P-Adrenergic blocking agents

P-Adrenergic-blocking agents, such as propranolol, have been synthesized by different chemoenzymatic methods where the key step to introduce the chirality is an enzymatic acylation or a hydrolysis process. The main reason to prepare these amino alcohols in optically pure form is due to the fact that the activity of these pharmaceuticals resides in the (S)-enantiomer. In Scheme 10.1 we have represented a chemoenzymatic approach that has been carried out for the preparation of this dmg where the key step is the resolution of the key intermediate 1-chloro-... 

Propranolol is another type of antihypertensive agent called a p-adrenergic blocking agent (p-blocker) because it competes with epinephrine... 

Sotalol (Betapace) [Antiarrhythmic, Antihypertensive/Beta Blocker] WARNING Monitor pts for 1st 3 d of Rx to 4- risks of arrhythmia Uses Ventricular arrhythmias, AF Action p-Adrenergic blocking agent Dose Adults. 80 mg PO bid may be T to 240-320 mg/d Peds. Neonates 9 mg/m tid... 

Most effective anti-essential tremor medication, but sedative side effects troublesome usually used second line to p-adrenergic blocking agents (nonselective)... 

The answer is c. (Hardman, pp 233—235.) The chief danger of therapy with P-adrenergic blocking agents, such as nadolol and propranolol, is associated with the blockade itself. P-adrenergic blockade results in an increase in airway resistance that can be fatal in asthmatic patients. Hypersensitivity reactions such as rash, fever, and purpura are rare and necessitate discontinuation of therapy. 

Class II— sympathoplegic drugs that reduce heart responsiveness to sympathetic autonomic nervous system excitation molecules that reduce adrenergic stimulation of the heart, usually P-adrenergic blocking agents... 

Propranolol is chemically a naphthol derivative (dl-(isopropylamino)-3-(l-naphthyloxy)-2-propanol). It is a racemic mixture, and the laevo form is the active P-adrenergic blocking agent [10]. After oral administration, it is completely absorbed [11]. However, the systemic availability is relatively low with considerable variation in plasma levels [12,13]. The hepatic extraction of propranolol is about 80- 90%, and thus the main route of drug elimination is via hepatic metabolism [14]. One of the maj or metabolites of propranolol is 4-hydroxypropranolol, and the half-life has been reported to be 3 l-l/2h [15-18]. Since the drug is rapidly metabolized after oral administration, it necessitates a multiple dosage after oral strict patient compliance. 

The advantages of the catalyzed version are particularly apparent in the case of allyl alcohol whose epoxide, glycidol (2), is unstable to the catalyst.2 It can be obtained by catalyzed epoxidation at 0° with cumene hydroperoxide instead of t-butyl hydroperoxide in 65% yield and 90% ee. However, for use in a synthesis of the P-adrenergic blocking agent (2S)-propranolol (5), the epoxide is not isolated but treated with sodium a-naphthoxide to furnish the diol 3. The synthesis of 5 is completed by conversion to an epoxide (4) and ring opening with isopropylamine. 

P-adrenergic blocking agent and various enantiomers Vancomycin bonded on LiChrospher diol silica, 5 pm Methanol-acetonitrile-acetic acid-triethylamine (80-20 20-80 0.1-0.3 0.1-0.4) 355 mm x 75 pm i.d. 265 mm effective length, chiral separation... 

The p-adrenergic blocking agents suppress the activation of the heart by blocking [It receptors (see p. 73). They also reduce the work of the heart by decreasing cardiac output and causing a slight decrease in blood pressure. Propranolol (see p. 74) is the prototype of this class of compounds, but other (3-blockers, such as metoprolol and atenolol are... 

Question A.18 Why are p adrenergic blocking agents needed in addition to thioamides at the onset of treatment of hyperthyroidism ... 

---