Psychostimulants

Psychostimulants (cerebrostimulators, psychotopics) are analeptic agents that cause psychomotor activation in both sick and healthy people.

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Indications for the use of psychostimulants

The main indications for treatment with psychostimulants are narcolepsy and severe asthenic conditions.

Before starting to take these drugs, patients should undergo a medical examination. Particular attention should be paid to the heart rate, heart rhythm and AP. Psychostimulants are prescribed to patients with arterial hypertension with caution, with mandatory subsequent monitoring of blood pressure. Psychostimulants should be avoided in patients with tachyarrhythmia. During the examination, attention should be paid to tics and impaired coordination of movements (psychostimulants can provoke or worsen the course of Gilles de la Tourette syndrome and dyskinesia). Psychostimulants should be avoided in cases with previous abuse of them, and possibly in all patients prone to drug abuse. Since physical and mental drug dependence may develop when taking these drugs, the duration of continuous treatment should not exceed 3-4 weeks. It should also be taken into account that psychostimulants, including mesocarb, lead to an exacerbation of the condition in patients with psychotic disorders.

Narcolepsy

Narcolepsy is characterized by excessive daytime sleepiness, combined with irresistible, short-term episodes of falling asleep. In addition, patients may experience catalepsy - periods of partial or complete loss of motor tone (often provoked by strong emotional arousal), sleep paralysis and/or hypnagogic hallucinations. Symptoms of daytime sleepiness and episodes of falling asleep are most effectively relieved by psychostimulants.

Severe asthenic conditions

Severe somatic patients may develop apathy, social withdrawal, and loss of appetite without obvious manifestations of a major depressive episode. This condition often leads to refusal of treatment, loss of interest in life, and consumption of less caloric food. Improvement of the condition of patients with antidepressant treatment is possible, but since a long course of therapy (several weeks) is necessary, patients may stop treatment. Psychostimulants, when used rationally, improve mood, interest in life, patient compliance with the treatment regimen, and in some cases, appetite. The effect of psychostimulants develops quickly.

Mechanism of action and pharmacological effects

Psychostimulants affect primarily the cerebral cortex. They temporarily increase performance, concentration, and maintain wakefulness. Some of them have a euphoric effect and can lead to the development of drug dependence. Unlike most antidepressants, psychostimulants reduce appetite and body weight, i.e. they have an anorectic effect. In psychiatric practice, psychostimulants are rarely used, as a short course, mainly in severe asthenic conditions and narcolepsy. The mechanism of action consists of direct stimulation of sympathomimetic receptors of the postsynaptic membrane and facilitating the presynaptic release of mediators. Amphetamines (phenamine, methylphenidate) stimulate dopamine receptors; sydnoneimines (mesocarb, feprosidine) have predominantly noradrenergic activity. In the Russian Federation, most psychostimulants are prohibited for use as drugs. Exceptions are the original domestic drugs mesocarb (sidnocarb) and feprosidnin hydrochloride (sidnofen).

Mesocarb is similar in chemical structure to phenamine, compared to which it is less toxic, does not have pronounced peripheral adrenergic stimulating activity, has a stronger effect on noradrenergic than on dopaminergic brain structures. Stimulates the reuptake of catecholamines and MAO activity. The stimulating effect develops gradually (there is no sharp initial activating effect), compared to phenamine it is longer, is not accompanied by euphoria, motor excitation, tachycardia, or a sharp increase in blood pressure. During the aftereffect, the drug does not cause general weakness and drowsiness. The effects of addiction are less pronounced.

Pharmacokinetics. After oral administration, it is rapidly absorbed from the gastrointestinal tract. It is metabolized by C-hydroxylation of the aliphatic chain of the phenylisopropyl substituent and the benzene ring of the phenylcarbamoyl radical to form alpha-oxydnocarb. As a result, the stimulating effect is reduced, since this metabolite poorly penetrates the blood-brain barrier. 60% is excreted by the kidneys, about 30% from the gastrointestinal tract, and 10% with exhaled air. 86% is excreted within 48 hours. It does not have a cumulative capacity.

Interactions. Incompatible with MAO inhibitors, TA. Mezocarb reduces muscle relaxation and drowsiness caused by benzodiazepine anxiolytics, while the anxiolytic effect of the latter is not reduced. Glutamic acid enhances the psychostimulant effect of mezocarb.

