Adrenaline effects

Systemic reactions to added adrenaline (norepinephrine) are unusual, but can occur and are usually expressed as temporary blood pressure increase, palpitations and anxiety. These reactions rarely require any other treatment than calming explanations. Adrenaline containing local anaesthetics should only be given with particular caution to individuals with increased susceptibility to adrenaline effects - e.g. patients treated with noradrenaline reuptake inhibitors or patients with certain heart diseases. 

In other cells, i.e. in rat submandibular gland, adrenaline (100 pmol/l) has been shown to decrease the percentage of dye-coupled cells [Kanno et al., 1993], whereas isoproterenol was ineffective, so that the authors concluded that the mechanism was transmitted via action on the -adrenoceptors. This was supported since the adrenaline effect could be suppressed by coadministration of 10 pmol/1 phenoxybenzamine. 

However, the exercise effect has been demonstrated with assays involving (supposedly maximal) activation of factors XI and XII with kaolin (13), and a system to which activation product was added (VI) duly registered the adrenaline effect. Furthermore, a rise in factor VIII concentration has now been produced by exercise in patients with severe deficiencies of factors XI and XII. Egeberg (E13) tested two patients with gross deficiencies of factor XI, and Goudemand et al. (G2) and A. Parquet-Gemez (personal communication, 1964) tested factor Xll-deficient patients. 

Evidence was given above (Section 3.4.1) that the exercise or adrenaline effect was demonstrated by assay systems in which precautions had been taken to provide full surface activation. The comparative data of both Ikkala (12, 13) and Ingram (15) show, however, that the effects were more marked when these precautions were not taken, and Ikkala (12) also showed that the effect was more marked when phospholipid was not added to the system, although it was still clearly seen in its presence. The reduction in the effect either by surface contact or by phospholipid, or both (12), raises the suspicion that if even more efficient agents had been added to the assay the effect would have been eliminated altogether, but so far this has not been achieved. 

Not only the nutritional status but also the age of animals influences the lipid-mobilizing reactions Dury (1961) and Jelinkova-Tenorovd and Hr a (1963) found a marked falling off of the adrenalin effect in aged animals. 

It now appears that many hormones (e.g. glucagon and adrenaline) in both animals and plants exert their effects by, as a first step, decreasing or increasing cyclic AMP within the cell. This may possibly occur by modification of the activity of the enzyme AMP cyclase which generates cyclic AMP from ATP. 

Epinephrine is also known as adrenaline and is a hormone with profound physiological effects designed to prepare the body for fight or flight... 

Catecholamines. The catecholamines, epinephrine (EPl adrenaline) (85), norepinephrine (NE noradrenaline) (86) (see Epinephrine and norepinephrine), and dopamine (DA) (2), are produced from tyrosine by the sequential formation of L-dopa, DA, NE, and finally EPl. EPl and NE produce their physiological effects via CC- and -adrenoceptors, a-Adrenoceptors can be further divided into CC - and a2-subtypes which in turn are divided... 

The modern usage of P2" go Asts for the treatment of asthma dates to 1903 when the effect of injected epinephrine [51-43-4] (adrenaline) C2H23NO2, (1 R = CH3) was investigated (see Epinephrine and norepinephrine) (33). As in some other modem treatments, eg, xanthines and anticholinergics, the roots of P2" go Ast therapy for asthma can be found in historical records which document the use of herbal extracts containing ephedrine [299-42-3] C qH NO, (2) as bronchodilators. Epinephrine and ephedrine are stmcturaHy related to the catecholamine norepinephrine [51-41-2] CgH NO, (1, R = H), a neurotransmitter of the adrenergic nervous system (see Neuroregulators). 

L-Tyrosine metabohsm and catecholamine biosynthesis occur largely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andhpid metabohsm. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bUe acids and the detoxification process of aromatic dmgs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabohsm related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

According to Powell and Chen, gramine, used as the unstable hydrochloride, m.p. 191° (dec.), raises the blood pressure in anaesthetised cats in Small doses, but lowers it in doses of 30 to 40 mgm. per kilo., with a secondary rise. It reduces the chief effects of adrenaline without reversal. The toxic dose for rats is about 63 mgm./kilo. Supniewski and Serafinowna state that gramine excites the central nervous system in mammals, but in large doses causes paralysis. At 1 in 25,000 it causes contraction of the isolated uterus. 

Raymond-Hamet has made a special study of the vascular action of the harmala alkaloids and certain of their proximate derivatives, including their influence on the pressor and other effects of adrenaline in comparison with that of yobyrine and ketoyobyrine (pp. 505-6). 

Raymond-Hamet has given much attention to the action of the Rauwolfia alkaloids. Using Siddiqui s ajrhalinine, he found that it provokes hypotension accompanied by renal dilatation and exerts a true sympathi-colytic action. 1 Ajmaline and serpentine also induce hypotension and a decrease in intestinal action serpentinine diminishes the renal constrictive action of adrenaline, but does not alter its hypertensive effects. ... 

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

Hi-receptors in the adrenal medulla stimulates the release of the two catecholamines noradrenaline and adrenaline as well as enkephalins. In the heart, histamine produces negative inotropic effects via Hr receptor stimulation, but these are normally masked by the positive effects of H2-receptor stimulation on heart rate and force of contraction. Histamine Hi-receptors are widely distributed in human brain and highest densities are found in neocortex, hippocampus, nucleus accumbens, thalamus and posterior hypothalamus where they predominantly excite neuronal activity. Histamine Hrreceptor stimulation can also activate peripheral sensory nerve endings leading to itching and a surrounding vasodilatation ( flare ) due to an axonal reflex and the consequent release of peptide neurotransmitters from collateral nerve endings. 

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. 

LAs are not often used as a single substance, but are mixed preparations with adrenaline and preservatives. This has to be differentiated by the diagnostic procedure [9]. Pharmacologic effects of adrenaline (paleness, tachycardia, hypertension, feeling of fear) have to be differentiated from anaphylactic reactions to the LA substance [10]. 

Marsden, CA (1987) Measurements of hypothalmic adrenaline release in vivo—effects of drugs and electrical stimulation. Neuropharmacol. 22 823-830. 

The organ also contains neuroactive compounds as constituents of the vasomotor and neuro-glandular tissues (Zancanaro et al., 1997). These include the amine transmitters Nor-adrenalin and Serotonin (5-HT), whose presence is presumably related to the non-olfactory innervations. Local stimulation effects [Figs. 5.2 and 5.5(a)] can alter the biogenic amine levels in the VNO of female mice, as a result of exposure to male conspecific urine, and consequent arousal of the suction-pump [c.f. Fig. 5.7(a)]. 

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