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Cocaine

Brain

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Cocaine (benzoylmethylecgonine) - is an alkaloid extracted from the leaves of the Erythroxylon plant, which is a shrub native to the Andes Mountains in western South America. When treated with hydrochloric acid, it turns into the hydrochloride salt of cocaine, which easily dissolves in water within 0.4 seconds. It has a melting point of 195 C.
Cocaine hydrochloride is a white (or slightly yellowish/beige/cream) powder or powder with colorless needle-like small crystals without any smell at all, or sometimes with a weak non-specific smell. The powder has a bitter taste; it has the ability to numb mucous membrane on contact.

On the market, cocaine is presented in the following forms: a solution of cocaine hydrochloride (4%), a solid form (fine powder or powder in the form of “rocks” with small crystals), a form of a liniment “coca paste” with soft aggregates (a result of primary extraction of coca leaves). A special form of cocaine, known as "crack", is a "free base" and has a higher melting point. Therefore, it is often used for smoking. "Speedball" is a mixture of crack and heroin in different proportions and concentrations used intranasally.

IMG COC


Pharmacokinetics.
Cocaine is mainly metabolized by hepatic and intestinal carboxylesterases, serum butyrylcholinesterases and CYP450 3A4, resulting in the formation of the following metabolites: methyl esters of ecgoin (up to 15%), methylecgoil (up to 60%) and benzoyl ecgoin (up to 80%). Less than 10% of cocaine is metabolized by N-demethylation into norcocaine, which is a metabolite of cocaine with significant pharmacological activity. From 1% to 5% of cocaine is not metabolized at all and is excreted unchanged in urine.

The half-life of cocaine hydrochloride is 0.5-1.5 hours, while the half-life of its metabolites is about 3-5 hours. The bioavailability of cocaine exceeds 90% when used intravenously or inhalated (smoking). When used intranasally, its bioavailability reaches only 80%, orally - up to 20%. The volume of distribution is 2.7 l/kg, and about 90% of cocaine binds to plasma protein.

3 PROD
4 PROd
1 PROD

Mechanism of action.
Cocaine has a complex effect on the peripheral sympathetic system and the central nervous system. The main central effects of cocaine are achieved by blocking the reverse neuronal capture of monoamines (competitively binding to monoamine transporters) at the pre-synapse, resulting in the accumulation of neurotransmitters in synaptic slits (mainly dopamine, norepinephrine and serotonin). The local anesthetic effect of cocaine is associated with the competitive blocking of fast potential-dependent sodium channels of the peripheral nervous system, reducing the rate of polarization and the amplitude of the action potential, thereby temporarily disrupting the conduction of the nerve impulse.

Cocrrenneuron
MECHANISM 2


Methods of use and doses.
Weight-based calculation for intranasal dosing is performed, considering the gradation of the severity and duration of effects:

1. Low - 0.3 mg/kg.
2. Medium - 0.9 mg/kg.
3. High - 1.5 mg/kg.


The higher the dosage, the greater the severity of side effects. With this method of use, the mucous membrane of the nasal cavity and oropharynx often gets damaged, resulting in short-term side effects associated with rhinitis, sinusitis, inflammation of the paranasal sinuses, and long-term effects associated with perforation of the nasal septum, purulent diseases of the ENT organs.

That's why proper care of the nasal cavity and mouth is essential, which includes rinsing with special solutions, using creams, respiratory gymnastics, irrigations with special nasal sprays. The manifestation of cocaine action with this method of use is up to 5 minutes, the peak of the effects and the plateau is up to 30 minutes, the total duration of action is 70-90 minutes.

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It is strongly recommended to use only clean or purified solutions intravenously, ideally - a solution of cocaine hydrochloride 40 mg/ml. The most common complications of this method of use include phlebitis or thrombophlebitis, which require special conservative therapy using creams, venotonics and sometimes anticoagulants, as well as special instrumental ultrasound methods of examination.

When used orally, the dosage of cocaine is usually 2-2. 5 mg/kg, considered the low bioavailability. The oral administration involves using gelatin capsules containing cocaine, or cocaine hydrochloride dissolved in water (preferably warm) in certain dosage in one dose. With this method of use, the effects are much less severe, but their duration may last longer. The inhalation method is appropriate for crack. The effects occur instantly, as they do with intravenous administration, however, the duration of the effects remains short.
Clinical presentation of intoxication due to cocaine use:
1. Euphoria and a feeling of increased energy;
2. Prolonged wakefulness;
3. Grandiose ideas or actions;
4. Violent or aggressive behaviour;
5. Confirmation bias;
6. Mood lability;
7. Behavior characterized by repeated stereotypes,
8. Auditory, visual or tactile illusions;
9. Personality distortion
Also, people who use cocaine must have at least two of the following signs to be diagnosed:
1. Tachycardia;
2. Arterial hypertension;
3. Sweating and feverish chills;
4. Nausea or vomiting;
5. Muscle weakness;
6. Pain or discomfort behind the sternum;
7. Psychomotor agitation;
8. Pupil dilation.