Feprosidnine hydrochloride belongs to the group of phenylalkyl sydnonimines and is similar in structure to mesocarb. It has a stimulating effect on the central nervous system and at the same time has antidepressant activity. The antidepressant effect of the drug is associated with its ability to reversibly inhibit MAO activity. It reduces the depressant effects of reserpine, enhances the effect of adrenaline hydrochloride and noradrenaline, and causes a moderate increase in blood pressure. It has anticholinergic activity.

Interactions. The drug should not be used simultaneously with antidepressants - MAO inhibitors and TA. Between the use of feprosidine hydrochloride and antidepressants of the above groups, as well as between antidepressants and this drug, it is necessary to take a break of at least a week.

In addition, caffeine, which is included in many analgesics, is considered a weak stimulant.

Dextroamphetamine, methylphenidate and pemoline are used in clinical practice abroad. Dextroamphetamine is the D-isomer of phenylisopropanolamine, which is three times more active as a CNS stimulant than the L-isomer (amphetamine). Methylphenidate is a piperidine derivative that is structurally similar to amphetamine. Pemoline differs from other psychostimulants in its chemical structure.

Side effects of psychostimulants

Side effects on the central nervous system occupy the main place in the structure of side effects. The main side effects include loss of appetite, insomnia (reduced when taking the drug in the first half of the day), disturbance of the level of wakefulness (either increased irritability and anxiety, or, conversely, lethargy and drowsiness) and mood changes (either euphoria or, less often, despondency and increased sensitivity to external stimuli). Dysphoric reactions are most often found in children. Sometimes, when taking therapeutic doses, toxic psychosis develops. Large doses (most often used for narcolepsy and drug abuse) can cause psychosis with pronounced hallucinatory-delusional symptoms.

In patients with stable or unstable arterial hypertension, a moderate increase in blood pressure is possible. Sometimes, with a significant increase in blood pressure, the use of psychostimulants is stopped. Sinus tachycardia and other tachyarrhythmias occur rarely when using therapeutic doses. In addition, headaches and abdominal pain may be observed when using psychostimulants.

Overdose of psychostimulants

Overdose of psychostimulants causes sympathetic hyperactivity syndrome (hypertension, tachycardia, hyperthermia). This syndrome is often accompanied by the development of toxic psychosis or delirium. Irritability, aggressive behavior, or paranoid ideas are typical. Hypertension, hyperthermia, arrhythmia, or uncontrolled seizures can cause death. Treatment of overdose is therapy that supports the physiological functions of the body. In case of loss of consciousness or epileptic seizures, it is necessary to ensure airway patency. In case of severe fever, antipyretic drugs and cooling wraps are recommended. To eliminate seizures, benzodiazepines are administered intravenously.

Antipsychotic drugs are usually prescribed for delirium or paranoid psychosis. Patients with arterial hypertension are best treated with chlorpromazine, which blocks both alpha-adrenergic receptors and dopamine receptors. Benzodiazepines, such as lorazepam, can be prescribed for additional sedation. Delirium usually resolves within 2-3 days, while paranoid psychosis resulting from long-term abuse of large doses of psychostimulants may last longer. For the treatment of severe hypertension syndrome or cardiac tachyarrhythmia

Abuse of psychostimulants

The main disadvantage of using psychostimulants due to their ability to cause euphoria is the possibility of abuse, drug dependence and addiction. Patients abuse amphetamines by taking them orally or injecting them intravenously. Methylphenidate is taken only orally. Pemoline is usually not abused. When large doses are used, signs of adrenergic hyperactivity appear (rapid pulse, increased blood pressure, dry mouth and dilated pupils). In large doses, amphetamine can cause stereotypies, irritability, emotional lability and delusional symptoms. With prolonged abuse, the development of a full-blown delusional psychosis with paranoid delirium, ideas of reference, as well as auditory, visual or tactile hallucinations is possible.

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Withdrawal from psychostimulants

Despite the absence of physical withdrawal symptoms after long-term use of high doses of drugs, patients experience pronounced signs of CNS damage for some time, including fatigue, drowsiness, hyperphagia, depression, and anhedonia, dysphoria, and cravings for taking the drug persist for a long time. There is currently no effective pharmacological treatment for drug dependence and withdrawal syndrome caused by psychostimulants. Usually, complex treatment is carried out. For timely detection of depression or repeated abuse, the patient needs medical supervision.

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