Heroin - is a semisynthetic agonist of opioid receptors. Other names: acetylmorphine; 3,6-diacetylmorphine; H, dope, smack, junk, brown, boy.
Physical and chemical properties.
2. Excessive constriction of the pupils (persistent miosis), a decrease in their reaction to light, ptosis, nystagmus and convergence insufficiency.
3. Muscle hypotension and a decrease in the tendon reflex (sometimes there may be muscle hypertonus).
4. Reduction or absence of pain sensitivity.
5. Reduction of the frequency of respiratory movements to 12-10 per minute, or respiratory arrest.
First aid algorithm for overdose:
1. If a person is unconscious or has impaired consciousness of any stage, call paramedics (911) or one more person to help.
2. If the person is not breathing, is unconscious and has no pulse, it is mandatory to clean the oral cavity of foreign bodies (remove false teeth, teeth, mucus, vomit) and start resuscitation measures with indirect heart massage and artificial respiration in compliance with hygiene rules.
3. If there is naloxone, inject 2 mg intranasally or 0.4 mg intramuscularly. After two minutes, you should repeat the administration of a dose of 0.4 mg until the effect appears. If the person reacts to stimuli in any way – carry out intensive stimulation of consciousness and breathing (up to pain irritation). At the same time you should monitor the person`s condition.
4. Implement the algorithm before the arrival of paramedics.
More detailed information on opiate overdose and first aid will be in a separate article.
Physical and chemical properties.
The molecule of diacetylmorphine contains a polycyclic core which consists of three benzene rings united in the form of a "zigzag" - a phenanthrene ring. It is connected to a nitrogen-containing fourth ring, which is called morphinan. Heroin, like other morphinans, has an ester bridge between two of its rings, which connects R4 and R5 via an oxygen group. Heroin has two (CH3COO-) acetate groups, connected to R3 and R6, and a methyl group, connected to the nitrogen atom at R17. At that same ring, there is a double bond.
According to its physical properties, heroin is usually a solid-crystalline or solid-powdered substance, while pure heroin is a white crystalline powder. The untreated product is a bitter, grayish-brown powder in the form of small crystals with an unpleasant smell. Acetylation associated with the substitution of hydrophilic hydroxyl groups for more hydrophobic acetyl groups makes heroin less water-soluble than morphine, but highly soluble in lipophilic solvents. The melting point of this substance is about 170 degrees Celsius. The most common heroin additive is noscapine. In "pure" substance, the number of impurities usually does not exceed 0.5% and most often contains acetylcodeine and 6-acetylmorphine.
Brown heroin or “basic” heroin is a result of the first stage of diacetylmorphine purification. It burns at a lower temperature, has an unpleasant smell and is most often used by smoking(inhalation method of use).
White heroin or “diamorphine hydrochloride” is a result of purification by ester, hydrochloric acid e. t. c. It is usually dissolved in water and injected; it has a high melting point.
Black heroin in the form of black resin (black tar, Mexican brown, mud) is a dark, sticky viscous substance, originated in Mexico. It is a result of incomplete acetylation of morphine. This form is not recommended for intravenous use because of the high risks.
“Continental” kinds of heroin are classified according to the following principle. Substance of south-west Asia: the color of the powder is variable from beige (frequently) to dark brown; the powder contains small inclusions of soft aggregates that crumble when lightly pressed, and has a distinctive opium smell. Middle-Eastern heroin: fine powder with a very small amount of "beige" aggregates, typically contains additives like procaine, acetylcodeine, papaverine, caffeine. Heroin of South-East Asia: mainly consists of solid granules 1-5 mm in diameter that does not crumble when pressed, and a small amount of powder. The color of the granules is usually gray, but there is also heroin with dark brown and, less often, with pink or red (Penang Pink) granules.
Pharmacokinetics.
