Antipyretics for children are prescribed by a pediatrician. But there are emergency situations for fever when the child needs to be given medicine immediately. Then the parents take responsibility and use antipyretic drugs. What is allowed to give to infants? How can you bring down the temperature in older children? What medicines are the safest?
sleeping pills called medicinal substances that, under certain conditions, contribute to the onset of normal physiological sleep.
Types of insomnia:
There are 3 main forms of sleep disturbance:
1. Violation of the process of falling asleep. It is more often observed in young people with symptoms of neurasthenia or overwork. The patient takes several hours to fall asleep. After that comes a deep and long sleep with all phases. In accordance with the pathogenesis, hypnotics of short or medium duration of action are used here.
2. The process of falling asleep and sleep in general is disturbed. Sleep superficial, restless, with frequent awakenings. The ratio between the phases of sleep changes with a predominance of "REM" sleep (the patient notes that he tossed and turned in bed all night). Long-acting sleeping pills are used.
3. Difficulty falling asleep and short sleep. It is more common in older people with cerebral vascular sclerosis. The patient wakes up after 2-5 hours and can no longer fall asleep (“the dream of the elderly”). Short-acting sleeping pills are used at the time of awakening at night or long-acting before bedtime.
Classification:
1. Benzodiazepine derivatives:
1.1. Average duration of action:
Nitrazepam - Nitrazepamum (Radedorm, Eunoctin, Berlidorm) (T1 / 2 = 24 hours)
Flunitrazepam - Flunitrazepamum (Rohypnol) (T1 / 2 = 20 hours)
Triazolam - Triazolamum (Halcyone) (T1 / 2 = 7h)
1.2. Short action:
Midazolam - Midazolamum (Dormicum, Flormidal) (T1 / 2 = 1.5 - 2.5 hours)
1.3. Long acting:
Phenazepam (T1 / 2 = 100 h)
Diazepam (Sibazon, Relanium, Seduxen) (T1 / 2 = 48 hours)
2. Derivatives of barbituric acid:
2.1. Long acting drugs:
Phenobarbital - Phenobarbitalum (Luminal). Included in combined preparations: Bellataminal, Corvalol, Valocordin, Andipal. (T1/2 = 85 h)
Estimal - Aesthymalum (Amobarbital) (T1 / 2 \u003d 24 - 48 hours)
2.2. Intermediate-acting drugs:
Cyclobarbital - Cyclobarbitalum (combination drug - Reladorm) (T1 / 2 \u003d 12 - 24 hours)
3. GABA derivatives (gamma-aminobutyric acid):
Sodium oxybutyrate - Natrii oxibutyras
Phenibut - Phenibutum
4. Drugs of other groups:
Imovan - Imovanum (Zopiklon, Piklodorm, Relaxon, Somnol)
Ivadal – Ivadalum (Zolpidem)
Donormil - Donormilum (Doxylamine)
Chloral Hydrate - Chlorali hydras
Bromisoval - Bromisovalum (Bromural)
Melatonin (Melaxen)
Comparative characteristics drugs of different groups:
benzodiazepine derivatives:
They have anti-anxiety (anxiolytic), hypnotic, anticonvulsant effects. At intravenous administration in high doses - the properties of general anesthetics. The anti-anxiety effect in combination with sleeping pills is useful, since insomnia is very often caused by neurotic disorders (stress, conflicts, psycho-emotional stress, mental fatigue). To a lesser extent than barbiturates affect the structure of sleep. Mostly used drugs of medium duration of action. Long-acting drugs (sibazon, phenazepam - T1 / 2 \u003d 48 - 100 hours) are rarely used as hypnotics.
Mechanism of action: enhance the inhibitory effect of GABA in the central nervous system. GABA is the main inhibitory neurotransmitter in the CNS.
Benzodiazepines shorten the period of falling asleep, reduce the number of nocturnal awakenings, and increase the total duration of sleep. Does not significantly affect the phase of "rapid" sleep.
Falling asleep occurs after 20 - 30 minutes. Duration hypnotic effect 6-8 hours (midazolam 2-4 hours).
Apply:
For difficulty falling asleep, drugs
With sleep disturbance in general, of medium duration
With short sleep in the elderly. actions
Midazolam is used for short-term sleep at the time of awakening and for long-term therapy for insomnia.
Side effects:
After awakening syndrome effects (lethargy, muscle weakness, dizziness, impaired coordination, drowsiness, decreased mood and memory, difficulty coordinating attention);
With prolonged use, addiction, drug dependence and the “recoil” syndrome develop (especially in midazolam);
Potentiate the depressive effect of alcohol (drinking against the background of alcohol intoxication can lead to CNS depression and respiratory failure).
Contraindicated for drivers of vehicles and people whose profession requires concentration.
Barbiturates:
Duration of action cyclobarbital and reladorm- 4 - 6 hours, phenobarbital and estimal - 6 - 8 hours. The effect occurs in 30 - 40 minutes (for phenobarbital 60 - 90 minutes).
Mechanism of action:
Enhance the inhibitory effect of GABA on the central nervous system;
Block activating mediators - glutamine and aspartate;
They inhibit the ascending activating system of the brain stem, which leads to a weakening of the transmission of impulses to the cortex.
Barbiturates shorten falling asleep, reduce the number of nocturnal awakenings, and increase the total duration of sleep. They affect the phases of sleep: increase the phase of "slow sleep", selectively suppress the phase of "rapid" sleep.
Applied in violation of sleep in general with a clear predominance of the phase of "rapid" sleep. Drugs of medium duration can be prescribed for sleep disturbances.
Side effect: the "recoil" syndrome, which manifests itself:
Aggravation of the manifestations of insomnia compared with the pre-treatment period;
Increase in the proportion of "REM" sleep;
Slow recovery of normal sleep physiology;
Increased frequency and duration of nocturnal awakenings, superficial sleep, fragments of dreams (the patient has a feeling that he does not sleep at all);
Irritability, anxiety, fatigue, decreased mood, performance;
After awakening, the effects are more pronounced than those of benzodiazepines;
drug addiction;
Due to the small therapeutic latitude, when the dose is exceeded, they can cause deep anesthesia and respiratory depression.
GABA derivatives:
Increase the natural concentration of GABA, depress the central nervous system.
Sodium hydroxybutyrate prolongs the phase of "slow" sleep in the absence of influence on the phase of "rapid" sleep. Consequences and the “recoil” syndrome are absent or slightly expressed. The effect comes in 30-40 minutes. Duration of action individually - from 2-3 hours to 6-8 hours.
Phenibut increases the rate of falling asleep, reduces the number and duration of awakenings, does not affect the structure of sleep. As a hypnotic, it is less active, it is used mainly as a sedative daytime drug.
Preparations of other groups:
Imovan and Ivadal: used for various sleep disorders. Increase the inhibitory effect of GABA on the central nervous system. The effect occurs after 30 minutes, the duration of action is 6-8 hours. They do not violate the structure of sleep, do not cause consequences and the "recoil" syndrome. It is not recommended to take more than 4 weeks continuously.
Side effects: possible allergic reactions.
Donormil: drug of medium duration of action. It has a sedative effect due to the central H1 - antihistamine and M - anticholinergic action. Reduces the time to fall asleep, increases the duration and improves the quality of sleep. Causes no consequences.
