Lidocaine, drug reaction

A study in 6 healthy subjects receiving 30-hour infusions of lidocaine at a rate of 2 mg/minute found that pretreatment with propranolol 80 mg every 8 hours for 3 days raised the steady-state plasma lidocaine levels by 19% (from 2.1 to 2.5 micrograms/mL) and reduced the plasma clearance by 16%. Other similar studies have found a 22.5 to 30% increase in steady-state serum lidocaine levels and a 14.7 to 46% fall in plasma clearance due to the concurrent use of propranolol. Two cases of lidocaine toxicity attributed to a lidocaine-propranolol interaction were revealed by a search of the FDA adverse drug reaction file in 1981. A further case of lidocaine toxicity (seizures) has been described in a man on propranolol after accidental oral ingestion of lidocaine for oesophageal anaesthesia. High serum levels of lidocaine were detected. ... 

The answer is e. (Hardman, pp 858-874.) Because verapamil, a Ca channel blocker, has a selective depressing action on AV nodal tissue, it is an ideal drug for both immediate and prophylactic therapy of supraventricular tachycardia (SVT). Nifedipine, another Ca channel blocker, has little effect on SAT Lidocaine and adenosine are parenteral drugs with short ha If-lives and, thus, are not suitable for prophylactic therapy. Procainamide is more suitable for ventricular arrhythmias and has the potential for serious adverse reactions with long-term use. 

Antiarrhythmic therapy carries with it a number of risks. In some cases, the risk of an adverse reaction is clearly related to high dosages or plasma concentrations. Examples include lidocaine-induced tremor or quinidine-induced cinchonism. In other cases, adverse reactions are unrelated to high plasma concentrations (eg, procainamide-induced agranulocytosis). For many serious adverse reactions to antiarrhythmic drugs, the combination of drug therapy and the underlying heart disease appears important. 

Drugs such as lidocaine and sulfamethoxazole seem to be able to cause hypersensitivity reaction by this mechanism. 

This reaction is the first step in a synthesis of the drug lidocaine. 

Mexiletine is similar to lignocaine (lidocaine) but is effective by the oral route (t) 10 h). It has been used for ventricular arrhythmias especially those complicating myocardial infarction. The drug is usually poorly tolerated. Adverse reactions are almost universal and dose-related and include nausea. 

All basic and advanced life-support measures should be implemented. Gastric decontamination should be performed. Butyrophenones are readily absorbed by activated charcoal. Aggressive supportive care should be instituted. Dystonic reactions respond well to intravenous benztropine or diphenhydramine. Oral therapy with diphenhydramine or benztropine should be continued for 2 days to prevent recurrence of the dystonic reaction. For patients suffering from neuroleptic malignant syndrome, a potentially fatal condition associated with the administration of antipsychotic drugs, dantrolene sodium, and bromocriptine have been used in conjunction with cooling and other supportive measures. Arrhythmias should be treated with lidocaine or phenytoin. Diazepam is the drug of choice for seizures phenytoin is used to prevent recurrence. Hemodialysis and hemoperfu-sion have not been shown to be effective. 

With the multiplicity of drugs that are administered, one must constantly be aware of interferences in methodology, not only by the parent drug but also its metabolites. Even very specific methods are not exempt for example, it was shown that JV-ethylglycine, the metabolite of lidocaine, was an interferent in the sarcosine oxidase coupled-enzymatic reaction for the measurement of creatinine... 

A man with Parkinson s disease was given quinidine 300 mg every 6 hours for the control of ventricular ectopic beats. After receiving two doses he was given lidocaine as well, initially as a bolus of 80 mg, followed by an infusion of 4 mg/minute because persistent premature ventricular beats developed. Within 2.5 hours the patient complained of dizziness and weakness, and was found to have sinus bradycardia, sinoatrial arrest and atrioventricular escape rhythm. Normal sinus rhythm resumed when the lidocaine was stopp. Whether quinidine was a contributing factor in this reaction is uncertain. However, this case emphasises the need to exercise caution when giving two drugs that have cardiac depressant actions. 

Physicochemical methods will confirm or deny a straightforward reaction between two drugs, and this information may be of value because some of the medical documentation is of a deductive (or it may be expected that... ) nature, which is recorded and repeated as observed fact. The alleged interaction between heparin and lidocaine hydrochloride, discussed later, in Section 7, is an example of this. 

Isolation of 25 involves filtering the reaction mixture to remove the diethylammonium hydrochloride, followed by extraction of the basic 25 into aqueous hydrochloride. All nonbasic contaminants, such as unchanged 37, remain in the toluene solution. Lidocaine is liberated from its hydrochloride acid salt with aqueous base and then extracted into diethyl ether. After removal of the diethyl ether, the lidocaine is isolated as a low-melting solid or oil, depending upon its purity. In order to facilitate purification of lidocaine in this procedure, it is converted into its solid bisulfate salt 42 by reaction with sulfuric acid (Eq. 21.24). Many drugs that contain a basic site, like lidocaine, are sold in the form of their hydrochloride or sulfate salts because these salts are typically more stable and more soluble in water than the free base. 

Patients with hypersensitivity reactions to amide local anesthetics should not receive lidocaine. Lidocaine should be used with caution in patients with severe hepatic dysfunction or congestive heart failure, both of which may impair hepatic metabolism and lead to toxic serum levels of the drug. 

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