The main effects of diacetylmorphine are determined by its agonist metabolites: 6 monoacetylmorphine(6-MAM), morphine (MOR) and morphine6glucuronide (M6G). The speed and effector mechanisms of diacetylmorphine depend on the ways of its administration, so, with oral administration, heroin undergoes a fairly rapid biotransformation through deacetylation and is detected 3-5 minutes after administration, whereas with intravenous use, diacetylmorphine does not pass the first stage (acetyl groups make it more lipophilic than morphine) and immediately enters the brain through the blood-brain barrier. In the brain, diacetylmorphine is deacetylated to inactive 3-monoacetyl morphine and active 6-monoacetylmorphine (6 MA), and then to morphine. Both morphine and 6-monoacetylmorphine are opioid agonists that bind to receptors located in almost all parts of the brain, and are also present in the spinal cord and in the intestines. The resulting metabolite morphine-3-glucuronide does not act on opioid receptors, but with prolonged abuse, it can have a neurotoxic effect. In the brain, it turns mainly into 6-monoacetylmorphine and morphine (and to a small extent into morphine-6-glucuronide and morphine-3-glucuronide). Once in the brain, it is deacetylated differently into inactive 3-monoacetylmorphine and active 6-monoacetylmorphine (6-MAM), and into morphine, which binds to the m-opioid receptors. This leads to euphoric, analgesic and anxiolytic effects. Heroin itself exhibits a relatively low affinity for the μ-receptor. Analgetic effect is a result of µ-receptor activation. G-protein coupled receptor indirectly hyperpolarizes the neuron, reducing the release of nociceptive neurotransmitters and, consequently, causes analgesia and increased pain tolerance.
Due to the lower polarity and high lipid and membrane solubility, the act of absorption and overcoming the blood-brain barrier is much faster than of morphine. With intravenous administration after critical increase in diacetylmorphine concentration in blood there is a significant decrease, and after 45 minutes it is possible for the drug to be undetected. Decrease in diacetylmorphine concentration in plasma has a two-phase dynamics: the initial phase of ultra-fast distribution, and then the phase of rapid elimination. In 24 hours after injection, about 80% diacetylmorphine is excreted in urine in form of morphine-3-glucuronide, morphine and 6-monoacetylmorphine. About 3% is excreted in bile. Half-life of heroine is about 3 minutes, 6-MAM – about 38 minutes, conjugated metabolites – 7,9-8,2 hours. After intravenous injection maximum concentration in plasma is reached after 1-2 minutes, and after 10 minutes it starts to decrease rapidly due to fast metabolism and deposition in tissue. Concentration range of 6-MAM in urine after intramuscular injection 3-6 mg of heroine is 42-236 ng/ml. Toxic and lethal dosages depend on individual tolerance of morphine. 20 mg of diacetylmorphine is the absolute lethal dosage. There are cases of death after taking 10 mg. Plasma concentration of morphine after lethal intoxication varied from 0.01 to 0.09 mg/l. In experimental studies, lethal doses of diacetylmorphine in mice: LD50 subcutaneously — 261.6 mg/kg, LD50 intravenously-21.8 mg/kg. In experiments on dogs: LD50 subcutaneously-25 mg / kg; on pigs LD50 subcutaneously-400 mg/kg; on cats LD50 orally-20 mg/kg; on rabbits LDmin subcutaneously-150 mg/kg, LDmin intravenously-9 mg/kg. For humans, the LD50 is 18-25 mg/kg according to various sources. After a single use heroin and its metabolites can be detected in urine for 72 hours, with long-term use – up to 10 days. Heroin is detected in plasma for 48 hours regardless of the duration of use.
Pharmacodynamics.
It is generally recognized that the action (therapeutic and toxic) of opioid narcotic substances is realized with the participation of three well-researched "classical" types of opioid receptors. Each of them consists of seven segments with amino and carboxyl groups.
