Cocaine Epinephrine

Serious adverse effects of epinephrine potentially occur when it is given in an excessive dose, or too rapidly, for example, as an intravenous bolus or a rapid intravenous infusion. These include ventricular dysrhythmias, angina, myocardial infarction, pulmonary edema, sudden sharp increase in blood pressure, and cerebral hemorrhage. The risk of epinephrine adverse effects is also potentially increased in patients with hypertension or ischemic heart disease, and in those using (3-blockers (due to unopposed epinephrine action on vascular Ui-adrenergic receptors), monoamine oxidase inhibitors, tricyclic antidepressants, or cocaine. Even in these patients, there is no absolute contraindication for the use of epinephrine in the treatment of anaphylaxis [1,5,6]. 

Avakian, E.V., and Manneh, V.A. Cardiac responsivity to epinephrine following chronic cocaine administration. Proc West Pharmacol Soc 30 281-284, 1987. 

In the vertebrate CNS monoamines have been associated with a number of physiological functions (reviewed in Kandel et al., 1991). Serotonin has functions associated with mood, pain, sleep, learning, and memory. Dopamine has functions associated with schizophrenia, Parkinson s disease, and cocaine addiction. In vertebrates, dopamine is further metabolized into two additional neurotransmitters, norepinephrine and epinephrine. Norepinephrine increases the excitability of cells in response to sudden sensory input such as fear. Epinephrine has been identified in specific neurons of the brain, but the function of these cells is unknown. In addition, AADC has also been found in a class of neurons that do not have any of the four neurotransmitters discussed above (Jaeger et al., 1983). These neurons may use one of the trace amines, tyramine, tryptamine, or phenylethylamine, as a neurotransmitter. 

TAC (tetracaine, adrenalin [epinephrine], and cocaine) is a combination topical anesthetic frequently used in pediatric emergency departments for repair of minor lacerations. The usual mixture is tetracaine 0.5%, epinephrine 1 2,000, and cocaine 11.8%. Because of potential complications (seizures), lower concentrations of cocaine and epinephrine in a tetracaine 1% solution have been suggested (TAC III). 

D. Epinephrine is by far the most commonly employed vasoconstrictor. Phenylephrine is occasionally used with procaine for dental procedures. Levonordefrin is also used rarely in dental procedures. Dopamine has no vasoconstrictor activity. Cocaine is itself a local anesthetic with some vasoconstrictor properties. However, cocaine, because of its abuse potential and toxicity, is seldom used. Its only use is topical. 

Previously used as component of "Magic Numbing Solution" or TAC Sol (epinephrine 1 2,000, tetracaine 0.5%, cocaine 11.8%) and LET Sol (lidocaine 4%, epinephrine 0.1%, tetracaine 0.5%), which are used as topical anesthesia for repair of minor lacerations. Topical tetracain solutions no longer available... 

Each neuron has specific synthetic machinery that enables it to both synthesize and eliminate a specific neurotransmitter. For example, neurons of the sympathetic nervous system employ norepinephrine and epinephrine as their transmitters. Other neurons, particularly in the central nervous system, employ dopamine as their transmitter. Dopamine is a particularly important transmitter for a variety of neuronal functions. Its loss is associated with Parkinson disease, and it is a critical agent in the mediation of pleasure and reward processes. Dopamine, due to its association with pleasurable sensations, is widely implicated in the actions of a number of drugs of abuse, including cocaine, opiates, and methamphetamines. 

Amphetamines Local anesthetic drags containing epinephrine or cocaine... 

The duration of action of a local anaesthetic is proportional to the time that the drug remains bound to the sodium channels. Measures that prolong contact time will prolong the duration of the local anaesthetic effect. Cocaine has a vasoconstricting effect on blood vessels and prevents its own absorption. Many local anaesthetics are prepared with adrenaline (epinephrine) in order to achieve this effect. Concentrations are usually of the order of 1 200000 or more dilute than this. Care should be exercised when using adrenaline-containing solutions in the presence of halothane as it is known to sensitise the myocardium to the effects of catecholamines. 

Topical local anesthesia is often used for eye, ear, nose, and throat procedures. Satisfactory topical local anesthesia requires an agent capable of rapid penetration across the skin or mucosa, and with limited tendency to diffuse away from the site of application. Cocaine, because of its excellent penetration and local vasoconstrictor effects, has been used extensively for ear, nose and throat (ENT) procedures. Cocaine is somewhat irritating and is therefore less popular for ophthalmic procedures. Recent concern about its potential cardiotoxicity when combined with epinephrine has led most otolaryngology surgeons to switch to a combination containing lidocaine and epinephrine. Other drugs used for topical anesthesia include lidocaine-bupivacaine combinations, tetracaine, pramoxine, dibucaine, benzocaine, and dyclonine. 

