Adrenaline Epinephrine

FIGURE 27.5 Tyrosine is the biosynthetic precursor to a number of neurotransmitters. Each transformation is enzyme-catalyzed. Hydroxy-lation of the aromatic ring of tyrosine converts it to 3,4-dihydroxy phenylalanine (L-dopa), decarboxylation of which gives dopamine. Hy-droxylation of the benzylic carbon of dopamine converts it to norepinephrine (noradrenaline), and methy-lation of the amino group of norepinephrine yields epinephrine (adrenaline). 

Adrenergic. Relating to epinephrine (adrenaline) or norepinephrine (noradrenaline). Commonly used to describe neurons that utilize norepinephrine as a neurotransmitter and the drugs that interact with these neurons. 

Epinephrine (adrenaline). A biogenic amine released from the adrenal medulla, particularly in moments of stress. 

Epinephrine (adrenalin) 0.1 to 0.5 mg may be given by subcutaneous or intramuscular injection. Hypotension and shock may be treated with fluids and vasopressors. Bronchodilators are given to relax the smooth muscles of the bronchial tubes. Antihistamines may be given to block the effects of histamine. 

Examples of sympathomimetic bronchodilators include albuterol (Ventolin), epinephrine (Adrenalin), salme-terol (Serevent), and terbutaline (Brethine). Many of the sympathomimetics used as bronchodilators have die subclassification of beta-2 ((32) receptor agonists (eg, albuterol, salmeterol, and terbutaline). Additional information concerning the various sympathomimetic dragp is given in the Summary Drug Table Bronchodilators. 

Among the antianaphylactic drugs, epinephrine (adrenaline) is the essential substance. In the acute treatment of the anaphylaxis in addition to the classical ABC (airway, breathing, circulation) rule for cardiopulmonary resuscitation [26, 27], one can apply the AAC rule (antigen off, adrenaline, cortisone) [18], Other drugs playing a role in the treatment of anaphylaxis include antihistamines (Hi-antagonists). 

For nearly a century, epinephrine (adrenaline) has been the cornerstone of the acute management of anaphylaxis [1-6], a sudden-onset multi-systemic allergic reaction that can cause death. The World Health Organization lists epinephrine as an essential medication for anaphylaxis [7], Where national guidelines are available for the acute management of anaphylaxis, they universally recommend injection of epinephrine as the initial medication of choice [8]. 

The chemistry of most of the drugs in this family is quite simple, accounting in part for the very large number of analogues which have been made. The foundation for the chemistry in this series was laid long ago by Stolz in his classic synthesis of the ophthalmic agent adrenal one (3) in which he reacted catechol with chloroacetyl chloride and then displaced the reactive chlorine atom with methylamine to complete the synthesis. Borohydride reduction would have given epinephrine (adrenaline). 

Inhalation of certain hydrocarbons, including some anesthetics, can make the mammalian heart abnormally sensitive to epinephrine, resulting in ventricular arrhythmias, which in some cases can lead to sudden death (Reinhardt et al. 1971). The mechanism of action of cardiac sensitization is not completely understood but appears to involve a disturbance in the normal conduction of the electrical impulse through the heart, probably by producing a local disturbance in the electrical potential across cell membranes. The hydrocarbons themselves do not produce arrhythmia the arrhythmia is the result of the potentiation of endogenous epinephrine (adrenalin) by the hydrocarbon. 

Tyrosine (Tyr or Y) (4-hydroxyphenylalanine ((5)-2-amino-3-(4-hydroxyphenyl)-propanoic acid)) is a polar, neutral, aromatic amino acid with the formula H00CCH(NH2)CH2C6H50H and is the precursor of thyroxin, dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), and the pigment melanin. Being the precursor amino acid for the thyroid gland hormone thyroxin, a defect in this may result in hypothyroidism. Tyr is extremely soluble in water, a property that has proven useful in isolating this amino acid from protein hydrolysates. The occurrence of tyrosine- 0-sulfate as a constituent of human urine and fibrinogen has been reported. ... 

Tyrosine is also the metabolic precursor to the neurotransmitter dopamine and the catecholamine hormones norepinephrine (noradrenaline) and epinephrine (adrenaline), as well as to the alkaloids in opium, including morphine. 

Selective hydroxylation of some aromatic compounds can be achieved using HRP C in the presence of oxygen and dihydroxyfumaric acid (270). This process afforded l-DOPA from L-tyrosine, D-(-)-3,4-dihydroxy-phenylglycine from D-(—)-4-hydroxyphenylglycine, and L-epinephrine (adrenalin) from L-(-)-phenylephrine in yields of up to 70%. 

A number of very important natural and synthetic biochemicals belong to the phenylethylamine family. Two of these compounds, dopamine and epinephrine (adrenaline), are neurotransmitters, substances that carry chemical messages through the nervous system of humans and other animals. A third phenylethylamine, tyrosine, is an essential amino acid. And a familiar phenylethylamine found in plants is mescaline, whose chemical name is 2-(3,4,5-trimethoxy-phenyl)ethylamine. The primary natural sources of mescaline are four varieties of cactus two peyote species (Lophophora wiUiamsii and Lophophora diffusa), the San Pedro cactus (Trichocereus pacha-noi), and the Peruvian Torch cactus (Trichocereus peruvianus). 

Finally, N-methylation of norepinephrine yields epinephrine (adrenaline). The coenzyme for this reaction is S-adenosylme-thionine (SAM see p. 110). 

Skeletal muscle glycogen delivers glucose primarily as a response to contractile stress. Regulation occurs through both modification of the enzyme phosphorylase, primarily by the action of epinephrine-adrenaline and allosteric regulation of phosphorylase related to a demand for ATP. 

Monoaminooxidase is a complex enzymatic system that is present in practically every organ that catalyzes deamination or inactivation of various natural, biogenic amines, in particular norepinephrine (noradrenaline), epinephrine (adrenaline), and serotonin. Inhibition of MAO increases the quantity of these biogenic amines in nerve endings. MAO inhibitors increase the intercellular concentration of endogenous amines by inhibiting then-deamination, which seems to be the cause of their antidepressant action. 

It is believed that the mechanism of action of amphetamines lies in their ability to release epinephrine (adrenaline) and dopamine from presynaptic nerve endings, which stimulate the corresponding receptors in the CNS. It is also possible that they reduce neuronal uptake of amines as well as inhibit their degradation by monoaminoxidase (MAO). Characteristic of this series of compounds is the effect on the respiratory center, on the satiation center located in the hypothalamus, which leads to suppression of feelings of hunger, thus allowing analog of the examined compounds to be used as anorectics. 

In terms of chemical structure, amphetamines are very close to epinephrine (adrenaline), norepinephrine (noradrenaline), and dopamine, differing in the absence of a hydroxyl group in the aromatic ring and in the aliphatic chain. 

Adrenergic drugs are natural or synthetic compounds that either partially or completely replicate the effects of norepinephrine (noradrenaline), epinephrine (adrenaline), and dopamine, and which cause a biological response similar to the activation of the sympathetic nervous system. They are also referred to as sympathomimeties beeause they mimic the stimulation of the sympathetic nervous system. 

The distinctive feature of a-adrenoblockers is their ability to reduce the pressor effect of pharmacological doses of epinephrine (adrenaline). 

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