Side effect:
dry mouth;
visual impairment;
urinary retention;
Melatonin: a synthetic analog of the hormone of the pineal gland (pineal gland). It has an adaptogenic, sedative, hypnotic, immunostimulating, antioxidant effect. Regulates the sleep-wake cycle. Improves sleep quality, mood, makes dreams vivid, reduces headaches. Penetrates through the BBB. Increases the concentration of serotonin. Used for circadian rhythm disorders. Does not cause consequences syndrome and rebound syndrome. When using the drug can not be in the sun.
Chloral hydrate: rarely used, as it irritates the mucous membranes of the gastrointestinal tract. Assign more often in the form of an enema. Sleep comes in 30 - 60 minutes, lasts 6 - 8 hours. Leaves the consequences of the application, causes side effects from the kidneys, liver, myocardium.
Bromisoval: rarely used due to weak action.
Complications and toxic effects:
1. Consequences: lethargy, drowsiness, impaired performance, etc. Occurs when taking sleeping pills of medium and long duration of action with a half-life of more than 8 hours. Not typical for drugs that are rapidly metabolized (imovan, ivadal, midazolam);
2. Syndrome of "recoil": prolonged sleep disturbance, worsening general condition sick. Occurs when the drug is discontinued. Most characteristic of barbiturates (may occur after 5 - 7 days of admission);
3. Addictive: with prolonged use, there is a decrease therapeutic effect, the dose of the drug must be increased. This is especially true for barbiturates.
4. Drug dependence: With long-term use, mental and physical dependence occurs (with barbiturates after 2 weeks of continuous use). Most often cause drugs of short action and medium duration of action. In the case of addiction (severe addiction), withdrawal of the drug can cause severe convulsions and delirium;
5. Allergic reactions (jaundice, skin rashes, fever) - occur in 3 - 5% of patients. Most often on phenobarbital.
Acute drug poisoning:
Coma with severe respiratory depression;
Suppression of all reflexes;
The pupils are at first narrow and react to light, then paralytic dilation occurs;
downgrade blood pressure;
Acidosis, impaired renal function due to respiratory and circulatory disorders;
Atelectasis and pulmonary edema.
Death occurs due to circulatory disorders and paralysis of the respiratory center.
Gastric lavage;
forced diuresis;
Appointment of alkalis;
Sleeping pills These are substances that promote the onset of sleep, normalize its depth, phase, duration, and prevent night awakenings.
The following groups are distinguished:
1) derivatives of barbituric acid (phenobarbital, etc.);
2) drugs of the benzodiazepine series (nitrazepam, etc.);
3) preparations of the pyridine series (ivadal);
4) preparations of the pyrrolon series (imovan);
5) ethanolamine derivatives (donormil).
Requirements for sleeping pills:
1. Must act quickly, induce deep and prolonged (6-8 hours) sleep.
2. Induce sleep as close as possible to normal physiological sleep (do not disturb the structure).
3. Should have a sufficient breadth of therapeutic action, should not cause side effects, cumulation, addiction, mental and physical dependence.
Classification of hypnotics based on the principle of their action and chemical structure
Hypnotics - benzadiazepine receptor agonists
1 Benzodiazepine derivatives
Nitrazepam
Lorazepam
Diazepam
Phenazepam
temazepam
Flurazepam
2. Preparations of different chemical structure
Zolpidem
Zopiclone
1. Heterocyclic compounds
Barbituric acid derivatives (barbiturates)
Etaminal - sodium
2. Aliphatic compounds
Chloral hydrate
Hypnotics - benzadiazepine receptor agonists
Benzodiazepines are a large group of substances whose preparations are used as hypnotics, anxiolytics, antiepileptics, and muscle relaxants.
These compounds stimulate benzodiazepine receptors in the membranes of CNS neurons, which are allosterically associated with GABA receptors. When stimulating benzodiazepine receptors, the sensitivity of GABA receptors to GABA (inhibitory mediator) increases.
When GABAA receptors are excited, C1 channels open; C1 ~ ions enter the nerve cells, this leads to hyperpolarization of the cell membrane. Under the action of benzodiazepines, the frequency of opening of C1 channels increases. Thus, benzodiazepines enhance the processes of inhibition in the central nervous system.
Benzodiazepines(BD) stimulate benzodiazepine receptors and thus increase the sensitivity of GABA-receptors to GABA. Under the action of GABA, Cl-channels open and hyperpolarization of the neuron membrane develops. Pharmacological effects of benzodiazepines: 1) anxiolytic (elimination of feelings of anxiety, fear, tension); 2) sedative; 3) sleeping pills; 4) muscle relaxant; 5) anticonvulsant; 6) amnestic (in high doses, benzodiazepines cause anterograde amnesia for about 6 hours, which can be used for premedication before surgical operations).
With insomnia, benzodiazepines promote the onset of sleep, increase its duration. However, at the same time, the structure of sleep changes somewhat: the duration of REM sleep phases decreases (REM sleep, paradoxical sleep: periods of 20-25 minutes, which are repeated several times during sleep, are accompanied by dreams and rapid movements eyeballs- Rapid Eye Movements).
The effectiveness of benzodiazepines as hypnotics undoubtedly contributes to their anxiolytic properties: anxiety, tension, and overreaction to environmental stimuli are reduced.
Nitrazepam(radedorm, eunoctin) is administered orally 30-40 minutes before bedtime. The drug reduces excessive reactions to extraneous stimuli, promotes the onset of sleep and provides sleep for 6-8 hours.
With the systematic use of nitrazepam, its side effects may appear: lethargy, drowsiness, decreased attention, slow reactions; possible diplopia, nystagmus, pruritus, rash. Of the other benzodiazepines, flunitrazepam (Rohypnol), diazepam (Seduxen), midazolam (Dormicum), estazolam, flurazepam, temazepam, triazolam are used for sleep disorders.
With the systematic use of benzodiazepines, they develop mental and physical drug dependence. A pronounced withdrawal syndrome is characteristic: anxiety, insomnia, nightmares, confusion, tremor. Due to the muscle-relaxing effect, benzodiazepines are contraindicated in myasthenia gravis.
Benzodiazepines are generally of low toxicity, but in high doses they can cause CNS depression with respiratory failure. In these cases, the specific benzodiazepine receptor antagonist flumazenil is administered intravenously.
Nonbenzodiazepine benzodiazepine receptor stimulants
zolpidem (ivadal) and zopiclone (imovan) have little effect on the structure of sleep, do not have a pronounced muscle relaxant and anticonvulsant effect, do not cause withdrawal syndrome and, therefore, are better tolerated by patients. Sleeping pills with a narcotic type of action
This group includes derivatives of barbituric acid - pentobarbital, cyclobarbital, phenobarbital, as well as chloral hydrate. In large doses, these substances can have a narcotic effect.
Barbiturates- highly effective sleeping pills; promote the onset of sleep, prevent frequent awakenings, increase the total duration of sleep. The mechanism of their hypnotic action is associated with the potentiation of the inhibitory action of GABA. Barbiturates increase the sensitivity of GABA receptors and thus activate C1 channels and cause hyperpolarization of the neuronal membrane. In addition, barbiturates have a direct inhibitory effect on the permeability of the neuronal membrane.
Barbiturates significantly disrupt the structure of sleep: they shorten the periods of fast (paradoxical) sleep (REM-phase).
The constant use of barbiturates can lead to disorders of higher nervous activity.
Abrupt cessation of the systematic use of barbiturates manifests itself in the form of a withdrawal syndrome (rebound syndrome), in which the duration of REM sleep is excessively increased, which is accompanied by nightmares.
With the systematic use of barbiturates, physical drug dependence develops.
