Phenylephrine, oxidation

FIGURE 8.11 II S mediated vasorelaxation. Rat aorta segments suspended in an organ bath containing the miniature PHSS and equilibrated with 40pM 02 are stimulated to constrict with lOOnM phenylephrine (PE). Subsequent addition of H2S causes an immediate relaxation event that gradually recovers as the H2S is oxidized or removed by the gas perfusion stream. Repeated additions of H2S at physiologically relevant concentrations demonstrate a predictable kinetic response. 

Phenylephrine (27) is a low-potency sympathomimetic amine used as a decongestant. Solutions become coloured due to an auto-oxidation accelerated by light. In a series of experiments, aqueous solutions of the hydrochloride were left under a UV lamp until a tan colour developed. HPLC analysis showed four main products of which one was identified as adrenaline (19). Even after prolonged irradiation, there was never more than 2% adrenaline in the solution. It was assumed that the catecholamine was removed as it formed by further reaction to adrenochrome and melanine, which accounted for the colour [34],... 

Trace metal impurities in buffer salts were found to enhance the oxidative degradation of prednisolone (78). Phenylephrine hydrochloride decomposes in the presence of heavy metal ions (79). The autooxidation of procaterol, a sympathomimetic amine, is enhanced in the presence of ferric ions (80). The photodegradation of riboflavin is enhanced by the presence of polysorbate 80 and sodium lauryl sulfate (81). 

Some antioxidants possess antimicrobial properties, such as propyl gallate and butylated hydroxy anisole, which are somewhat effective against bacteria. Butylated hydroxy toluene has demonstrated some antiviral activity. Compatibility of antioxidants with the drug, packaging system and the body should be studied carefully. For example, tocopherols may be absorbed onto plastics ascorbic acid is incompatible with alkalis, heavy metals, and oxidizing materials such as phenylephrine, and sodium nitrite and propyl gallate forms complexes with metal ions such as sodium, potassium and iron. 

Incompatible with alkalis, heavy metal ions, especially copper and iron, oxidizing materials, methenamine, phenylephrine hydrochloride, pyrilamine maleate, salicylamide, sodium nitrite, sodium salicylate, theobromine salicylate, and picot-amide. Additionally, ascorbic acid has been found to interfere with certain colorimetric assays by reducing the intensity of the color produced. ... 

Pastor, C. M., and Billiar, T. R. (1995). Nitric oxide causes hyporeactivity to phenylephrine in isolated perfused livers from endotoxin-treated tats. Am. J. Physiol, in press. 

Simultaneous acetylcodeine, amphetamine, benzphetamine, benzylmorphine, bromo-STP, buprenorphine, chlorphentermine, codeine, codeine-N-oxide, dextromoramide, dextropro-poxyphene, diamorphine, diethylpropion, dihydrocodeine, dihydromorphine, dimethylam-phetamine, dipipanone, ephedrine, epinephrine, ethoheptazine, ethylmorphine, etorphine, fencamfamin, fenfluramine, fentanyl, hydrocodone, 4-hydroxyamphetamine, levorphanol, mazindol, meperidine, mephentermine, mescaline, methadone, methamphetamine, meth-ylenediojQramphetamine, methylephedrine, monoacetylmorphine, morphine, morphine-3-glucuronide, morphine-N-oxide, naloxone, norcodeine, norlevorphanol, normetanephrine, normethadone, normorphine, norpethidine, norpseudoephedrine, noscapine, o codone, papaverine, pemoline, pentazocine, 2-phenethylamine, phenoperidine, phentermine, phenylephrine, phenylpropanolamine, pholcodeine, pipradol, piritramide, prolintane, pseudoephedrine, STP, thebacon, thebaine, trimethoxyamphetamine, tyramine... 

Cloricromene (8-monochloro-3j8-diethylamino-ethyl-4-methyl-7-ethoxycarbonyl-methoxy-couma-rine) inhibited the induction of nitric oxide synthase (ZiNGARELLi et al. 1993). Rings of thoracic aortas from fipopolysaccharide (4 mg/kg, i.v.)-shocked rats, contracted with phenylephrine, showed a progressive decrease in tone, that was of a greater magnitude than that of aortas from naive rats. Moreover, a decreased response to the constrictor effect of phenylephrine was observed in aortas from shocked rats. In vivo treatment with cloricromene (2 mg/kg, i.v.) 30 min before fipopolysaccharide administration partially prevented the loss in tone of aortic rings and improved their reactivity to phenylephrine. 

An example of a simple oxidatiim reaction is the craiver-sion of Fe " into Fe. Examples of active substances that are prone to oxidation are acetylcystein, adrenaline, apomorphine, clioquinol, dithranol, dobutamine, ergotamine, hydroquinone, isoniazid, mesalazine, naloxone, neomycin, oxycodone, paracetamol, peptides, salbutamol, phenothiazine derivatives (promazine, promethazine, chlorpromazine), phenylephrine, physostigmine, tetracycline, tretinoin, the vitamins A and D, and the excipients flavouring agents, fragrances and unsaturated fats (vegetable oils, suppository bases). 

The alkaline oxidations of etamsylate (ETM) and salbutamol (SBL) , and the acidic oxidations of phenylephrine (PHE) and butacaine sulfate (BCS) " with N-chlorobenzenesulfonamide (CAB) in MeOH have some common features. The rates in each case increase with decreasing dielectric constant of the solvent. The reactions are of fractional order in ETM, SBL, PHE, and BCS. A fractional order in OH and H" " ions is noted in the reaction of ETM and PHE, respectively. However, a negative fractional order in OH ions and rate retardation with benzenesulfonamide (BSE) is observed in the oxidation of SBL. The observed Michaelis-Menten kinetics provide the basis of the proposed mechanism in each case. The Ir(IIl)-catalysed A-chlorobenzenesulfonamide (CAB) oxidation of DMSO in acidic solution has an order less than one in Ir(III) and the rate decreased with increase in H" " ions. A suitable mechanism involving formation of an intermediate is proposed. ... 

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