Beta-adrenergic receptor pharmacology

Liggett SB. Pharmacogenetics of beta-land beta-2-adrenergic receptors. Pharmacology 2000 61 167-173. 

Clinical Trials. In Phase I studies, good documentation and additional investigations should be standard practice. Serious reactions are pretty unusual in these studies, which will detect only very common ADRs, in particular those that are pharmacologically mediated (e.g., bradycardia with beta adrenergic receptor antagonists). 

Levodopa shonld be nsed with cantion in patients with varions cardiovascnlar disorders. The peripheral decarboxylation of levodopa markedly increases the concentration of dopamine in the blood. Dopamine is a pharmacologically active catecholamine that inflnences alpha- and beta-adrenergic receptors. 

The pharmacologic effects of beta-adrenergic agonist drugs, including albuterol, are at least in part attributable to stimulation through beta-adrenergic receptors of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3, 5 -adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. 

I. Pharmacology. Inamrinone is a positive inotropic agent with vasodilator activity. It is not a beta-adrenergic receptor agonist, and its exact mechanism of action is unknown. It appears to work by inhibition of myocardial cell phosphodiesterase activity, thereby increasing cellular concentrations of cyclic AMP. Cardiac afterload and preload are reduced owing to a direct vasodilator effect. 

I. Pharmacology. Isoproterenol is a catecholamine-like drug that stimulates beta-adrenergic receptors (beta-1 and -2). Pharmacologic properties include positive inotropic and chronotropic cardiac effects, periphery vasodilation, and bron-chodilation. Isoproterenol is not absorbed orally and shows variable and erratic absorption from sublingual and rectal sites. The effects of the drug are rapidly terminated by tissue uptake and metabolism effects persist only a few minutes after intravenous injection. 

I. Pharmacology. Phentolamine is a competitive presynaptic and postsynaptic alpha-adrenergic receptor blocker that produces peripheral vasodilation. By acting on both venous and arterial vessels, it decreases total peripheral resistance and venous return. It may also stimulate beta-adrenergic receptors, causing cardiac stimulation. Phentolamine has a rapid onset of action (usually 2 minutes) and short duration of effect (approximately 15-20 minutes). 

Murmann, W., Rumore, G. and Gamba, A. (1967) Pharmacological properties of l-(4 -nitrophenyl)-2-isopropylamino-ethanol (INPEA), a new beta-adrenergic receptor antagonist. V. Effects of the optical isomers D(minus) and L(plus) INPEA on heart rate, oxygen consumption and body temperature and on the cardiac and metabolic effects of adrenaline and noradrenaline in urethane-anesthetized rats. Boll. Chim. Farm., 106, 251-268. 

Wit, A. L., Hoffman, B. F. and Rosen, M. R.(1975) Electrophysiology and pharmacology of cardiac arrhythmias. IX. Cardiac electrophysiology effects of beta adrenergic receptor stimuiation and biockade. Part B. Amer. Heart J., 90, 665. 

In summary, adrenergic receptors can be subclassified according to their location and affinity for specific pharmacologic agents. Table 18-2 summarizes the receptor subtypes that are located on the primary organs and tissues in the body, and the associated response when the receptor is stimulated. Exactly which receptor subtype is located on any given tissue depends on the tissue in question. Note that some tissues may have two or more different subtypes of adrenergic receptor (e.g., skeletal muscle arterioles appear to have alpha-1 and beta-2 receptors). Also, the response of a tissue when the receptor is stimulated is dependent on the specific receptor-cell interaction. Stimulation of the vascular alpha-1 receptor, for instance, results in smooth-muscle contraction and vasoconstriction, whereas stimulation of the intestinal alpha-1 receptor results in relaxation and decreased intestinal motility. This difference is caused by the way the receptor is coupled to the cell s internal biochemistry at each location. As discussed in Chapter 4, the surface receptor at one cell may be coupled to the... 

Beta-Adrenergic Blocking Agents ((3-Blockers) - Studies on the identification and characterisation of p-adrenergic receptors have been reviewed.56 p-Receptors have been identified in the rat brain57 and localised using a fluorescent p-blocker.58 The clinical pharmacology of P-blockers has been summarised.59 The use of propranolol (ICI) (lo) in hypertension has been reviewed.8° It is now available in the U.S.A. for this indication.8la Atenolol (ICI 66082, Tenormin ) (11) has been... 

Fig. 5. The physiologic and pharmacologic pathway of P2 agonist on [It. XR. This pathway is complex and many signal cascade proteins shown may have relevant genetic variations that may modify sensitivity to pharmacotherapy. (From Johnson M. Molecular mechanisms of beta(2)-adrenergic receptor function, response, and regulation. J Allergy Clin Immunol 2006 117 18-24 with permission.)...

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