Pentobarbital(etaminal sodium, nembutal) is taken orally 30 minutes before bedtime; duration of action is 6-8 hours. After awakening, drowsiness is possible.
Cyclobarbital has a shorter effect - about 4 hours. The aftereffect is less pronounced. It is mainly used for sleep disorders.
Phenobarbital(luminal) acts more slowly and for a long time - about 8 hours; has a pronounced aftereffect (drowsiness). Currently, it is rarely used as a sleeping pill. The drug is used to treat epilepsy.
Acute poisoning with barbiturates is manifested by a coma, respiratory depression. There are no specific barbiturate antagonists. Analeptics in severe poisoning with barbiturates do not restore breathing, but increase the brain's need for oxygen - oxygen deficiency is aggravated.
The main measures for poisoning with barbiturates are methods of accelerated removal of barbiturates from the body. The best method is hemosorption. In case of poisoning with dialyzable substances, hemodialysis is used, in case of poisoning with drugs that are excreted by the kidneys at least partially unchanged, forced diuresis is used.
The aliphatic compound chloral hydrate also belongs to hypnotic drugs with a narcotic type of action. It does not violate the structure of sleep, but is rarely used as a sleeping pill, as it has irritating properties. Sometimes chloral hydrate is used in medicinal enemas to stop psychomotor agitation. Narcotic analgesics
Pain is an unpleasant subjective sensation that, depending on its location and strength, has a different emotional coloring, signaling damage or a threat to the existence of the body and mobilizing its defense systems aimed at conscious avoidance of the harmful factor and the formation of nonspecific reactions that ensure this avoidance.
Analgesics(from Greek an - denial, logus - pain) - this is a group of drugs that selectively suppress pain sensitivity without turning off consciousness and other types of sensitivity (tactile, barometric, etc.)
Narcotic analgesics are drugs that suppress pain and, upon repeated administration, cause physical and mental dependence, i.e. addiction. Classification of narcotic analgesics. 1. Agonists:
Promedol;
fentanyl;
Sufentanil
2. Agonists - antagonists (partial agonists):
Pentazocine;
Nalbufin
butorfano
buprenorphine
3. Antagonists:
Naloxone.
Mechanism of action of narcotic analgesics
It is caused by the interaction of NA with opiate receptors located mainly in presynaptic membranes and playing an inhibitory role. The degree of NA affinity for the opiate receptor is proportional to the analgesic activity.
Under the influence of NA, there is a violation of the interneuronal transmission of pain impulses at different levels of the CNS. This is achieved in the following way:
HA mimic the physiological action of endopioids;
The release of "mediators" of pain into the synaptic cleft and their interaction with postsynaptically located nociceptors is disrupted. As a result, the conduction of the pain impulse and its perception in the central nervous system are disturbed. The end result is analgesia.
Indications for the use of narcotic analgesics 1. To eliminate pain in cancer patients.
2. In the postoperative period to eliminate pain, prevent shock.
3. With myocardial infarction (in a pre-infarction state) and with traumatic shock.
4. When coughing a reflex character, if the patient has a chest injury.
5. For labor pain relief.
6. With colic - renal - promedol (since it does not affect the tone of the urinary tract), with biliary colic - lixir. Codeine can be used as an antitussive if there is a dry, debilitating cough associated with whooping cough, severe bronchitis, or pneumonia.
Contraindications to the appointment of narcotic analgesics: 1. respiratory disorders, respiratory depression.
2. Increased intracranial pressure, because morphine increases intracranial pressure, can provoke epilepsy.
3. It is contraindicated to prescribe drugs to children under 2 years of age. This is due to the fact that in children the physiological function of the respiratory center is formed by the age of 3-5 years, and it is possible to get paralysis of the respiratory center and death when using drugs, since its effect on the respiratory center is practically absent.
Clinic for acute poisoning with narcotic analgesics
Euphoria;
Anxiety;
dry mouth;
feeling of heat;
dizziness, headache;
Drowsiness;
Urge to urinate;
Coma;
Miosis, followed by mydriasis;
Rare (up to five respiratory movements per minute), shallow breathing;
BP is reduced.
Assistance in case of poisoning with narcotic analgesics
Elimination of respiratory disorders using a ventilator with tracheal intubation;
Administration of antidotes (nalorphine, naloxone);
Gastric lavage.
Morphine
Pharmacodynamics.
1. Effects from the side of the central nervous system:
Analgesia;
Sedative (hypnotic) effect;
respiratory depression;
Decrease in body temperature;
Antiemetic (emetic) effect;
Antitussive effect;
Euphoria (dysphoria);
Decreased aggressiveness;
Anxiolytic effect;
Increased intracranial pressure;
Decreased sex drive;
addictive;
Oppression of the center of hunger;
Hypermanifestations of the knee, elbow reflexes.
2. Effects from the gastrointestinal tract:
Increased tone of sphincters (Oddi, bile ducts, bladder);
Increased tone of hollow organs;
Inhibition of bile secretion;
Decreased secretion of the pancreas;
Decreased appetite.
3. Effects from other organs and systems:
Tachycardia, turning into bradycardia;
Hyperglycemia.
Pharmacokinetics of morphine.
With all routes of entry into the body, NA are well absorbed into the blood and quickly penetrate into the brain, through the placenta, and into breast milk. Bioavailability with oral administration - 60%, with intramuscular and subcutaneous administration - 100%. The half-life is 3-5 hours. Smakh with intramuscular and subcutaneous injection after 20 minutes. In the process of biotransformation, 35% of the drug interacts reversibly with serum albumins. In phase I of biotransformation, NA undergoes dimethylation and diacetylation. In phase II, paired compounds with glucuronic acid are formed. Excretion - 75% with urine, 10% with bile.
Indications for the use of morphine
1. Prevention of pain shock in case of:
Acute pancreatitis;
peritonitis;
Burns, severe mechanical injuries.
2. For sedation, in the preoperative period.
3. For pain relief in the postoperative period (with the ineffectiveness of non-narcotic analgesics).
4. Relief of pain in cancer patients.
5. Attacks of renal and hepatic colic.
6. For labor pain relief.
7. For neuroleptanalgesia and tranquiloanalgesia (a kind of general anesthesia with consciousness).
Contraindications
1. Children under three years of age and the elderly (due to respiratory depression);
2. traumatic brain injury (due to respiratory depression and increased intracranial pressure);
3. with an "acute" abdomen.
Side effects of morphine
1. Nausea, vomiting;
2. bradycardia;
3. dizziness.
Promedol
Pharmachologic effect:
Opioid receptor agonist (mainly mu-receptors), has analgesic (weaker and shorter than morphine), anti-shock, antispasmodic, uterotonic and mild hypnotic effect.
It activates the endogenous antinociceptive system and thus disrupts the interneuronal transmission of pain impulses at various levels of the central nervous system, and also changes the emotional coloring of pain.
To a lesser extent than morphine, it depresses the respiratory center, and also excites the n.vagus centers and the vomiting center.
Has an antispasmodic effect on smooth muscles internal organs(the spasmogenic effect is inferior to morphine), promotes the opening of the cervix during childbirth, increases tone and enhances contractions of the myometrium.
