Metabolize procainamide

For example, it has been suggested that the adverse reactions caused by a number of drugs such as isoniazid, procainamide, hydralazine could be due to metabolic activation by myeloperoxidase in neutrophils. Thus neutrophils will metabolize procainamide (Fig. 4.38) to a hydroxylamine metabolite. In the presence of chloride ion, myeloperoxidase will produce hypochlorous acid, a strong oxidizing agent, which may be responsible for metabolic activation and toxicity. One of the products is N-chloroprocainamide (see also sect. "Hydralazine," chap. 7). 

D The prolonged administration of procainamide often leads to the development of a positive ANA test result, with or without symptoms of a lupus erythematous-like syndrome. The common symptoms of lupus erythematous-like syndrome are arthralgia, malaise, rash, fever, chills, and arthritis, which may occur more often in slow acetylators because they do not metabolize procainamide as well. If a positive ANA titer develops, assess the benefit/risk ratio related to continued procainamide therapy. 

Procainamide may be adininistered by iv, intramuscular (im), or po routes. After po dosing, 75—90% of the dmg is absorbed from the GI tract. About 25% of the amount absorbed undergoes first-pass metaboHsm in the fiver. The primary metabolite is A/-acetylprocainamide (NAPA) which has almost the same antiarrhythmic activity as procainamide. This is significant because the plasma concentration of NAPA relative to that of procainamide is 0.5—2.5. In terms of dmg metabolism there are two groups of patients those that rapidly acetylate and those that slowly acetylate procainamide. About 15—20% of the dmg is bound to plasma proteins. Peak plasma concentrations are achieved in 60—90 min. Therapeutic plasma concentrations are 4—10 lg/mL. Plasma half-lives of procainamide and NAPA, which are excreted mainly by the kidneys, are 2.5—4.5 and 6 h, respectively. About 50—60% is excreted as unchanged procainamide (1,2). 

The answer is b. (Hardman, pp 868 869.) Persons with low hepatic iY-acetyltransferase activity are known as slow acetylators. A major pathway of metabolism of procainamide, which is used to treat arrhythmias, is iV-acetylation. Slow acetylators receiving this drug are more susceptible than normal persons to side effects, because slow acetylators will have higher-than-normal blood levels of these drugs N-acetylprocainamide, the metabolite of procainamide, is also active. 

A good example to illustrate the difference in the rates of hydrolysis of esters and amides is to compare the metabolism of procaine and procainamide because the only difference between the two drugs is that one is an ester and the other is an amide (Fig. 6.2). Procaine has a half-life of about 1 minute due to the rapid hydrolysis of the ester, whereas... 

T Pancreatic insulin release Metformin Peripheral insulin sensitivity hepatic glucose output/production i intestinal glucose absorption Dose Ist-line (naive pts), 1.25/250 mg PO daily-bid 2nd-line, 2.5/500 mg or 5/500 mg bid (max 20/2000 mg) take w/ meals, slowly T dose hold before 48 h after ionic contrast media Caution [C, -] Contra SCr >1.4 mg/dL in females or >1.5 mg/dL in males hypoxemic conditions (sepsis, recent MI) alcoholism metabolic acidosis liver Dz Disp Tabs SE HA, hypoglycemia, lactic acidosis, anorexia, N/V, rash Additional Interactions T Effects W/ amiloride, ciprofloxacin cimetidine, digoxin, miconazole, morphine, nifedipine, procainamide, quinidine, quinine, ranitidine, triamterene,... 

In addition to oxygen free radicals, other compounds such a clozapine, olanzapine and procainamide induce reactive intermediates [8, 9]. Clozapine and olanzapine bioactivation is thought to occur through a nitrenium ion [20] however clozapine but not olanzapine induce toxicity to neutrophils. This can lead to an immune-mediated depletion of neutrophils and their precursors (CFU-GM) [21]. Also, nonsteroidal antiinflammatory drugs (NSAIDs) have pro-oxidant radicals that when metabolized could cause oxidative stress [22]. 

The inherent anticholinergic properties of procainamide may interfere with the therapeutic effect of cholinergic agents. Patients receiving cimetidine and procainamide may exhibit signs of procainamide toxicity, as cimetidine inhibits the metabolism of procainamide. Simultaneous... 

It is a cleavage of drug molecule by taking up a molecule of water. The most hydrolytic enzymes are found outside the endoplasmic reticulum, and in higher concentrations in liver, kidney and plasma. The metabolism of an ester by an enzyme esterase results in the formation of an acid and alcohol. The examples are meperidine, procaina-mide, pethidine and lidocaine etc. Meperidine is catalyzed by esterases to be changed into meperidinic acid and procainamide is catalyzed by amidases. 

Procainamide is eliminated by hepatic metabolism to NAPA and by renal elimination. Its half-life is only 3-4 hours, which necessitates frequent dosing or use of a slow-release formulation (the usual practice). NAPA is eliminated by the kidneys. Thus, procainamide dosage must be reduced in patients with renal failure. The reduced volume of distribution and renal clearance associated with heart failure also require reduction in dosage. The half-life of NAPA is considerably longer than that of procainamide, and it therefore accumulates more slowly. Thus, it is important to measure plasma levels of both procainamide and NAPA, especially in patients with circulatory or renal impairment. 

Procainamide INa (primary) and IKr (secondary) blockade Slows conduction velocity and pacemaker rate prolongs action potential duration and dissociates from INa channel with intermediate kinetics direct depressant effects on sinoatrial (SA) and atrioventricular (AV) nodes Most atrial and ventricular arrhythmias drug of second choice for most sustained ventricular arrhythmias associated with acute myocardial infarction Oral, IV, IM eliminated by hepatic metabolism to /V-acetylprocainamide (NAPA see text) and renal elimination NAPA implicated in torsade de pointes in patients with renal failure Toxicity Hypotension long-term therapy produces reversible lupus-related symptoms... 

H2 antagonists compete with creatinine and certain drugs (eg, procainamide) for renal tubular secretion. All of these agents except famotidine inhibit gastric first-pass metabolism of ethanol, especially in women. Although the importance of this is debated, increased bioavailability of ethanol could lead to increased blood ethanol levels. 

The heme iron in the peroxidase is oxidized by the peroxide from III+ to V4- in compound I. The compound I is reduced by two sequential one-electron transfer processes giving rise to the original enzyme. A substrate-free radical is in turn generated. This may have toxicological implications. Thus the myeloperoxidase in the bone marrow may catalyze the metabolic activation of phenol or other metabolites of benzene. This may underlie the toxicity of benzene to the bone marrow, which causes aplastic anemia (see below and chap. 6). The myeloperoxidase found in neutrophils and monocytes may be involved in the metabolism and activation of a number of drugs such as isoniazid, clozapine, procainamide, and hydralazine (see below). In in vitro systems, the products of the activation were found to be cytotoxic in vitro. 

De Souich P, Erill S. Metabolism of procainamide in patients with chronic heart failure, chronic respiratory failure and chronic renal failure. Eur J Clin Pharm 1976 10 283-287. 

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. 

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