Opioid receptors belong to the family of receptors associated with G protein. Activation of opioid receptors leads to activation of the Gi protein. Activation of opioid receptors inhibits adenylate cyclase, as a result, the amount of cellular cyclic adenosine monophosphate (cAMP) decreases. Electrophysiologically, the potential-dependent Ca2+channels are blocked, and the K+channels of internal rectification are activated. As a result, when opioid receptors are activated, the excitability of neurons decreases. In addition, opioids contribute to an increase in the concentration of arachidonic acid by the protein kinase mechanism, which leads to the activation of free radical processes in the cell. In the toxicodynamic aspect, the effect of diacetylmorphine is similar to the effect of morphine and is caused by the intake of a toxic agent, the dose and tolerance of the patient.
There can also be changes in the excitability of neurons, stimulating the presynaptic release of gamma-aminobutyric acid (GABA). Although GABA is an inhibitory mediator, the final effect depends on the state of postsynaptic neurons and which part of the nervous system is involved. Kappa-ketocyclazocin-type receptors (correlators, OR2receptors) - are located mainly in the spinal cord, antinoceptive centers of the brain and the substantia nigra. When they are stimulated, analgesia develops at the level of the spinal cord, miosis, polyuria. Unlike the stimulation of the μ-receptors, the κ-receptors do not cause the respiratory depression and constipation.
Both morphine and 6-MAM are opioid agonists that bind to the receptors of the brain, spinal cord and intestines of all mammals. M-opioid receptor also binds endogenous opioid peptides such as beta-endorphin, lissencephaly and methencephalon. Repeated use of heroin leads to a number of physiological changes, including an increase in the production of m-opioid receptors. These physiological changes lead to tolerance and addiction. So stopping heroin use leads to unpleasant symptoms, including pain, anxiety, muscle spasms and insomnia - "opiate withdrawal syndrome". Depending on the use, it manifests itself 4-24 hours after the last dose of heroin. Morphine also binds to the δ-and κ-opioid receptors. There is also evidence that 6-MAM binds to a subtype of the μ-opioid receptors, which are also activated by the morphine metabolite morphine-6β-glucuronide, but not by morphine itself. The third subtype of the third type of opioids is the mu-3 receptor, which may be shared by other morphine monoesters with six positions.
Clinical presentation of opiate intoxication and side effects:
According to its physical properties, heroin is usually a solid-crystalline or solid-powdered substance, while pure heroin is a white crystalline powder. The untreated product is a bitter, grayish-brown powder in the form of small crystals with an unpleasant smell. Acetylation associated with the substitution of hydrophilic hydroxyl groups for more hydrophobic acetyl groups makes heroin less water-soluble than morphine, but highly soluble in lipophilic solvents. The melting point of this substance is about 170 degrees Celsius. The most common heroin additive is noscapine. In "pure" substance, the number of impurities usually does not exceed 0.5% and most often contains acetylcodeine and 6-acetylmorphine.
Brown heroin or “basic” heroin is a result of the first stage of diacetylmorphine purification. It burns at a lower temperature, has an unpleasant smell and is most often used by smoking(inhalation method of use).
White heroin or “diamorphine hydrochloride” is a result of purification by ester, hydrochloric acid e. t. c. It is usually dissolved in water and injected; it has a high melting point.
Black heroin in the form of black resin (black tar, Mexican brown, mud) is a dark, sticky viscous substance, originated in Mexico. It is a result of incomplete acetylation of morphine. This form is not recommended for intravenous use because of the high risks.
“Continental” kinds of heroin are classified according to the following principle. Substance of south-west Asia: the color of the powder is variable from beige (frequently) to dark brown; the powder contains small inclusions of soft aggregates that crumble when lightly pressed, and has a distinctive opium smell. Middle-Eastern heroin: fine powder with a very small amount of "beige" aggregates, typically contains additives like procaine, acetylcodeine, papaverine, caffeine. Heroin of South-East Asia: mainly consists of solid granules 1-5 mm in diameter that does not crumble when pressed, and a small amount of powder. The color of the granules is usually gray, but there is also heroin with dark brown and, less often, with pink or red (Penang Pink) granules.
Pharmacokinetics.
