What is cocaine:
Cocaine is a crystalline tropane alkaloid obtained from the leaves of the coca plant. It is a Central Nervous System (CNS) stimulant, an appetite suppressant and a topical anesthetic. Because of the way it affects the mesolimbic reward pathway of the brain, cocaine is addictive.
The possession, cultivation and distribution of cocaine is illegal in virtually all parts of the world, yet its widespread use and abuse as a recreational drug remains widespread throughout the world. According to the medical journal The Lancet, cocaine is listed as the 2nd most addictive and 2nd most harmful drug among 20 popular recreational drugs. In the US, cocaine is scheduled as a Schedule II stimulant under the Controlled Substances Act of the United States. In other words, cocaine cannot be possessed or used unless directly prescribed or dispensed by a practitioner.
History:
For over a thousand years, South American indigenous peoples have chewed the leaves of Erythroxylon coca, a plant that contains cocaine as well as other nutrients. The locals believed that the leaves gave them strength and energy, claims which were denied by the Spanish when they came to South America. The Spanish declared it the work of the Devil, but after discovering the claims were true, they legalized and taxed the leaf, taking 10% off the value of each crop. The Spanish, as well as other European scientists performed experiments, and determined the stimulant and appetite-suppressant properties of cocaine, but were unable to isolate it, due to insufficient knowledge of chemistry in those times. In fact, the isolation of cocaine was not possible until 1855, when Albert Niemann, a German Ph. D student, developed an improved purification process. The first synthesis and elucidation of cocaine structure was by Richard Willstatter in 1898 so this is what is cocaine.
Popularization:
In 1859, an Italian doctor Paolo Mantegazza witnessed use of cocaine firsthand in South America and returned to Italy where he experimented upon himself and wrote in a medical journal about the medicinal usefulness of cocaine. His views were quite popular and allowed cocaine to be embraced by the European community.
A ‘’pinch of coca leaves’’ was included in John Styth Pemberton’s original recipe for Coca Cola in 1886. A wine called Vin Mariani was sold in Italy throughout the 19th Century, which had been treated with coca leaves. It is rumoured the Pope Leo XIII carried Vin Mariani with him.
In 1879 cocaine was used to treat morphine addiction. It was introduced as a local anesthetic in Germany in 1884. Sigmund Freud, the famous Austrian neurololgist, published his work Uber Coca, in which he mentioned the various physical bebnefits of using cocaine.
US manufacturer Parke-Davis sold cocaine in various forms such as cigarettes, powder and even an injectable mixture. Its use was encouraged by white employers among black labourers, because of its perceived physicality enhancing properties.
In the late Victorian era, cocaine use had appeared as a vice in literature. There is no example more popular than cocaine injection by Arthur Conan Doyle’s famous detective Sherlock Holmes.
During the mid-1940s, during World War II, cocaine was considered for inclusion in a future generation of ‘pep-pills’ for the German military code named D-IX.
Inhibition:
By the turn of the 20th century, the addictive properties of cocaine had become clear, and perceived problems with cocaine use began to catch attention in the United States. Several laws were passed in the United States in the following years, finally outlawing the possession, use and distribution of cocaine in 1970 (mentioned earlier).
However, cocaine use has more than trebled in that period in the US and it continues to be a popular recreational drug. Cocaine use is prevalent among all socioeconomic strata, including age, demographics, economic, social, political, religious and livelihood.
Available forms of Cocaine
Pure Cocaine
Cocaine in its purest form (see above) is in the form of a white, pearly product. Medically, it is applied topically. However, as a recreational drug, various forms of cocaine exist, each providing a varied ‘’high’’ to the user.
Freebase and ‘crack’ cocaine:
The freebase and ‘crack’ forms of cocaine are usually administered by vaporization of the powdered substance into smoke, which is then inhaled. The origin of the name ‘crack’ comes from the ‘crackling’ sound that is produced when cocaine and its impurities are heated past the point of vaporization. Crack and freebase cocaine are highly addictive.
Powder:
Nasal insufflation (also known as snorting) is the most common method of recreational powdered cocaine. The drug is rapidly absorbed from the mucous membranes. Nosebleeds occur from snorting cocaine due to irritation of the mucous lining. The cocaine is insufflated using rolled up banknotes, hollowed out pens and special straws called ‘’coke-straws’’ thats what is cocaine.
It is reported that cocaine insufflation by sharing straws can spread blood-borne diseases just like sharing needles.
Injection:
Drug injection provides the highest blood levels in the shortest amount of time. Tinnitus and audio distortion may occur moments after injection, lasting upto 5 minutes. The euphoria passes quickly. Another potential danger is the formation of emboli due to impurities. Blood-borne disease may also be contracted by sharing unsterile needles.
Other forms of the drug and routes of administration include oral (chewing coca leaf), inhalation and suppositories.
Pharmacology:
Mechanism of Action:
The primary mechanism of action underlying the central and peripheral effects of cocaine is blockade of reuptake of the monoamines norepinephrine, serotonin and dopamine into the presynaptic terminals from which these neurotransmitters are released. This blockade is caused by cocaine thightly binding to the monoaminergic reuptake transporters, leading to potentiation and prolongation of the CNS and peripheral effects of these monoamines.
