Adrenaline applications

Heterologous desensitisation refers to the desensitisation of the response to one agonist by the application of a different agonist. For example, desensitisation of a response to adrenaline by application of 5-HT is mediated by protein kinase A or protein kinase C because these kinases can phosphorylate receptors which are not occupied by agonist. Phosphorylation disrupts the receptor-G-protein interaction and induces the binding of specific proteins, arrestins which enhance receptors internalisation via clathrin-coated pits. Thus desensitisation of G-protein-coupled receptors results in a decrease in the number of functional receptors on the cell surface. 

At the bronchi, predominantly /32-adrenoceptors are present on the smooth muscle cells. Therefor noradrenaline has hardly any influence on the muscular tonus whereas adrenaline induce a dilatation especially of precontracted bronchi, independent of the cause (histamine, acetylcholine, kinines, prostanoides). This effect can be used therapeutically in the therapy of bronchial asthma. In general the local application by aerosol is more useful than the systemic application, due to lesser side effects and the additional, beneficial effect of the reduction of mucosa swelling. 

Adrenoceptors of the /3-subtype are important mediators of the sympathetic activation of the heart, kidney, and bronchi. /3-Adrenoceptors are also found in other organs and tissues such as blood vessels and the central nervous system. Accordingly, /3-adrenoceptor antagonists or jS-blockers inhibit the stimulating influence of the endogenous catecholamines (noradrenaline, adrenaline) on the various organs and tissues which are subject to sympathetic innervation. In cardiovascular medicine the /3-blockers are used in particular to blunt the sympathetic activation of the heart and kidneys. These effects are mediated by the /3i-subtype of the /3-adrenoceptors. The currently used /3-blockers are all competitive antagonists of the /3i-adrenoceptor, which is the basis of their therapeutic application. 

Noradrenaline and adrenaline are the classic catecholamines and neurotransmitters in the sympathetic nervous system. Noradrenaline stimulates the following subtypes of adrenoceptors P, a, U2. It has positive inotropic and chronotropic activities as a result of /3i-receptor stimulation. In addition, it is a potent vasoconstrictor agent as a result of the stimulation of both subtypes (ai,a2) of a-adrenoceptors. After intravenous infusion, its effects develop within a few minutes, and these actions disappear within 1-2 minutes after stopping the infusion. It may be used in conditions of acute hypotension and shock, especially in patients with very low vascular resistance. It is also frequently used as a vasoconstrictor, added to local anaesthetics. Adrenaline stimulates the following subtypes of adrenoceptors /3i, P2, oil, 0L2. Its pharmacological profile greatly resembles that of noradrenaline (see above), as well as its potential applications in shock and hypotension. Like noradrenaline, its onset and duration of action are very short, as a result of rapid inactivation in vivo. Both noradrenaline and adrenaline may be used for cardiac stimulation. Their vasoconstrictor activity should be kept in mind. A problem associated with the use of /3-adrenoceptor stimulants is the tachyphylaxis of their effects, explained by the /3-adrenoceptor downregulation, which is characteristic for heart failure. 

Tetrahydropyrrolo[3,2-f]pyridine derivatives, 148, inhibit platelet aggregation induced by adrenaline and ADP <2003JPL323>. Compounds such as 148 have been selected due to their lower lipophilicity compared to thienopyr-idine compounds used in similar applications. 

Clinical use Because of its poor penetration of intact mucous membranes, procaine is largely ineffective for topical applications and has been mainly used in injection in combination with adrenaline, although in general it has been replaced by other LAs such as lidocaine. For infiltration anesthesia, 0.25 to 0.5 % solutions of procaine have been used in doses up to 600 mg. For peripheral nerve block, a common dose of 500 mg of procaine has been given as a 0.5 to 2.0 % solution. 