The main effects of diacetylmorphine are determined by its agonist metabolites: 6 monoacetylmorphine(6-MAM), morphine (MOR) and morphine6glucuronide (M6G). The speed and effector mechanisms of diacetylmorphine depend on the ways of its administration, so, with oral administration, heroin undergoes a fairly rapid biotransformation through deacetylation and is detected 3-5 minutes after administration, whereas with intravenous use, diacetylmorphine does not pass the first stage (acetyl groups make it more lipophilic than morphine) and immediately enters the brain through the blood-brain barrier. In the brain, diacetylmorphine is deacetylated to inactive 3-monoacetyl morphine and active 6-monoacetylmorphine (6 MA), and then to morphine. Both morphine and 6-monoacetylmorphine are opioid agonists that bind to receptors located in almost all parts of the brain, and are also present in the spinal cord and in the intestines. The resulting metabolite morphine-3-glucuronide does not act on opioid receptors, but with prolonged abuse, it can have a neurotoxic effect. In the brain, it turns mainly into 6-monoacetylmorphine and morphine (and to a small extent into morphine-6-glucuronide and morphine-3-glucuronide). Once in the brain, it is deacetylated differently into inactive 3-monoacetylmorphine and active 6-monoacetylmorphine (6-MAM), and into morphine, which binds to the m-opioid receptors. This leads to euphoric, analgesic and anxiolytic effects. Heroin itself exhibits a relatively low affinity for the μ-receptor. Analgetic effect is a result of µ-receptor activation. G-protein coupled receptor indirectly hyperpolarizes the neuron, reducing the release of nociceptive neurotransmitters and, consequently, causes analgesia and increased pain tolerance.
Due to the lower polarity and high lipid and membrane solubility, the act of absorption and overcoming the blood-brain barrier is much faster than of morphine. With intravenous administration after critical increase in diacetylmorphine concentration in blood there is a significant decrease, and after 45 minutes it is possible for the drug to be undetected. Decrease in diacetylmorphine concentration in plasma has a two-phase dynamics: the initial phase of ultra-fast distribution, and then the phase of rapid elimination. In 24 hours after injection, about 80% diacetylmorphine is excreted in urine in form of morphine-3-glucuronide, morphine and 6-monoacetylmorphine. About 3% is excreted in bile. Half-life of heroine is about 3 minutes, 6-MAM – about 38 minutes, conjugated metabolites – 7,9-8,2 hours. After intravenous injection maximum concentration in plasma is reached after 1-2 minutes, and after 10 minutes it starts to decrease rapidly due to fast metabolism and deposition in tissue. Concentration range of 6-MAM in urine after intramuscular injection 3-6 mg of heroine is 42-236 ng/ml. Toxic and lethal dosages depend on individual tolerance of morphine. 20 mg of diacetylmorphine is the absolute lethal dosage. There are cases of death after taking 10 mg. Plasma concentration of morphine after lethal intoxication varied from 0.01 to 0.09 mg/l. In experimental studies, lethal doses of diacetylmorphine in mice: LD50 subcutaneously — 261.6 mg/kg, LD50 intravenously-21.8 mg/kg. In experiments on dogs: LD50 subcutaneously-25 mg / kg; on pigs LD50 subcutaneously-400 mg/kg; on cats LD50 orally-20 mg/kg; on rabbits LDmin subcutaneously-150 mg/kg, LDmin intravenously-9 mg/kg. For humans, the LD50 is 18-25 mg/kg according to various sources. After a single use heroin and its metabolites can be detected in urine for 72 hours, with long-term use – up to 10 days. Heroin is detected in plasma for 48 hours regardless of the duration of use.
Pharmacodynamics.
It is generally recognized that the action (therapeutic and toxic) of opioid narcotic substances is realized with the participation of three well-researched "classical" types of opioid receptors. Each of them consists of seven segments with amino and carboxyl groups.
