This group neurotropic drugs, capable of selectively influencing the central nervous system, selectively suppressing pain sensitivity. Unlike anesthetics, which indiscriminately suppress all types of sensitivity, analgesics selectively suppress only pain. Pain is a protective reaction of the body, warning it about the influence of prohibitive irritating factors, which allows a person to avoid destruction.
At the same time, pain of extreme intensity can create a state of pain shock, which can cause the death of the patient. Low intensity, but constant pain can cause significant suffering to a sick person, worsening the quality and even the prognosis of his life. To combat such types of pathological pain, analgesic drugs are used.
Based on their origin, mechanisms of action and principles of use, analgesic drugs are classified into 2 large groups: drugs of narcotic and non-narcotic analgesics.
Classification of analgesics.
I. Drugs of narcotic analgesics.
A. Classification by chemical structure:
Phenanthrene derivatives: morphine, buprenorphine
Phenylpiperidine derivatives: trimepyridine, fentanyl
Morphinans: tramadol.
B. Classification by interaction with different subtypes of opioid receptors:
Agonists of μ - and κ - receptors: morphine, trimepyridine,
fentanyl
Partial agonist μ - receptors: buprenorphine
Agonist - antagonist of μ - and κ - receptors: tramadol.
B. Opioid receptor antagonist drugs: naloxone, naltrexone
II. Non-narcotic analgesic drugs.
1. Non-opioid (non-narcotic) analgesics:
● centrally acting cyclooxygenase inhibitors: acetaminophen.
● non-steroidal anti-inflammatory drugs: ibuprofen.
2. Drugs of different pharmacological groups with analgesic activity:
● sodium channel blockers
● neuronal monoamine reuptake inhibitors
● α 2 -adrenergic agonists
● antagonists of glutamate NMDA receptors
● GABA mimetics
● antiepileptic drugs
3. Drugs with mixed opioid-non-opioid action: panadeine etc.
Narcotic analgesics.
This is the oldest group of analgesics. People have used the milky juice of the heads of the sleeping pill poppy for thousands of years to combat pain. Narcotic analgesics can cause the development of addiction (drug addiction), which imposes serious restrictions on their modern use.
The mechanism of action of narcotic analgesics has been established quite precisely. In the human body, there are 2 systems associated with pain sensitivity: nociceptive and antinociceptive. Nociceptive is activated when damaged and creates a feeling of pain - see the course for more details. pathophysiology. In response to an extreme pain impulse, the body’s anti-pain antinociceptive system is triggered. It is represented by endogenous opioid receptors and substances - endogenous opioids - that affect them: endorphins, enkephalins, dynorphins. These substances excite opioid receptors, being their mimetics. As a result, the threshold of pain sensitivity increases and the emotional coloring of pain changes. All this creates the most powerful analgesic effect among drugs. In addition, narcotic analgesic drugs can cause other effects, since opioid receptors are widely distributed in the human body, both in the central nervous system and in the periphery. Today it has been established that there are different types and subtypes of opioid receptors, which explains the formation of many effects of narcotic analgesics. The most significant reactions are those obtained when the following types of opioid receptors are excited:
μ - analgesia, sedation, euphoria, respiratory depression are formed, intestinal motility decreases, bradycardia and miosis develop.
δ - analgesia, respiratory depression develops, and intestinal motility decreases.
κ - analgesia is formed, the effect of dysphoria is formed, intestinal motility decreases, and miosis develops.
Old drugs of narcotic analgesics indiscriminately excite all types of opioid receptors, causing their high toxicity. In recent years, narcotic analgesic preparations have been synthesized that interact only with certain types of opioid receptors described above (mainly κ). This made it possible, while maintaining the high analgesic activity of the drugs, to sharply reduce their toxicity, in particular, minimizing the risk of developing addiction (drug addiction).
Morphine hydrochloride - available in tablets of 0.01 and in ampoules containing a 1% solution in an amount of 1 ml.
A drug of plant origin, an alkaloid of the sleeping pill poppy. Two types of alkaloids are obtained from poppy seeds: 1) derivatives: morphine, codeine, omnopon; they have clear narcotic activity; 2) isoquinoline derivatives: papaverine, which does not have narcotic activity.
The drug is prescribed orally, subcutaneously, intravenously up to 4 times a day. It is well absorbed from the gastrointestinal tract, but the bioavailability of this route of administration is low (25%) due to pronounced presystemic elimination in the liver. Therefore, the drug is more often used parenterally. Morphine penetrates histohematic barriers, in particular through the placental barrier, which paralyzes fetal breathing in the womb. In the blood, the drug is 1/3 bound to plasma proteins. The drug is metabolized in the liver by a conjugation reaction with glucuronic acid; it is these metabolites that penetrate the barriers. 90% of the drug is excreted in the urine, the rest in bile, and enterohepatic circulation may occur. T ½ is about 2 hours.
For the mechanism of action, see above. Morphine indiscriminately stimulates all types of opioid receptors. The drug has a direct effect on the centers of the medulla oblongata and cranial nerves: it reduces the tone of the respiratory and cough centers and increases the tone of the vagus and oculomotor nerves. Morphine is a histamine liberator, which increases the content of the latter in the blood and leads to the dilation of peripheral vessels and the deposition of blood in them. This leads to a decrease in pressure in the pulmonary circulation.
O.E.
4) powerful antitussive;
5) potentiating;
6) lowers pressure in the pulmonary circulation.
