Cocaine

Cocaine is a powerfully addictive stimulant drug made from the leaves of the coca plant native to South America. It is an alkaloid with a tropane ester chemical structure and belongs of the family of drugs that stimulate the activity of brain and sympathetic peripheral nervous systems by enhancing neurotransmitter activity at catecholaminergic synapses.

Cocaine along with caffeine and ephedra are naturally occurring plant alkaloids.

Cocaine is produced mainly in Bolivia, Colombia, and Peru and smuggled primarily to North America and Europe.

Cocaine was first isolated and synthesized in 1859 in Germany. Merck pharmaceutical produced only 0.75 pounds of cocaine in 1983 and this number was increased to 158,352 within in a year, in 1984. The number of cocaine users in the world in 2005 was estimated at 14.3 million which represents 0.3% of the 15- to 64-year-old population. Of these, 44% were in North America which can be translated to 6.4 million people with a prevalence of 2.2%.

Cocaine is legally available in the United States only as a 4% or 10% injectable solution (or powder for reconstitution) or viscous liquid for use as a local or topical anesthetic.

An estimated 530 to 710 metric tons of cocaine entered the United States in 2006 (USONDCP 2007). The average purity of cocaine was found to be 50% to 60% in the United States in 2007 (USDEA 2008).

Diluents (also called “cut”) such as dextrose, lactose, mannitol, starch, benzocaine, lidocaine, procaine, ephedrine, amphetamine, caffeine, benzene, acetone, allergy pills, or sodium bicarbonate or PCP are commonly added to cocaine in retail stage to increase the margin of profit (Shesser 1991). Stimulants also have been used to augment the response to standard antidepressants (DeBattista 2006)

Why do people use cocaine?

• To feel confident
• To be excited
• To take more risks than usual
• To be less hungry or loos weight
• To feel alert and energetic
• Want to have sex

 Stimulants have been used in medicine in the treatment of the following clinical conditions:

1. Cocaine
   1. Local or topical anesthetic (Harper 2006).
   2. Brompton’s cocktail: a combination of cocaine, alcohol and opiate has been used in the treatment of cancer pain.
2. Methamphetamine
   1. ADHD,
   2. Weight control
3. Amphetamine (as d-isomer or racemic mixture)
   1. Amphetamines have been used to improve recovery after stroke, but their efficacy is questionable (Martinsson 2007)
   2. to counteract opiate-induced sedation and respiratory suppression, thus allowing larger doses of opiates to be used (Homsi 2000)
   3. ADHD,
   4. Narcolepsy
   5. weight control
   6. depression
4. Methylphenidate (as d-isomer or racemic mixture)
   1. ADHD,
   2. Narcolepsy (Banerjee 2004; Morgenthaler 2007)
5. Lisdexamfetamine (l-lysine-d-amphetamine
   1. For treatment of ADHD
6. Benzphetamine
   1. Used for weight control
7. Phenmetrazine
   1. Used for weight control
8. Phenmetrazine
   1. Used for weight control

Nonmedical Use, Abuse, and Dependence

Stimulants, both prescription and OTC, have been widely used in workplace, school, military, truck drivers, and sports settings for their alerting, sleep-suppressing, and performance-enhancing properties (Svetlov 2007; Wilens 2008)

Both animal and human studies has demonstrated stimulants do increase aggressive and violent behavior to stimulant-induced irritability, paranoia, or frank psychosis (Licata 1993; Fukushima 1994)

Cocaine is commonly used with heroin (speedballing) to get a better high and enhance the acute psychological effects of cocaine (Foltin 1996) Cocaine users commonly use alcohol, benzodiazepines, opiates, and marijuana after cocaine to reduce anxiety, paranoia and restlessness effects of cocaine and/or to relieve symptoms of cocaine withdrawal. This is called “Up and Down”.