Opioid receptors belong to the family of receptors associated with G protein. Activation of opioid receptors leads to activation of the Gi protein. Activation of opioid receptors inhibits adenylate cyclase, as a result, the amount of cellular cyclic adenosine monophosphate (cAMP) decreases. Electrophysiologically, the potential-dependent Ca2+channels are blocked, and the K+channels of internal rectification are activated. As a result, when opioid receptors are activated, the excitability of neurons decreases. In addition, opioids contribute to an increase in the concentration of arachidonic acid by the protein kinase mechanism, which leads to the activation of free radical processes in the cell. In the toxicodynamic aspect, the effect of diacetylmorphine is similar to the effect of morphine and is caused by the intake of a toxic agent, the dose and tolerance of the patient.
There can also be changes in the excitability of neurons, stimulating the presynaptic release of gamma-aminobutyric acid (GABA). Although GABA is an inhibitory mediator, the final effect depends on the state of postsynaptic neurons and which part of the nervous system is involved. Kappa-ketocyclazocin-type receptors (correlators, OR2receptors) - are located mainly in the spinal cord, antinoceptive centers of the brain and the substantia nigra. When they are stimulated, analgesia develops at the level of the spinal cord, miosis, polyuria. Unlike the stimulation of the μ-receptors, the κ-receptors do not cause the respiratory depression and constipation.
Both morphine and 6-MAM are opioid agonists that bind to the receptors of the brain, spinal cord and intestines of all mammals. M-opioid receptor also binds endogenous opioid peptides such as beta-endorphin, lissencephaly and methencephalon. Repeated use of heroin leads to a number of physiological changes, including an increase in the production of m-opioid receptors. These physiological changes lead to tolerance and addiction. So stopping heroin use leads to unpleasant symptoms, including pain, anxiety, muscle spasms and insomnia - "opiate withdrawal syndrome". Depending on the use, it manifests itself 4-24 hours after the last dose of heroin. Morphine also binds to the δ-and κ-opioid receptors. There is also evidence that 6-MAM binds to a subtype of the μ-opioid receptors, which are also activated by the morphine metabolite morphine-6β-glucuronide, but not by morphine itself. The third subtype of the third type of opioids is the mu-3 receptor, which may be shared by other morphine monoesters with six positions.
Clinical presentation of opiate intoxication and side effects:
- Severe sedation - a typical "nodding off" effect, when the head falls, the eyes close and the user uncontrollably falls into an instant unconsciousness (like a syncope while standing).
- Intense euphoria - very pronounced and intense.
- Analgesic effect-of varying degrees of severity, usually, according to various scales of pain syndrome assessment, the indicators are medium-high or high.
- Respiratory depression - a decrease in the frequency of respiratory movements up to complete respiratory arrest. The so-called opioid-induced respiratory depression associated with a decrease in the central reaction to CO2 leads to hypoventilation, an increase in the partial pressure of carbon dioxide in the arterial blood. As a result, the depression of consciousness causes asphyxia, and a decrease in the tone of the respiratory tract.
- Suppression of appetite, libido.
- Reduction of heart rate and blood pressure.
- Persistent narrowing of the pupil.
- Nausea and vomiting - at high doses, in the absence of consciousness, aspiration complications may occur, associated with the obturation of the respiratory tract with vomit and, as a result, death.
- The "double vision" effect - at high doses, an uncontrolled "focusing-defocusing" of vision occurs due to impaired accommodation.
- The effect of "Internal hallucination" is the perception of visual hallucinations that occur exclusively in an imaginary environment, which can usually be seen only with closed eyes, like those occurring in a dream.
- Decrease in the activity of the basal metabolic processes and body temperature.
- Stimulation of release of antidiuretic hormone, a decrease in production of primary urine in the renal system.
- Inhibition of secretory activity of the gastrointestinal tract.
- At high doses, nausea and the act of vomiting are leveled due to specific irritation of the chemoreceptors of the gastrointestinal tract.
- Increase in the tone of the bladder, sphincter Oddi/Lutkens/Mirizzi, sphincters of the rectum and all parts of the colon. An increase in the tone of smooth muscles, an increase in the reactivity of the bronchi, an increase in the secretion of the mucous component of the bronchi, an increase in the processes of excretion of the bronchial glands.