P.P. 1) acute (shockogenic) pain that threatens the patient’s life
2) chronic pain in doomed patients
3) cough that threatens the patient’s life
4) premedication
5) complex therapy of a patient with pulmonary edema
P.E. Dysphoria, euphoria (especially dangerous with repeated use), drug dependence (addiction), tolerance (desensitization of opioid receptors when they are phosphorylated by protein kinase), overdose and death from respiratory and cardiac paralysis. Nausea, vomiting, constipation, urinary retention, bradycardia, decreased blood pressure, bronchospasm, hyperhidrosis, decreased body temperature, constriction of the pupil, increased intracranial pressure, teratogenic, allergies.
Contraindications for use: with respiratory depression, children under 14 years of age, pregnant women, with traumatic brain injuries, with general severe exhaustion of the body.
Trimepyridine (promedol) - available in tablets of 0.025 and in ampoules containing 1 and 2% solutions in an amount of 1 ml.
Synthetic agonist of all types of opioid receptors. It acts and is used like morphine, it was created to replace it with the aim of destroying poppy plantations. Differences: 1) somewhat inferior in activity and effectiveness; 2) does not penetrate the placenta and can be used for pain relief during labor; 3) has a less spasmogenic effect, in particular does not provoke spasm of the urinary tract and urinary retention, and is the drug of choice for pain relief when renal colic; 4) generally better tolerated.
Fentanyl (sentonil) - available in ampoules containing a 0.005% solution in an amount of 2 or 5 ml.
The drug is prescribed intramuscularly, more often intravenously, sometimes administered epidurally, intrathecally. Fentanyl, due to its high lipophilicity, penetrates well through the BBB. The drug is metabolized in the liver and excreted in the urine. T ½ lasts 3-4 hours and lengthens when using high doses of the drug.
Synthetic drug, piperidine derivative. The drug is much more lipophilic than morphine, so the risk of delayed respiratory depression due to the spread of the drug through the cerebrospinal fluid from the injection site to the respiratory center is significantly reduced.
In the patient's body, fentanyl indiscriminately stimulates all types of opioid receptors, the action and use are based on stimulation μ - receptors. It acts quickly (in 5 minutes compared to 15 for morphine), briefly. In terms of analgesic activity and toxicity, fentanyl is approximately a hundred times superior to morphine, which determines the tactics of using the drug in medicine.
O.E. 1) powerful analgesic (increasing the pain threshold, changing the emotional coloring of pain);
2) euphoria (change in the emotional coloring of pain);
3) sedative (change in the emotional coloring of pain);
P.P.
P.E. see morphine + skeletal muscle rigidity (during operations + muscle relaxants), in high doses - central nervous system stimulation.
For contraindications, see morphine.
Buprenorphine (norphine). The drug is prescribed intramuscularly, intravenously, orally, sublingually, up to 4 times a day. Buprenorphine is well absorbed by any route of administration. In the blood, it is 96% bound to plasma proteins. The drug is metabolized in the liver by N-alkylation and conjugation reactions. Most of the drug is excreted unchanged in the feces, some in the form of metabolites in the urine. T ½ is about 3 hours.
Is a partial agonist μ - receptors, and binds to them very firmly (so T ½ complex μ - receptors + buprenorphine is 166 minutes, and the complex with fentanyl is about 7 minutes). Its analgesic activity is 25-50 times greater than morphine.
O.E. 1) powerful analgesic (increasing the pain threshold, changing the emotional coloring of pain);
2) euphoria (change in the emotional coloring of pain);
3) sedative (change in the emotional coloring of pain);
P.P. 1) acute (shockogenic) pain that threatens the patient’s life;
2) chronic pain in doomed patients;
3) neuroleptanalgesia during certain operations;
P.E. see morphine, better tolerated. For contraindications, see morphine.
Tramadol is a synthetic analogue of codeine, a weak stimulant μ - receptors. Moreover, the drug’s affinity for this type of receptor is 6000 times lower than that of morphine. Therefore, the analgesic effect of tramadol is generally small, and for mild pain it is not inferior to morphine, but for chronic and acute shockogenic pain it is significantly inferior to morphine. Its analgesic effect is also partly due to disruption of neuronal reuptake of norepinephrine and serotonin.
Bioavailability when administered orally is 68%, and when administered intramuscularly - 100%. Tramadol is metabolized in the liver and excreted in the urine through the kidneys. T ½ tramadol is 6 hours, and its active metabolite is 7.5 hours.
P.E. see morphine, less pronounced + excitation of the central nervous system to the point of convulsions.
Butorphanol selective agonist drug κ - receptors. It is used mainly as an analgesic for acute and chronic pain. It is superior to morphine in analgesic activity. Unlike the above-mentioned drugs, if the dosage regimen is observed, it is much better tolerated and does not cause the development of addiction.
When using narcotic analgesics, cases of acute medicinal poisonings. This is facilitated by the relatively small breadth of therapeutic action of such drugs, tolerance, which forces an increase in doses of prescribed drugs, and low qualifications of medical staff.
Symptoms of poisoning are as follows: miosis, bradycardia, respiratory depression, suffocation, moist rales when breathing, contracted intestines, difficulty urinating, hyperhidrosis, moist and cyanotic skin.
Specific measures to help with opiate poisoning are as follows: 1) for gastric lavage, use a slightly pink solution of potassium permanganate, which oxidizes opiates, which suppresses their absorption in the gastrointestinal tract and accelerates excretion in feces; 2) among saline laxatives, preference is given to sodium sulfate, which does not cause CNS depression; 3) to stop the enterohepatic circulation of opiates, cholestyramine is prescribed orally, which absorbs them and accelerates the excretion of opiates in feces; 4) IV naloxone and naltrexone are used as antagonists
Naloxone - is available in ampoules containing a 0.04% solution in an amount of 1 ml.