With parenteral administration, the analgesic effect develops after 10-20 minutes, reaches a maximum after 40 minutes and lasts 2-4 hours or more (with epidural anesthesia - more than 8 hours)
I. SLEEPING DRUGS WITH NON-NARCOTIC
ACTION TYPE
Benzodiazepine receptor agonists
benzodiazepine derivatives
A) short-acting drugs:
TRIAZOLAM(HALCION)
MIDAZOLAM(DORMIKUM)
B) drugs of medium duration of action:
NOZEPAM(OXAZEPAM, TAZEPAM)
LORAZEPAM(ATIVAN)
TEMAZEPAM(NORMISON, RESTAURANT)
NITRAZEPAM(RADEDORM, EUNOKTIN, NITROSAN)
C) long-acting drugs:
FLUNITRAZEPAM(ROHYPNOL, SOMNUBENE)
PHENAZEPAM
DIAZEPAM(RELANIUM, SIBAZON)
Preparations of different chemical structure
- derivative of cyclopyrrolone
ZOPYCLONE(IMOVAN, RELAXON, PIKLODORM)
- imidazopyridine derivative
ZOLPIDEM(IVADAL, SANVAL)
is a derivative of pyrazolopyrimidine.
ZALEPLON ( ANDANTE )
2. Melatonin receptor agonists (synthetic analogues of melatonin)
RAMELTEON ( ROSEREM )
3. H1 blockers - histamine receptors (ethanolamine derivative)
DOXYLAMINE(DONORMIL)
II. SLEEPING DRUGS WITH NARCOTIC
ACTION TYPE
Heterocyclic compounds (manufactured by barbituric acid)
PHENOBARBITAL ( LUMINAL)
ETAMINAL-SODIUM(PENTOBARBITAL, NEMBUTAL)
Aliphatic compounds
SODIUM OXYBUTYRATE
BROMISOVAL ( BROMURAL)
CHLOROALHYDRATE
Benzodiazepine derivatives
MECHANISM OF ACTION
Drugs interact with special benzodiazepine receptors (BR). There are 3 subtypes of BR ω-receptors (ω 1 , ω 2 , ω 3). Receptors ω 1 are located in the cerebral cortex, hypothalamus, limbic system, ω 2 and ω 3 - in the spinal cord and peripheral nervous system. It is believed that the hypnotic effect of benzodiazepines is due to preferential binding to ω 1 receptors. Activation of ω 2 and ω 3 receptors is accompanied by the development of anticonvulsant and central muscle relaxant effects.
BRs are part of the macromolecular complex of the GABA A receptor, which includes receptors sensitive to GABA, benzodiazepines, and barbiturates, as well as chloride ionophores. Due to allosteric interaction with specific receptors, benzodiazepines increase the affinity of GABA to GABA A receptors and enhance the inhibitory effect of GABA. There is a more frequent opening of chlorine ionophores. This increases the flow of chloride ions into neurons, which leads to an increase in the inhibitory postsynaptic potential. At the same time, GABA activity does not increase, which leads to the absence of a narcotic effect in benzodiazepines.
ACTION FEATURES
1. They have anxiolytic activity (eliminate feelings of anxiety, restlessness, tension and have a hypnotic, and in small doses, a calming (sedative) effect. Eliminate mental stress, which helps to calm and develop sleep.
2. Reduce the tone of skeletal muscles (the effect is associated with the suppression of polysynaptic reflexes at the level spinal cord) and exhibit anticonvulsant activity.
3. Potentiate the action of substances that depress the central nervous system, including alcohol and anesthetics.
4. They have an amnestic effect (cause anterograde amnesia).
5. When using benzodiazepines, especially for a long time active drugs, after-effects are possible during the day, which are realized in the form of drowsiness, lethargy, slowing down of reactions. Therefore, benzodiazepines should not be prescribed to patients whose professional activities require quick response and increased attention.
6. With a sharp cancellation, the phenomenon of "recoil" is possible.
7. With repeated use of benzodiazepines, addiction develops, and in order to obtain the same hypnotic effect, it is necessary to increase the dose of the drug.
8. With prolonged use, the development of drug dependence (both mental and physical) is possible.
9. Shorten the phase of REM sleep, but to a lesser extent than derivatives of barbituric acid.
The principle of GABA-mimetic action of benzodiazepines and barbiturates.
A conditional scheme of the GABA A -benzodiazepine-barbiturate receptor complex with a chlorine ionophore is presented:
I - state of rest; II - increase in the conductivity of chloride channels under the influence of GABA. Benzodiazepines (III) and barbiturates (IV) allosterically enhance the action of GABA. The flow of chloride ions into the neuron increases, which enhances the inhibitory effect. GABA A -R - GABA A receptor; BD-R - benzodiazepine receptor; B-R - barbiturate receptor
INDICATIONS FOR USE
1. Insomnia associated with anxiety, stress, jet lag.
2. Neuroses (nitrazepam, nozepam, phenazepam)
3. Relief of seizures (phenazepam, diazepam)
4. Alcohol withdrawal (nitrazepam, phenazepam, diazepam)
5. For the purpose of sedation during anesthesia (flunitrazepam, diazepam)
6. Induction anesthesia (flunitrazepam)
7. Itching dermatoses (diazepam).
SIDE EFFECTS
1. Postsomnic action (more pronounced in drugs of long and medium duration of action):
- drowsiness;
- lethargy muscle weakness;
- slowing down mental and motor reactions;
- violation of coordination of movements and the ability to concentrate;
- anterograde amnesia (loss of memory for current events);
- loss of sexual desire;
- arterial hypotension;
- increased bronchial secretion.
EXCEPTION: nosepam does not violate the physiological structure of sleep, does not cause an aftereffect.
2. A paradoxical reaction to taking drugs of this group: euphoria, lack of a sense of rest, hypomanic state, hallucinations.
3. “Recoil phenomenon” (more typical for drugs with long and medium duration of action) - with a sharp withdrawal of the drug: “recurrent insomnia”, nightmares, bad mood, irritability, dizziness, tremor, lack of appetite.
4. In patients with lung diseases, there is a danger of hypoventilation and hypoxemia, as the tone of the respiratory muscles and the sensitivity of the respiratory center to carbon dioxide decrease.
5. Worsening of the course of breathing disorders during sleep. Due to the central muscle relaxant action of the product. benzodiazepine, there is an imbalance in the movements of the muscles - uvula dilators, soft palate and pharynx, which leads to occlusion of the upper respiratory tract, the flow of air into Airways accompanied by snoring. At the end of the episode, hypoxia causes a "half-awakening" that returns muscle tone to the waking state and resumes breathing.
CONTRAINDICATIONS
1. Drug addiction,
2. Respiratory failure.
3. Myasthenia.
4. With caution prescribed for: cholestatic hepatitis, renal failure, organic brain damage, obstructive pulmonary disease, depression.
CHAPTER 7 SLEEPING DRUGS
CHAPTER 7 SLEEPING DRUGS
Sleeping pills promote falling asleep and provide the necessary duration of sleep.
As sleeping pills, drugs of different pharmacological groups are used. Traditional sleeping pills (barbiturates, some aliphatic compounds), which have been used for a long time, are classified as narcotic-type substances by the nature of their effect on the central nervous system and the absence of selective action. In small doses, they have a sedative 1 (soothing), in medium - sleeping pills, and in large doses - a narcotic effect. For their anesthesia
1 From lat. sedatio- calm.
do not use because of the small narcotic breadth and long-term action - you can not control the depth of anesthesia (see Fig. 6.1).
Currently, of the drugs that have a hypnotic effect, anxiolytics (tranquilizers) of the benzodiazepine series, related to psychotropic substances, are mainly prescribed (see chapter 11.4).
Hypnotics have a depressing effect on interneuronal (synaptic) transmission in various formations of the central nervous system (for example, in the cerebral cortex, afferent pathways, limbic system). Each group of hypnotics is characterized by a certain localization of action.