- Suppression of basal secretion with a decrease in passage of intestinal contents with an increase in fluid absorption, which usually leads to constipation or dynamic small intestinal obstruction/coprostasis.
- Dyspeptic disorders, functional dyspepsia syndrome, dry mucous membranes of the nasopharyngeal region, eyes. Increase in heat transfer with preservation of heat production.
Development of pulmonary hypertension makes a significant contribution to respiratory insufficiency, which leads to an aggravation of hypoxia, the development of cardiac arrhythmia (atrial fibrillation), functional respiratory failure and lung damage. With prolonged exposure to the poison, hypostatic or aspirational pneumonia develops in some cases. In addition to central mechanisms of acute respiratory failure development, pulmonary lesions in the form of non-cardiogenic pulmonary edema can also get involved. These are several mechanisms of its pathogenesis: anaphylactic reaction, bronchospasm, arterial hypoxemia, increased capillary permeability and interstitial edema. It is impossible to exclude the presence of a direct toxic effect of diacetylmorphine and its application to the lung tissue. The main risk factors for opioid-induced respiratory depression are: female sex, the presence of sleep apnea syndrome, obesity, chronic kidney parenchyma diseases, chronic lung and bronchial parenchyma diseases, polymorphism of CYP450 enzymes.
Other forms of damage to life support systems in acute diacetyl morphine poisoning include disorders of the cardiovascular system, clinically manifested in the development of arterial hypotension. Cardiac arrest, as a rule, is of a secondary nature and occurs due to the progression of hypoxia or due to hyperkalemia.
Gastrointestinal effects are associated with the effect of diacetylmorphine on the μ and σ-receptors. There is a decrease in gastrointestinal peristalsis, deterioration of digestive reflux, a decrease in bile secretion, pancreatic and intestinal secretions. Gastric congestion can last up to 12 hours. An increase in the tone of the Oddi sphincter leads to an increase in pressure in the biliary tract, up to the level of pressure in the intestine. The most typical symptoms are nausea and vomiting, which can lead to aspiration complications. In people with chronic drug use, constipation is described, sometimes leading to obstruction.
Most often, in acute severe opiate poisoning, hypoxia is complex in nature, characterized by disruption of almost all links of oxygen transport. Thus, the most frequent and severe manifestation of acute opiate poisoning is the development of mixed hypoxia caused by hypoxic hypoxia due to respiratory disorders, circulatory hypoxia as a result of disorders of general and regional blood circulation and microcirculation, hemic and secondary tissue hypoxia. Ultimately, hypoxia is the leading factor in various metabolic disorders that manifest themselves at the cellular, subcellular and molecular levels.
Methods of use and doses:
Other forms of damage to life support systems in acute diacetyl morphine poisoning include disorders of the cardiovascular system, clinically manifested in the development of arterial hypotension. Cardiac arrest, as a rule, is of a secondary nature and occurs due to the progression of hypoxia or due to hyperkalemia.
Gastrointestinal effects are associated with the effect of diacetylmorphine on the μ and σ-receptors. There is a decrease in gastrointestinal peristalsis, deterioration of digestive reflux, a decrease in bile secretion, pancreatic and intestinal secretions. Gastric congestion can last up to 12 hours. An increase in the tone of the Oddi sphincter leads to an increase in pressure in the biliary tract, up to the level of pressure in the intestine. The most typical symptoms are nausea and vomiting, which can lead to aspiration complications. In people with chronic drug use, constipation is described, sometimes leading to obstruction.
Most often, in acute severe opiate poisoning, hypoxia is complex in nature, characterized by disruption of almost all links of oxygen transport. Thus, the most frequent and severe manifestation of acute opiate poisoning is the development of mixed hypoxia caused by hypoxic hypoxia due to respiratory disorders, circulatory hypoxia as a result of disorders of general and regional blood circulation and microcirculation, hemic and secondary tissue hypoxia. Ultimately, hypoxia is the leading factor in various metabolic disorders that manifest themselves at the cellular, subcellular and molecular levels.
