Cocaine Adrenaline

Over the years it has been interesting to note that many compounded products eventually become commercially available products. Recent examples might include fentanyl lozenges, minoxidil topical solution, nystatin lozenges, clindamycin topical solution, tetracaine-adrenalin-cocaine (TAG) solution, dihydroergotamine mesylate nasal spray, buprenorphine nasal spray, buffered hypertonic saline solution, and erythromycin topical solution as well as numerous other dermatological and pediatric oral liquids and some... 

A variety of naturally occurring and synthetic amines and amides are physiologically active. The amines include pain killers (heroin, codeine, morphine) and stimulants and decongestants (adrenalin, cocaine, dopamine, amphetamines, nicotine). The amides include pain relievers (acetaminophen), tranquilizers (phenobarbital, diazepam), and local anesthetics (novocaine). Caffeine is both an amine and an amide. Polypeptides, proteins, and synthetic nylon are amides. 

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). 

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. 

Clinical use Tetracaine is employed by ophthalmologists for surface anesthesia as a 0.5 % solution and by endoscopists for anesthesia of mucous membranes including airways as a 2.0 % solution. For topical anesthesia, a 4.0 % cream of tetracaine can also be used, which is, however, less effective than a lidocaine/prilocaine cream in preventing venipuncture-induced pain in children (van Kan et al., 1997). A combination of tetracaine with adrenaline and cocaine (TAC) is widely used for repair of... 

Blood glucose concentrations can become labile in people with diabetes mellitus who use cocaine, not only because their diet changes, but also because adrenaline concentrations affect the mobilization of glucose (311). 

Most surgeons in the UK use local anesthesia with cocaine for nasal operations because of the superior operative field it provides and because they consider it to be safe, even with adrenaline. The incidence of adverse reactions to cocaine given in this way is reportedly low, and serious complications are less common than with general anesthesia. These conclusions were based on a postal survey of all British Associations of Otolaryngologists and Head and Neck Surgeons. Only... 

Amphetamines are synthetic stimulants that were invented in Germany in the 1930vS. Their chemical structures resemble those of adrenaline and noradrenaline, the body s own stimulants. Their effects resemble those of cocaine but arc much longer lasting. A single oral dose of amphetamine usually stimulates the body for at least four hours. 

The effect of a local anaesthetic is terminated by its removal from the site of application. Anything that delays its absorption into the circulation will prolong its local action and can reduce its systemic toxicity where large doses are used. Most local anaesthetics, with the exception of cocaine, cause vascular dilation. The addition of a vasoconstrictor such as adrenaline (epinephrine) reduces local blood flow, slows the rate of absorption of the local anaesthetic, and prolongs its effect the duration of action of lidocaine is doubled from one to two hours. Normally, the final concentration of adrenaline (epinephrine) should be 1 in 200 000, although dentists use up to 1 in 80 000. 

Cocaine (alkaloid) is used medicinally solely as a surface anaesthetic (for abuse toxicity, see p. 192) usually as a 4% solution, because adverse effects are both common and dangerous when it is injected. Even as a surface anaesthetic sufficient absorption may take place to cause serious adverse effects and cases continue to be reported only specialists should use it and the dose must be checked and restricted. Cocaine prevents the uptake of catecholamines [adrenaline (epinephrine), noradrenaline (norepinephrine)] into S5nnpathetic nerve endings, thus increasing their concentration at receptor sites, so that cocaine has a built-in vasoconstrictor action, which is why it retains a (declining) place as a... 

Severe seizures have been reported after topical use of TAG, a combination of tetracaine, adrenaline, and cocaine, in children (23,24). 

Uptake blocker (Table 12) display a certain degree of structural relatedness to the endogenous neurotransmitter whose transport is inhibited dopamine uptake by the anonaine, cocaine, ibogaine, and salsolinol (see Scheme II) serotonin by 12-hydroxyibogaine, ibogaine, and norharman noradrenaline and adrenaline by cathinone, ephedrine, salsolinol GABA by arecaidine, and guvacine. Reserpine and deserpidine... 

Cells can also recover from the signal for the fight or flight reaction by taking hormones that they have released back up into themselves. Cocaine interferes with the reuptake of adrenalin by cells in the cortex of the brain, thus intensifying the effects of adrenalin and producing a sense of euphoria and (sometimes) hallucinations. Cocaine use leads to psychological dependency and can cause convulsions, respiratory failure, and death. 

S5mthesized via tyramine (Fig. 30-26), apparently functions in place of noradrenaline. Note fhe precursor-product relationship between dopamine, noradrenaline, and adrenaline. The synthetic pathways to these neurotransmitters involve decarboxylation and hydroxylahon, types of reacfion imporfanf in formation of other transmitters as well. The most important process for ferminafing fhe acfion of released catecholamine transmitters is reuptake by the neurons. High-affinity uptake systems transport the catecholamine molecules back into the neurons and then into the synaptic vesicles. The uptake is specifically blocked by the drug reserpine (Fig. 25-12).7 The dopamine transporter is a major binding site for cocaine (see Fig. 30-28).7 7-7Si Catecholamine trans-miffers are catabolized by two enzymes. One is the... 

The first topical anesthetic agent was TAC, which is a combination of tetracaine, adrenaline (epinephrine), and cocaine, and was used for face and scalp lacerations. A version of TAC called LET is used today. LET is a combination of lidocaine, epinephrine, and tetracaine. Lidocaine replaced cocaine. LET gel is... 

Propranolol reduces the clearance of bupivacaine and so theoretically the toxicity of bupivacaine may be increased. There has been a single report of enhanced bupivacaine cardiotoxicity in a patient also receiving metoproioi and digoxin. The coronary vasoconstriction caused by cocaine is increased by propranolol. Beta blockers may interact with adrenaline (epinephrine)-containing local anaesthetics. 

Two children and one adult patient undergoing general anaesthesia developed arrhythmias shortly after nasal application of a paste containing cocaine 25% and adrenaline (epinephrine) 0.18%. All 3 patients received doses of cocaine that exceeded the maximum dose (1.5 mg/kg) currently recommended in the BNF for healthy adults. 

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