Epinephrine stability

Important products derived from amino acids include heme, purines, pyrimidines, hormones, neurotransmitters, and biologically active peptides. In addition, many proteins contain amino acids that have been modified for a specific function such as binding calcium or as intermediates that serve to stabilize proteins—generally structural proteins—by subsequent covalent cross-hnk-ing. The amino acid residues in those proteins serve as precursors for these modified residues. Small peptides or peptide-like molecules not synthesized on ribosomes fulfill specific functions in cells. Histamine plays a central role in many allergic reactions. Neurotransmitters derived from amino acids include y-aminobutyrate, 5-hydroxytryptamine (serotonin), dopamine, norepinephrine, and epinephrine. Many drugs used to treat neurologic and psychiatric conditions affect the metabolism of these neurotransmitters. 

Stablizers. Stabilizers are ingredients added to a formula to decrease the rate of decomposition of the active ingredients. Antioxidants are the principal stabilizers added to some ophthalmic solutions, primarily those containing epinephrine and other oxidizable drugs. Sodium bisulfite or metabisulfite are used in concentration up to 0.3% in epinephrine hydrochloride and bitartrate solutions. Epinephrine borate solutions have a pH range of 5.5 7.5 and offer a more difficult challenge to formulators who seek to prevent oxidation. Several patented antioxidant systems have been developed specifically for this compound. These consist of ascorbic acid and acetylcysteine, and sodium bisulfite and 8-hydroxyquinoline. Isoascorbic acid is also an effective antioxidant for this drug. Sodium thiosulfate is used with sodium sulfacetamide solutions. 

Cuanethidine possesses high affinity for the axolemmal and vesicular amine transporters, it is stored instead of NE, but is unable to mimic the functions of the latter, in addition, it stabilizes the axonal membrane, thereby impeding the propagation of impulses into the sympathetic nerve terminals. Storage and release of epinephrine from the adrenal medulla are not affected, owing to the absence of a re-uptake process. The drug does not cross the blood-brain barrier. 

Death from SNA Intoxication appears to Involve both cardiovascular and respiratory systems. 2 SNA Increases the effects of pentobarbital on both respiration and heart rate. The depressant effects of SNA on the myocardium and on the Purklnje system are antagonized effectively by epinephrine, but not by Metrazol (pentylenetetrazol) and caffeine. Artificial respiration restored cardiac stability and regularity. It was suggested that SNA Interferes with oxygen utilization In animals. The circulatory and respiratory responses to SNA were considered to be mediated through the medulla oblongata. 2... 

Although the hydrolytic stability of some phosphazene polymer makes them attractive as structural materials, it is possible to create hydrolytically sensitive phosphazenes that may be useful medically as slow-rdease drugs. Steroids, antibiotics. and catecholamines (e.g., dopamine and epinephrine) have been linked to a polyphosphazene skeleton (Fig. 16.27) with the intention that slow hydrolysis would provide these drugs in a therapeutic steady state. 

Since Clenbuterol dilates blood vessels in skeletal muscle but relaxes smooth muscle blood vessels, the physical reactions are quite similar to the body s own epinephrine and can effect heart rate. It also reduces the level of the amino acid taurine in the heart which stabilizes cardiac rhythms, or the electrical activity in the heart. Increased intake for taurine during use was noted as wise. 

Beta blockers bind to beta-1 receptors on the myocardium and block the effects of norepinephrine and epinephrine (see Chapter 20). These drugs therefore normalize sympathetic stimulation of the heart and help reduce heart rate (negative chronotropic effect) and myocardial contraction force (negative inotropic effect). Beta blockers may also prevent angina by stabilizing cardiac workload, and they may prevent certain arrhythmias by stabilizing heart rate.40 These additional properties can be useful to patients with heart failure who also have other cardiac symptoms. 

This alkaloid was first isolated from Ephedra equisetina, a plant (ma huang) that has been used as medicine by the Chinese since antiquity. Most of the present supply is probably synthetic. Its chemical structure is closely related to epinephrine and tyramine, and differs from epinephrine chiefly by the absence of the two phenolic hydroxyls. Its effects on the circulation, intestines, bronchi, iris, etc., are superficially similar to those of epinephrine. It requires that larger doses be given but they are more lasting, due probably to ephedrine s much greater stability and resistance to oxidation. The effects can be produced by oral administration. Unlike epinephrine, it is not sensitized by cocaine or by denervation. From this, it has been argued that its point of attack is not sympathomimetic but muscular. It also stimulates the CNS. A number of isomers with similar actions are known. Ephedrine is used therapeutically in hay fever and asthma, in which it is less... 

S. M. Waraszkiewicz, E. A. Milano, and R. L. DiRubio, A stability indicating LCEC method for epinephrine and its application to the analysis of lidocaine hydrochloride injectable solutions, Curr. Sep., 4(2) 23 (1982). 

EDTA is also used as a synergist to increase the activity of antioxidants, and to complex small amounts of heavy metal ions. EDTA has been frequently used to stabilize preparations of penicillins, ascorbic acid, epinephrine and prednisolone [4], Over the past 35 years, EDTA has been used to induce hypocalcaemia in cows and other species, primarily for the induction of hypocalcaemia as a model for milk fever [8]. 

Li et al. [77] reported the electrocatalytic oxidation of norepinephrine at a GCE modified with SWCNTs. The electrode showed a very good reproducibility and stability. A linear relationship was obtained between the oxidation peak current and norepinephrine concentration between 1.0 x 10 and 1.1 x 10" M and the detection limit was 6.0 x 10 M. The electrocatalytic activity of the SWCNTs-modified-GCE was also demonstrated with dopamine, epinephrine and ascorbic acid. 

Wolknann H, Gruenert R. Influence of visible light on stability of isoprenaline, epinephrine and levarterenol solutions in different containers. Part 86 contributions about the problem concerning the use of plastic containers for liquid medicinal preparations. Part 21 stability of pharmaceuticals and preparations. Pharmazie 1984 39(3) 161-163. 

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... 

---