Methods of use and doses:
- Oral administration of heroin is the least popular due to insufficient “high”, unlike with intravenous and intranasal methods, which is an implication of heroin metabolism. Oral administration usually involves the use of gelatin capsules or “bombs”. Single low oral dose is 5 mg, medium – 15 mg, high – 25 mg.
- Intranasal administration involves the metabolism of the "first pass", the effect occurs quickly enough, but the duration of action is shortened, compared to oral administration. Low dose of heroin with intranasal use - 0.09 - 0.12 mg/kg; medium - 0.235 - 0.325 mg/kg; high – more than 0.420 mg/kg. The manifestation of effects is in 60 seconds, duration of action is 3-7 hours.
- Intravenous administration is recommended only after thorough purification of the substance, and high quality of heroin (HQ). Low dose - 0.015 - 0.09 mg/kg. Medium- 0.09 - 0.15 mg/kg; high – more than 0.15 mg/kg. The manifestation of effects is instant; duration of action is 4-5 hours.
- Smoking heroin is a rare route of administration, it involves vaporizing it to inhale the resulting fumes, rather than burning and inhaling the smoke. The slang phrase for it is “chasing the dragon”. Doses vary from 2 mg (is considered a low dose) to 25 mg(which is considered a high dose). Effects manifest instantly due to high lung absorption rate, duration is 3 hours.
- Another rare route of administration is the use of rectal or vaginal suppositories, which usually involves a syringe and other absorbable elements (cotton pads, gauze bandages soaked in a solution, etc.).
Special instructions, interaction with other psychoactive substances.
The joint use of heroin (as well as other opioid receptor agonists) with psychostimulants in small doses does not cause critical conditions if opiates are used first. However, with each following increase in the dose, myocardial ischemia disproportionately occurs due to the resulting vasospasm with reflex bradycardia (which, in turn, is a complete decompensation of the heart), which can lead to negative cardiovascular events up to a disorder of atrioventricular conduction and acute coronary syndrome.
The combination of heroin and alcohol is dangerous. Thus, both substances are potentiating negative effects (mainly sedative, emetic, ataxic), which can eventually lead to serious consequences, ranging from transient disturbances of consciousness (up to coma), ending with a fatal outcome due to obstruction of the respiratory tract by vomit or respiratory arrest of central genesis.
The most dangerous combinations of heroin, in addition to alcohol, are combinations with GHB, GBL, ketamine, tramadol and MXE due to the increased depressive effect on the central nervous system, as well as an increase in cardiac conduction disorders risk, pressure overload of the heart, hypercapnia and respiratory distress syndrome. As for benzodiazepines and neuroleptics, when used together with heroin, in addition to the high risk of impaired consciousness, there is a danger of an excessive miotic effect, as well as sedative and analgesic effects. There are also several cases of myoclonus described. When using heroin with dopa, reduction of the analgesic effect is possible. When using with ketamine, depressing effect of heroin on the respiratory center and sedation up to coma or stage 3, anesthesia without the stage of arousal can be present. Ketoprofen and other NSAIDs of this group reduce respiratory depression caused by the action of heroin.
MAO inhibitors and phenothiazine derivatives cause negative cardiovascular complications. The analgetic and hypotensive effects increase, the risk of respiratory depression increases up to complete respiratory arrest. Inducers of microsomal oxidation during systemic use (including barbiturates and carbamazepine) reduce the analgetic effect of heroin, and also lead to the development of cross-tolerance.
NK1 receptor antagonists currently represent a new generation of antiemetics that can be used for treatment and prevention of nausea and vomiting when using heroin, instead of metoclopramide. Combinations of antiemetics can be more effective than monotherapy. Prevention of vomiting by a combination of a 5HT3-receptor antagonist and dexamethasone is preferable. With prolonged use of heroin, the main central complications developing are: tolerance, neurotoxicity and opioid-induced hyperalgesia. A specific clinical presentation includes hyperalgesia, myoclonus, allodynia and transistor or permanent confusion, and is an indication for preventive pharmacological therapy.
