Epinephrine pharmacokinetics

D. Fisher, P. Schwartz, and A. Davis, Pharmacokinetics of exogenous epinephrine in critically ill children, Crit. Care Med, 21, 111 (1993). 

Pharmacokinetics Onset of action occurs within 30 min and peak effect in 1 hr. Dipivefrin is more lipophilic than epinephrine. Distributed to cornea. Dipivefrin is converted to epinephrine inside the eye by enzyme hydrolysis. 

Pharmacokinetics Epinephrine has a rapid onset but brief duration of action. In emergency situations epinephrine is given intravenously for the most rapid onset of action it may also be given subcutaneously, by endotracheal tube, by inhalation, or topically to the eye. Oral administration is ineffective, since epinephrine and the other catecholamines are inactivated by intestinal enzymes. Only metabolites are excreted in the urine. 

Methods for Reducing Toxic Effects. Limited information is available on treatments to alleviate the symptoms of tetryl exposure. These include treatment of the dermatitis with calamine lotion and/or zinc oxide preparations, treatment of dermatitis and ocular irritation with aluminum acetate or boric acid compresses, and treatment of hypersensitivity-like symptoms (including severe dermatitis and asthma-like symptoms) with epinephrine or antihistamines (Bain and Thomson I 954 Bergman 1952 Cripps 1917 Eddy 1943 Ruxton 1917 Smith 1916 Troup 1946 Witkowski et al. 1942). The data on the pharmacokinetics of tetryl are also limited (Zambrano and Mandovano 1956). In order to develop mitigating agents, further studies are needed on its kinetics and mechanisms of action. 

Hypotension not responsive to intravenous fluids should be managed with vasopressors, such as dopamine, norepinephrine, epinephrine, and/or phenylephrine. If seizures occur, benzodiazepines should be administered. Due to their pharmacokinetic characteristics, moderate volume of distribution, and low protein binding, procainamide and NAPA may be removed via hemodialysis and hemoperfu-sion. Both procainamide and NAPA serum concentrations should be obtained. Normal therapeutic ranges are procainamide, 3-14pgml NAPA, 12-35 pg ml Measurement of electrolytes, renal function tests, and arterial blood gases should be considered. 

Unfortunately the still low number of available 1-ASP preparations limits the number of possible switches. If one wants to take advantage of 1-ASP s oncolytic potential over a longer period of time, new approaches are required. Concomitant infusion of epinephrine in parallel to 1-ASP [148] may be helpful with respect to anaphylaxis but does not solve the basic problem of immunogenicity and altered pharmacokinetics. 

C. Pharmacokinetics. With local subcutaneous injection, peak blood levels are reached in 10-60 minutes, depending on the vascularity of the tissue and whether a vasoconstrictor such as epinephrine has been added. Ester-type drugs are rapidly hydrolyzed by plasma cholinesterase and have short half-lives. Amide-type drugs are metabolized by the liver, have a longer duration... 

Pharmacokinetic Parameters after the Intratumoral Injection of Cisplatin/Epinephrine Gel and Intravenous Infusion of Cisplatin... 

Vree, T.B. Beumer, E.M. Lagerwerf, A.J. Simon, M.A. Gielen, M.J. Clinical pharmacokinetics of R(-l-)- and S(—)-mepivacaine after high doses of racemic mepivacaine with epinephrine in the combined psoas compartment/ sciatic nerve block. Anesth. Analg. 1992, 75, 75-80. 

In 7 women given epidural anaesthesia for caesarean section the pharmacokinetics of 400 mg of lidocaine 2%, (given with adrenaline (epinephrine) 1 200 000) were unchanged after a single 150-mg oral dose of ranitidine given about 2 hours preoperatively. A similar study in 8 women also found no statistically significant rises in whole blood lidocaine levels in the presence of ranitidine 150 mg given orally at least 2 hours preoperatively. ... 

Its duration of action is 60-120 minutes, depending on the vascularity of the site blocked as well as added adjuvants such as epinephrine. The drug is 70% protein-bound, with 30% in the free unbound form. It is this 30% that is rapidly cleared by the systemic circulation for hepatic metabolism. The vasoconstrictive properties of epinephrine help to decrease this systemic uptake of the drug and thus to prolong its duration of action. Other adjuvants such as the alpha-2 receptor agonists clonidine and dexmedetomidine have been studied recently and found to prolong the duration of action of lidocaine. Their mechanism of action (specific receptor vs. pharmacokinetic/phar-macodynamic interaction with local anesthetics) and site (central vs. peripheral) of action have not been fully elucidated [6-8]. 

Cuvhlon P, NouveUon E, Ripart J, Boyer JC, Dehour L, Mahamat A, L hermite J, Boisson C, ViaUes N, Lefrant JY, de La Coussaye JE. A comparison of the pharmacodynamics and pharmacokinetics of bupivacaine, ropivacaine (with epinephrine) and their equal volume mixtures with lidocaine used for femoral and sciatic nerve blocks a double-blind randomized study. Anesth Analg 2009 108(2) 641-649. 

Breuer C, Wachall B, Gerbeth K, Abdel-Tawab M, Fuhr U. Pharmacokinetics and pharmacodynamics of moist inhalation epinephrine using a mobile inhaler. Eur J Qin Pharmacol 2013 69(6) 1303-10. 

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