Naloxone is completely absorbed from the gastrointestinal tract, but almost all of it is inactivated during the first passage through the liver, which is why it is used exclusively parenterally. The drug is metabolized in the liver by a conjugation reaction with glucuronic acid and is excreted mainly in feces. T ½ is about 1 hour.
It is a complete opioid receptor antagonist and has a particularly strong effect on μ - receptors, blocking them and displacing opiates from communication with them. The drug is prescribed intramuscularly or intravenously up to 4 times a day.
O.E. 1) blocks all types of opioid receptors;
2) reduces toxic effect opiates;
P.P. Acute opiate poisoning.
P.E. Not described.
The ability of opiates to cause euphoria can stimulate the development of addiction (opiate addiction), and this, in turn, can form physical and mental dependence. Treatment of such pathology is carried out by narcologists; medications can be used naltrexone . It, like naloxone, is a full opioid receptor antagonist drug, but its effect is 24 hours, which is convenient for chronic treatment.
To reduce cases of iatrogenic drug addiction, the following conditions should be observed: 1) prescribe narcotic analgesics strictly according to indications; 2) comply with the terms of treatment and dosage regimen; 3) avoid repeated courses of treatment; 4) give preference to drugs that have little or no effect on μ - receptors; 5) steadily improve the professional level of health workers. Order No. 330 of the USSR Ministry of Health also serves these purposes. It regulates all issues related to the circulation of drugs within the walls of a medical institution. The rules for prescribing narcotic drugs are regulated by Order No. 110 of the Ministry of Health of the Russian Federation.
An expert on human souls, Fyodor Mikhailovich Dostoevsky once said that pain is mandatory for “a broad consciousness and a deep heart.” The words of the classic should not be taken literally. Untreated pain is a serious blow to health and psyche. Moreover, doctors have learned to cope with it: they have dozens of different painkillers in their arsenal.
Acute pain occurs suddenly and lasts for a limited period of time. It is caused by tissue damage - bone fractures, sprains, injuries internal organs, caries and many other diseases. Usually, acute attacks are successfully treated with analgesics, and this is undoubtedly a positive phenomenon that gives hope for relief.
Chronic pain lasts longer than 6 months and is most likely associated with a chronic illness. Osteoarthritis, rheumatism, gout, and malignant tumors make themselves felt with severe, debilitating attacks that are resistant to treatment. Prolonged pain is not only the result of damaged tissue, but also often a consequence of damaged nerves.
Both acute and chronic pain can be so severe that the person experiencing it sometimes becomes deeply depressed. Sadly, up to 80% of the world's population suffers from chronic pain - this figure was obtained as a result of large epidemiological studies. And that’s why doctors never tire of studying this phenomenon and looking for new ways to combat it. So, what are they, painkillers?
The diverse world of analgesics
When you go to the pharmacy for painkillers, it seems that there is nothing complicated in your request. And only when the pharmacist starts asking a lot of additional questions, it becomes clear: in reality, everything is not so simple.
In pharmacology - the science of drugs - there are many groups of painkillers, each of which is used for a specific type of pain.
So, all analgesics are conventionally divided into:
- pyrazolones and their combinations;
- combined analgesics containing several components at once;
- antimigraine drugs indicated for the treatment of migraine headaches;
- non-steroidal anti-inflammatory drugs (NSAIDs);
- COX-2 inhibitors;
- narcotic analgesics;
- antispasmodics;
- specific analgesics.
Let's look at each of these groups separately and find out which painkillers to choose in this or that case.
Pyrazolones and their combinations: traditional painkillers
Typical representatives of painkillers are pyrazolones. This group includes the “father” of all analgesics, who has become the “gold standard” for pain treatment, His Majesty Analgin.
Analgin
Analgin, or metamizole sodium, has not only an analgesic effect. It also has minor antipyretic and anti-inflammatory effects. Nevertheless, analgin gained wide popularity and even fame as a drug against many types of pain.
The negative side of Analgin is not the highest safety. With frequent long-term use, metamizole sodium causes significant changes in the blood picture, so it is recommended to take it “rarely and accurately.” On the Russian market, metamizole sodium is produced under the traditional name Analgin. In addition, the Indian drug Baralgin M and Metamizole sodium produced in Macedonia are registered in the Russian Federation.
The complex painkiller drug Analgin-quinine, produced by the Bulgarian company Sopharma, contains two components: metamizole sodium and quinine. The main task that quinine performs in this complex is to reduce elevated body temperature. Due to the combination of the powerful antipyretic quinine and analgesic metamizole, Analgin-quinine is an excellent choice for fever and joint pain due to colds. In addition, the drug is also used for dental, joint, periodic and other types of pain.
Baralgetas, Spazmalgon
Both drugs are among the most popular combined analgesics and antispasmodics in our country. They contain the same combination: metamizole sodium, pitofenone, fenpivirinium bromide.
Each of the components enhances the effect of each other. Metamizole is a classic analgesic, pitofenone has an antispasmodic effect on smooth muscles, and fenpivirinium bromide additionally relaxes smooth muscles. Thanks to the very successful combination, Baralgetas and Spazmolgon are used for the widest range of indications in adults and children. We list the main ones:
- various types of pain caused by spasm of blood vessels or smooth muscle organs: headache, periodic, ureteral spasm, renal, hepatic, biliary colic, colitis;
- fever.
Baralgetas and Spazmolgon in injection form - an ambulance for very high temperature body when traditional antipyretics are powerless. The drugs are even used to relieve fever in children, including those up to one year of age. For each year of life, use 0.1 ml of Baralgetas (Spazmolgon) injection solution; - increased arterial pressure.
