Adrenaline stability

Chemical stability. Some medicaments undergo chemical change in aqueous soluhons. If the change is due to oxidation, a reducing agent such as sodium metabisulphite is included (e.g. Adrenaline Injection BP). 

The experimental observations were interpreted by assuming that the redox cycle starts with the formation of a complex between the catalyst and the substrate. This species undergoes intramolecular two-electron transfer and produces vanadium(II) and the quinone form of adrenaline. The organic intermediate rearranges into leucoadrenochrome which is oxidized to the final product also in a two-electron redox step. The +2 oxidation state of vanadium is stabilized by complex formation with the substrate. Subsequent reactions include the autoxidation of the V(II) complex to the product as well as the formation of aVOV4+ intermediate which is reoxidized to V02+ by dioxygen. These reactions also produce H2O2. The model also takes into account the rapidly established equilibria between different vanadium-substrate complexes which react with 02 at different rates. The concentration and pH dependencies of the reaction rate provided evidence for the formation of a V(C-RH)3 complex in which the formal oxidation state of vanadium is +4. 

It appears that the intermediates formed from different catecholamines are of different stability. The intermediate open-chain quinones derived from catecholamines with a primary amino group in the side chain do not appear to undergo intramolecular cyclization very readily and consequently would be able to take part in competing reactions this would account for the fact that in general it is difficult to obtain efficient conversions of such catecholamines (e.g. noradrenaline) into the corresponding aminochromes. This factor is important in catecholamine assay procedures (see Section V, E) and probably explains the wide variability in the apparent efficiency of the noradrenaline oxidation procedures used (as measured by the intensity of the fluorescence of the noradrenolutin obtained by the particular method). The fact that noradrenaline-quinone is relatively more stable than adrenaline-quinone accounts for the formation of entirely different types of fluorescent products from adrenaline and noradrenaline, respectively, in the Weil-Malherbe assay procedure for catecholamines (see Sections IV, H and V, E, 5). 

L. Bonhomme, D. Benhamou, E. Conroy, and N. Preaux, Stability of adrenaline pH-adjusted solutions of local anaesthetics, J. Pharm. Biomed. Anal., 9 497 (1991). 

Fentanyl citrate is stable if stored at room temperature up to 48 hours under normal conditions. Fentanyl should not be formulated with alkaline drugs and stored in PVC containers for product stability reasons. Formulations containing fentanyl and bupivacaine were found to be adsorbed in PVC containers. The formulation containing adrenaline or fentanyl citrate becomes degraded.55-57... 

In intensive care settings, sympathomimetic catecholamines [e.g., dobutamine, dopamine, epinephrine (adrenaline), isoprenaline (isoproterenol), norepinephrine (noradrenaline, and levarterenol] are often administered via continuous infusion. In clinical practice, reservoirs and administration sets of these drugs are routinely changed every 12 or 24 hours. As the pharmacological efficacy of catecholamines is directly related to their intact phenolic groups, their stability over these dosing periods is questionable. 

Adrenaline acid tartrate (0.4mg/L in normal saline and packaged in polypropylene syringes) exposed for 24 hours to ambient illuminating conditions also showed no loss of potency (78). However, various epinephrine preparations may vary in their stability, depending on the form of epinephrine as well as the preservatives and packaging used. Hoechst (today, Sanofi-Aventis) claims that, according to their experimental studies, diluted solutions (0.2,1,2mg/L) of Arterenol (norepinephrine HCL) and Suprarenin (epinephrine HCL) are stable for up to 24 hours in polypropylene syringes, if stored without photoprotection. 

Epinephrine. Epinephrine (Adrenalin) finds use in a number of situations because of its potent stimulatory effects on both a- and /3-adrcncrgic receptors. Like the other catecholamines, epinephrine is light sensitive and easily oxidized on exposure to air because of the catechol ring system. The development of a pink to brown color indicates oxidative breakdown. To minimize oxidation, solutions of the drug are. stabilized by the addition of reducing agents such as sodium bisulfite. As the free amine, it is used in aqueous solution for inhalation. Like other amines, it forms salts with acids, for example, those now used include the hydrochloride and the bitartratc. Epinephrine is destroyed readily in alkaline solutions and by metals (c.g.. Cu, Fe, Zn), weak... 

Lidocaine without adrenaline is therefore the best choice of LA for FNB before a full-face phenol peel. Lidocaine stabilizes the heartbeat, so accidental intravascular injection of... 

Adrenaline and noradrenaline can both give rise to melanins (c/. below). An intermediate in such a transformation of adrenaline is adrenochrome, a molecule stabilized by resonance (359). Adrenochrome has a powerful effect on the maturation of reticulocytes (281) and might play a part in normal physiological processes. The extent to which adrenaline is converted to adrenochrome and melanin, and its significance, is still unknown. 

The aromatic ring of adrenaline is stabilized by means of TT-TT interactions with Phe and Phe ... 

The detection limit of the autoxidation assay is 0.5 nM superoxide dismutase The oxidation of adrenalin is followed at 480 nm spectrometrically. 850 pi 100 mM carbonate buffer, pH 10 and 100 pi water or sample are mixed. The reaction is started with 50 pi catecholamine stabilized at pH 2. AA/min is followed. Due to its convenience, this method can be employed in homogenates and other biological samples However, the assay can interfere with reduced glutathione, causing an... 

Comment This patient s blood pressure dropped to a dangerously low level. A bolus dose of adrenaline was given to stabilize him until the adrenaline infusion was restarted. 

Upon degradation, adrenaline solution first turns into pink, then red, and finally brown. Adrenaline is first oxidised into adrenochrome, which is consecutively oxidised into the fluorescent adrenolutin and brown melanin products [18]. The oxidation rates increase with increasing pH. The stability is the best at pH 3.2-3.6, by virtue of the relatively low reaction rate of the first step at this pH [19]. At pH 7.4, the rate of the second step is relatively high, whilst at pH 6.9, accumulation of adrenochrome occurs [18]. 

To add to the complexity of the preparation, bisulfite has a negative effect on the stability of adrenaline in presence of light. Therefore, it may be necessary to avoid the use of bisulfite if the solution is exposed to light during the administration, especially during continuous infusion [31]. 

The vasoconstrictor effect of adrenaline should cause hypertension. However, paradoxical hypotension has been reported in three patients with massive quetiapine overdose, in whom the blood pressure fell dramatically after infusion of adrenaline hemodynamic stability was restored when noradrenaline was substituted for adrenaline [67 ]. 

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