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European Review For Medical and... Nov 2017Dry mouth (xerostomia), is a fairly common, well-researched condition, which is an indirect cause of oral malodour. This systematic literature review looked into another... (Review)
Review
Dry mouth (xerostomia), is a fairly common, well-researched condition, which is an indirect cause of oral malodour. This systematic literature review looked into another cause of bad breath: adverse drug reactions in the orofacial region causing halitosis. The study focused on extraoral halitosis, and its subdivisions, particularly blood borne halitosis in which malodourous compounds in the blood stream are carried to the lungs, passively diffused across the pulmonary alveolar membrane to enter the breath. An electronic search was conducted in various databases. Inclusion criteria were: editorials, case control studies, retrospective studies and randomized double-blind studies published in English between 1983 and March 2017. The search identified a total of 23 articles. According to these, drug-related halitosis may be caused by nine medications. Dimethyl sulfoxide, cysteamine and suplatast tosilate are metabolised to dimethyl sulfide, a malodourous compound that is stable in blood and is transported into the breath. Disulfiram is reduced to carbon disulfide, also a stable compound in blood. Nitric oxide reacts with foul-smelling volatile organosulfur compounds. The degradation of penicillamine raises the pH level, favouring the growth of gram-negative bacteria in the oral cavity producing halitosis. Chloral hydrate, phenothiazine, and paraldehyde could not be related to halitosis. The analysis showed that halitosis can be caused by medication but does not correlate to any specific disease or specific form of drug therapy. The pharmacological compounds identified as causes of halitosis are administered to treat a broad spectrum of diseases, or in therapeutic regimes.
Topics: Gram-Negative Bacteria; Halitosis; Humans; Hydrogen Sulfide; Penicillamine; Smell; Sulfhydryl Compounds; Sulfides
PubMed: 29164566
DOI: No ID Found -
Journal of Veterinary Internal Medicine 2013D-Penicillamine is the most commonly used copper-chelating agent in the treatment of copper-associated hepatitis in dogs. Response to therapy can be variable, and there...
BACKGROUND
D-Penicillamine is the most commonly used copper-chelating agent in the treatment of copper-associated hepatitis in dogs. Response to therapy can be variable, and there is a lack of pharmacokinetic information available for dogs. Coadministering the drug with food to alleviate vomiting has been recommended for dogs, which contradicts recommendations for drug administration to humans.
HYPOTHESIS
Coadministration of d-penicillamine with food decreases relative bioavailability and maximum plasma drug concentrations (C(max)) in dogs.
ANIMALS
Nine purpose-bred dogs with a median body weight of 17.0 kg.
METHODS
Dogs received D-penicillamine (12.5 mg/kg PO) fasted and with food in a randomized, crossover design. Blood samples were collected before and 0.25, 0.5, 1, 2, 3, 4, 8, 12, and 24 hours after dosing. Total d-penicillamine concentrations were measured using liquid chromatography coupled with tandem quadrupole mass spectrometry. Pharmacokinetic parameters were calculated for each dog.
RESULTS
Two fasted dogs (22%) vomited after receiving d-penicillamine. Mean C(max) ± standard deviation (SD) was 8.7 ± 3.1 μg/mL (fasted) and 1.9 ± 1.6 μg/mL (fed). Mean area under the plasma concentration curve ± SD was 16.9 ± 5.9 μg/mL·h (fasted) and 4.9 ± 3.4 μg/mL·h (fed). There were significant reductions in relative bioavailability and C(max) in fed dogs (P < .001).
CONCLUSIONS AND CLINICAL IMPORTANCE
Coadministration of d-penicillamine with food significantly decreases plasma drug concentrations in dogs. Decreased drug exposure could result in decreased copper chelation efficacy, prolonged therapy, additional cost, and greater disease morbidity. Administration of d-penicillamine with food cannot be categorically recommended without additional studies.
Topics: Animals; Area Under Curve; Chelating Agents; Dogs; Female; Food Deprivation; Half-Life; Male; Penicillamine
PubMed: 23875792
DOI: 10.1111/jvim.12147 -
BioMed Research International 2022The purpose of this study is to investigate the exchange reaction taking place among the bovine serum albumin (BSA), 5,5'-dithiobis-(2-nitrobenzoic acid (ESSE), reduced...
The purpose of this study is to investigate the exchange reaction taking place among the bovine serum albumin (BSA), 5,5'-dithiobis-(2-nitrobenzoic acid (ESSE), reduced glutathione, N-acetylcysteine, D-penicillamine (thiolates), and silver metal (Ag). For this purpose, stock solutions of BSA and Ellman's reagent were prepared by dissolving 264 mg of BSA in 5 ml of reaction buffer (0.1 M KHPO at pH 7.8) and 23.8 mg of ESSE in 1.0 ml of reaction buffer which were mixed together. Mixture of BSA-Ag was prepared in a separate procedure by dissolving 0.17 mg of silver nitrate in 1 ml of reaction buffer and then dissolving BSA (200 mg) in the same solution of silver nitrate. Blocking of Cys-34 of BSA with Ag was confirmed by treating different dilutions of BSA-Ag (500 M) solutions with the solutions of ESSE (85 M) and ES (85 M) and recording the spectra (300-450) with a UV-visible spectrophotometer. The chromatographed Ag-modified BSA ((BSA-S)Ag)) samples (typically 500 M) were subsequently mixed with thiolates (reduced glutathione, N-acetylcysteine, and D-penicillamine). Ag and modified BSA (typically 500 M each) were treated with these low molecular weight thiolates and allowed to react overnight followed by chromatographic separation (Sephadex G25). The redox reactions of Ag-modified BSA with various low molecular weight thiols revealed a mechanically important phenomenon. In the case of reduced glutathione and N-acetylcysteine, we observed the rapid release of a commensurate amount of Ellman's anion, indicating that an exchange has taken place and low molecular weight thiols (RSH) substituted Ag species at the Cys-34 of BSA eventually forming disulfide (BSA-SSR) at Cys-34. It can be anticipated from the phase of study involving bovine serum albumin that low molecular weight thiolates (reduced glutathione and N-acetylcysteine) take off Ag which are attached to proteins elsewhere in the physiological system, making these toxic metals free for toxic action.
