Plasma lidocaine levels

Lidocaine [NE] Decreased clearance of intravenous idocaine increased plasma lidocaine levels. 

Some studies suggest that both cimetidine and ranitidine can raise plasma bupivacaine levels, whereas other evidence suggests that no significant interaction occurs. Ranitidine does not appear to significantly affect lidocaine. Some studies found that cimetidine does not affect lidocaine when used as an anaesthetic. Other studies found that cimetidine increased plasma lidocaine levels and that famotidine had less effect. See also Lidocaine + H2-receptor antagonists , p.264 for interactions of lidocaine used as an an-tiarrhythmic. 

A confusing situation. No clinically important interaction has been established, but be alert for any evidence of increased bupivacaine toxicity resulting from raised total plasma levels and rises in unbound bupivacaine levels during the concurrent use of cimetidine and possibly ranitidine. Cimetidine (but not ranitidine) has been shown to raise plasma lidocaine levels when lidocaine is used as an antiarrhythmic (see Lidocaine + H2-receptor antagonists , p.264), but some of the studies cited above found cimetidine did not affect lidocaine levels when lidocaine is used as an anaesthetic. However, in the studies comparing the effects of cimetidine and famotidine, cimetidine was found to increase lidocaine levels and it was suggested that famotidine may be preferable to cimetidine as pretreatment before epidural lidocaine. ... 

Fl3mn RJ, Moore J, Collier PS, Howard PJ. Single dose oral H2-antagonists do not affect plasma lidocaine levels in the parturient. zictozlnaesi/resio/iScanif (1989) 33, 593-6. 

Plasma lidocaine levels following slow intravenous injection may be modestly lower in patients who are taking barbiturates. 

Heinonen J, Takki S, Jarho L. Plasma lidocaine levels in patients treated with potential inducers of microsomal enzymes. zl<7to/l ae5i/2e5io/5 <7a if(1970) 14, 89-95. 

A study in 6 healthy subjects receiving 30-hour infusions of lidocaine at a rate of 2 mg/minute found that pretreatment with nadolol 160 mg daily for 3 days raised the steady-state plasma lidocaine levels by 28% (from 2.1 to 2.7 micrograms/mL) and reduced the plasma clearance by 17%. ... 

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. ... 

Nordstrom H, Stonge K. Plasma lidocaine levels and risks after liposuction with tumescent anaesthesia. Acta Anaesthesiol Scand 2005 49(10) 1487-90. 

Once absorbed, foreign compounds may react with plasma proteins and distribute into various body compartments. In both neonates and elderly human subjects, both total plasma-protein and plasma-albumin levels are decreased. In the neonate, the plasma proteins may also show certain differences, which decrease the binding of foreign compounds, as will the reduced level of protein. For example, the drug lidocaine is only 20% bound to plasma proteins in the newborn compared with 70% in adult humans. The reduced plasma pH seen in neonates will also affect protein binding of some compounds as well as the distribution and excretion. Distribution of compounds into particular compartments may vary with age, resulting in differences in toxicity. For example, morphine is between 3 and 10 times more toxic to newborn rats than adults because of increased permeability of the brain in the newborn. Similarly, this difference in the blood-brain barrier underlies the increased neurotoxicity of lead in newborn rats. 

The most commonly used technique of sonophoresis in these studies was to apply hydrocortisone in the form of an ointment on the skin and then apply ultrasound by keeping the transducer in contact with the ointment. In some cases, the transducer was moved in circular patterns to avoid a continuous exposure of a certain part of the skin to ultrasound. Although these studies were performed using different animal models, application techniques, hydrocortisone concentrations in the ointment, and exposure time, a measurable enhancement of hydrocortisone transport was reported in almost all cases. In contrast, most of the attempts to enhance transdermal transport of lidocaine and salicylates have been less successful. In the case of lidocaine, the sonophoretic enhancement was measured in terms of reduction of onset time for anesthesia or prolonging duration of anesthesia. In most cases, no significant effect of ultrasound application on either induction time or duration of anesthesia has been reported. Similarly sonophoresis of salicylates from ointments has not been found to induce any significant increase in plasma salicylate levels. ... 

The clinical importance of these interactions is uncertain, but anaesthetists should be aware that increased bupivacaine plasma levels have been seen with diazepam, and reduced lidocaine levels have been seen with midazolam. More study is needed. 

