Cocaine dependence

Etiological factors and nature of the active substance

When examining the etiology of this pathological process, it is first necessary to look at the primary source. The disease and its associated acute conditions develop as a result of the use of specific plant alkaloids. The natural reservoir and source of this compound are the leaves of a shrub botanically known as Erythroxylon coca. The toxin is extracted precisely from this plant material.

From a chemical and pharmacological perspective, the active principle is a complex organic compound — benzoylecgonine methyl ester. Upon entering the human body, this molecule exhibits a triad of core pharmacological properties that entirely determine the clinical picture of intoxication. First, the substance acts as a potent central nervous system stimulant, drastically altering mental status. Second, it possesses local anesthetic properties, blocking impulse conduction at the local level. Third, it acts as an aggressive vasoconstrictor, causing generalized narrowing of blood vessel lumens.

Pathogenesis and molecular mechanisms of damage

The central link in the pathogenesis is the severe disruption of normal synaptic function in the nervous system by the toxin. The mechanism of action is based on altering neurotransmitter dynamics. Normally, signal transmission is strictly regulated; however, benzoylecgonine methyl ester causes persistent blockade of transmembrane transport of biogenic amines into neurons.

The primary blow is dealt to adrenergic nerve fibers. There is a pronounced inhibition of catecholamine reuptake by their terminals. Because the neurotransmitters cannot return to the presynaptic terminal, they accumulate in excess within the synaptic cleft, continuously stimulating receptors.

The logical outcome of such molecular failure is a total and uncontrolled activation of the sympathoadrenal system. Notably, when performing a differential analysis of pathogenetic mechanisms (among which one might mistakenly assume a primary effect on the nigrostriatal, parasympathetic, or hypothalamic-pituitary-adrenal systems), it is precisely the hyperactivation of the sympathoadrenal link that is the true cause of all subsequent systemic disorders.

Clinical presentation of single-use intoxication

Even a single exposure to Erythroxylon coca alkaloids provokes vivid clinical symptoms that are a direct consequence of the pathogenesis described above. The symptom complex of acute exposure can be divided into psychoemotional and somatic manifestations.

Regarding the psyche and subjective sensations, the patient notes a sharp improvement in mood and general well-being. This effect is driven by central nervous system stimulation and an excess of biogenic amines.

Somatic manifestations are dictated by sympathoadrenal activation and vasoconstriction:

• There is a rapid increase in heart rate (HR).
• Concurrently, a sharp spike in blood pressure (BP) is recorded. In clinical practice, this frequently results in dangerous hypertensive reactions requiring emergency medical intervention.
• Thermoregulation processes are impaired: an increase in body temperature is noted, which under unfavorable conditions can progress to life-threatening hyperthermia.

Metabolism and elimination pathways

To understand the duration of effects and the principles of detoxification, it is crucial to know the metabolic pathways of benzoylecgonine methyl ester. Once the substance enters the systemic circulation and begins exerting its pathological effects, enzymatic degradation processes are simultaneously triggered.

The main stage of toxin degradation takes place directly in blood plasma. This reaction is catalyzed by specific enzymes known as esterases. Under the action of esterases, the parent molecule is cleaved into metabolites.

The final stage of cleansing the body falls to the excretory system. The breakdown products formed in the blood are transported to the kidneys, filtered, and ultimately excreted in the urine, which is of key importance for laboratory confirmation of substance use.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Mechanisms of blockade of transmembrane transport of biogenic amines at the molecular level.
• The role of blood esterases in the metabolic rate of benzoylecgonine methyl ester.
• Pathophysiology of hypertensive reactions resulting from the inhibition of catecholamine reuptake.
• Causes of hyperthermia during sympathoadrenal system hyperactivation.
• The mechanism of the local anesthetic action of Erythroxylon coca alkaloids.

Other topics in «Chapter 18. Drug Addiction. Substance Abuse. Poisoning»

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