Quinidine Propranolol

ATRIAL FLUTTER Quinidine Propranolol Verapamil IH Digoxln... 

Propranolol (at high doses) has been noted to have quinidine-like activity. 

The answer is b. (Hardmanr p 906.) Cimetidine reversibly inhibits cytochrome P450. This is important in phase I bio transformation reactions and inhibits the metabolism of such drugs as warfarin, phenytoin, propranolol, metoprolol, quinidine, and theophylline. None of the other enzymes are significantly affected. 

Mepivacine, bupivacine, doxapram, quinine, quinidine, atenolol, metoprolol, propranolol, pethidine, methadone (5)-N-(3,5-dinitro-benzoyl) tyrosine Acetonitrile—ammo 208 nium acetate (60 40)... 

Concurrent administration of propafenone with digoxin, warfarin, propranolol, or metoprolol increases the serum concentrations of the latter four drugs. Cimetidine slightly increases the propafenone serum concentrations. Additive pharmacological effects can occur when lidocaine, procainamide, and quinidine are combined with propafenone. 

Propranolol has local anesthetic properties and exerts actions similar to those of quinidine on the atrial membrane action potential. Membrane responsiveness and action potential amphtude are reduced, and excitability is decreased conduction velocity is reduced. Because these concentrations are similar to those that produce p-blockade, it is impossible to determine whether the drug acts by specific receptor blockade or via a membrane-stabilizing effect. 

The depressant effects of propranolol on the A-V node are more pronounced than are the direct depressant effects of quinidine. This is due to propranolol s dual actions of p-blockade and direct myocardial depression. Propranolol administration results in a decrease in A-V conduction velocity and an increase in the A-V nodal refractory period. Propranolol does not display the anticholinergic actions of quinidine and other antiarrhythmic agents. 

Omeprazole can inhibit the metabolism of drugs metabolised mainly by the cytochrome P-450 enzyme subfamily 2C (diazepam, phenytoin), but not of those metabolished by subfamilies lA (caffeine, theophylline), 2D (metoprolol, propranolol), and 3A (ciclosporin, lidocaine (lignocaine), quinidine). Since relatively few drugs are metabolised mainly by 2C compared with 2D and 3A, the potential for omeprazole to interfere with the metabolism of other drugs appears to be limited, but the half lives of diazepam and phenytoin are prolonged as much as by cimetidine. 

Rifampin Coumarin anticoagulants, digitoxin, glucocorticoids, itraconazole, methadone, metoprolol, oral contraceptives, prednisone, propranolol, quinidine, saquinavir... 

Propafenone has some structural similarities to propranolol and possesses weak 3-blocking activity. Its spectrum of action is very similar to that of quinidine, but it does not prolong the action potential. Its sodium channel-blocking kinetics are similar to that of flecainide. Propafenone is metabolized in the liver, with an average half-life of 5-7 hours. The usual daily dosage of propafenone is 450-900 mg in three divided doses. The drug is used primarily for supraventricular arrhythmias. The most common adverse effects are a metallic taste and constipation arrhythmia exacerbation can also occur. 

In overdose, 3 blockers block both and 32 adrenoceptors selectivity, if any, is lost at high dosage. The most toxic blocker is propranolol. As little as two to three times the therapeutic dose can cause serious toxicity. This may be because propranolol has additional properties At high doses it may cause sodium channel blocking effects similar to those seen with quinidine-like drugs, and it is lipophilic, allowing it to enter the CNS (see Chapter 10). 

Alpharacid glycoprotein exists in concentrations that are 50 to 100 times lower than those of albumin. Basic drugs (quinidine, imipramine, propranolol, and lidocaine) bind to the single site present on alpharacid glycoprotein. 

Antiarrhythmic agents such as quinidine, procainamide, and propranolol have all been shown to augment d-tubocurarine-induced blockade. Quinidine has also been reported to unmask or worsen the symptoms of myasthenia gravis and to cause postoperative respiratory depression after the use of muscle relaxants. 

The cardiac arrhythmias are life-threatening, so the patient must be closely monitored, with facilities available for possible resuscitation. Drugs such as quinidine and procainamide are contraindicated, but lidocaine, propranolol, or phenytoin has been used safely and effectively. The arterial blood gas levels, pH, and electrolyte concentrations should be monitored so that metabolic acidosis or hypokalemia can be identified that would further aggravate the arrhythmias. Electrical pacing may be required if the antiarrhythmic drugs fail. Hyperpyrexia is treated by cooling. Seizures may be managed by intravenous doses of diazepam. 

Fig. 4.5 Relationship between the Kp value of quinidine (A), propranolol (B), and imipramine (C) and the concentration of PS in rat tissue. 1, lung 2, spleen 3, kidney 4, pancreas 5, liver ...

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