Relaxing spasmodic blood vessels, pain relievers medications Baralgin and Spazmolgon help with slightly elevated blood pressure (10–20 mm Hg above normal); - increased uterine tone during pregnancy.
In recent years, painkillers Baralgetas (Spazmolgon) have become increasingly used during pregnancy to reduce increased uterine tone. At the same time, they have a certain advantage over another antispasmodic, which has traditionally been used to relax the uterus - drotaverine. It was recently discovered that after 20 weeks of pregnancy, drotaverine can help soften the cervix. This is extremely undesirable, especially for women suffering from isthmic-cervical insufficiency. But it is precisely this category of patients who more than others need antispasmodics that reduce uterine tone.
Unlike drotaverine, Baralgetas (Spazmolgon) does not affect the cervix and can be safely used at any stage of pregnancy.
In addition to Baralgetas and Spazmolgon, their Ukrainian analogue, Renalgan tablets, is registered on the Russian market.
The famous tablets, coated with a spring-green coating, have been known since the times of the Soviet Union. The painkiller, which has been consistently produced by the Bulgarian company Sopharma for many decades, contains two active ingredients: metamizole sodium (analgin) and triacetonamine-4-toluenesulfonate. The latter has a so-called anxiolytic effect, reducing anxiety, tension, and agitation. In addition, it increases the effect of analgin.
Tempalgin and its analogue Tempanginol are used for pain of moderate and mild severity.
Combined painkillers: difficult but effective
The central component of most combination analgesics is usually paracetamol. Safe drug, which is sometimes mistakenly classified as a non-steroidal anti-inflammatory drug, has several effects at once: moderate analgesic and antipyretic, as well as extremely slight anti-inflammatory. Paracetamol in its pure form is a fairly strong analgesic, but when added to it additional components its qualities are enhanced. As a rule, combination analgesics, which include paracetamol, are used to relieve pain from colds. Let's move on to specifics.
Vicks Active SymptoMax and Vicks Active SymptoMax Plus
Vicks Active SymptoMax contains paracetamol in combination with phenylephrine. The latter has a vasoconstrictor effect, so the drug not only effectively reduces joint and muscle pain characteristic of a cold, but also reduces nasal congestion.
In addition to paracetamol and phenylephrine, Vicks Active SymptoMax Plus also contains guaifenesin, a substance that helps thin nasal secretions.
Drugs with fairly pronounced analgesic and anti-inflammatory activity. Brustan and Ibuklin contain paracetamol and one of the most powerful antipyretic and analgesic non-steroidal anti-inflammatory drugs - ibuprofen. Moreover, the concentrations of both components are quite high (paracetamol 325 mg, and ibuprofen at a dose of 400 mg). Due to the effective combination and high dosage, Brustan and Ibuklin have a pronounced analgesic and antipyretic effect. Ibuklin Junior is intended to reduce pain and fever in children and is available in dispersible form (in the form of tablets soluble in the oral cavity).
Analogues of Brustan also include the widely advertised drug Next, containing 400 mg of ibuprofen and 200 mg of paracetamol, as well as Nurofen MultiSymptom (400 mg + 325 mg).
An Austrian drug that contains caffeine, paracetamol and propyphenazone - a drug from the pyrazolone group that has a moderate analgesic and antipyretic effect. Caffeine in the composition of combined analgesics plays a very significant role - it dilates blood vessels and enhances the effect of the main analgesic components. Gevadal is recommended for use for moderate headache, muscle, and periodic pain.
Dolaren
Both the first and second tablets have same composition, including paracetamol and the myotropic antispasmodic dicycloverine, which relieves spasms of smooth muscle organs. It is due to the content of dicycloverine that Dolospa and Trigan quite effectively relieve pain in renal, biliary and intestinal colic, including urolithiasis. In addition, they can be taken for spastic constipation and spasms of other origins in the gastrointestinal tract.
Caffetin line
The Caffetin line is also very popular among combined analgesics. It includes three drugs that differ in both composition and indications:
- Caffetin Cold contains a classic anti-cold combination;
- Caffetin is a true combination pain reliever in tablets, including codeine, caffeine, paracetamol and propyphenazone.
Codeine is a natural narcotic analgesic that blocks opiate receptors. The remaining components of the drug (with the exception of caffeine, which we have already discussed) have antispasmodic and general analgesic properties. Due to its rich composition, caffetin relieves toothache and headaches, including migraines, and muscle pain. of various origins, joint, as well as periodic pain in women. Due to the inclusion of codeine, Caffetin is sold exclusively by prescription; - Caffetin Light.
A “light” variation of the analgesic containing paracetamol, propyphenazone and caffeine. Painkiller Caffetin Light can be purchased without a prescription and used for various types of mild to moderate pain.
The list of fairly strong painkillers is supplemented by the well-known Russian combined analgesic in tablets. The number of components is “hidden” in the name of the drug: “penta” translated from Greek means “five”. So, Pentalgin includes:
- drotaverine - myotropic antispasmodic;
- caffeine;
- naproxen is a non-steroidal anti-inflammatory drug;
- paracetamol;
- Pheniramine maleate is a component that has an antiallergic effect.
Pentalgin is quite effective for headaches, fever, as well as severe pain accompanying neuralgia.
Migraine: a pain that is not easy to relieve
Migraine pain is persistent and severe. Migraine attacks are not easy to stop. The pathological chain, which leads to a sudden and significant narrowing of blood vessels, has already started and is difficult to break. Conventional analgesics are often powerless, and anti-migraine painkillers that dilate blood vessels come to the rescue.
Sumatriptan is an active substance (and drug) that relieves migraine pain. It begins to act 30 minutes after application. The standard dosage of sumatriptan is 50 mg, and if it is ineffective, you can take two tablets per day (total 100 mg). The maximum daily dose is 300 mg.