Absorption and Distribution

1. Smoked:
   1. Stimulants are rapidly absorbed through the lungs and can reach the brain within 6 to 8 seconds.
   2. The onset of peak effects after smoking occurs within minutes of administration.
   3. Positron emission tomography (PET) studies with radiolabeled cocaine showed that intravenous administration produces peak brain uptake in 4 to 7 minutes (Telang 1999)
2. Intranasal and oral use:
   1. Stimulants have a slower absorption and onset of effect (30 to 45 minutes), a longer peak effect, and a more gradual decline from peak.
   2. The peak intensity of effect is weaker than with smoked or intravenous administration because less active drug reaches its site of action in the brain.

Elimination

Stimulants and their metabolites are largely eliminated in the urine. (Jenkins 1998) Benzoylecgonine is the cocaine metabolite found in highest concentration in urine for several days after cocaine use which is measured in Urine Drug Screening tests.

Cocaine intoxication can present with a combination of some of the following symptoms:

1. Increased energy, alertness, and sociability;
2. Elation or euphoria; and
3. decreased fatigue, need for sleep, and appetite (Romanelli 2006)
4. Anxiety
5. Irritability
6. Panic attacks
7. Interpersonal sensitivity
8. Hypervigilance
9. Suspiciousness
10. Paranoia
11. Grandiosity
12. Impaired judgment
13. Delusions and hallucinations
14. Psychosis
15. Hallucinations
16. Tactile hallucinations (formication)
17. Restlessnes
18. Agitation
19. Tremor
20. Dyskinesia, and repetitive or stereotyped behaviors such as picking at the skin or foraging for drug
21. Tachycardia
22. Pupil dilation
23. Diaphoresis
24. Nausea

 Some of the chronic Effects of cocaine use:

1. Cognitive impairment (Rogers 2001) such as visuomotor performance, attention, inhibitory control, and verbal memory.
2. Reduced gray and white matter volumes in the frontal cortex of the brain
3. Enlarged basal ganglia (Magalhaes 2005)
4. Psychotic flashbacks have been reported in methamphetamine abusers up to 2 years after their last drug use and often are precipitated by threatening experiences (Yui 1998)
5. Hemorrhagic stroke
6. movement disorders as the result of increased dopamine activity in the basal ganglia and other brain areas that control movement (Warner 1993):
   1. Acute dystonic reactions,
   2. Choreoathetosis
   3. Akathisia (crack dancers)
   4. Buccolingual dyskinesias
   5. Exacerbation of Tourette’s syndrome and tardive dyskinesia.

 Withdrawal symptoms of the cocaine dependence can be:

1. Depressed mood,
2. Anhedonia
3. Fatigue
4. Difficulty concentrating,
5. Increased total sleep and rapid eye movement sleep duration

 Cardiovascular System

1. Increase heart rate, blood pressure, and systemic vascular resistance
2. Myocardial infarction
3. Cardiac arrhythmias
4. Blockade of myocyte sodium channels
5. Cardiomyopath
6. Myocarditis

 Pulmonary effect of cocaine use:

1. Acute and chronic pulmonary toxicity
2. Cough
3. Shortness of breath,
4. Wheezing
5. Chest pain
6. Hemoptysis
7. Exacerbation of asthma

 Effect of cocaine use in kidneys:

1. Acute renal failure

 Gastrointestinal effects of cocaine use:

1. Cocaine reduces gastric motility and delays gastric emptying
2. Gastroduodenal ulceration and perforation,
3. Intestinal infarction and perforation, and
4. Ischemic colitis (Glauser 2007)
5. Concealing cocaine by swallowing large packets (“body packing”) may result in severe acute toxicity if the wrapping deteriorates and allows cocaine into the gastrointestinal tract

 Effect of cocaine in Liver:

1. Cocaine is hepatotoxic in rodents, but is no direct evidence that cocaine is hepatotoxic in humans.
2. Liver abnormalities reported in case series of cocaine users can be accounted for by viral hepatitis from injection drug use, alcoholic liver disease, or other consequences of a drug-using lifestyle.