HPLC analysis of polycyclic aromatic hydrocarbons (PAH) in drinking water is one of the current and classical applications of fluorescence. In this case, the detector contains a fluorescence flow cell placed after the chromatographic column. This mode of detection is specifically adapted to obtain threshold measurements imposed by legislation. The same process allows the measurement of aflatoxins (Fig. 12.11) and many other organic compounds (such as adrenaline, quinine, steroids and vitamins). 

S. Trumpp-KaUmeyer, 1. Hofladc, A. Bruinvels. and M. Hibert. Modeling of G protein coupled receptors application to dopamine, adrenaline, semtinine, acetylcholine and mammalian opsin receptors, / Med. Chem. 35 3448-3462 (1992). 

Figure 2.10 Amphetamine 30, methamphetamine 31, and methylenedioxymethamphetamine 32 (MDMA, ecstasy, XTC) are lipophilic compounds with good oral bioavailability they easily cross the blood-brain barrier to exert central nervous system effects. Dopamine 33, norepinephrine (noradrenalin) 34, and epinephrine (adrenaline) 35 are polar phenethylamines they have poor oral efficacy and do not pass the blood-brain barrier, producing only peripheral effects after intravenous application. Ephedrine 36 has intermediate lipophilicity besides its peripheral effects it also acts as a central stimulant. Although L-dopa 37 is even more polar than dopamine 33, it is orally active and crosses the blood-brain barrier by active transport mediated by the amino acid transporter.

Trumpp-Kallmeyer, S., Hoflack, J., Bruinvels, A., Hibert, M. Modelling of G-protein-coupled receptors Applications to Dopamine, Adrenaline, Serotonin, Acetylcholine and Mammalian Opsin receptors. J. Med. Chem., 1992, 35, 3448-3462. 

The effect of a local anaesthetic is terminated by its removal from the site of application. Anything that delays its absorption into the circulation will prolong its local action and can reduce its systemic toxicity where large doses are used. Most local anaesthetics, with the exception of cocaine, cause vascular dilation. The addition of a vasoconstrictor such as adrenaline (epinephrine) reduces local blood flow, slows the rate of absorption of the local anaesthetic, and prolongs its effect the duration of action of lidocaine is doubled from one to two hours. Normally, the final concentration of adrenaline (epinephrine) should be 1 in 200 000, although dentists use up to 1 in 80 000. 

Hypersensitivity reactions to potassium metabisulfite and other sulfites, mainly used as preservatives in food products, have been reported. Reactions include bronchospasm and anaphylaxis some deaths have also been reported, especially in those with a history of asthma or atopic allergy. " These reactions have led to restrictions by the FDA on the use of sulfites in food applications. However, this restriction has not been extended to their use in pharmaceutical applications. Indeed, epinephrine (adrenaline) injections used to treat severe allergic reactions may contain sulfites. ... 

Topical application of 2% lidocaine solution with adrenaline (epinephrine), poured directly onto sterile gauze... 

Chapter 33 is devoted to the details of anesthesia for a phenol peel. Lip Eyelid formula can be applied without any anesthetic on small areas, however. Patients feel an intense burning sensation a few seconds after application. They will have been told that the burning sensation only lasts for 15 seconds and that they can have a nerve block if they want. Vocal anesthesia plays an important part, and the patient can take a paracetamol (acetaminophen) plus codeine tablet 1 hour before the treatment. Nerve blocks are often used to increase patient comfort 2% Hdocaine without adrenaline (epinephrine) is used, and its duration of action is sufficient. The patient should be given paracetamol plus codeine tablets for the post-peel pain, which is inevitable during the first 24 hours because of the severity and rapidity of inflammation caused by the peel. 

Hyaluronidase has found applications as an additive to the anesthetic agents used for peribulbar anesthesia for vitreoretinal surgery. Combinations of hyaluronidase with bupivacaine [119], lidocaine and epinephrine [120], lignocaine and adrenaline [121], or lidocaine and bupivacaine [122] were judged very... 

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