Drugs with hypnotic activity are classified based on the principle of their action and chemical structure.
I. Hypnotics - benzodiazepine receptor agonists
1. Benzodiazepine derivatives Nitrazepam Lorazepam Nozepam Temazepam Diazepam Phenazepam Flurazepam
2. Drugs of different chemical structure (“non-benzodiazepine” compounds) Zolpidem Zopiclone
II. Sleeping pills with a narcotic type of action
1. Heterocyclic compounds Barbituric acid derivatives (barbiturates) Etaminal sodium
2. Aliphatic compounds Chloral hydrate
To normalize sleep, separate drugs of other groups that have hypnotic properties are also used: histamine H-receptor blockers(diphenhydramine; see chapter 25), oral anesthetic drug(sodium oxybutyrate; see chapter 5; 5.2). In case of sleep disturbance associated with long-distance air travel, it is recommended pineal hormone preparations- melatonin (see chapter 20.2).
Despite a large amount of research, the mechanism of action of hypnotics can only be hypothesized. The main difficulties are related to the fact that the mechanisms of development of physiological sleep are unknown. According to modern concepts, sleep is an active process in which the function of hypnogenic 1 (synchronizing) structures of the brain is increased, and the activating ascending reticular formation 2 (causing EEG desynchronization) is reduced. Obviously, under the influence of sleeping pills, the interaction of these two systems changes in favor of the hypnogenic one. Indeed, many of the hypnotics, such as barbiturates, have a depressing effect on the activating reticular formation of the brainstem, which should favor the development of sleep. However, this is only one of the possible, but not the only mechanism of action of hypnotics. Thus, anxiolytics of the benzodiazepine series (see Chapter 11; 11.4), which promote the development of sleep, unlike barbiturates, act mainly on the limbic system and its connections with other parts of the brain that provide a cyclic change of wakefulness and sleep.
1 From Greek. hypnos- dream. Hypnogenic zones include a number of structures of the thalamus, hypothalamus and caudal sections of the reticular formation.
2 Rostral part of the reticular formation.
Substances that are formed in the brain tissues and have hypnotic activity (for example, the δ-sleep peptide) attract much attention. Naturally, the isolation of endogenous compounds with hypnogenic properties is of great interest not only for understanding the mechanism of sleep development, but also for creating medicines new type.
It should be borne in mind that sleep, caused by most hypnotics, differs in its course from natural sleep. As you know, under normal conditions during sleep, the so-called “slow” sleep 1 (orthodox, forebrain, synchronized; non-REM-sleep) and “REM” sleep (paradoxical, hindbrain, desynchronized; sleep accompanied by rapid eye movements) alternate several times. apples; REM-sleep 2). Last
1 In turn, in "slow" sleep, 4 phases are distinguished: Phase I - on the EEG: α-, β- and θ-rhythms; Phase II - on the EEG: θ-rhythm, spindles, K-complexes; Phase III - on the EEG: θ- and δ-rhythms, spindles; IV phase - on the EEG: δ-rhythm; III and IV phases - δ-sleep.
2 REM(R apide yem ovement)-sleep (English) - a dream accompanied by rapid movements of the eyeballs.
accounts for 20-25% of total sleep duration. Long-term disturbances during each of these phases adversely affect the state of the body (behavioral, mental disorders). It turned out that most sleeping pills (barbiturates, etc.) significantly change the structure of sleep. First of all, this concerns "REM" sleep (the latent period of the appearance of phase I of "REM" sleep increases, its total duration decreases). Cancellation of sleeping pills may be accompanied by the so-called "recoil" phenomenon, the severity of which depends on the dose of drugs and the period of their use. At the same time, the duration of REM sleep for a certain time exceeds the usual values, its latent period is shortened, an abundance of dreams, nightmares, and frequent awakenings are noted. Due to this Special attention attract hypnotics that have no effect or minimal effect on the ratio of sleep phases and contribute to the development of sleep close to natural.
There was no effect on REM sleep of sodium oxybutyrate and chloral hydrate or this effect is insignificant, but both drugs have a number of disadvantages. Zolpidem and zopiclone have little effect on the structure of sleep. Drugs from the group of benzodiazepines (nitrazepam, diazepam, etc.) shorten the REM sleep phase to a lesser extent than barbiturates.
7.1. Benzodiazepine receptor agonists
Many anxiolytics related to benzodiazepine derivatives have a pronounced hypnotic activity (nitrazepam, diazepam, phenazepam, etc.). Their main action is to eliminate mental stress. The resulting sedation contributes to the development of sleep.
Anxiolytics of the benzodiazepine series (see Chapter 11; 11.4) have anxiolytic, hypnotic, sedative, anticonvulsant, muscle-relaxing and amnestic activity. Anxiolytic and hypnotic effects are associated mainly with their inhibitory effect on the limbic system (hippocampus) and, to a lesser extent, on the activating reticular formation of the brain stem and cerebral cortex. The muscle-relaxing effect is due to the suppression of polysynaptic spinal reflexes. The mechanism of anticonvulsant (antiepileptic) action is obviously the result of the activation of inhibitory processes in the brain, which limits the spread of pathological impulses.
The mechanism of sedative, hypnotic and other effects of benzodiazepines is associated with their interaction with special benzodiazepine receptors 1 . The latter are part of the macromolecular complex of the GABA A receptor, which includes receptors sensitive to GABA, benzodiazepines and barbiturates, as well as chlorine ionophores (Fig. 7.1) 2 . Due to allosteric interaction with specific receptors, benzodiazepines increase the affinity of GABA for GABA A receptors and increase the inhibitory effect of GABA. There is a more frequent opening of chlorine ionophores. At the same time, increasing
1 Benzodiazepines non-selectively interact with different subtypes of benzodiazepine receptors (abbreviated as BZ 1 , BZ 2 , BZ 3 , or respectively ω 1 , ω 2 , ω 3 ).
2 The macromolecular complex also includes a separate picrotoxin binding site (an analeptic that blocks chloride channels; causes convulsions in large doses).
Rice. 7.1.The principle of GABA-mimetic action of benzodiazepines and barbiturates. A schematic diagram of a GABA A-benzodiazepine-barbiturate receptor complex with a chloride ionophore is presented.
I - state of rest; II - increase in the conductivity of chloride channels under the influence of GABA. Benzodiazepines (III) and barbiturates (IV) allosterically enhance the action of GABA. The flow of chloride ions into the neuron increases, which enhances the inhibitory effect. GABA A -R - GABA A receptor; BD-R - benzodiazepine receptor; B-R - barbiturate receptor.
there is an influx of chloride ions into neurons, which leads to an increase in the inhibitory postsynaptic potential.
The benzodiazepines used differ mainly in pharmacokinetics. Some of them undergo biotransformation with the formation of active long-acting metabolites (flurazepam, diazepam, etc.). For such drugs, the total duration of action is the sum of the duration of the effects of both the parent substance and its metabolites.
A number of benzodiazepines do not form active metabolites or they are rapidly inactivated (lorazepam, temazepam, etc.). Preparations of this type are preferable as hypnotics, since their aftereffect is less pronounced.
According to the duration of the psychosedative action, benzodiazepine derivatives can be represented by the following groups 1 .
1. Intermediate-acting drugs.
A (t 1/2 = 12-18 hours): lorazepam (ativan), nozepam (oxazepam, tazepam), temazepam (restroil).
