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Chloroquine‐induced venodilation in human hand veins
Author(s) -
Abiose Ademola K.,
Grossmann Matthias,
Tangphao Oranee,
Hoffman Brian B.,
Blaschke Terrence F.
Publication year - 1997
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(97)90103-x
Subject(s) - chloroquine , medicine , vasodilation , pharmacology , anesthesia , vein , phenylephrine , agonist , receptor , blood pressure , pathology , malaria
Objective Hypotension induced by parenteral administration of chloroquine is a common and serious adverse effect of this drug. Our aim was to investigate whether chloroquine produces venodilation in vivo and to explore the underlying mechanisms. Methods Vascular effects of chloroquine were studied in healthy volunteers with use of the dorsal hand vein technique at the Geriatric Research Education and Clinical Center, Veterans Affairs Palo Alto Health Care System. We studied 22 healthy volunteers (19 men and three women). Venous responsiveness was determined with the dorsal hand vein technique, which measures the diameter of the vein. Results Chloroquine was found to produce a dose‐dependent relaxation of hand veins preconstricted with the α 1 ‐receptor selective agonist phenylephrine. The venodilatory response to chloroquine ranged from 15% ± 19% at an infusion rate of 0.75 μg/min to 61% ± 24% at 48 μg/min. Venodilation was attenuated by the nitric‐oxide synthase inhibitor N G ‐monomethyl‐ L ‐arginine ( L ‐NMMA) so that the dose of chloroquine required to produce 20% venodilation was increased from 3.7 μg/min to 15 μg/min ( p < 0.01). In the presence of a combination of histamine receptor antagonists, there was also a diminution of the vasodilatory response to chloroquine from 72% ± 5% to 44% ± 5% at the infusion rate of 96 μg/min. The response was further reduced to 33% ± 7% by the coinfusion of H 1 ‐/H 2 ‐receptor antagonists with L ‐NMMA. Conclusion Chloroquine produces venodilation at infusion rates that achieve local concentrations likely similar to those observed systematically after clinically relevant intravenous doses. The data also suggest a role for nitric oxide and histamine release in mediating this response. Clinical Pharmacology & Therapeutics (1997) 61 , 677–683; doi: