points to an incident of considerable severity.There is no apparent difference between the temperatures of the two groups of babies whose mothers had received pethidine (B and C), whether the babies were apnoeic for three minutes after birth or not. Their pattern of temperature change after birth is very similar to that of babies with pure asphyxia. Either the initial asphyxia or mild persisting respiratory depression from the drug could explain the similarity to the group D babies. A second possibility is vasodilatation, since J. Ginsburg (1958, personal communica-tion) has found an approximate doubling of skin-blood flow in the human subject for periods up to an hour after 100 mg. of pethidine intramuscularly. Thus the temperature of babies after maternal pethidine might be lowered both by diminished heat production and by increased heat loss.To some extent the absence of a difference between groups B and C may be due to artificial selection, because severely asphyxiated babies who were felt to need oxygen for a number of hours after birth have not been included in the series, although some of them had much lower temperatures and these would have enlarged group B.When the babies in group C were divided according to whether or not they had received N-allyl morphine, the fall in temperature was the same in each subgroup. While the drug proved a very effective antidote to pethidine in the initiation of breathing (Paterson and Prescott, 1954) it did not appear to have any subsequent effect on the course of temperature. Roberts et al. (1957) similarly found that the reduction of the baby's minute-volume after maternal pethidine was not influenced by this antidote.We conclude that a somewhat reduced rectal temperature is a natural phenomenon in babies suffe...

New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?

“…Chloroquine is a well-known immunomodulatory agent capable of mediating an anti-inflammatory response [11]. Therefore, there are clinical applications of this drug in inflammatory diseases such as rheumatoid arthritis [74][75][76], lupus erythematosus [6,77] and sarcoidosis [78]. Chloroquine inhibits interleukin-1 beta (IL-1) mRNA expression in THP-1 cells and reduces IL-1release [72].…”

Tissue and blood concentrations of chloroquine following chronic administration in the rat

“…A peak tissue/plasma concentration ratio greater than 300 is obtained in many tissues and after a single dose the drug can be found in the liver and urine for up to five years (Gaudette & Coatney 1961;. Chronic administration of chloroquine for the treatment of rheumatoid arthritis has revealed an ocular toxicity due to accumulation of the drug in the pigmented layers of the eye, particularly the choroid (Fuld & Horwish 1958;Fuld 1959). A more recent indication for chronic administration of chloroquine is in the prophylaxis of malaria, for which the drug is administered at a dose of 300-600 mg weekly to adults.…”

“…The long term toxic effects of chloroquine when administered in this way are unknown but no ocular toxicity has been reported even after five years of such use. Since tissue toxicity and other untoward effects are largely determined by tissue stores (Fuld & Horwish 1958;Fuld 1959) and blood levels (Laaksonen et a1 1974;Frisk-Holmberg et a1 1979) of the drug, it is useful to know the changes occurring in tissue and plasma concentrations during chronic administration. Previous studies in animals have given conflicting results.…”

Chloroquine in Rheumatoid Arthritis

“…Many papers have appeared (Forestier and Certonciny, 1954;Scherbel, Schuchter, and Harrison, 1957; Erlendsson, 1958;Fuld and Horwich, 1958), but controlled trials have been few. The first (Freedman, 1956) dealt with 66 patients each observed for a period of 16 weeks.…”