B (t 1/2 ≈ 24 h): nitrazepam (radedorm, eunoctin).
2. Long acting drugs(t 1/2 = 30-40 hours or more): phenazepam, flurazepam (dalman), diazepam (sibazon, seduxen).
All the given benzodiazepines cause sleep lasting 6-8 hours. However, the longer the effect of the drug, the greater the likelihood of an aftereffect, which manifests itself during the day in the form of a sedative effect, slowing motor reactions, and memory impairment. With repeated appointments, cumulation of drugs occurs, which is directly dependent on the duration of their action.
1 For orientation, figures are given that reflect the "half-life" of drugs (t 1/2).
The "recoil" phenomenon that occurs with abrupt discontinuation of the drug is more typical of short-acting benzodiazepines. To avoid this complication, benzodiazepines should be discontinued gradually.
One of the drugs of this group widely used in our country is nitrazepam. The hypnotic effect of nitrazepam after its oral administration occurs after 30-60 minutes and lasts up to 8 hours. The aftereffect is not very pronounced. Nitrazepam enhances and prolongs the action of anesthetics, ethyl alcohol, narcotic hypnotics. For the cardiovascular system healthy people practically no effect.
Well absorbed from the intestines. Biotransformation of nitrazepam occurs in the liver. The drug accumulates. With repeated use, addiction develops.
From barbiturates, nitrazepam (and other benzodiazepine derivatives) differs for the better in the following ways: a) changes the structure of sleep to a lesser extent; b) has a greater breadth of therapeutic action, so there is less danger of acute poisoning; c) the induction of microsomal liver enzymes is less pronounced; d) less risk of developing drug dependence (however, this must be taken into account).
Similar to nitrazepam, temazepam and flurazepam are mainly used as hypnotics. Other drugs are used more widely: as anxiolytics, hypnotics, in status epilepticus and for a number of other indications (see chapter 14.4).
Currently, benzodiazepines are among the most optimal drugs for use as hypnotics. They are especially effective in sleep disorders associated with emotional stress, anxiety, and anxiety.
For pharmacology of other drugs, see chapter 14.4.
Flumazenil is an antagonist of benzodiazepine agonists.
Behind last years hypnotic drugs that are not related to benzodiazepines, but have an affinity for benzodiazepine receptors, have been synthesized. This group of drugs includes zolpidem and zopiclone (Table 7.1). The sites of their binding to benzodiazepine receptors differ from those of benzodiazepines. However, they also lead to the activation of GABA A receptors, more
Table 7.1.Comparative evaluation of zolpidem and zopiclone
frequent opening of chloride ionophores and development of hyperpolarization. The process of inhibition intensifies, which underlies the developing hypnotic and sedative effects.
Zolpidem (ivadal) is an imidazopyridine derivative. It has a pronounced hypnotic and sedative effect. Anxiolytic, muscle-relaxing, anticonvulsant and amnestic effects are expressed to a small extent. Selectively interacts with the first subtype of benzodiazepine receptors (BZ 1 -, or ω 1 -subtype). Little effect on sleep phases.
From side effects allergic reactions, hypotension, agitation, hallucinations, ataxia, dyspeptic symptoms, drowsiness in daytime. The phenomenon of "recoil" is expressed to a small extent. With prolonged use, addiction and drug dependence (mental and physical) occur, therefore a short-term use of the drug is desirable (no more than 4 weeks).
Zopiclone (Imovan) is similar to zolpidem. It is a derivative of cyclopyrrolone. It has hypnotic, sedative, anxiolytic, muscle-relaxing and anticonvulsant effects.
With prolonged use, addiction and drug dependence (mental and physical) occur. Side effects include a metallic bitter taste, sometimes nausea, vomiting, headache, dizziness, and allergic reactions. Mental and behavioral disorders, impaired coordination are possible. The phenomenon of "recoil" is expressed to a small extent. The duration of use should be limited to 4 weeks. In this case, addiction and drug dependence may not be detected, and side effects are negligible.
In case of an overdose of zolpidem and zopiclone, flumazenil is used as an antidote.
7.2. SLEEPING DRUGS WITH NARCOTIC TYPE OF ACTION
A significant number of such sleeping pills are derivatives of barbituric acid.
It has been shown that barbiturates interact with the allosteric site of the GABA d-benzodiazepine-barbiturate receptor complex and increase the affinity of GABA for GABA d-receptors (see Fig. 7.1). This leads to a longer opening of channels for chloride ions in neuronal membranes and an increase in their entry into the cell. In this case, the inhibitory effect of GABA is enhanced. Thus, in the case of barbiturates, the sedative and hypnotic effects are also largely due to their GABA mimetic action. However, there is reason to believe that barbiturates, interacting with the membrane of neurons and changing its physicochemical properties, disrupt the function of other ion channels (sodium, potassium, calcium). The significance of barbiturate antagonism with respect to a number of excitatory mediators (glutamate, etc.) is also discussed.
The group of barbiturates includes phenobarbital (luminal, phenobarbitone), etaminal sodium (pentobarbital sodium, nembutal) and other drugs.
Allocate drugs long-acting(phenobarbital) and average duration of action(etaminal-sodium). However, according to clinical observations, sleeping pills from both groups contribute to the development of sleep lasting about 8 hours. Different duration of action is manifested in the severity of the aftereffect and the degree of cumulation.
Various processes are involved in the termination of the hypnotic action of barbiturates. One of them is enzymatic inactivation of substances by microsomal liver enzymes. Most often, oxidation occurs (hydroxylation of radicals at C 5). In this regard, with liver pathology, accompanied by a decrease in the activity of its enzyme systems, the duration of the action of barbiturates increases. The latter, of course, refers to those drugs, the main amount of which undergoes biotransformation (etaminal sodium). It should be borne in mind that barbiturates (especially phenobarbital) cause the induction of microsomal enzymes. Therefore, with repeated administration of barbiturates, the rate of their metabolism increases. Obviously, the latter is one of the important reasons for the development of addiction to them. In addition, the induction of microsomal enzymes affects the rate of biotransformation of compounds from other chemical groups.
The duration of action of a number of derivatives of barbituric acid also depends on the rate of their excretion by the kidneys. This applies to compounds that are largely excreted unchanged by the kidneys (phenobarbital). In case of impaired renal function, the action of such barbiturates is noticeably prolonged.
The duration of the hypnotic effect also depends on the redistribution of substances in the body. This refers mainly to a decrease in the content of barbiturates in brain tissues and their deposition in adipose tissue in the case of high lipophilicity of the compounds.
When using barbiturates (even once) the next day after waking up, aftereffects may be noted - a feeling of lethargy, weakness, impaired psychomotor reactions, attention. The slower the drug is excreted (inactivated), the more pronounced the aftereffect. Thus, a decrease in the content of phenobarbital in the blood plasma by 50% of the administered dose (t 1/2) occurs after about 3.5 days, so the aftereffect is observed relatively often. To a lesser extent, it is noted after the use of etaminal sodium (its t 1/2 is 30-40 hours).
For barbiturates, with their repeated use, material cumulation is characteristic. It is most pronounced in drugs that are slowly excreted from the body (for example, in phenobarbital).
With prolonged use of barbiturates, a deficit in the REM sleep phase develops. As noted, with the abrupt withdrawal of drugs, the so-called “recoil” phenomenon occurs, which can persist for several weeks.