Topics: Acetylcysteine; Coordination Complexes; Cysteine; Glutathione; Metals; Penicillamine; Serum Albumin, Bovine; Silver Nitrate; Sulfhydryl Compounds
PubMed: 35978640
DOI: 10.1155/2022/3619308 -
British Medical Journal (Clinical... Mar 1981
Topics: Drug Administration Schedule; Humans; Kidney Diseases; Penicillamine; Proteinuria
PubMed: 6783160
DOI: No ID Found -
British Medical Journal Nov 1964
Topics: Cystinuria; Humans; Metabolism; Penicillamine; Toxicology; Vitamin B 6 Deficiency
PubMed: 14208217
DOI: 10.1136/bmj.2.5421.1395 -
Annals of the Rheumatic Diseases Jun 1979Information has been collected on 10 patients, 9 with marrow depression and 1 in whom the diagnosis was presumed. Six of the 10 patients died. The sequentially recorded...
Information has been collected on 10 patients, 9 with marrow depression and 1 in whom the diagnosis was presumed. Six of the 10 patients died. The sequentially recorded blood counts on at least 5 of the patients showed a downward trend of the white cell and platelet counts while D-penicillamine was still being administered. One patient suddenly developed leucopenia and thrombocytopenia with a streptococcal septicaemia.
Topics: Adult; Aged; Arthritis, Rheumatoid; Blood Cell Count; Bone Marrow Diseases; Female; Humans; Male; Middle Aged; Penicillamine; Time Factors
PubMed: 485580
DOI: 10.1136/ard.38.3.232 -
British Medical Journal Dec 1976
Topics: Adult; Arthritis, Rheumatoid; Humans; Penicillamine; Pulmonary Fibrosis
PubMed: 1000275
DOI: 10.1136/bmj.2.6050.1507-c -
Proceedings of the Royal Society of... 1977
Comparative Study Review
Topics: Alkylating Agents; Copper; Humans; Penicillamine; Tissue Distribution; Trientine
PubMed: 122660
DOI: No ID Found -
British Medical Journal Mar 1977
Topics: Abnormalities, Drug-Induced; Cystinuria; Female; Humans; Infant, Newborn; Penicillamine; Pregnancy; Teratogens
PubMed: 851752
DOI: 10.1136/bmj.1.6064.838-b -
Hepatology (Baltimore, Md.) May 2024Trientine (TRI) and D-penicillamine (PEN) are used to treat copper overload in Wilson disease. Their main mode of action is thought to be through the facilitation of...
BACKGROUND AND AIMS
Trientine (TRI) and D-penicillamine (PEN) are used to treat copper overload in Wilson disease. Their main mode of action is thought to be through the facilitation of urinary copper excretion. In a recent study, TRI was noninferior to PEN despite lower 24-hour urinary copper excretion than PEN. We tested whether TRI and/or PEN also inhibit intestinal copper absorption.
APPROACH AND RESULTS
Sixteen healthy volunteers were examined with positron emission tomography (PET)/CT 1 and 15 hours after an oral Copper-64 ( 64 Cu) dose. They then received 7 days of either PEN or TRI (trientine tetrahydrochloride), after which the 64 Cu PET/CT scans were repeated. Venous blood samples were also collected. Pretreatment to posttreatment changes of the hepatic 64 Cu uptake reflect the effect of drugs on intestinal absorption. 64 Cu activity was normalized to dose and body weight and expressed as the mean standard uptake value. TRI (n=8) reduced hepatic 64 Cu activity 1 hour after 64 Cu dose from 6.17 (4.73) to 1.47 (2.97) standard uptake value, p <0.02, and after 15 hours from 14.24 (3.09) to 6.19 (3.43), p <0.02, indicating strong inhibition of intestinal 64 Cu absorption. PEN (n=8) slightly reduced hepatic standard uptake value at 15 hours, from 16.30 (5.63) to 12.17 (1.44), p <0.04.
CONCLUSIONS
In this mechanistic study, we show that TRI inhibits intestinal copper absorption, in addition to its cupriuretic effect. In contrast, PEN has modest effects on the intestinal copper absorption. This may explain why TRI and PEN are equally effective although urinary copper excretion is lower with TRI. The study questions whether the same therapeutic targets for 24-hour urinary excretion apply to both drugs.
Topics: Humans; Penicillamine; Trientine; Copper; Positron Emission Tomography Computed Tomography; Copper Radioisotopes; Hepatolenticular Degeneration; Positron-Emission Tomography
PubMed: 38088886
DOI: 10.1097/HEP.0000000000000708