Catecholamines Epinephrine, Isoprenaline

Owing to its equally high af nity for all a-and p-receptors, epinephrine does not permit selective activation of a particular receptor subtype. Like most catecholamines, it is also unsuitable for oral administration (cat-echole is a trivial name for o-hydroxyphe-nol). Norepinephrine differs from epinephrine by its high af nity for a-receptors and low af nity for p2-receptors. The converse holds true for the synthetic substance, isoproterenol (isoprenaline) (A). 

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. 

Catecholamines degrade rapidly via oxidative reactions and are catalyzed by oxygen, pH s >6, heavy metal ions, heat, and UV-VIS radiation. UV-VIS radiation is more deleterious than temperature, and UV is 15 times more deleterious than VIS radiation. The degradation rates, of individual catecholamines, vary and are dependent on the position of their phenolic groups and the type of N-substituents in the aminoalkyl side chain. For instance, norepinephrine is more stable than epinephrine, and epinephrine is more stable than isoprenaline. 

Drugs that contain two phenolic groups, such as adrenaline (epinephrine) and other catecholamines such as noradrenaline (norepinephrine) and isoprenaline are particularly susceptible to oxidation and have to be formulated at acidic pH. All of these compounds are white crystalline solids that darken on exposure to air. Adrenaline forms the red coloured compound adrenochrome on oxidation (Figure 8.10), which can further polymerise to give black compounds similar in structure to melanin, the natural skin pigment. Injections of adrenaline that develop a pink colour, or that contain crystals of black compound, should not be used for this reason. Adrenaline for injection is formulated as the acid tartrate... 

Fig. 4.4.12. Separation of a mixture of acidic and basic catecholamines on a LiChrosorb RP-8 column (0.28x25 cm). Eluent Water containing 0.02 M citrate (pH 2.5)/l% propanol/NaCIQ4 (0.08 M)/0.3% sodium dodecyl sulphate. Peaks DHMA, 3,4-dihydroxymandelic acid VMA, vanilmandelic acid HGA, 2,5-dihydroxyphenylacetic acid DOPAC, 3,4-dihydroxyphenylacetic acid 5-HIAA, 5-hydroxyindole-3-acetic acid HVA, homovanillylmandelic acid E, epinephrine NE, norepinephrine N-Syn, norsyneph-rine Syn, synephrine Dopa, 3,4-dihydroxyphenylalanine NM, normetanephrine MN, metanephrine Isopren, isoprenaline 3-H-Tyrm, dopamine Tyrm, tyramine 3-M-Tyrm, 3-methoxytyramine. Reprinted from Ref. 21 with permission.

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