 Endocrine effects of cocaine use:

1. Acute cocaine use activates the hypothalamic-pituitary-adrenal (HPA) axis, stimulating secretion of epinephrine, corticotropin-releasing hormone (CRH), ACTH, and cortisol (Mello 1997; Warner 1998)
2. Decreases plasma prolactin concentrations in cocaine-naive individual

 Musculoskeletal effects of cocaine use:

1. Rhabdomyolysis

 Head and Neck symptoms can be:

1. Chronic rhinitis, perforated nasal septum and nasal collapse, oropharyngeal ulcers, and osteolytic sinusitis
2. Gingival ulceration
3. Dental enamel erosion
4. Crack cocaine may cause corneal ulcers (Ghosheh 2007)

 Effect of cocaine use in immune system:

1. Variety of vasculitic syndromes primarily affecting skin and muscle
2. Henoch Schönlein purpura,
3. Steven-Johnson syndrome, or
4. Raynaud phenomenon.
5. Wegener’s granulomatosis (Peikert 2008)

 Effect of cocaine use on sexual function:

1. Stimulants are commonly thought of as an aphrodisiac, but chronic use usually impairs sexual function (Palha 2008)
2. Men may experience erectile dysfunction or delayed or inhibited ejaculation.
3. Priapism is rare.
4. Women may develop irregular menses.

 Reproductive, Fetal, and Neonatal Health

1. Prescription stimulants, including cocaine and amphetamines, are classified by the FDA in pregnancy category C, meaning that risk cannot be ruled out because human studies are lacking.
2. vaginal bleeding,
3. abruptio placenta,
4. placenta previa,
5. premature rupture of membranes,
6. decreased head circumference,
7. low birth weight, tremulousness,
8. irritability
9. poor feeding, and
10. autonomic instability

Stimulant medications: Such interactions with medications that enhance catecholamine activity risk overstimulation of the sympathetic nervous system, with possible cardiac arrhythmia, hypertension, seizure, cardiovascular collapse, and death.

MAOIs: Prescription stimulants, such as amphetamine and methamphetamine, should not be used within 2 weeks of MAOI use.

TCAs: Stimulants should be used cautiously in conjunction with tricyclic antidepressants, many of which block presynaptic reuptake of catecholamines.

Alcohol: When cocaine is used in combination with alcohol, a new compound, cocaethylene is formed (Penningers 2002) which may contribute to more severe or longer-lasting toxic effects of cocaine.

Antidepressants:

• A review of 18 double-blind clinical trials found only three of studies with significant differences between the study regimen and placebo. Overall the review did not support the clinical use of antidepressants in the treatment of cocaine dependence.

Dopamine Agonists:

• Three most studied dopamine agonists (Amantadine, bromocriptine and pergolide) from 17 randomized double-blind, placebo controlled studies found inconsistent results. (Soares et al 2010)

Dopamine Antagonists:

• Antipsychotics such as Olanzapine, Risperidone, and Ecopipam have been tried in several studies. Their results suffer from poor compliance, high side effects and high subjective attrition. (Amato et al 2007; Grabowski 2004)

Disulfiram:

• Disulfiram has been found promising in reducing quantity and frequency of use and reducing number of cocaine positive UDS. (Pani et al 2010; Sofuoglu 2006)

Topiramate

• Is a GABAergic antiepileptic drug
• Reduces the number of cocaine positive urines, so it might be an effective treatment but further studies are needed. (Sofuoglu 2006)

Baclofen

• have been found to be superior to placebo in reducing cocaine use and its use in treatment of cocaine dependence has been supported. (Kenna 2007)

Propranolol

• Propranolol is an Alpha Adrenergic Antagonist (alpha blocker)
• When administered in dose of 100 mg/day have been found to reduce withdrawal symptoms and increase treatment retention among heavy cocaine users. (Kampman 2001; Kampman 2006)

Modafimil

• Modafinil is an stimulant drug used in treatment of narcolepsy and excessive daytime sleepiness.
• It may block cocaine-induced euphoria, enhance periods of abstinence and reduce total cocaine use. (Dackis 2003; Dackis 2005; Martinez-Raga 2008)

This document is prepared by Dr Siavash Jafari, MD, MHSc, FRCPC, ABAM. This document is provided for information purposes only and does not necessarily represent endorsement by or an official position of the Essentials of Medicine. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient’s medical history.

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