Psychostimulants

Psychostimulants (cerebro-stimulants, psychotopes) are means of analeptic action that cause psychomotor activation in both patients and healthy individuals.

[1], [2], [3], [4], [5], [6], [7],

Indications for the appointment of psychostimulants

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

Before starting these medications, patients should undergo a medical examination. Particular attention should be paid to heart rate, heart rate and AT. Patients with hypertension psychostimulants are appointed cautiously, with mandatory follow-up monitoring of blood pressure. It is necessary to refrain from prescribing psychostimulants to patients with tachyarrhythmias. On examination, attention is drawn to tics and impaired coordination of movements (psychostimulants can provoke or worsen Gilles de la Tourette syndrome and dyskinesia). It is necessary to avoid the appointment of psychostimulants in cases with the former abuse of them, and possibly all patients, prone to abuse of medicines. Since the reception of these drugs is possible the formation of physical and mental drug dependence, the duration of continuous treatment should not exceed 3-4 weeks. It should also be taken into account that psychostimulants, including mesocarb, in patients with psychotic disorders lead to an exacerbation of the condition.

Narcolepsy

Narcolepsy is characterized by excessive daytime drowsiness, combined with insurmountable, brief episodes of falling asleep. In addition, patients may experience catalepsy - periods of partial or complete loss of motor tone (often provoked by intense emotional excitement), sleep paralysis and / or hypnagogic hallucinations. Symptoms of daytime sleepiness and episodes of falling asleep most effectively stop psihostimulyatory.

Severe asthenic states

Severe somatic patients may develop apathy, social isolation and loss of appetite without obvious manifestations of a major depressive episode. This condition often leads to a rejection of treatment, loss of interest in life and consumption of less caloric nutrition. Improving the condition of patients with antidepressant medication is possible, but since a long course of therapy is required (several weeks), patients may stop treatment. Psychostimulants, when rationally applied, increase mood, interest in life, adherence to patients treatment regimen and in some cases - appetite. The effect of psychostimulants develops rapidly.

Mechanism of action and pharmacological effects

Psychostimulants mainly affect the cerebral cortex. They temporarily increase efficiency, concentration of attention and maintain the state of wakefulness. Some of them have an euphoric effect and can lead to the development of drug dependence. Unlike most antidepressants, psychostimulants reduce appetite and body weight, i.е. Have an anorectic effect. In psychiatric practice, psychostimulants are rarely used, in the form of a short course, mainly in severe asthenic conditions and narcolepsy. The mechanism of action consists in direct stimulation of the sympathomimetic receptors of the postsynaptic membrane and facilitating the presynaptic release of the mediators. Amphetamines (phenamine, .methylphenidate) stimulate dopamine receptors; sydnoniminy (mesocarb, fepprozidnin) have predominantly noradrenergic activity. In the Russian Federation, most psychostimulants are banned for use as medicines. Exceptions are the original domestic preparations of mesocarb (sydnocarb) and feprozidnin hydrochloride (sydnofen).

Mesocarb is similar in chemical structure to phenamine, compared to which it is less toxic, has no pronounced peripheral adrenostimulating activity, more strongly acts on noradrenergic than on dopaminergic structures of the brain. Stimulates the re-uptake of catecholamines and MAO activity. The stimulating effect develops gradually (there is no sharp initial activating effect), compared with phenamine it is longer, not accompanied by euphoria, motor excitation, tachycardia, a sharp increase in blood pressure. During the aftereffect, the drug does not cause general weakness and drowsiness. Less pronounced phenomenon of habituation.

Pharmacokinetics. After ingestion, it is rapidly absorbed from the digestive tract. Metabolized by the C-hydroxylation of the aliphatic chain of the phenylisopropyl substituent and the benzene ring of the phenylcarbamoyl radical to form an alpha-oxide hydroxide. As a result, the stimulating effect diminishes, as this metabolite poorly penetrates the blood-brain barrier. The kidneys deduce 60%, from the digestive tract - about 30%, with the exhaled air - 10%. Within 48 hours, 86% is output. Has no cumulative ability.