Cocaine [50-36-2] - [ALKALOIDS] (Vol 1) - [ALKALOIDS] (Vol 1) -and catecholamines [EPINEPHRINE AND NOREPINEPHRINE] (Vol 9) -forensic testing for [FORENSIC CHEMISTRY] (Vol 11) -substance abuse of [PSYCHOPHARMACOLOGICAL AGENTS] (Vol 20)... 

Cocaine is used medically by otorhinolaryngologists and plastic surgeons as an epinephrine cocaine mixture. Solutions for topical application are typically less than 4% cocaine hydrochloride. In the U.S. cocaine is a scheduled drug under the federal Controlled Substances Act of 1970. Refined cocaine, in the form of the base or hydrochloride salt, is self-administered by many routes, including snorting, smoking, genital application, and by injection. 

Four substances have been described as having pressor effects, which are probably amines or aminelike. Urosympathin, described by Holtz, Credner, and Kronberg (34), is a substance found in normal urine in amounts per day, giving a pressor response equal to 2 to 3 mg. of hydroxytyramine or 100 to 150 micrograms of epinephrine or arterenol. In cases of essential hypertension the amount is said to be increased three- to fourfold. Because its action was intensified by cocaine and lessened by ergotoxin and yohimbine, they believed that it represented a mixture of hydroxytyramine, epinephrine, and arterenol. The material was recovered by lead acetate precipitation of urine with subsequent acid hydrolysis. 

Epinephrine is not directly anesthetic either alone or in combination with cocaine for it does not increase the anesthetic effect when the circulation has previously been arrested. It also does not lower the threshold concentration in wheals, although the duration of the anesthesia is greater for a given concentration. 

As the anesthetic agent is absorbed and thus removed from the site of application, its local action ceases, and its systemic and toxic effects start. Because most of these drugs, especially cocaine, are rapidly destroyed in the body, the systemic toxicity increases with the rapidity of absorption. It is therefore desirable and often necessary to delay the absorption. This may be done by restricting the local circulation. Cocaine itself tends to do this by producing a local vasoconstriction, an action that is not shared by its substitutes. This vasoconstriction should be reinforced by the addition of epinephrine. More dilute solution may thus be used, and the anesthetic effect is much more prolonged. With intracutaneous infiltration, the pressure and edema also result in ischemia. In suitable situations, the circulation may be slowed by bandages, or arrested by temporarily clamping the arterial blood supply. 

The phenomena of systemic cocaine poisoning are largely those of sympathetic stimulation but not as consistently as with epinephrine. The sympathetic stimulation is mainly central (midbrain) but partly peripheral. The chief manifestations of sympathetic stimulation are (1) sensitization to epinephrine (but antagonization to ephedrine) by peripheral action, (2) mydriasis and slight exophthalmos by central and peripheral action, and (3) cardiac acceleration (chiefly central). Other sympathetic symptoms are constriction of the blood vessels, erection of hair, and relaxation of the intestines. High concentrations of cocaine paralyze all smooth muscles. Procaine also produces... 

This alkaloid was first isolated from Ephedra equisetina, a plant (ma huang) that has been used as medicine by the Chinese since antiquity. Most of the present supply is probably synthetic. Its chemical structure is closely related to epinephrine and tyramine, and differs from epinephrine chiefly by the absence of the two phenolic hydroxyls. Its effects on the circulation, intestines, bronchi, iris, etc., are superficially similar to those of epinephrine. It requires that larger doses be given but they are more lasting, due probably to ephedrine s much greater stability and resistance to oxidation. The effects can be produced by oral administration. Unlike epinephrine, it is not sensitized by cocaine or by denervation. From this, it has been argued that its point of attack is not sympathomimetic but muscular. It also stimulates the CNS. A number of isomers with similar actions are known. Ephedrine is used therapeutically in hay fever and asthma, in which it is less... 

Novocaine (procaine hydrochloride) is a local anesthetic that is considered to be less toxic than cocaine, and does not have the danger of habituation. It is used frequently in conjunction with a vasoconstrictor such as epinephrine to secure a prolonged anesthetic action. 

Impaired platelet aggregation to epinephrine resistance to fatal thromboembolism exaggerated response to cocaine, reduced effect of morphine and antidepressant drugs (Yang et al. 2000). 

Hypertensive crisis with headache, intracranial bleeding, and death may result from combining MAO inhibitors with sympathomimetic drugs (e.g., amphetamines, methylphenidate, cocaine, dopamine, epinephrine, norepinephrine, and related compounds methyidopa,... 

There are a limited number of reports of immunomoduladon by cocaine. In vivo aclminisdradon of cocaine i.v. to humans elevated NK cell acdvity in peripheral blood, but exposure of leukocytes to the drug in vidro had no effect (Van Dyke et al., 1986). It W as hypothesized that the in vivo effects occurred via release of epinephrine from the SNS (Van Dyke et al., 1986). CondracUctory results have been reported for the effect of cocaine on NK acdvity in rats, w ith no effect in vivo (Bayer et al., 1996) or suppression of acdvity after acute or chronic in vivo aclminisdradon (Pacifici et al., 2003). 

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