Metoprolol

Topically applied beta-blocking agents are used in glaucoma treatment. In 5 of 11 patients with ocular and periorbital dermatitis, a reproducible positive patch test to metoprolol 3% in water was found (van Joost et al. 1979). 

If manufacturers made available patch test guidelines (i.e., appropriate concentration and vehicle) for individual chemicals and final formulations, the physician could patch test with greater facility and frequency. Unfortunately, it seems probable that the impetus for making this information routinely available will have to be government regulation. 

Aagren-Jonsson S, Magnusson B (1976) Sensitization to propantheline bromide, trichlor-carbanilide and propylene glycol in an antiperspirant. Contact Dermatitis 2 79-80 

Adams RM (1972) Photoallergic contact dermatitis to chloro-2-phenylphenol. Arch Dermatol 106 711-714 

Aeling JL, Panagotacos PJ, Andreozzi RJ (1974) Allergic contact dermatitis to vitamin E aerosol deodorant (letter). Arch Dermatol 108 579-580 

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Metoprolol. Metoprolol tartrate (Table 1), also a Class II antiarrhythmic agent, is a HpophiHc, cardioselective P -adrenoceptor blocking agent... 

The absorption of metoprolol after po dosing is rapid and complete. The dmg undergoes extensive first-pass metabolism in the liver and only 50% of the po dose in bioavailable. About 12% of the plasma concentration is bound to albumin. The elimination half-life is 3—7 h and less than 5% of the po dose is excreted unchanged in the urine. The excretion of the dmg does not appear to be altered in patients having renal disease (98,99,108). 

The adverse effects noted with metoprolol result from the -adrenoceptor blocking actions and are similar to those noted for propranolol... 

The use of selective P-antagonists for treatment of CHF has included the P -blocker metoprolol (Table 1) and results of clinical trials suggest long-term beneficial effects. Selective P -antagonists have also been tested, an example of which is xamoterol [81801 -12-9], C2 H25N20, which is (i)-A/-(2-hydroxy-3-(4-hydroxyphenoxy)propylamino)ethylmorphine-4-carboxamide. Xamoterol exhibits approximately 50% of the activity of isoproterenol, and serves to provide modest inotropic effects (128,129). 

P-Adrenoceptor blockers for the treatment of hypertension include (/) the cardioselective P -adrenoceptor blockers without intrinsic sympathomimetic activity (ISA), ie, atenolol (Table 3), bisoprolol (Table 3), and metoprolol (Table 1) (2) the cardioselective with ISA, ie, acebutolol (Table 1) (J) the noncardioselective without ISA, ie, propranolol (Table 1) and timolol [26839-75-8] C23H24N4O2S and (4) the noncardioselective with ISA, ie, oxprenolol [6452-71-7] C 3H23N03, and pindolol. 

The enandoselecdve nltro-aldol reacdon catalyzed by C/fi-LLB is effecdvely applied to the synthesis of three kmds of opdcally acdve fi-receptor blocking dnigs fS -metoprolol, " fS -propanolol, " and fS -pindolol " " fScheme 3.17i. 

Endomethylene-A -tetrahydro benzaldehyde Cyclothiazide Epibromohydrin Carteolol Epichlorohydrin Acebutolol Atenolol Befunolol Betaxolol HCI Bufetrol Bunitrolol Bupranolol Carazolol Carnitine Celiprolol Colestipol Cromolyn sodium I ndenolol Mazindol Mepindolol Metoprolol tartrate Nadolol Nifuratel Oxprenolol Penbutolol Practolol Propafenone HCI Propranolol HCI Viloxazine HCI Xanthinol niacinate Epinephrine... 

The efficiency of many CSPs increases dramatically when liquid eluents are replaced with sub- or supercritical fluids. During a comparison of LC and SFC performed with a Chiralcel OD CSP, Lynam and Nicolas reported that the number of theoretical plates obtained was three to five times higher in SFC than in LC [26]. The separation of metoprolol enantiomers by LC and SFC on a Chiralcel OD CSP is illustrated in Fig. 12-2. Although impressive selectivity is achieved by both techniques, resolution is higher in SFC (R = 12.7) than in LC (R = 4.8), and the higher flowrate in SFC reduces the analysis time. The increased efficiency of SFC also improves peak symmetry. 

Fig. 12-2. Separation of metoprolol enantiomers by LC and SFC on a Chiralcel OD CSP. Chromatographic conditions for LC 20% 2-propanol in hexane, with 0.1 % diethylamine, 0.5 mL min f Chromatographic conditions for SFC 20 % methanol with 0.5 % isopropylamine in carbon dioxide, 2.0 mL min 15 MPa, 30 °C.

Clinically used p-adrenergic receptor antagonists ( P-blockers ) are either px-selective (e.g. bisoprolol, metoprolol, atenolol, betaxolol) or non-selective,... 

Class II drugs are classical (3-adrenoceptor antagonists such as propranolol, atenolol, metoprolol or the short-acting substance esmolol. These drugs reduce sinus rate, exert negative inotropic effects and slow atrioventricular conduction. Automaticity, membrane responsiveness and effective refractory period of Purkinje fibres are also reduced. The typical extracardiac side effects are due to (3-adrenoceptor blockade in other organs and include bronchospasm, hypoglycemia, increase in peripheral vascular resistance, depressions, nausea and impotence. 

Class II antiarrhythmic drugs are (3-adrenoceptor antagonists such as propranolol, metoprolol or atenolol. (3-adrenoceptor antagonists slow sinus rate and atrioventricular conduction and exert negative inotropic effects. 

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