Continuous long-term use of barbiturates leads to the development of addiction and may be the cause of drug dependence (mental and physical). With daily use of barbiturates, addiction to them is detected approximately 2 weeks after the start of administration. The rate of development of drug dependence is largely determined by the dose of the drug. If the doses are large enough, drug dependence may develop after 1-3 months. Cancellation of the drug in the presence of drug dependence is accompanied by severe mental and somatic disorders (withdrawal syndrome). Anxiety, irritability, fear, vomiting, blurred vision, convulsions, orthostatic hypotension, etc. occur. In severe cases, death can occur.
Barbiturates are usually administered orally, less often - rectally. They are well absorbed gastrointestinal tract. Partially bind to plasma proteins (mainly albumin). Easily penetrate tissue barriers. Excreted by the kidneys.
Basically, barbiturates are prescribed as hypnotics (30-60 minutes before bedtime). Recently, however, their use has declined sharply due to the advent of benzodiazepine receptor agonists. Phenobarbital is practically not used as a sleeping pill. Barbiturates are also used as sedatives (1/3-1/5 or less of the hypnotic dose). In addition, phenobarbital is an antiepileptic drug (see Chapter 9).
When using barbiturates in therapeutic doses, there are usually no significant violations of the internal organs and their systems. However, allergic reactions are possible (skin lesions, jaundice, fever, etc.). Most often they occur with the appointment of phenobarbital.
Acute barbiturate poisoning occurs as a result of accidental or intentional overdose. CNS depression sets in. In severe poisoning, a coma develops, consciousness is absent, reflex activity is suppressed. The centers of the medulla oblongata are oppressed. In connection with the oppression of the respiratory center, the volume of respiration decreases. Arterial pressure drops (hypotension is associated not only with the central action, but also with the inhibitory effect of substances on the heart, ganglia, as well as with direct myotropic vasodilating action). Kidney function is impaired.
Treatment of acute poisoning is to accelerate the excretion of the drug from the body and to maintain vital functions. If the introduced barbiturate is not completely absorbed from the gastrointestinal tract, gastric lavage is done, adsorbents, saline laxatives are given. To accelerate the excretion of the already absorbed substance, large amounts of electrolyte solutions and osmotic diuretics or furosemide (see Chapter 16) are prescribed, which cause a rapid and significant increase in diuresis (the so-called forced diuresis). The removal of barbiturates can also be facilitated by the use of alkaline solutions. At very high concentrations of barbiturates in the blood, hemosorption is carried out, as well as peritoneal dialysis and hemodialysis.
One of the main objectives of the treatment of barbiturate poisoning is to establish adequate breathing and eliminate or prevent hypoxia. In severe cases, artificial respiration is performed. Analeptics (bemegrid, corazol, etc.; see Chapter 12) are prescribed only for mild forms of poisoning; in case of severe poisoning, they not only do not contribute to the restoration of breathing, but can even worsen the patient's condition. Consideration should be given to the possibility of developing pneumonia. In the event of hypotension, collapse, blood, blood substitutes, and norepinephrine are administered. In renal failure (oliguria 1, anuria 2), hemodialysis is often indicated. The prognosis depends on the dose of the sleeping pill, the timeliness of the start of treatment, the state of the body.
The principles outlined for the treatment of acute poisoning with barbiturates are also used for overdose of hypnotics from other groups.
Chronic poisoning most often occurs when taking barbiturates with pronounced cumulation (phenobarbital). This is manifested by apathy, drowsiness, weakness, imbalance, slurred speech, dizziness. Hallucinations, psychomotor agitation, convulsions are possible. Blood circulation, digestion, liver and kidney functions may also suffer. At the same time, the possibility of developing drug dependence should be taken into account, in which it is impossible to immediately stop the administration of the drug, since
1 Decrease in the amount of urine produced. From Greek. oligos- small, damage- urine.
2 Cessation of urine excretion by the kidneys. An(Greek) - negation.
abstinence syndrome disappears. In this regard, in the treatment of chronic poisoning, the dose of barbiturate is gradually reduced until it is completely canceled. Simultaneously carry out symptomatic treatment and psychotherapy.
A number of hypnotics are aliphatic compounds. One of them is chloral hydrate. This is the first synthetic sleeping pill used in practical medicine. It has a pronounced hypnotic effect. Promotes the development of sleep lasting up to 8 hours. It differs from barbiturates in that it practically does not disturb the structure of sleep. In large doses, it causes anesthesia. The narcotic latitude of chloral hydrate is small (the centers of the medulla oblongata are quickly depressed).
Absorbed from the intestine quickly. Freely passes through tissue barriers. In the body it turns into trichloroethanol (similar in properties to chloral hydrate). Chloral hydrate to a small extent stimulates the synthesis of microsomal liver enzymes. Metabolites and conjugates of chloral hydrate are excreted by the kidneys.
With repeated administration of chloral hydrate, addiction develops to it, drug dependence (mental and physical) is possible. Cumulation practically does not occur.
The drug is used orally or rectally (in enemas) as a hypnotic (15-30 minutes before sleep), a sedative or anticonvulsant.
Chloral hydrate has a number of negative properties. These include a possible adverse effect on parenchymal organs: liver, kidneys, heart. These toxic effects appear mainly against the background of pathological changes in these organs, as well as in case of overdose. In addition, chloral hydrate has a pronounced irritant effect, so it is usually prescribed in combination with mucus. The most appropriate short-term use of chloral hydrate (1-3 days).
Sleeping pills are widely used. When prescribing these drugs, one should take into account the possibility of developing addiction to them and drug dependence. Therefore, it is advisable to prescribe them in the minimum effective dose and not longer than 1 month, or to make intervals between doses of 2-3 days. It is necessary to orientate patients in the ability of drugs to cause aftereffects, which may adversely affect their professional activities. It is also important to keep in mind the interaction with others medicinal substances and ethyl alcohol. It is impossible not to take into account the change in the pharmacokinetics of hypnotics in the pathology of the liver and kidneys. Drugs should be discontinued gradually so that the “recoil” syndrome does not develop (and with physical drug dependence, withdrawal syndrome).
Hypnotics are a wide group of psychoactive drugs whose action is aimed at accelerating the onset of sleep, as well as to ensure its physiological duration. In the modern classification, all hypnotic drugs are not united by a common "denominator", and they include drugs of various drug groups.
Substances with hypnotic activity began to be used by man thousands of years ago. In those days, narcotic or toxic substances were used for this purpose - belladonna, opium, hashish, mandrake, aconite, high doses of ethanol. Today they have been replaced by safer and more effective means.
Classification
Since insomnia has become a constant companion modern man, drugs that facilitate the onset of sleep are in great demand. But for safe use, all of them must be prescribed by a doctor, who will first find out the cause of sleep disturbance. All drugs currently used for its correction are divided into several main groups:
- benzodiazepine receptor agonists (GABA A);
- melatonin receptor agonists;
- orexin receptor agonists;
- drug-like drugs;
- aliphatic compounds;
- blockers of H1 receptors of histamine;
- preparations based on the hormone of the epiphysis;
- means for correcting sleep disorders of various chemical structures.
Most sleeping pills can be addictive. In addition, they violate the physiological structure of sleep, so the appointment of a specific medication should be trusted only by a doctor - it is impossible to choose the right drug on your own.
Indications and contraindications for the appointment of sleeping pills
Any sleeping pill for insomnia is prescribed only after a thorough examination, as a rule, for a short period of time and in the minimum effective dosage. Any insomnia is the result of various external or internal causes, therefore, all drugs are prescribed taking into account the main cause that leads to physiological disturbance. proper sleep. Insomnia associated with factors such as:
- chronic stressful situation;
- vegetovascular dystonia;
- epilepsy;
- panic or anxiety disorders;
- neuroses;
- alcohol withdrawal syndrome;
- severe fatigue.
