Showing papers by "Ian D. Pavord published in 1991"

Effect of inhaled prostaglandin E2 on bronchial reactivity to sodium metabisulphite and methacholine in patients with asthma.

Abstract: Inhaled frusemide protects against the bronchoconstrictor response to a wide range of stimuli that cause bronchoconstriction by indirect mechanisms. One possible explanation for this protection relates to the known ability of frusemide to enhance synthesis of prostaglandin E2 (PGE2). Studies in vitro suggest that PGE2 might protect against indirectly acting bronchoconstrictor challenges rather than those that act directly on airway smooth muscle, though little is known about the effects of PGE2 in vivo. The effect of inhaled PGE2 on the bronchoconstrictor response to inhaled sodium metabisulphite (a stimulus with an indirect action) and methacholine (which acts directly on airway smooth muscle) was studied in nine patients with asthma. Subjects were studied on four days, inhaling PGE2 (100 micrograms) or placebo in a double blind fashion followed immediately by a cumulative dose challenge with sodium metabisulphite or methacholine. The response to the constrictor stimuli was measured as the provocative dose causing a 20% fall in FEV1 (PD20). There was no significant change in FEV1 after inhaled PGE2 compared with placebo, nor any significant change in the response to methacholine; the geometric mean methacholine PD20 was 0.9 mumol after PGE2 and 0.56 mumol after placebo (mean difference 0.7 (95% confidence limits--0.1, 1.5) doubling doses). PGE2, however, protected against sodium metabisulphite, the geometric mean sodium metabisulphite PD20 being 11.8 mumol after PGE2 and 1.8 mumol after placebo (mean difference 2.5 (95% CL 1.9, 3.1) doubling doses). PGE2 conferred significantly greater protection against sodium metabisulphite than methacholine (mean difference 1.8 (95% CL 0.8, 2.8) doubling doses). This suggests that PGE2, like frusemide, has an inhibitory effect on pathways relevant to the bronchoconstriction induced by sodium metabisulphite, with little or no effect on those relevant to methacholine.

Will I get addicted to my asthma treatment

Abstract: It is not uncommon fora letter of referral fora respiratory assessment to suggest that patients may be overusing their inhaler, usually their {i2-iigonis.{ inhaler, and that they might be addicted to these drugs. In our experience, this increased need for relief treatment is nearly always due to deteriorating asthma control, and not addiction. The distinction is easily made by charting peak flow measurements and by the dramatic reduction in ^i-^gonist use that occurs after starting inhaled steroids (Fig. I) Deteriorating asthma requires prompt treatment and must not be confused with addiction. The term addiction implies a state of psychological and/or physical dependence on a drug. Psychological dependence on drugs without significant central nervous system effects is unusual and is generally not a problem with anti-asthma drugs. Physical dependence implies adaption by the body to the continued presence of the drug., a gradual reduction in the response to the drug with time, and an increase in the opposing effect of the drug after cessation of treatment. This is a widespread pharmacological phenomenon which teleologically could be useful by helping to avoid the excessive effects of the drug. The reduction in response to a drug after continued exposure has been variously referred to as tolerance, resistance, tachyphylaxis, refractoriness or desensitization. We have used the word tolerance for the development of a reduced drug effect after continued treatment and tachyphylaxis for an acute loss of effect after exposure of a tissue to drug in vitro. We have attempted to answer the question posed by the title of the article for each of the main classes of anti-asthma medication currently prescribed in the U.K.