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Biomedical subjects

P E Carson

Publications and source records attributed to P E Carson.

At least 19 recordsLinked to original sources
PubMed1990

Severe bradycardia following electrical cardioversion for atrial tachyarrhythmias in patients with acute myocardial infarction.

Bradycardia following electrical cardioversion is an uncommon complication. The present report describes three patients who developed life-threatening bradycardia following electrical cardioversion for atrial tachyarrhythmias in the setting of an acute myocardial infarction. All three patients had multivessel coronary artery disease with a totally occluded right coronary artery and a possibility of ischemic sinus node dysfunction. When electrical cardioversion is undertaken for new onset of atrial tachyarrhythmia in the setting of an acute myocardial infarction, measures for immediate, temporary pacing should be easily available.

Aged↗
PubMed1987

Biotransformation of primaquine in vitro with human K562 and bone marrow cells.

Although the antimalarial activity, hemolytic and methemoglobinemic side effects, and detoxification of primaquine are all thought to depend on various biotransformation products of the drug, their site and mechanism of formation and degradation are unknown and their specific biologic effects remain very poorly understood, particularly in humans. We have therefore explored the feasibility of studying primaquine metabolism in cultured human cells. We found that the biotransformation of primaquine can be investigated in vitro in serum-supplemented liquid cultures of partially synchronized and exponentially growing human erythroleukemic K562 cells. Further, these cells can be replaced by cells present in normal bone marrow. Primaquine is rapidly and predominantly converted in vitro into carboxyprimaquine (CPQ) in a quantitative manner and without further modification. In addition to CPQ, a compound Xc that is not 6-methoxy-8-aminoquinoline, and is not derived from CPQ, appears in minor amounts in a delayed fashion. With the K562 as well as with the bone marrow cells the formation of CPQ from primaquine can be totally blocked by large concentrations of the nitrosourea, 1,3-bis-(2-chloroethyl)-nitrosourea (BCNU). With bone marrow, increasing blockade of CPQ formation by BCNU leads invariably to a progressive and striking accumulation of Xc. The availability of reproducible, quantitative, and practical new tools for the study of primaquine metabolism in vitro raises a number of challenging questions and may improve understanding of the mode of action, toxicology, and pharmacogenetics of 8-aminoquinolines.

Biotransformation↗
PubMed1984

High-performance liquid chromatographic-ultraviolet determination of primaquine and its metabolites in human plasma and urine.

A high-performance liquid chromatographic method was developed for the simultaneous determination of primaquine and its metabolites from plasma and urine samples obtained after oral administration of primaquine diphosphate. Following partial deproteinization with acetonitrile, samples were chromatographed by direct injection onto a cyano column with UV detection at 254 nm. Levels as low as 100 ng/mL per 20-microL injection were quantitated. Preliminary pharmacokinetic analysis is reported for two human volunteers after oral doses of 60 mg and 90 mg. Two apparent plasma metabolites and two possible urinary metabolites of primaquine are also reported.

Chromatography, High Pressure Liquid↗
PubMed1981

Toxicology of the 8-aminoquinolines and genetic factors associated with their toxicity in man.

In vitro studies on primaquine have been carried out to examine its ability to stimulate the oxidative pathway of glucose metabolism in human erythrocytes and in vivo studies were carried out after ingestion of the drug to determine plasma levels and to investigate the formation of metabolites and the effects of the drug on human erythrocytes. These investigations showed that:1) Two mechanisms are involved in the stimulation of the oxidative pathway. This was demonstrated by comparing the effects of methylene blue, ascorbic acid, primaquine, and other drugs on normal, glutathione-reductase-deficient, and G6PD-deficient erythrocytes. A start was made towards classifying drugs according to the mechanism by which they stimulate CO(2) production.2) Following oral ingestion of primaquine, three as yet unidentified metabolites were present, two in the plasma and one in the urine. The rapid disappearance of primaquine from the plasma (within 24 hours) was confirmed.3) Two factors that stimulate glucose oxidation in human erythrocytes were found in plasma; one occurred only in fresh plasma, when EDTA was present, and the other occurred in all plasma and serum samples studied.4) The erythrocytes of blood drawn 24 hours after the ingestion of primaquine (after primaquine had disappeared from the plasma) showed increased ability to oxidize glucose.It is not yet known whether serum or plasma prepared from blood drawn 24 hours after ingestion of primaquine has the ability to increase the oxidation of glucose.

Aminoquinolines↗
PubMed1978

Therapy and prophylaxis of malaria.

Physicians should be prepared to provide prophylactic medications for travelers to malarious areas and to treat patients with malaria. Chloroquine hydrochloride is the suppressive agent of choice for treatment of mild infections due to all species of malaria except for those due to chloroquine-resistant strains of Plasmodium falciparum. For treatment of severe infections with P falficparum, quinine is the suppressive agent of choice. Chloroquine is also the prophylactic agent of choice for most travelers. To prevent infection with P vivax or P ovale, primaquine must also be given. A RBC glucose-6-phosphate dehydrogenase level should be obtained before administration of primaquine. For prophylaxis of chloroquine-resistant strains of P falciparum, no completely satisfactory regimen is presently available in the United States.