Drugs containing sumatriptan include Amigrenin, Imigran, Migrepam, Rapidmed, Sumamigren, Trimigren.
Zolmitriptan
A drug that acts similarly to sumatriptan. The original drug zolmitriptan is produced by the British corporation Astra Zeneca under the name Zomig and Zomig Rapimelt.
Eletriptan
An effective pain reliever that is used to treat migraines, including severe pain. Eletriptan shows the best results when used at the very beginning of a migraine attack, but the effectiveness remains at any time. Today, only one eletriptan drug is registered in Russia - the original Relpax, which is produced by the American supergiant Pfizer.
Frovatriptan
Another active ingredient that effectively dilates blood vessels and helps with migraines. Presented by a drug produced in Germany, Frovamigran.
NSAIDs - effective pain relief
A special place among painkillers undoubtedly belongs to non-steroidal anti-inflammatory drugs. And although almost all of them have an analgesic effect, we will mention only those of them that are distinguished by the most pronounced analgesic activity.
Ibuprofen
One of the safest NSAIDs, which has antipyretic and analgesic properties. The safety of Ibuprofen is emphasized by the fact that the medicine is approved for pain relief and fever reduction even in newborns and infants. The drug is available in tablets, syrups, suppositories, as well as in local forms (ointments and gels) for pain relief in joints and muscles. Adult dosage sufficient to relieve pain moderate degree, is 400 mg. The most famous ibuprofen preparations: Dolgit, Ibuprom, Ipren, Nurofen.
Aspirin
Despite some analgesic activity, Aspirin is not used so often for pain relief. This is due to the aggressiveness of high doses of acetylsalicylic acid - the active ingredient of Aspirin - towards the mucous membrane of the digestive tract. However, Bayer produces an effervescent and tablet form of Aspirin designed to relieve pain and reduce fever.
Naproxen
A representative of NSAIDs, which, along with ibuprofen, is mainly used as an analgesic. Like all other drugs in the group of non-steroidal anti-inflammatory drugs, naproxen drugs are used with caution for diseases of the digestive tract. Naproxen is most often prescribed for the relief of dental, headache, periodic and rheumatic pain. In addition, naproxen can be used as an effective modern pain reliever for bone fractures or soft tissue injuries.
In Russian pharmacies, naproxen is sold under trade names: Apranax, Nalgesin and Nalgesin forte, Naprobene, Pronaxen, Sanaprox.
Ketorolac
Ketorolac is on the list of the most powerful painkillers. Its analgesic properties are comparable to the effectiveness of some opioid narcotic analgesics. However, ketorolac preparations should be used only in extreme cases when other means don't work. This is due to the side effects that occur with regular or long-term pain relief. Treatment with ketorolac is accompanied by irritation of the gastric mucosa (in 13% of cases), nausea (in 12% of cases), abdominal pain and even diarrhea (in 12 and 7% of patients, respectively). In addition, ketorolac can cause headache (in 17% of patients), dizziness (7%) and drowsiness (6%). There have been cases of severe gastric damage, including perforation and subsequent bleeding, as well as liver and kidney failure in patients taking ketorolac for a long time.
Nevertheless, the potent ketorolac can be indispensable for severe pain resulting from fractures and injuries, as well as as a drug for pain relief during cancer and after surgery. By the way, it does not have anti-inflammatory or antipyretic effects. There are several trade names on the domestic market, including Dolak, Dolomin, Ketalgin, Ketanov, Ketorol, Ketofril, Toradol, Torolak and others.
Safe painkillers COX-2 inhibitors, or coxibs
These drugs are classified as non-steroidal anti-inflammatory drugs. However, the special mechanism of action and the associated special effectiveness and, most importantly, safety, give reason to classify them as a separate subgroup of painkillers.
COX-2 inhibitors, unlike other NSAIDs, do not block COX-1, which protects the gastric mucosa. Therefore, they are not aggressive towards the organs of the gastrointestinal tract, and they can be used by people who have a history of gastric ulcers. However, most experts agree that coxibs should be taken with caution in such cases.
During treatment with COX-2 inhibitors in patients with peptic ulcers or stomach bleeding In the past, it was recommended to take proton pump inhibitors. These agents block the production of hydrochloric acid and thus protect the gastric mucosa.
We add that the most well-known proton pump inhibitors include Omeprazole, Lanzoprazole, Esomeprazole and Pantoprazole.
Celecoxib
The first of the coxib-type painkillers registered in Russia. Excellently reduces inflammation and relieves pain. It is used for exacerbation of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and other rheumatic diseases, including those with severe pain.
Celecoxib is available under the trade names Dilaxa, Coxib, Celebrex - the original drug manufactured by Pfizer.
Rofecoxib
Another representative of coxibs, which is prescribed to reduce pain and inflammation in acute and chronic osteoarthritis, pain syndrome of any origin. It is available in Russian pharmacies under the name Vioxx in the form of a suspension and tablets. The manufacturer of the drug is the Dutch company Merck.
Parecoxib
This drug occupies a special position among analgesics - it has parenteral, that is, injection form release. Parecoxib has less pronounced anti-inflammatory activity, but this disadvantage is more than compensated by its high analgesic capabilities. In Russia, parecoxib is sold under the name Dynastat. It is produced by the British company Pharmacia in the form of a lyophilized powder, from which a solution for intramuscular or intramuscular injections is prepared immediately before use. intravenous injections.
