Anaesthetics, local Cocaine

Trachelantamine, according to Syrneva, has a weak atropine-like action and also produces local anaesthesia. Its hydrolytic product, trache-lantamidine, which is structurally identical with tsoretronecanol, yields a p-aminobenzoyl derivative of -which the crystalline hydrochloride, m.p. 230-2°, is said to be as potent a local anaesthetic as cocaine hydrochloride. The chloro- -heliotridane (p. 606) formed by the aetion of thionyl ehloride on trachelantamidine reacts with 6-methoxy-8-aminoquinoline to form 6-methoxy-8-(pseMdoheliotridylamino)-quinoline,... 

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. 

Cocaine has sympathomimetic actions (tachycardia, peripheral vasoconstriction, and hypertension). Combined use with sympathomimetics such as adrenaline increases these effeets, and the risk of life-threatening arrhythmias. This risk may be further inereased if halothane anaesthesia is used (two of the above patients reeeived halothane ). See also Anaesthetics, general + Anaesthetics, local , p.92 and Anaesthetics, general + Ino-tropes and Vasopressors , p.99. 

Cocaine is the oldest of the local anaesthetics. It is a central nervous system stimulant and is habit-forming. See ecgonine. 

Cocaine. This lias a bitter taste, is mydriatic, produces local anaesthesia and is toxic. After absorption, or when taken internally, it acts chiefly by stimulation of the central nervous system, succeeded by depression. Since the two phases may be present in different areas simultaneously, a mixed result may ensue. With large doses the chief symptoms are those of medullary depression. Death is due to paralysis of the respiratory centre. The main use of cocaine in medicine is as a local anaesthetic. 

A series of papers on the pharmacological action of akuammine has been published by Raymond-Hamet in which it is established inter alia that the alkaloid has a local anaesthetic action almost equal to that of cocaine. 

The ending caine stems from cocaine, the first clinically employed local anaesthetic. Procaine and tetracaine are ester-linked substances, the others are amides. Amide bonded local anaesthetics usually contain two i s in their name, ester-bonded only one. In the structure drawings, the lipophilic portion of the molecule is depicted at the left, the amine at the right. The asterisk marks the chiral centre of the stereoisomeric drugs. Lipid solubility is given as the logarithm of the water octanol partition coefficient, log(P). 

Cocaine Clinically used as a local anaesthetic during eye surgery recreational use widespread tolerance develops readily highly addictive, especially crack cocaine severe potential problems similar to amphetamine users often become suspicious and paranoid, displaying antisocial and troublesome behaviour patterns. 

Cocaine A potent psychostimulant with local anaesthetic properties extracted from the South American plant Erythroxylon coca. 

This local anaesthetic was photodemethylated in an organic chemical experiment. The cocaine (231) was irradiated at 300 nm in methanol for 43 h under nitrogen to give a 20% yield of norcocaine (232) [145],... 

Cocaine is obtained from the coca tree (Erythroxylon coca). It has had a legitimate medical use as a local anaesthetic but has now been superseded by more effective and safer agents. Ecstasy, methylenedioxymethamphetamine (MDMA), is a synthetic amphetamine with no medical use. 

Cocaine readily penetrates mucous membranes and is an effective topical local anaesthetic that demonstrates intensive vasoconstrictor action. It has stimulant effects on the central nervous system and is a drug of addiction. It causes agitation, dilated pupils, tachycardia, hypertension, hallucinations, hyperthermia, hypertonia, hyperreflexia and cardiac effects. 

When we look at another tropane alkaloid, cocaine, we get a different scenario. Cocaine is obtained from the coca plant Erythroxylum coca, and is a powerfnl local anaesthetic, bnt now known primarily as a dmg of abuse. There is no chiral centre in the acid portion, which is benzoic acid, but the optical activity of cocaine comes from the alcohol methylecgonine. Because of the ester function in methylecgonine, the tropane system is no longer symmetrical, and the four chiral centres all contribute towards optical activity. 

This holds true especially for the alkaloid cocaine from Erythroxylon coca. Cocain has various mechanisms of action it is a local anaesthetic and an indirect, central acting sympathomimetic. It increases the effects of released or externally applied catecholamines but reduce the effect of other indirect sympathomimetic drugs. 

Ester linked local anaesthetics e.g. cocaine, procaine, tetracaine, benzocaine, chloroprocaine. 

Action on CNS Local anaesthetics stimulate CNS and produce restlessness, tremor, mental confusion, convulsion. In toxic doses, it causes respiratory depression, coma and death. Cocaine is a powerful stimulant while procaine and other agents produce less CNS stimulant effect. 

Local anaesthetics also produce decrease in blood pressure which may be due to sympathetic blockade. Only cocaine has the property to raise the BP due to its sympathomimetic property. 

These drugs are of similar structure and size (mol. wt. 220-329) and are simultaneously lipophilic and hydrophilic—properties which are essential to their mode of action. With the exception of cocaine, all local anaesthetics in clinical use are synthetic compounds. 

Local anaesthetic and CNS stimulant Cocaine. Alkaloid from leaves of Erythroxylon coca narcotic agent... 

Medicinally, cocaine is of value as a local anaesthetic for topical application. It is rapidly absorbed by mucous membranes and paralyses peripheral ends of sensory nerves. This is achieved by blocking ion channels in neural membranes. It was widely used in dentistry, but has been replaced by safer drugs, though it still has applications in ophthalmic and ear, nose, and throat surgery. As a constituent of Brompton s cocktail (cocaine and heroin in sweetened alcohol) it is available to control pain in terminal cancer patients. It increases the overall analgesic effect, and its additional CNS stimulant properties counteract the sedation normally associated with heroin (see page 332). 

William Halstead was a founder of Johns Hopkins University, and the inventor of the radical mastectomy (removal of the breast). Halstead was also the first American surgeon to investigate cocaine as a local anaesthetic, a painkiller applied directly to the wound or other source of pain. Unfortunately, Halstead took his work home with him. 

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