phenanthrenes and Drug-Hypersensitivity

The incidence and nature of pruritus induced by chloroquine and halofantrine were studied in 82 patients with acute malaria and in 40 healthy subjects, using a visual analogue scale for quantitating pruritus. Results showed that the proportion of patients with acute malaria manifesting itch to halofantrine was significantly lower than the proportion manifesting itch to chloroquine. Furthermore, the intensity and duration of halofantrine-induced pruritus were significantly lower than those of chloroquine-induced pruritus. The few patients who itched to halofantrine all had a history of itching to chloroquine. The incidence and intensity of chloroquine-induced pruritus were significantly higher in patients with malaria than in healthy subjects. By contrast, there was no significant difference between malaria patients and healthy subjects as regards halofantrine-induced pruritus. These results suggest that itchers to halofantrine may constitute a small group within the population of itchers to chloroquine. Malaria infection appears to enhance chloroquine-induced pruritus but not halofantrine-induced pruritus and this may be of therapeutic importance.

Topics: Acute Disease; Adolescent; Adult; Antimalarials; Chloroquine; Drug Eruptions; Drug Hypersensitivity; Female; Humans; Kinetics; Malaria; Male; Middle Aged; Pain Measurement; Phenanthrenes; Pruritus

Triptolide (TP) is a major active component of Tripterygium wilfordii Hook F (TWHF), which is used to treat rheumatoid arthritis (RA). TP has a narrow therapeutic window. To increase the therapeutic index of TP, a novel TP-loaded transdermal delivery system, named TP-loaded hydrogel-thickened microemulsion (TP-MTH), has been developed to treat RA. Our previous studies have demonstrated the good efficacy of TP-MTH in animals. This paper evaluated the safety of TP-MTH with several animals. Results demonstrated no obvious toxicities in a series of toxicity tests: acute toxicity study of TP-MTH (1.2mg/kg) in rabbits, 6-month long-term toxicity study of TP-MTH (0.06, 0.18, 0.54mg/kg) in rabbits, safety pharmacology study of TP-MTH (0.03, 0.09, 0.27mg/kg, for 5 d) in mice and beagle dogs, skin irritation study in rabbits, and skin allergic reaction test in guinea pigs. Only mild reversible skin irritation signs were observed on the skin of animals. These studies suggest that topical TP-MTH is a promising drug formulation for the treatment of RA.

Topics: Administration, Cutaneous; Animals; Antirheumatic Agents; Blood Cell Count; Blood Chemical Analysis; Blood Pressure; Diterpenes; Dogs; Drug Hypersensitivity; Emulsions; Epoxy Compounds; Guinea Pigs; Hydrogels; Indicators and Reagents; Irritants; Mice; Motor Activity; Phenanthrenes; Rabbits; Skin; Tissue Distribution

Four patients with a clinical picture resembling that of scarlatina are described. This clinical picture was found to be based on a delayed-type allergy for codeine and morphine. Investigation showed that the codeine or morphine allergy is essentially dependent on the hydroxyl group at the 6 position of the basic phenanthrene structure but only when this group is bound equatorially, as is the case for codeine and morphine.

Topics: Adult; Codeine; Drug Hypersensitivity; Female; Humans; Hypersensitivity, Delayed; Male; Middle Aged; Molecular Conformation; Morphine; Phenanthrenes; Recurrence; Scarlet Fever

A patient is described with a clinical picture resembling that of relapsing scarlatina. The complaints were found to be based on two types of delayed-type allergy: one to the equatorially bound hydroxyl grouip at the 6 position of the basic phenanthrene structure as occurs in morphine and codeine, and the other to the D(-)-alpha-position of the amino group as occurs in some penicillin derivatives.

Topics: Adolescent; Drug Hypersensitivity; Female; Humans; Penicillins; Phenanthrenes; Scarlet Fever; Skin Tests; Stereoisomerism

Topics: Adult; Chemical Phenomena; Chemistry; Codeine; Drug Eruptions; Drug Hypersensitivity; Female; Humans; Male; Morphine; Phenanthrenes; Scarlet Fever

Quinine was compared with a 9-phenanthrene methanol (WR33063) and a 4-quinoline methanol (WR30090) for the treatment of 207 patients with falciparum malaria in Southeast Thailand. Quinine eradicated parasitaemia (average 70 hours) more rapidly than either WR30090 (72 hours) or WR33063 (77 hours). But WR33063 had a higher cure rate (92%) than WR30090 (86%) or quinine (85%). The mean duration of fever and of parasitaemia were combined with the failure rate to form an arbitrary efficacy index. Using this concept WR33063 was the most effective drug. The recrudescence rate correlated with the degree and duration of parasitaemia and with the duration of fever. WR33063 was the least toxic drug. Side effects associated with WR30090 appeared to be headache, backache and urticaria. Quinine was the most toxic drug. All 3 drugs were inconvenient in having to be administered every 8 hours for 6 days. One patient did not respond to oral quinine but did respond to an intravenous quinine infusion (IVQ). A "Medication Ward Round" was perfected during the study and comprised sequential history, drug administration, physical examination, dose notation and patient observation. Falciparum nephrosis was diagnosed in one patient.

Topics: Adolescent; Drug Administration Schedule; Drug Evaluation; Drug Hypersensitivity; Drug Resistance, Microbial; Humans; Malaria; Male; Phenanthrenes; Plasmodium falciparum; Proteinuria; Quinine; Quinolines; Thailand; Urticaria

Topics: Biotransformation; Carcinogens; Cheese; Chromosome Aberrations; Circadian Rhythm; Drug Hypersensitivity; Drug Incompatibility; Drug-Related Side Effects and Adverse Reactions; Gynecomastia; Headache; Humans; Iatrogenic Disease; Monoamine Oxidase Inhibitors; Pharmaceutical Preparations; Phenanthrenes