Dynastat is widely used as a powerful injectable analgesic for severe pain, including after surgery or fairly sensitive diagnostic tests (for example, colonoscopy), as well as pain from fractures and injuries. In addition, Dynastat is sometimes prescribed for pain relief cancer patients in order to reduce the dose of narcotic analgesics.
Etoricoxib
One of the most modern coxibs, which organically combines anti-inflammatory and analgesic effects. The drug is used for symptomatic, that is, analgesic therapy of osteoarthritis, osteochondrosis, rheumatoid arthritis and other joint diseases. Etoricoxib is marketed by Pfizer under the name Arcoxia.
Reserve drugs - narcotic analgesics
Narcotic analgesics block opioid receptors and thereby inhibit the transmission of pain impulses. In addition, they reduce the emotional assessment of pain and reaction to it, and also cause euphoria and a feeling of mental comfort. To avoid the formation of addiction, narcotic analgesics are used only in extreme cases, for example, to relieve acute pain. In addition, opioid analgesics are used in anesthesiology for so-called premedication - preparing the patient before the introduction of an epidural and spinal anesthesia.
Narcotic painkillers registered in the Russian Federation include preparations of codeine, fentanyl, morphine and some others.
Due to the codeine content, the group of opioid narcotic analgesics in combination also included the fairly well-known drugs Nurofen Plus and Sedalgin Neo.
Nurofen Plus
The drug from the Nurofen line, which is produced by the British company Reckit Healthcare, contains ibuprofen in a dose of 200 mg and 10 mg of codeine. Nurofen Plus tablets effectively relieve headaches and toothaches, migraine pain, periodic pain in women, back pain, muscle and joint pain, pain due to neuralgia and spinal hernias. In addition, the drug is good for fever and pain characteristic of colds and flu. Nurofen Plus should not be taken by children under 12 years of age.
The Bulgarian painkiller produced by Activis Sedalgin Neo, known for a long time, also fell into the group of combined opioid analgesics. Sedalgin Neo contains a combination of five active ingredients, including codeine, caffeine, metamizole sodium, paracetamol and phenobarbital. Due to the latter, the medicine has not only an analgesic, but also a sedative effect. Sedalgin Neo is effective for neuralgia, neuritis, migraine, as well as pain of various origins, including rheumatic, headache, dental, phantom, post-burn, traumatic, postoperative and periodic. In addition, the drug can be used for fever and aches during ARVI and influenza.
Myotropic antispasmodics: both pain and spasm
Myotropic antispasmodics can reduce the flow of active calcium into the cells of smooth muscle fibers. As a result, smooth muscles and blood vessels expand, pressure decreases, which provides the drugs with an antispasmodic and analgesic effect.;
In addition, drotaverine weakens uterine contractions and is used in obstetrics to reduce tone, as well as reduce spasm of the cervix during childbirth.
Sometimes drotaverine is used at high body temperatures against the background of peripheral vascular spasm. In such cases, the patient experiences severe fever and contrastingly cold extremities.
For effective normalization body temperature with peripheral vascular spasm, traditional antipyretics are used - paracetamol or ibuprofen - in combination with drotaverine.
Dozens of drotaverine analogues are sold on the domestic market. We will list the most popular of them: Vero-Drotaverin, Droverin, Drotaverin-Teva, No-shpa, No-shpa forte (80 mg dosage), Spasmol and others.
Dicetel
The drug, which is produced by the French company Abbott, contains pinaverium bromide as an active ingredient. It, like drotaverine, relieves spasm of smooth muscle fibers and blood vessels. Dicetel tablets are used to relieve pain from spastic intestinal contractions, including irritable bowel syndrome and biliary dyskinesia.
Duspatalin
The same Abbott company produces another myotropic antispasmodic Duspatalin. It contains mebeverine, which has antispasmodic and analgesic effects.
Duspatalin is an original brand drug. There are also its analogues, which are more economical in price. These include Mebeverine hydrochloride, Niaspasm, Sparex.
Combined antispasmodics
A small group of drugs, which includes only a few medicinal compositions.
The original French drug from Sanofi Aventis contains three active ingredients: drotaverine, codeine and paracetamol. An effective combination provides multiple effects. Paracetamol reduces the severity of pain and reduces temperature, drotaverine reduces spasms, and codeine further enhances the analgesic effect.
No-shpalgin is used for headaches of various origins: tension headaches, vascular headaches, as well as pain due to overwork or stress. The Indian analogue of No-shpalgin Unispaz has the same composition and a more favorable price.
Nomigren
Very interesting drug combination is a drug Nomigren, which is produced in Bosnia and Herzegovina. It contains five components: propyphenazone, caffeine, camilofine chloride, mecloxamine citrate and ergotamine tartrate.
The active ingredients of the drug Nomigren, enhancing the effect of each other, have a strong analgesic effect for migraines and vascular headaches. The medicine shows the best results if it is taken at the very beginning of the attack.
Specific pain medications
This group of drugs is indirectly related to analgesics, and people far from medicine and pharmacology are unlikely to draw an analogy between them and painkillers. Officially, specific analgesics belong to the group of anticonvulsants. And even in the instructions for use in the column “Pharmacological group” it is written in black and white “Anti-epileptic” or “Anticonvulsant”. However, against the background of some anticonvulsant effect, drugs in this group effectively reduce severe postoperative and other types of pain. In addition, they reduce sensitivity in severe wounds, such as after breast removal and other invasive major procedures, which are characterized by damage to peripheral nerves and associated hypersensitivity of the postoperative wound.
Gabapentin
Gabapentin effectively blocks the release of neurotransmitters that have an excitatory effect. Large clinical studies have proven the role of gabapentin in the treatment of chronic and neuropathic pain. It is associated with the ability of the drug to reduce sensitivity spinal cord, including after surgery or traumatic injury fabrics.