Interactions. Incompatible with MAO inhibitors, TA. Mesocarb reduces miorelaxation and drowsiness caused by anxiolytics of the benzodiazepine series, while the anxiolytic effect of the latter does not decrease. Glutamic acid enhances the psychostimulating effect of mesocarb.

Feprosidnin hydrochloride belongs to the group of phenylalkylsidnonimines and is close in structure to mesocarb. It has a stimulating effect on the central nervous system and at the same time it has antidepressant activity. The antidepressant effect of the drug is related to its ability to reversibly inhibit MAO activity. It reduces the depressant effects of reserpine, increases the effect of epinephrine hydrochloride and noradrenaline, causes a moderate increase in blood pressure. Has anticholinergic activity.

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

In addition, to weak stimulants include caffeine, which is part of many analgesics.

Abroad in clinical practice use dextroamphetamine, methylphenidate and pemoline. Dextroamphetamine is the D-isomer of phenyl isopropanolamine, which is three times more active than the L-isomer (amphetamine) as a CNS stimulant. Methylphenidate is a piperidine derivative that has a structural similarity to amphetamine. Pemolin is different in chemical structure from other psychostimulants.

Side effects of psychostimulants

Side effect on the central nervous system takes the main place in the structure of side effects. The central side effects include loss of appetite, insomnia (decreased when taking the drug in the morning), violation 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 common in children. Sometimes, when taking therapeutic doses, toxic psychoses develop. Large doses (most often used in narcolepsy and drug abuse) can cause psychoses with severe hallucinatory-delirious 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 reception of psychostimulants is stopped. Sinus tachycardia and other tachyarrhythmias rarely occur with the use of therapeutic doses. In addition, when using psychostimulants, headaches and abdominal pain may occur.

Overdosage with psychostimulants

When an overdose of psychostimulants, sympathetic hyperactivity syndrome (hypertension, tachycardia, hyperthermia) arises. This syndrome is often accompanied by the development of toxic psychosis or delirium. Characteristic of the appearance of irritability, aggressive behavior or paranoid ideas. Hypertension, hyperthermia, arrhythmias or uncontrolled seizures can cause death. Treatment of overdose - supporting physiological functions of the body therapy. If you lose consciousness or epileptic seizures, you must ensure that the airways are passable. With severe fever recommend antipyretic drugs, cooling wraps. To eliminate seizures, intravenous benzodiazepines are administered.

When delirium or paranoid psychosis is usually prescribed antipsychotic drugs. Patients with hypertension are more likely to prescribe chlorpromazine, which blocks both alpha-adrenergic receptors and dopamine receptors. To achieve an additional sedative effect, benzodiazepines, for example lorazepam, can be prescribed. Delirium usually passes in 2-3 days, and the paranoid psychoses which have arisen as a result of long abuse of large doses of psychostimulants, can proceed longer. For the treatment of severe hypertension syndrome or cardiac tachyarrhythmia

Abuse of psychostimulants

The main drawback of using psychostimulants due to their ability to cause euphoria is the possibility of abuse, the development of drug dependence and addiction. Patients abuse amphetamines, taking them inside or injecting intravenously. Methylphenidate is taken only by mouth. Pemoline usually does not cause abuse. When using large doses, signs of adrenergic hyperactivity appear (frequent pulse, increased blood pressure, dry mouth and dilated pupils). In large doses amphetamine can cause stereotypes, irritability, emotional lability and delusional symptoms. With prolonged abuse, it is possible to develop an unfolded delusional psychosis with paranoid delusions, relationship ideas, as well as auditory, visual or tactile hallucinations.

[8], [9],

Cancellation of psychostimulants

Despite the absence of physical symptoms of withdrawal after long-term administration of large doses of drugs in patients for a while, there are marked signs of CNS damage, including fatigue, drowsiness, hyperphagia, depression, and long-lasting anhedonia, dysphoria and desire to take the drug. Currently, there is no effective pharmacological treatment of drug dependence and withdrawal syndrome caused by psychostimulants. Usually, complex treatment is carried out. For timely detection of depression or repeated abuse of the patient, medical supervision is necessary.

[10], [11], [12], [13], [14]