Beta blockers Epinephrine

Clinically important, potentially hazardous interactions with beta-blockers, epinephrine, insulin detemir, propranolol, sympathomimetics... 

The answer is d, (Hardman, pp 855-856.) Propranolol, as well as other non selective beta blockers, tends to slow the rate of recovery in a hypoglycemic attack caused by insulin. Beta blockers also mask the symptoms of hypoglycemia and may actually cause hypertension because of the increased plasma epinephrine in the presence of a vascular beta2 blockade. 

Drugs that may be affected by beta blockers include flecainide, gabapentin, haloperidol, hydralazine, phenothiazines, anticoagulants, benzodiazepines, clonidine, disopyramide, epinephrine, ergot alkaloids, lidocaine, nondepolarizing muscle relaxants, prazosin, sulfonylureas, and theophylline. 

Consider interactions that occur with systemic use of epinephrine, including beta blockers and chymotrypsin. 

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). 

Beta-blockers block norepinephrine and epinephrine from binding to beta-adrenoceptors and a calcium channel blocker inhibits the flow of calcium ions into muscles. Both slow down and relax the heart. 

Drugs that block beta-1 receptors on the myocardium are one of the mainstays in arrhythmia treatment. Beta blockers are effective because they decrease the excitatory effects of the sympathetic nervous system and related catecholamines (norepinephrine and epinephrine) on the heart.5,28 This effect typically decreases cardiac automaticity and prolongs the effective refractory period, thus slowing heart rate.5 Beta blockers also slow down conduction through the myocardium, and are especially useful in controlling function of the atrioventricular node.21 Hence, these drugs are most effective in treating atrial tachycardias such as atrial fibrillation.23 Some ventricular arrhythmias may also respond to treatment with beta blockers. 

In the past, beta blockers were considered detrimental in patients with heart failure.60 As indicated in Chapter 20, these drugs decrease heart rate and myocardial contraction force by blocking the effects of epinephrine and norepinephrine on the heart. Common sense dictated that a decrease in myocardial contractility would be counterproductive in heart failure, and beta blockers were therefore contraindicated in heart failure.60,69 It is now recognized that beta blockers are actually beneficial in people with heart failure because these drugs attenuate the excessive sympathetic activity associated with this disease.56,64 As indicated earlier,... 

Beta blockers bind to beta-1 receptors on the myocardium and block the effects of norepinephrine and epinephrine (see Chapter 20). These drugs therefore normalize sympathetic stimulation of the heart and help reduce heart rate (negative chronotropic effect) and myocardial contraction force (negative inotropic effect). Beta blockers may also prevent angina by stabilizing cardiac workload, and they may prevent certain arrhythmias by stabilizing heart rate.40 These additional properties can be useful to patients with heart failure who also have other cardiac symptoms. 

Other drugs that may be prescribed in conjunction with diuretics for the treatment of CHF include vasodilators (drugs that dilate blood vessels, such as ACE inhibitors) inotropics (drugs that increase the heart s ability to contract, such as digoxin) and beta blockers (drugs that inhibit the action of epinephrine, such as carvedilol). 

Beta-blockers. Beta-blocking agents (including atenolol [Tenormin] and metoprol [Lopressor]) are a class of drugs that block substances such as adrenaline (epinephrine), a key agent in the autonomic (involuntary) nervous system and in the activation of heart muscle. 

Beta-blockade (especially with nonselective agents such as propranolol) alters response to sympathomimetics with 13-agonist activity (eg, epinephrine). Beta-blockers that undergo extensive first-pass metabolism may be affected by drugs capable of altering this process. Beta-blockers may reduce hepatic blood flow. 

Remember that T BP can occur when epinephrine-containing local anaesthetics are used with patients on beta-blockers - Sympathomimetics, below ... 

BETA-BLOCKERS LIDOCAINE 1. Risk of bradycardia (occasionally severe), 1 BP and heart failure with intravenous lidocaine 2. Risk of lidocaine toxicity due to t plasma concentrations of lidocaine, particularly with propranolol and nadolol 3. t plasma concentrations of propranolol and possibly some other beta-blockers 1. Additive negative inotropic and chronotropic effects 2. Uncertain, but possibly a combination of beta-blocker-induced reduction in hepatic blood flow (due to 1 cardiac output) and inhibition of metabolism of lidocaine 3. Attributed to inhibition of metabolism by lidocaine 1. Monitor PR, BP and ECG closely watch for development of heart failure when intravenous lidocaine is administered to patients on beta-blockers 2. Watch for lidocaine toxicity 3. Be aware. Regional anaesthetics should be used cautiously in patients with bradycardia. Beta-blockers could cause dangerous hypertension due to stimulation of alpha-receptors if epinephrine is used with focal anaesthetic... 

The toxicities of the beta blockers are directly related to their pharmacologic effects. These agents block the effects of catecholamines such as epinephrine and norepinephrine on the beta-1 and beta-2 receptors. Beta-1 receptors are located in the heart, kidneys, and eyes. Toxicity is most often due to antagonism of the cardiac beta-1 receptors. 

Clinically important, potentially hazardous interactions with alcohol, amiodarone, beta-blockers, cimetidine, donidine, digoxin, diltiazem, disopyramide, ephedrine, epinephrine, ergot alkaloids, guanethidine, halothane, isoprenaline, lidocaine, noradrenaline, NSAIDs, phenylephrine, quinidine, reserpine, verapamil... 

Figure II-4-11 No autonomic reflexes are possible in isolated preparations Arterial contraction due to the alpha agonist (choice E) is reversed by the alpha-blocker (choice C). Arteriolar relaxation and tachycardia due to epinephrine (choice B) is reversed by the beta-blocker (choice D). Bethanechol (choice A) causes both arteriolar relaxation and bradycardia.

Of the drugs listed, only isoproterenol causes a decrease in mean blood pressure, because it activates beta receptors and has no effect on alpha receptors. This permits identification of drug 3 as isoproterenol. Prazosin is an alpha blocker, so one can anticipate that this drug would antagonize any increases in blood pressure that result from activation of (Xj receptors in the vasculature. Epinephrine (high dose), norepinephrine, and tyramine all exert pressor effects via activation of (Xj receptors. However, only epinephrine is active on P2 receptors, and this action would be revealed by vasodilation and a reversal of its pressor effects following treatment with an alpha blocker— epinephrine reversal. Thus, drug 4 can be identified as epinephrine. 

Figure II-4-2 The effects of Drug R are changed by treatment with either an alpha or beta-blocker, so Drug R must have activity at both receptors (choices C, D, and E are ruled out). A pressor dose of epinephrine would be reversed by an alpha-blocker, not just decreased Drug R is norepinephrine.

Figure II-4-4 The effects of Drug S are changed by treatment with the beta-blocker, but not by the alpha blocker (choices A, B, and C are ruled out). Terbutaline is P2 selective and would not increase heart rate direcdy. Drug S is isoproterenol. Note that option A would have been a possibility but one would have to assume a low-dose of epinephrine.

B. Epinephrine is occasionally used for hypotension resulting from overdose by beta blockers, calcium antagonists, and other cardiac-depressant dmgs. 

---