The Main Cocaine’s Mechanism of Action Essay

Cocaine is one of the commonly used illegal drugs. In its pure form, it is a white, crystal-like salt. It can be inhaled, snorted, or injected into the vein. Its effects can be seen within minutes of administration, and it gives a feeling of intense pleasure. Cocaine easily crosses the blood–brain barrier where it acts at the synapse blocking the reuptake of neurotransmitters, the most common being dopamine. It also interferes with the propagation of action potentials by blocking the sodium ion channels. On the other hand, the body reacts to cocaine by metabolizing it with the help of the enzyme cholinesterase. Earlier cocaine was used as a topical anesthetic during the painful procedures of nose and mouth, but its use has now been limited due to the increased availability of other anesthetics. Adverse effects include hallucinations, irregular heartbeat, numbness, increased body temperature, and increased blood pressure. Prolonged usage increases the risk of hemorrhage and stroke. Addiction to cocaine causes altered neuronal transcription regulation and withdrawal of cocaine presents with emotional-motivational symptoms.

Cocaine acts through the reward pathway of the brain. The reward pathway is activated in response to a stimulus associated with wants or a desire for a reward. It is present in the region of the mid-brain known as the ventral tegmental area. This area then further extends into the nucleus accumbens. In the normal process, neurotransmitters such as dopamine are released by the pre-synaptic neuron at the synapse which then binds to the receptors present on the post-synaptic neuron. By this way, neurotransmitter acts as a signaling molecule. Dopamine so released is transported back from the synaptic cleft into the pre-synaptic neuron via a transporter. The transporter pumps the dopamine from the synaptic cleft into presynaptic neurons where it is packaged into synaptic vesicles. Cocaine forms a complex with the dopamine transporter by binding tightly to it, thus inhibiting a hydrogen bond specific to the transporter. This causes the accumulation of dopamine at the synaptic cleft, which causes continuous activation of post-synaptic receptors. This makes the drug rewarding, promoting compulsive cocaine use.

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Apart from dopamine, it also inhibits the reuptake of serotonin and norepinephrine.

Chronic exposure to cocaine is known to affect other parts of the brain too. Studies have shown diminished functioning of the orbitofrontal cortex. This causes poor decision-making ability of the individual, poor insight, and inability to adapt to the environment. It is also known to act upon the sigma receptors and N-methyl-d-aspartate (NMDA) receptors. It locks sodium ion channels interfering with the generation of the action potential as sodium ions are required to depolarize the membrane. In this way, it acts as a local anesthetic

Effects of Cocaine:
Cocaine causes several effects on the body. Acute effects include anxiety, euphoria, fear, delusions, arrhythmia, itching, and other cardiac events leading to cardiac arrest.

Chronic effects include insatiable hunger while some individuals reduce food intake leading to severe malnutrition. Other symptoms include insomnia, lethargy, and a continuously running nose. Dysphoria and depression are felt sometimes. Euphoria at later stages is replaced by loss of libido, nervousness, aggression, etc. Physiologic effects include impairment of sweating, blood flow, decreased heat perception, and elevated body temperature. Intranasal consumption of cocaine degrades the nasal septum, leading to its complete disappearance. It increases the risk of certain rare autoimmune disorders such as Goodpasture syndrome, glomerulonephritis, etc.

It also increases the risk of hemorrhage, stroke, and heart attack. It promotes blood clotting by increasing the activity of the plasminogen activator inhibitor. Cocaine has deleterious effects during pregnancy. It causes abnormalities in fetus and thus is teratogenic. In utero exposure to cocaine can result in cognitive impairment, cleft lip, and palate, behavioral abnormalities, and cardiovascular and urinary tract malformations. Intoxication presents with violent behavior, spasms, twitches, tremors, intense thirst, chest pain, convulsions, and coma. However, the role of cocaine neuropathologies is unclear.

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