Symptoms of cocaine intoxication mainly include signs of cardiovascular and nervous system complications. Respiratory disorders develop less often.
Cardiac disorders:
hypertension and tachycardia are the most common ones, when taking low doses. Initial bradycardia is also possible due to an increase in parasympathetic tone. Arrhythmias (supraventricular are frequent) can be caused by a sympathetic crisis or a blockade of fast sodium channels. Ischemia and myocardial infarction are caused by coronary spasm, which reaches a maximum 30 minutes after intranasal cocaine use and coincides with the peak concentration of the drug in blood. Further coronary spasm can develop after 90 minutes, which is associated with the accumulation of cocaine metabolites. An increase in platelet aggregation leads to formation of blood clots in coronary vessels. Moreover, the myocardial oxygen demand increases. A rare complication is aortic rupture.

Complications from the central nervous system: seizures are presented in 2-10% of patients admitted to hospitals with cocaine intoxication. Usually convulsions develop 1.5 hours after intoxication, butsome cases of convulsions are which occur after 12 hours. Cases of transient cerebral circulatory disorders, ischemic stroke, hemorrhagic stroke, subarachnoid hemorrhage are possible.

Complications from the respiratory system: when smoking cocaine, pneumothorax, pneumomediastinum, non-cardiogenic pulmonary edema are presented in rare cases.

Complications associated with cocaine use.

The most common symptoms of overdose are the following:
1. Intense headache (localized or non-localized, often pulsating) that occurs 10-30 minutes after use and lasts more than half an hour, often accompanied by nausea and vomiting.
2. Sternum pain, discomfort in the left hypochondrium, chest area on the left, irradiation of pain to the left, in the left upper limb, left clavicle, decreased superficial sensation in the left parts.
3. Panic attacks, psychosis, anxiety, depersonalization/derealization.
4. An increase in the pulse rate of more than 110 per minute, an increase in blood pressure of more than 140/95 mmHg.
5. An increase in body temperature of more than 37.5 C and hyperthermia lasting more than one hour after use.
6. Fine tremor, convulsions, impaired consciousness up to a coma.
7. Acute coronary syndrome.
8. Sudden cardiac death.
9. Serotonin syndrome.

Interactions of cocaine with other substances, contraindications to usage.
The “non-ADIOS" rule:
  • Non-Alcohol - it is not recommended using with alcohol.
  • Non-Dissociatives - it is not recommended using with dissociative drugs.
  • Non-iMAO - it is not recommended using with monoamine oxidase inhibitors.
  • Non-Opiates - it is not recommended using with opioid receptor agonists.
  • Non-Stimulators - it is not recommended using with stimulants.
1. When using cocaine together with drugs of the PDE-5 inhibitor group, the risk of developing side effects of both substances increases. Most common side effects: severe headache of a spastic nature, nausea. Incidence of developing severe critical conditions is low.
2. When using cocaine together with marijuana, there is a risk of occurrence of increased blood pressure, headache, fine tremor, dryness of the mouth. The probability of developing severe critical conditions is low.
3. When using cocaine with neuroleptics/tranquillizers, there is a high risk of levelling the main effects of cocaine. The probability of developing severe critical conditions is low (in cases where there are no contraindications to taking neuroleptics).
4. It is not recommended to use cocaine during treatment with antibacterial, antiviral and antifungal drugs, hormones, anticoagulants.
5. It is not recommended to use cocaine during any surgical manipulation and in time before and after that for a certain period (the period is identified individually).
6. It is not recommended to use cocaine if diagnosed with any disorder of cardiovascular system, kidneys, liver, lungs, central nervous system.
7. It is not recommended to use cocaine during pregnancy and lactation.

Cocaine detection times:
1. Approximate time period of cocaine detection in urine after a single use is 2-3 days, systematic use - up to 10 days (the terms vary depending on many factors).
2. The approximate time period of cocaine detection in blood serum is 1-36 hours.
3. The approximate time period of cocaine detection in saliva is up to 24 hours, in hair - up to 90 days.
 
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cubesquare

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The above is extremely helpful.
I also just read the UNODC 2021 Cocaine Insights – issue 2: Cocaine – A spectrum of products and it has a lot of supporting and additional information and I found it fascinating and wanted to share.

It was taken from this page: https://www.unodc.org/unodc/en/data-and-analysis/the-cocaine-market.html (CLEARNET WARNING)
 

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Brain

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PeterKeta

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May I ask for an elaboration on "form of a liniment “coca paste” with soft aggregate" Is this aiming for the step before the base?
 

Brain

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Yes, that's right.
 

Frit Buchner

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Minor grammatical correction, cocaine base has a LOWER melting point vs cocaine HCl, about 1/2 the temperature.
 

robotmr

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I say anything cocaine and below is not that bad really. You do you but some stuff such as fent is 1000 times stronger than morphine. Now I don't want anything to do with that. But again you do you.
 
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