Receptor Blocking Agents

Atropine and scopolamine, which are obtained from belladonna alkaloids, as well as other synthetic anticholinergic drugs, inhibit the actions of acetylcholine and cholinomimetic drugs at muscarinic receptors in smooth muscles, heart, and exocrine glands. In addition to these peripheral 

Atropine is absorbed orally and crosses the placental barrier, whereupon it causes fetal tachycardia. Atropine has been used to examine the functional integrity of the placenta. Atropine toxicity is characterized by dry mouth, burning sensation in the mouth, rapid pulse, mydriasis, blurred vision, photophobia, dry and flushed skin, restlessness, and excitement. 

Physostigmine, given intravenously, counteracts both the peripheral and central side effects of atropine and other anticholinergic drugs such as thioridazine (neuroleptic), imipramine (antidepressant), and benztropine (antiparkinsonian medication). 

The following are the various applications of synthetic muscarinic receptor antagonists. Ophthalmology 

To reduce severe bradycardia in hyperactive carotid sinus reflex Diagnostically in Wolff-Parkinson-White syndrome, to restore the PRS complex to normal duration 

Due to the need of extensive derivatization for GC-MS analysis (see Chapter 3), P-receptor blocking agents such as atenolol, bupranolol, metoprolol, and propranolol (Fig. 4.23,1-4) have been early subjects of LC-MS/MS analysis. The presence of a secondary amino function in all P-blockers provides sufficient proton affinity for positive ESI, and core structure-specific as well as individual product ions are derived from target analytes using low energy CID as summarized in Table 4.7. 

TABLE 4.7 Characteristic Product Ions of Selected P-blockers Generated by Positive ESI and CID 

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RNHCH.CH(OHlCH— R R P Adrenergic receptor blocking agents 473... 

RNHCH CH(OHiCH - heteroarvl H /3-Adrenergic receptor blocking agents 179... 

Qf-receptor blocking agent, 1, 176 Phenylalanine hydroxylase in tyrosine synthesis from phenylalanine, 1, 261 L-Phenylalanine hydroxylase mechanism, 1, 261 Phenyl azide formation... 

Bicuculline is an isoquinoline alkaloid elaborated from members of the family Fumariaceae (Papaverales), especially in Corydalis, Dicentra, and Fumaria species. Bicuculline, like picrotoxin, is a specific GABA receptor-blocking agent that impedes the... 

Kuzmin, A., Johansson, B., Gimenez, L., Ogren, S. O. Fredholm, B. B. (2005). Combination of adenosine A(l) and A(2A) receptor blocking agents induces caffeine-like locomotor stimulation in mice. Eur. Neuropsychopharmacol. 00, 000-000. 

Dopamine receptor blocking agents. Many of the neuroleptics used in the treatment of schizophrenia frequently produce parkinsonian symptoms as unwanted effects. Neuroleptics block dopamine receptors and their therapeutic effect seems to be related to this action. Although these drugs act on DA systems without distinction, some are more selective. Thioridazine, clozapine and molindone, for example, have electrophysiological effects in the limbic region of the brain but little action in the nigro-striatal area. This selectivity may be related to receptor subtype specificity (see Chs 12 and 54). 

While most -blocking agents on acute administration have little direct electrophysiological effects, studies in rabbits [94] and man [95] have shown that chronic administration of y -blockers increases APD. This increase in APD (and hence refractory period) has been postulated to contribute to the effectiveness of -receptor blocking agents in the prevention of sudden cardiac death [94]. Direct Class III action has been claimed for the y -blockers oxprenolol (30) [96,97], nadolol (31) [96] and atenolol (10) [98] in addition... 

Communication with the profession was at first maintained by continuing (until January 1985) the Adverse Reaction Series leaflets started by CSD, and later by a regularly published bulletin on Current Problems . The first issue of Current Problems in September 1975 led with the adverse oculo-cutaneous effects and sclerosing peritonitis associated with p-adrenergic receptor blocking agents and also included items on loss of consciousness associated with prazosin and on the risks of anti-inflammatory agents and asthma. 

The cardiovascular response to dopamine in humans depends on the concentration infused. Low rates of dopamine infusion can produce vasodilation in the renal, mesenteric, coronary, and intercerebral vascular beds with little effect on other blood vessels or on the heart. The vasodilation produced by dopamine is not antagonized by the p-adrenoceptor blocking agent propranolol but is antagonized by haloperidol and other dopamine receptor-blocking agents. 

The actions of p-blockers on blood pressure are complex. After acute administration, blood pressure is only slightly altered. This is because of the compensatory reflex increase in peripheral vascular resistance that results from a (3-blocker-induced decrease in cardiac output. Vasoconstriction is mediated by a-receptors, and a-receptors are not antagonized by (3-receptor blocking agents. Chronic administration of (3-blockers, however, results in a reduction of blood pressure, and this is the reason for their use in primary hypertension (see Chapter 20). The mechanism of this effect is not well understood, but it may include such actions as a reduction in renin release, antagonism of (3-receptors in the central nervous system, or antagonism of presynaptic facilita-tory (3-receptors on sympathetic nerves. 

In view of the effects of the (3-receptor blocking agents on coronary blood flow, it seems paradoxical that these drugs are useful for the prophylactic treatment of... 

The 3-receptor blocking agents have widespread and important uses in the management of cardiac arrhythmias, angina pectoris, and hypertension. Their uses in these conditions are reviewed in Chapters 16, 17, and 20, respectively. Even though acute administration of 3-blockers can precipitate congestive heart failure in patients who are largely dependent on enhanced sym-... 

Table 16.3 summarizes the cardiac electrophysiological effects of class II, III, and IV agents, and Table 16.4 summarizes the actions of the (3-receptor blocking agents... 

Mario Thevis, G.O.W.S. (2001) High Speed Determination of Beta-Receptor Blocking Agents in Hiunan Urine by Liquid Chro-matography/Tandem Mass Spectrometry. Biomed Chromatojjr, 15, 393—402. 

Suzman, M.M. Use of p-adrenergic receptor blocking agents in psychiatry. In Palmer,... 

TD varies in presentation, and should always be considered in the differential diagnosis of any abnormal involuntary movements in patients exposed to antipsychotics or DA-receptor blocking agents used for other medical conditions (e.g., prochlorperazine or metoclopramide). 

The effect in an anesthetized dog of the injection of epinephrine before and after propranolol. In the presence of a B-receptor-blocking agent, epinephrine no longer augments the force of contraction (measured by a strain gauge attached to the ventricular wall) nor increases cardiac rate. Blood pressure is still elevated by epinephrine because vasoconstriction is not blocked. 

Similar local effects may be produced by injecting histamine liberators (compound 48/80, morphine, etc) intradermally or by applying the appropriate antigens to the skin of a sensitized person. Although most of these local effects can be prevented by adequate doses of an H -receptor-blocking agent, H2 and H3 receptors may also be involved. 

Among the -adrenergic receptor-blocking agents used in food-producing animals for the prevention of shipment stress caused by transportation and formation of new herds, carazolol and propranolol are the best-known representatives (Fig. 8.7). 

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