Answer:
Cocaine is unique in that it has both local anesthetic and vasoconstrictive actions. It has considerable potential for abuse and addiction. It undergoes hydrolysis by plasma pseudocholinesterase. A small percentage of cocaine is metabolized in the liver.
As with the other local anesthetics, the mechanism of action of cocaine involves inhibition of conduction in nerve fibers by blockade of sodium channels, which, in turn, prevents an action potential from being generated. Cocaine is the only local anesthetic that is a potent sympathomimetic. It blocks reuptake of norepinephrine and epinephrine both in the central nervous system and systemically.
Cocaine has multiple effects on the central nervous system, resulting in intense behavioral stimulation, euphoria, and arousal. The seizure threshold is initially raised but with increasing dose it is lowered, and seizures may result. The adrenergic effects of cocaine are responsible for the increased heart rate, hypertension, mydriasis, tremors, and perspiration seen with an overdose.
The most common clinical use of cocaine is as a topical anesthetic. Plastic surgeons find topical cocaine advantageous primarily because of the improved hemostasis. The addition of epinephrine to the topical cocaine would enhance the vasoconstriction and improve hemostasis; however, this is not generally believed to be a safe practice. When mixed with cocaine and applied topically, epinephrine can cause arrhythmias.
General anesthesia and topical cocaine are frequently used together, and there are multiple studies and case reports describing the complexity of drug interactions that occur.
There is also widespread agreement that ketamine significantly enhances the arrhythmogenicity of cocaine. Additionally, the patient receiving monoamine oxidase (MAO) inhibitors is especially at risk for dangerous interactions with cocaine, and topical cocaine should be avoided unless the patient has been taken off the MAO inhibitor 2 weeks before the surgical procedure.
Because of its sympathomimetic effects, cocaine should be avoided in hypertensive patients as well. Unfortunately, individual response to cocaine varies. In some patients ventricular fibrillation and cardiac arrest may occur as a result of a dose as small as 0.4 mg/kg. The safe maximum dose for nasally administered 4% cocaine solution is 1.5 mg/kg. Each drop of 4% cocaine solution has approximately 3 mg cocaine.
The Casey Jones reaction is cardiac collapse from cocaine use. It derives from a story in which a railroad worker named Casey Jones competed against a machine in hammering down nails on railroad ties. Casey Jones won but died afterwards because his heart literally "exploded" from beating so fast and working so hard.