Anesthetics beta-blockers

Beta-blockers interact with a large number of other medications. The combination of beta-blockers with calcium antagonists should be avoided, given the risk for hypotension and cardiac arrhythmias. Cimetidine, hydralazine, and alcohol all increase blood levels of beta-blockers, whereas rifampicin decreases their concentrations. Beta-blockers may increase blood levels of phenothiazines and other neuroleptics, clonidine, phen-ytoin, anesthetics, lidocaine, epinephrine, monoamine oxidase inhibitors and other antidepressants, benzodiazepines, and thyroxine. Beta-blockers decrease the effects of insulin and oral hypoglycemic agents. Smoking, oral contraceptives, carbamazepine, and nonsteroidal anti-inflammatory analgesics decrease the effects of beta-blockers (Coffey, 1990). 

Drug Interactions Other antihypertensive agents Carbamazepine (vasodilators, ACE inhibitors, Rifampin diuretics, and beta-blockers) Phenobarbital Digoxin Cyclosporine Disopyramide Theophylline Flecainide Inhalation anesthetics Quinidine Neuromuscular blocking agents Cimetidine Lithium ... 

Clinically important, potentially hazardous interactions with beta-blockers, local anesthetics, muscle relaxants... 

Membrane stabilizing activity (MSA) Local anesthetic action typical of several beta-blockers, eg, propranolol... 

A. Classiflcation, Subgroups, and Mecbanisms All of the clinically used beta-blockers are competitive phanuacologic antagonists. Propranolol is the prototype. Drugs in this group are usually classified into subgroups on the basis of P, versus P selectivity, partial agonist activity, local anesthetic action, and lipid solubility (Table 10-2). 

Local anesthetic activity Local anesthetic activity ( membrane stabilizing activity ) is a disadvantage when beta-blockers are used topically in the eye because it decreases protective reflexes and increases the risk of corneal ulceration. Local anesthetic effects are absent from timolol and several other beta-blockers. 

Esmolol is a short-acting beta-blocker for parenteral use only. Nadolol is a nonselective beta-blocker, and metoprolol is a pj-selective blocker. Timolol is useful in glaucoma because it does not anesthetize the cornea. The answer is (E). 

A. Prototypes, Mechanisms, and Effects Beta-blockers are discussed in more detail in Chapter 10. Propranolol and esmolol are the prototype antiarrhythmic beta-blockers. Their mechanism in arrhythmias is primarily cardiac beta blockade and reduction in cAMP, which results in the reduction of both sodium and calcium currents and the suppression of abnormal pacemakers. The AV node is particularly sensitive to beta-blockers the PR interval is usually prolonged by class II drugs (Table 14-2). Under some conditions, these dmgs may have some direct local anesthetic (sodium channel-blocking) effect in the heart, but this is probably rare at the concentrations achieved clinically. 

Nonselective beta-blocker prototype local anesthetic action but no partial agonist effect. Used in HTN, angina, arrhythmias, migraine, hyperthyroidism, tremor. Tox asthma, AV block, CHF. 

Clozapine Bupropion eyelophosphamide Paelitaxel NSAIDs Dielofenae PPls Lansoprazole Beta-blockers Anesthetics Enflurane Macrolide antibiotics... 

Currently there is a trend toward the synthesis and large-scale production of a single active enantiomer in the pharmaceutical industry [61-63]. In addition, in some cases a racemic drug formulation may contain an enantiomer that will be more potent (pharmacologically active) than the other enantiomer(s). For example, carvedilol, a drug that interacts with adrenoceptors, has one chiral center yielding two enantiomers. The (-)-enantiomer is a potent beta-receptor blocker while the (-i-)-enantiomer is about 100-fold weaker at the beta-receptor. Ketamine is an intravenous anesthetic where the (+)-enantiomer is more potent and less toxic than the (-)-enantiomer. Furthermore, the possibility of in vivo chiral inversion—that is, prochiral chiral, chiral nonchiral, chiral diastereoisomer, and chiral chiral transformations—could create critical issues in the interpretation of the metabolism and pharmacokinetics of the drug. Therefore, selective analytical methods for separations of enantionmers and diastereomers, where applicable, are inherently important. 

Small quantities of adrenaline, such as are present as an additive in local anesthetic formulations, can be dangerously potentiated by beta-adrenoceptor blockers propranolol should be discontinued at least 3 days in advance of administering such products for local anesthesia. A combined infusion of adrenaline and propranolol has been used for diagnosing insulin resistance, but it can evoke cardiac dysrhythmias, even in patients without signs of coronary disease (17). 

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