The classic presentation of an opiate overdose (without taking into consideration the severity and stages).
1. Impaired consciousness (any stage of stunning or coma).The joint use of heroin (as well as other opioid receptor agonists) with psychostimulants in small doses does not cause critical conditions if opiates are used first. However, with each following increase in the dose, myocardial ischemia disproportionately occurs due to the resulting vasospasm with reflex bradycardia (which, in turn, is a complete decompensation of the heart), which can lead to negative cardiovascular events up to a disorder of atrioventricular conduction and acute coronary syndrome.
The combination of heroin and alcohol is dangerous. Thus, both substances are potentiating negative effects (mainly sedative, emetic, ataxic), which can eventually lead to serious consequences, ranging from transient disturbances of consciousness (up to coma), ending with a fatal outcome due to obstruction of the respiratory tract by vomit or respiratory arrest of central genesis.
The most dangerous combinations of heroin, in addition to alcohol, are combinations with GHB, GBL, ketamine, tramadol and MXE due to the increased depressive effect on the central nervous system, as well as an increase in cardiac conduction disorders risk, pressure overload of the heart, hypercapnia and respiratory distress syndrome. As for benzodiazepines and neuroleptics, when used together with heroin, in addition to the high risk of impaired consciousness, there is a danger of an excessive miotic effect, as well as sedative and analgesic effects. There are also several cases of myoclonus described. When using heroin with dopa, reduction of the analgesic effect is possible. When using with ketamine, depressing effect of heroin on the respiratory center and sedation up to coma or stage 3, anesthesia without the stage of arousal can be present. Ketoprofen and other NSAIDs of this group reduce respiratory depression caused by the action of heroin.
MAO inhibitors and phenothiazine derivatives cause negative cardiovascular complications. The analgetic and hypotensive effects increase, the risk of respiratory depression increases up to complete respiratory arrest. Inducers of microsomal oxidation during systemic use (including barbiturates and carbamazepine) reduce the analgetic effect of heroin, and also lead to the development of cross-tolerance.
NK1 receptor antagonists currently represent a new generation of antiemetics that can be used for treatment and prevention of nausea and vomiting when using heroin, instead of metoclopramide. Combinations of antiemetics can be more effective than monotherapy. Prevention of vomiting by a combination of a 5HT3-receptor antagonist and dexamethasone is preferable. With prolonged use of heroin, the main central complications developing are: tolerance, neurotoxicity and opioid-induced hyperalgesia. A specific clinical presentation includes hyperalgesia, myoclonus, allodynia and transistor or permanent confusion, and is an indication for preventive pharmacological therapy.
The classic presentation of an opiate overdose (without taking into consideration the severity and stages).
2. Excessive constriction of the pupils (persistent miosis), a decrease in their reaction to light, ptosis, nystagmus and convergence insufficiency.
3. Muscle hypotension and a decrease in the tendon reflex (sometimes there may be muscle hypertonus).
4. Reduction or absence of pain sensitivity.
5. Reduction of the frequency of respiratory movements to 12-10 per minute, or respiratory arrest.
First aid algorithm for overdose:
1. If a person is unconscious or has impaired consciousness of any stage, call paramedics (911) or one more person to help.
2. If the person is not breathing, is unconscious and has no pulse, it is mandatory to clean the oral cavity of foreign bodies (remove false teeth, teeth, mucus, vomit) and start resuscitation measures with indirect heart massage and artificial respiration in compliance with hygiene rules.
3. If there is naloxone, inject 2 mg intranasally or 0.4 mg intramuscularly. After two minutes, you should repeat the administration of a dose of 0.4 mg until the effect appears. If the person reacts to stimuli in any way – carry out intensive stimulation of consciousness and breathing (up to pain irritation). At the same time you should monitor the person`s condition.
4. Implement the algorithm before the arrival of paramedics.
More detailed information on opiate overdose and first aid will be in a separate article.
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