Antimalarials↗
PubMed1978

The influence of acetylator phenotype on the response to sulfalene in individuals with chloroquine-resistant falciparum malaria.

The disposition of sulfalene was studied in eight individuals before and during an infection with a chloroquine-resistant strain of Plasmodium falciparum. Isoniazid acetylator phenotype was determined in each individual prior to the administration of sulfalene. Following the administration of sulfalene before infection with malaria, a significant difference in half-life of non-acetylated sulfalene and percent acetylation of sulfalene in plasma was observed between rapid and slow acetylators. When sulfalene was administered during malaria, this difference was no longer apparent. Individuals who did not respond to the therapeutic administration of sulfalene alone were treated with a combination of sulfalene and pyrimethamine. Three individuals were cured by sulfalene without pyrimethamine and one was cured by the drug combination. Three of the four individuals who were not cured by any dose of sulfalene or the drug combination were slow acetylators. There was no distinct correlation between clinical response and maximum levels or half-life of nonacetylated sulfalene. These findings suggest that acetylator phenotype does not influence the therapeutic response of individuals infected with falciparum malaria to sulfalene or to the combination of sulfalene and pyrimethamine. Further information is presented, however, to confirm the importance of an as yet unidentified host factor(s) in determining therapeutic response to these agents.

Acetylation↗
PubMed1976

Quinine disposition during malaria and during induced fever.

Quinine disposition was studied in 5 subjects before and during an experimentally induced infection with a chloroquine-resistant strain of Plasmodium falciparum and in 2 individuals before and during artificially induced fever. Plasma quinine levels were determined by both a benzene extraction method (QB), which measures principally unmetabolized quinine, and a metaphosphoric acid precipitation method (QMPA), which measures quinine and quinine metabolites. The ratio QB/QMPA in plasma was used to estimate the extent of metabolism of quinine. In all individuals plasma levels of quinien and QB/QMPA ratios were increased during malaria, suggesting impaired hepatic metabolism of quinine. The changes observed during malaria were not due to altered renal excretion of quinine. In 2 subjects in whom fever was artificially induced there were similar changes in quinine metabolism. These observations suggest that quinine dosage should be modified during the initial period of treatment, when symptoms and fever are greatest, in acute falciparum malaria.

Erythrocytes↗
PubMed1975

Mefloquine (WR 142,490) in the treatment of human malaria.

Mefloquine hydrochloride, a new 4-quinolinemethanol, was administered as a single oral dose to 47 volunteers infected with malaria. Treatment resulted in rapid clearence of fever and parasitemia. No recrudescence of parasites was observed after treatment of chloroquine-sensitive infections of Plasmodium falciparum. More significantly, in nonimmune persons with chloroquine-resistant infections, 1 gram of mefloquine cured 10 of 12 patients and 1.5 grams cured all 8 patients who received this dose of the drug. The marked activity of a single dose of mefloquine against chloroquine-resistant strains of Plasmodium falciparum suggests that this agent may be more useful than currently available drugs are for the treatment of drug-resistant malaria.

Antimalarials↗
PubMed1975

Acetylator phenotype and response of individuals infected with a chloroquine-resistant strain of Plasmodium falciparum to sulfalene and pyrimethamine.

Acetylator phenotype was determined in 33 volunteers who were infected with a chloroquine-resistant strain of Plasmodium falciparum and who received, for cure, 2 g of sulfalene and 50 mg of pyrimethamine. This drug combination did not cure 5 of 14 rapid acetylators and 3 of 19 slow acetylators. This difference is not significant. Plasma levels of non-acetylated sulfalene, acetylated sulfalene, acetylation, and biologic half-life of non-acetylated sulfalene after administration of the combination did not differ importantly between the two groups. Acetylator phenotype does not appear to influence the response to sulfalene and pyrimethamine of individuals infected with chloroquine-resistant falciparum malaria.

Acetylation↗
PubMed1975

Host failure in treatment of malaria with sulfalene and pyrimethamine.

An individual infected with a multidrug-resistant strain of Plasmodium falciparum failed to respond to treatment with sulfalene and pyrimethamine. Subinoculation studies showed that parasite resistance to the drug combination was not present. Plasma levels of sulfalene and pyrimethamine in this individual were similar to those of three individuals, subinoculated from him, who were cured by the drug combination. Erythrocyte levels of sulfalene in this individual were similar to those in an individual, subinoculated from him, who was cured by the drug combination. After treatment with the drug combination, in vitro tests showed similar antimalarial activity in the serum of this individual in comparison with the serum of this individual in comparison with the serum of an individual subinoculated from him. The failure of this individual to respond to treatment with sulfalene and pyrimethamine is attributed to an undefined host factor (or factors) that appear(s) to be present in his erythrocytes.

Adult↗