Most of the adverse events related to lidocaine are associated with sermn toxicity, with various symptoms presenting at different sermn levels. Symptoms such as lightheadedness, perioral numbness, tinnitus, nausea, or metallic taste in the mouth may occur when plasma lidocaine concentrations are 1-5 pg/mL. Dysarthria, local muscle twitches, hallucinations, or nystagmus may present at plasma concentrations from 5 to 8 pg/ mL. Seizmes may occur at 8-12 pg/mL, followed by respiratory depression or coma at levels higher than 20 pg/mL. Hypotension, bradycardia, cardiac arrest, and arrhythmias may also occm at serum levels greater than 20 pg/mL. IntraUpid remains the only available treatment for adverse events related to serum toxicity. 

The patch adheres to the skin and when it is exposed to air, the contained heating element is activated and through oxidation releases heat. Local skin temperature remains between 39 and 41°C during the heating phase of application. Systemic absorption is minimal and even with sequential or simultaneous applications of up to four patches, lidocaine plasma levels were low (9-12 ng/mL in adults) and tetracaine levels were essentially non-detectable. The product insert indicates that application of one Synera patch for up to 30 minutes in children 4 months to 12 years of age produced maximum peak plasma concentrations of lidocaine and tetracaine of 63 ng/ mL and 65 ng/mL, respectively. Application of two Synera patches for up to 30 minutes to children 4 months to 12 years of age produced peak lidocaine levels of up to 331 ng/mL and tetracaine levels of less than 5 ng/mL. 

Tocainide is rapidly and well absorbed from the GI tract and undergoes very fitde hepatic first-pass metabolism. Unlike lidocaine which is - 30% bioavailable, tocainide s availability approaches 100% of the administered dose. Eood delays absorption and decreases plasma levels but does not affect bio availability. Less than 10% of the dmg is bound to plasma proteins. Therapeutic plasma concentrations are 3—9 jig/mL. Toxic plasma levels are >10 fig/mL. Peak plasma concentrations are achieved in 0.5—2 h. About 30—40% of tocainide is metabolized in the fiver by deamination and glucuronidation to inactive metabolites. The metabolism is stereoselective and the steady-state plasma concentration of the (3)-(—) enantiomer is about four times that of the (R)-(+) enantiomer. About 50% of the tocainide dose is efirninated by the kidneys unchanged, and the rest is efirninated as metabolites. The elimination half-life of tocainide is about 15 h, and is prolonged in patients with renal disease (1,2,23). 

Propranolol may increase procainamide plasma levels. Additive cholinergic effects may occur when procainamide is administered with other drugp with anticholinergic effects. There is the potential of additive cardiodepressant effects when procainamide is administered with lidocaine. When a beta blocker, such as Inderal, is administered with lidocaine, there is an increased risk of lidocaine toxicity. 

Lidocaine s most common adverse effects—like those of other local anesthetics—are neurologic paresthesias, tremor, nausea of central origin, lightheadedness, hearing disturbances, slurred speech, and convulsions. These occur most commonly in elderly or otherwise vulnerable patients or when a bolus of the drug is given too rapidly. The effects are dose-related and usually short-lived seizures respond to intravenous diazepam. In general, if plasma levels above 9 mcg/mL are avoided, lidocaine is well tolerated. 

Cohen LS, Rosenthal JE, Horner DW, et al. Plasma levels of lidocaine after intramuscular administration. Am J Cardiol 1948 29 520. 

Cardiac failure may also affect metabolism by altering hepatic blood flow. However, even after heart attack without hypotension or cardiac failure, metabolism may be affected. For example, the plasma clearance of lidocaine is reduced in this situation. Other diseases such as those, which affect hormone levels hyper-or hypothyroidism, lack of or excess growth hormone, and diabetes can alter the metabolism of foreign compounds. 

If a drug undergoes an extensive first-pass metabolism (e.g., morphine, metoclopramide, ergotamine, or lidocaine), rectal administration may produce an even higher plasma level. The prolonged rectal administration of multiple drugs may produce local irritation or even rectal ulceration. 

AAG is a protein known as an acute phase reactant. As a result of inflammation, injury during physiological trauma, and stress,an increase in the binding capacity of AAG is commonly observed in patients. For a drug that is highly bound, an increase in AAG plasma levels will result in a significant decrease in unbound plasma fraction. Examples include propranolol, lidocaine, and disopyra-mide after myocardial infarction and propranolol and chlorpromazine in Crohn s disease. 

Two reports have illustrated the need for particular care when using local anesthetics in neonates and small children. A 2-year-old child died from the combined effects of chloral hydrate, lidocaine, and nitrous oxide for a dental procedure (55). The doses used were not clarified, but in postmortem blood the plasma concentration of lidocaine was 12 pg/ml. The level and adequacy of perioperative monitoring was also not clear. 

Lidocaine hydrochloride administration is limited to the paienteial route and is usually given intravenously, though idequatc plasma levels are achieved after intramuscular in-... 

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