Gabapentin is recommended to be prescribed to patients after surgery, including for the purpose of reducing doses of narcotic analgesics. Gabapentin drugs have been proven to be highly effective for pain relief for severe tension headaches, as well as pain associated with cerebral vasospasm.
In domestic pharmacies, gabapentin is sold under the names Gabagamma, Gapentek, Catena, Neurontin, Tebantin, Egipentin and others.
Pregabalin
A drug that has properties similar to gabapentin. The main difference is the longer half-life, and therefore pregabalin is considered the drug of choice for the treatment of acute pain, especially in older people. Indications for pregabalin include neuropathic pain, fibromyalgia, and postoperative pain. The original pregabalin is produced by the American concern Pfizer under the name Lyrica. In addition, generics are also available on the market: Algerica, Prabegin, Pregabalin Zentiva, Pregabalin-Richter and Pregabalin Canon.
As you can see, there are a great variety of painkillers, which include prescription and over-the-counter, tablet and injectable, strong and not so strong, modern and time-tested drugs. It is not so easy to choose from this variety the medicine that you need right now, so it is better to rely on the knowledge of your doctor and pharmacist. Rely and live without pain.
Pain syndrome is a serious problem and literally knocks a person out of Everyday life. With such an ailment, performance decreases, it is difficult to study and carry out everyday activities. Special medications - analgesics - can help solve this problem. In this article we will tell you what characteristics they have, consider the mechanism of their action, and also give some tips on how you can quickly cope with pain.
Action of analgesics
Pain medications are called analgesics. They act selectively on certain tissues of the body. In their action, they, as a rule, not only eliminate pain, but also act as an antipyretic. But it is necessary to understand that this type of medication does not eliminate the cause of the pain syndrome, but only alleviates the patient’s sensations.
However, it is important to understand what can help the body overcome the consequences of any injury. Inflammation or disease. Let's look at the mechanism of action of various analgesics below.
Mechanism of action of analgesics
The action of drugs in this group differs in the mechanism of action on the brain and the site of damage. The most powerful drugs are those that act on opioid receptors in the nervous system and suppress pain at the level of impulse transmission to the brain. These substances are classified as narcotic medications. They can only be taken as prescribed by a doctor. To purchase them, you need a special prescription, since this category of analgesics can often be addictive. Mechanism of action of analgesics This type is quite simple. They enter the brain through the blood, blocking the sensation of pain.
Other types of painkillers are widely used - the so-called simple analgesics, often used as a analgesics for headaches. These medications are available to patients without a prescription. They act directly on the source of damage to the nervous system. Thus, the drugs eliminate pain at the site of its origin. In addition, these drugs do not cause any addiction, unlike the opiates described above.
Today there are quite a lot of them. Frequently used analgesics include medicines based paracetamol. Paracetamol is recognized by WHO as a reference analgesic in terms of efficacy/safety ratio and is included in the list of essential medicines*. One of the popular paracetamol-based drugs is Next®. This medicine also contains ibuprofen. Using the Next® drug as an example, we will consider the mechanism of action of these substances on the human body.
Paracetamol is a simple non-narcotic analgesic, most often used to reduce fever and as headache analgesic. When taken, it has an effect on the pain and thermoregulation centers in the human nervous system. Its distinctive feature is the low risk of side effects from the gastrointestinal tract and kidneys. In addition, due to rapid absorption, pain relief after taking paracetamol can be felt within 15-30 minutes**.
Second component headache analgesic Next® - ibuprofen. It is a non-steroidal anti-inflammatory drug, i.e. acts at the site of injury, suppressing inflammation and blocking pain at the site of its occurrence. The combination with paracetamol provides a complex effect on the central and peripheral mechanisms of pain syndrome formation.
For pain not associated with inflammatory processes, to alleviate the condition, it is often enough to take a drug with the active ingredient - paracetamol. If the pain is associated with damage accompanied by inflammation, a drug with the active ingredient ibuprofen is more suitable. Considering that Next® contains both of these components, this medicine can be considered more universal.
So when should you take Next®?
For every case there are different drugs. Due to its versatility, Next® can be taken in different situations. For example, in the case:
- back and lower back pain;
- headaches of different origins, incl. for migraines;
- menstrual pain;
- muscle pain, etc.
It is important to follow the dosage. However, you should not take an analgesic if discomfort occurs in the abdominal area. Remember that to relieve the symptoms of gastritis, dysbacteriosis or ulcers, it is pointless to use medicine - it will not give a beneficial effect, and may even be harmful. First you need to accurately determine the cause of the pain syndrome. Only after this can we begin to solve this problem.
5 rules for taking analgesics
To use the drug more correctly, we have prepared several rules.
- You cannot take an analgesic in a dose higher than the maximum permitted dose specified in the instructions. Such actions can cause Negative consequences. The risk of side effects directly depends on the dose of the drug.
- If the pain syndrome is quite intense, it is better to immediately take the maximum single (not daily!) dose of one drug than to use several drugs at the same time in a minimum dose.
- Always take analgesics with a glass of water.
- If you take painkillers, avoid drinking alcohol. The combination of medicine and alcohol can cause negative consequences.
- Choose the correct form of taking analgesics. The most common method of taking medications is orally, but in some cases, other methods may be used for one reason or another; it is best to discuss this with your doctor.
Compliance with these rules will reduce the risk of side effects when taking analgesics. Although ibuprofen and paracetamol-based drugs have a favorable safety profile and are available without a prescription, it is better to minimize possible risks.
Initially, it is advisable to make do with a minimum dose of medication. In this way, you can choose the most suitable dosage, because... it depends not only on the type and severity of pain, but also on the individual sensitivity of the body.