The most extensively studied effect of cocaine is blockade of the dopamine transporter protein. The result is that the dopamine receptor can no longer perform its function, and thus dopamine accumulates in the synaptic cleft. This results in an enhanced and prolonged postsynaptic effect of dopaminergic signalling at dopamine receptors at the receiving neuron. Dopamine-rich brain regions such as the ventral tegmental area, nucleus accumbens, and prefrontal cortex are frequent targets of cocaine-addiction research.
Cocaine also blocks sodium channels, thereby interfering with the propagation of action potentials. Thus it has found use as a local anesthetic. For example, cocaine is applied topically during eye, ear, nose and throat surgery. Its interaction with potassium channels may contribute to the ability of cocaine to cause arrhythmias.
Actions
Cocaine increases energy, feeling of competence and sexuality. Athletic performance may be enhanced in sports where sustained attention and endurance is required.
a. CNS: The behavioural effects of cocaine result from powerful stimulation of the cortex and the brainstem. Cocaine acutely increases mental awareness and produces a feeling of well-being and euphoria. Cocaine can produce hallucinations and delusions of paranoia or grandiosity. Cocaine increases motor activity, and at high doses, it causes tremors and convulsions, followed by respiratory and vasomotor depression.
b. Sympathetic Nervous System: Peripherally, cocaine potentiates the action of norepinephrine, and it produces the ‘’fight or flight’’ syndrome characteristic of adrenergic stimulation. This is associated with tachycardia, hypertension, papillary dilation and peripheral vasoconstriction. Recent evidence suggests that the ability of baroreceptor reflexes to buffer the hypertensive effect may be impaired.
c. Hyperthermia: Cocaine is unique among illicit drugs in that death can result not only as a function of dose but also from the drug’s propensity to cause hyperthermia. This is the reason why mortality rates to coaine overdose rise in hot weather. Even a small amount of intranasal cocaine impairs sweating and cutaneous vasodilation. Perception of thermal discomfort is decreased.
Therapeutic Use:
The only use of cocaine is as a local anesthetic during eye, ear, nose and throat surgery, due to its propensity to block voltage-gated sodium channels.
Adverse Effects:
a. Anxiety: The toxic response to acute cocaine ingestion can precipitate an anxiety reaction that includes hypertension, tachycardia, sweating, and paranoia. Because of the irritability, many users take cocaine with alcohol. A product of cocaine metabolites, cocaethylene, is more euphorigenic than cocaine itself and psychoactive and is considered to contribute towards cardiotoxicity.
b. Depression: Like all stimulant drugs, cocaine stimulation of the CNS is followed by a period of mental depression. Addicts withdrawing from cocaine exhibit physical and emotional depression as well as agitation.
c. Toxic effects: Cocaine can induce seizures as well as fatal cardiac arrhythmias. Use of IV diazepam and propranolol may be required to control cocaine-induced seizures and cardiac arrhythmias, respectively. The incidence of myocardial infarction in cocaine users is unrelated to dose, duration of use, or to route of administration.
Pharmacokinetics:
The peak effect after intranasal intake of cocaine occurs at 15 to 20 minutes, and the ‘high’ disappears in 1 to 1.5 hours. Rapid but short lived effects are achieved following IV injection of cocaine or by smoking the freebase form of the drug (‘’crack’’). Because the onset of action is most rapid, the potential for overdosage and dependence is the greatest with IV injection and crack smoking.
Cocaine is extensively metabolized, primarily in the liver, with only about 1% excreted unchanged in the urine. The metabolism is dominated by hydrolytic ester cleaveage, so the eliminated metabolites consist mostly of benzoylecgonine (BE), the major metabolite, and other significant metabolites in lesser amounts such as ecgonine methyl ester (EME) and ecgonine. Further minor metabolites of cocaine include norcocaine, p-hydroxycocaine and m-hydroxycocaine.
Depending on liver and kidney function, cocaine metabolites are detectable in the urine. BE can be detected in the urine within four hours after cocaine intake and remains detectable in concentrations greater than 150 ng/ml typically for upto eight days after cocaine is used.
Detection in Body Fluids:
Cocaine and its major metabolites may be quantitated in blood, plasma or urine to monitor for abuse, confirm a diagnosis of poisoning or assist in a forensic investigation of a traffic or other criminal violation or sudden death. Chromatographic techniques can easily detect, distinguish and measure each of these substances. Careful interpretation is necessary when determining whether the individual is a habitual user or a cocaine-naive individual because a chronic user can develop tolerance to doses that would incapacitate a cocaine-naive individual.
The above material should be enough to convince that cocaine has little therapeutic use, and is mostly used as a recreational drug. However, its addictive potential, coupled with its physical and psychological dependence far outweighs the recreational benefits of the drug. Hence it is best to steer clear of drugs such as cocaine, if one is to enjoy a healthy, fulfilling life.
BY:
Haris Ahmed
BPD 01091014
Doctor Of Pharmacy
University of Lahore