Even a strong sleeping pill, the dosage of which is chosen correctly, and the time of admission is short, does not harm the body. When prescribing such medicines, the doctor will take into account the existing contraindications, among which decompensated pathologies of the heart, blood vessels, liver and kidneys should be noted. There are also narrower restrictions for taking, characteristic of drugs of different chemical groups.
Rules for the safe use of sleeping pills
When prescribing a drug, the doctor is always guided by the following principles:
- the drug should be safe for patients of all age groups;
- the chosen remedy should not violate the physiological structure of sleep, or this action should be expressed to a minimum degree;
- no habituation effect;
- the therapeutic effect should be pronounced, but daytime sleepiness is undesirable.
Any medicine for insomnia, sleeping pills, is prescribed in minimal doses, which are not allowed to be exceeded on your own. In most cases, the dosage of the drug is halved from the average therapeutic. In this case, the patient is recommended to keep a diary on his own, where to record the effect that has occurred. If it turns out to be unexpressed, you need to inform the attending physician - he may slightly increase the dosage.
The medicine for insomnia can be prescribed exclusively at night, or in fractional doses taken throughout the day. Any, even a natural drug, is prescribed for a period of not more than one week. During this time, in most cases, it is possible to find the exact cause of the disease, and cancel the sleeping pill. During therapy, alcohol should be completely excluded from the patient's diet - even minimal doses can enhance the toxic properties of the drug.
Before starting to take sleeping pills prescribed by the doctor, the patient must inform him about all the medicines that he takes as prescribed by other specialists. This will help eliminate unwanted combinations of drugs, which in some cases can become deadly. The dosage of sleeping pills, especially prescription ones, should not be changed by the patient on their own.
Side effects of drugs
Doctors are well aware of what sleeping pills are, their classification and possible undesirable effects. It is difficult to avoid their development, and even taking the medicine in minimal doses is often accompanied by the following symptoms:
- paresthesia in the limbs;
- changes in taste preferences;
- dyspeptic disorders;
- daytime sleepiness;
- a constant desire to sleep during the daytime with sufficient time at night;
- dry mouth/thirst;
- headache or dizziness;
- weakness in the limbs;
- impaired concentration the next day after taking the drug;
- muscle spasms/convulsions.
In addition, if you take a sleeping pill, for example, a potent tranquilizer for too long, an addictive effect inevitably develops. This forces a person to increase the dose more and more to obtain the expected result, which is fraught with the development of a depressive state, and too large a dose of the drug can cause respiratory depression and death. The benzodiazepine group can cause effects such as sleepwalking and amnesia.
Excessive passion for such drugs is fraught with another nuisance. Many of them can change the correct alternation of sleep phases. Normally, there are two types of sleep - "fast" and "slow", smoothly replacing each other during the night. Sleeping pills help you fall asleep faster, but can often lengthen one and shorten the other phase of sleep. As a result, a person is deprived of proper rest despite the fact that he slept soundly all night.
The most common groups of sleeping pills
Pharmacotherapy currently plays a major role in the treatment of insomnia caused by different reasons. The classification of these drugs is extensive, but one thing is common in it - all drugs depress the central nervous system(CNS) and promote the onset of sleep. The most commonly prescribed groups of drugs prescribed for the correction of sleep disorders are the following.
- Barbiturates. These are one of the earliest drugs, so taking them to the greatest extent disrupts the structure of sleep. Any barbituric drug, for example, phenobarbital, has multiple effects on the body - antispasmodic, anticonvulsant, but it greatly depresses the respiratory center. Currently, it is practically not used in the treatment of insomnia, since even a few days of use contribute to the development of the “recoil effect”. It manifests itself after drug withdrawal in the form of frequent awakenings, nightmares, fears of having to go to bed. These drugs quickly become addictive. Contraindicated in childhood without extreme necessity.
- Benzodiazepines. Derivatives of this substance (phenazepam, fenzitat, etc.) have not only hypnotic, but also relaxing muscles and a pronounced sedative (calming) and anticonvulsant effect. Such drugs are undesirable in the elderly, their use at home is limited. These sleep aids are used in short courses to treat situational insomnia associated with stressful situations. They cause deep sleep, but have a lot of contraindications. They are sold by pharmacies only by prescription.
- Melatonin. medicinal product it is based on melaxen, a chemically synthesized analog of melatonin produced in the brain by the pineal gland. This hormone is produced only at night, and a drug based on it is used as an adaptogenic agent, with a disturbed sleep-wake cycle. Melaxen is harmless, and is not a sleeping pill in the literal sense. It promotes mild relaxation, reduces reactivity to external stimuli, making it easier to fall asleep. by the most modern drug of this group was vita-melatonin.
- Ethanolamines. These are antagonists of H 1 -histamine receptors, which are prescribed for insomnia detected in a patient for the first time, as well as for episodic sleep disorders. The constant use of such drugs is undesirable due to the abundance of side effects. It causes dryness of the mucous membranes of the mouth, decreased visual acuity, dyspeptic disorders and stool disorders, and fever. They can develop in both children and adults.
- Imidazopyridines. This modern generation drugs with a hypnotic effect, related to the pyrazolopyromidine type. In addition to sleeping pills, there is a sedative effect, in addition, the toxic properties of drugs in this group are least pronounced. They can be prescribed to a child, and are often optimal sleeping pills in old age. The drugs quickly normalize the emotional background, and these hypnotic contraindications are minimal. Among the advantages of drugs in this group, which include sanval and others, addiction and withdrawal syndrome. These sleeping pills should be taken just before bedtime, they reduce the time to fall asleep, have a mild sedative effect, and do not change the physiological phases of sleep. The therapeutic effect develops quickly, and the drugs in this group have the highest rating, being considered the "gold standard" in the treatment of insomnia.
If possible, it is better to use new drugs, the dose of which can be as low as possible. This will avoid the occurrence of serious complications and quickly stabilize the condition with insomnia.
Features of the treatment of insomnia in childhood
About 20% of parents face the problem of sleep disturbance in their children, who cannot sleep, or often wake up at night. The list of sleeping pills allowed in childhood is not so large, and without consulting a specialist, taking them is risky. A child under one year old is better suited for natural preparations that are commercially available (mint, motherwort, valerian). Sleep disorders in children are usually associated with active growth or some somatic pathologies, so self-medication is unacceptable.
When prescribing a specific drug, it is necessary to understand how sleeping pills help and what consequences can be. The most common complications in childhood include:
- stool disorders;
- headache;
- weakness;
- dyspeptic disorders;
- allergic reactions;
- uncontrolled limb movements.
Each type of sleeping pill can affect or change the phases of sleep, which is undesirable in childhood. The list of drugs that can be used in childhood is as follows:
- valerian root, especially effective in course treatment;
- motherwort, liquid extract is appropriate for children;
- sanosan - an extract containing valerian and hop cones, conveniently dosed in drops;
- Bayu Bai drops containing glutamic acid, mint, motherwort, peony and hawthorn;
- a mixture with citral, an indication for the use of which is not only insomnia, but also high intracranial pressure in a baby;
- children's tenoten;
- glycine - good effect with insomnia against the background of hyperactivity of the child.
None of the above means is unacceptable to appoint a child alone. Sleep disturbances or frequent nocturnal awakenings may be associated with a serious pathology that requires immediate medical attention.