Medicine for pain
If there is a need for analgesic for headaches, for lower back pain and a number of other pain syndromes, you can try Next®.
Next® is a drug that has a rapid and pronounced therapeutic effect***. The use of this analgesic does not require a doctor's prescription. Thanks to complex action on several mechanisms of pain, Next® can help with the most different types pain.
* SHIFMAN E. M., ERSHOV A. L. GENERAL RESUSCITATION, 2007, III; 1. WHO Model List of Essential Medicines for Adults, 18th edition, 2013.
** Moller PL, Sindet-Pedersen S, Petersen CT, Juhl GI, Dillenschneider A, Skoglund LA. Onset of acetaminophen analgesia: comparison of oral and intravenous routes after third molar surgery. Br J Anaesth. 2005 May;94(5):642-8.
Moller PL, Sindet-Pedersen S, Petersen ST. et al. Onset of analgesic action of acetaminophen: comparison of oral and injection administration for post-operative analgesia. British Journal of Analgesia. May 2005, 94(5):642-8.
***According to the instructions for medical use of the drug
These drugs selectively reduce and suppress pain sensitivity without significantly affecting other types of sensitivity and without disturbing consciousness (analgesia - loss of pain sensitivity; an - denial, algos - pain). For a long time, doctors have tried to relieve the patient from pain. Hippocrates 400 BC e. wrote: "...removing pain is divine work." Based on the pharmacodynamics of the corresponding drugs, modern painkillers are divided into 2 large groups:
I - narcotic analgesics or morphine group. This group of funds is characterized by the following points (conditions):
1) have strong analgesic activity, allowing them to be used as highly effective painkillers;
2) these drugs can cause drug addiction, that is, addiction, drug dependence associated with their special effect on the central nervous system, as well as the development of a painful state (withdrawal) in persons with developed addiction;
3) in case of an overdose, the patient develops deep sleep, which successively turns into anesthesia, coma and, finally, ending with the cessation of the activity of the respiratory center. That's why they got their name - narcotic analgesics.
The second group of drugs are non-narcotic analgesics, the classic representatives of which are: aspirin or acetylsalicylic acid. There are many drugs here, but all of them are not addictive, because they have different mechanisms of action.
Let's sort it out I group drugs, namely drugs of the morphine group or narcotic analgesics.
Narcotic analgesics have a pronounced inhibitory effect on the central nervous system. Unlike drugs that depress the central nervous system indiscriminately, it manifests itself as an analgesic, moderately hypnotic, antitussive effect that depresses the respiratory centers. In addition, most narcotic analgesics cause drug (mental and physical) dependence.
The most prominent representative of this group of drugs, from which this group got its name, is MORPHINE.
Morphini hydrochloridum (table of 0.01; amp. 1% - 1 ml). The alkaloid morphine is isolated from opium (Greek - opos - juice), which is the frozen, dried juice of unripe pods of the sleeping pill poppy (Papaver somniferum). The homeland of poppy is Asia Minor, China, India, Egypt. Morphine got its name from the ancient Greek god of dreams Morpheus, who, according to legend, is the son of the god of sleep Hypnos.
Opium contains 10-11% morphine, which is almost half the share of all alkaloids present in it (20 alkaloids). They have been used in medicine for a long time (5000 years ago as an analgesic, antidiarrheal agent). Despite the synthesis of morphine by chemists in 1952, it is still obtained from opium, which is cheaper and easier.
According to the chemical structure, all pharmacologically active opium alkaloids belong to either PHENANTHRENE derivatives or ISOQUINOLINE derivatives. The phenanthrene alkaloids include: morphine, codeine, thebaine, etc. It is the phenanthrene alkaloids that are characterized by a pronounced inhibitory effect on the central nervous system (analgesic, antitussive, hypnotic, etc.).
Isoquinoline derivatives have a direct antispasmodic effect on smooth muscles. A typical isoquinoline derivative is papaverine, which has no effect on the central nervous system, but affects smooth muscles, especially in a state of spasm. Papaverine acts in this case as an antispasmodic.
PHARMACOLOGICAL PROPERTIES OF MORPHINE
1. Effect of morphine on the central nervous system
1) Morphine primarily has an analgesic or analgesic effect, and the analgesic effect is exerted in doses that do not significantly alter the function of the central nervous system.
Analgesia caused by morphine is not accompanied by blurred speech, impaired coordination of movements, and the sense of touch, vibration sensitivity, and hearing are not weakened. The analgesic effect is the main one for morphine. IN modern medicine this is one of the most powerful painkillers. The effect begins a few minutes after injection. Morphine is most often administered intramuscularly or subcutaneously, but it can also be administered intravenously. The action lasts 4-6 hours.
As you know, pain consists of 2 components:
a) pain perception, depending on a person’s pain sensitivity threshold;
b) mental, emotional reaction to pain.
In this regard, it is important that morphine sharply inhibits both components of pain. It increases, firstly, the threshold of pain sensitivity, thus reducing the perception of pain. The analgesic effect of morphine is accompanied by a feeling of well-being (euphoria).
Second, morphine alters the emotional response to pain. In therapeutic doses, it may not even completely eliminate the sensation of pain, but patients perceive it as something extraneous.
How and in what way does morphine achieve these effects?
MECHANISM OF ACTION OF NARCOTIC ANALGESICS.
In 1975, Hughes and Kosterlitz discovered specific “opiate” receptors of several types in the nervous system of humans and animals, with which narcotic analgesics interact.
Currently, there are 5 types of these opiate receptors: mu, delta, kappa, sigma, epsilon.
It is with these opiate receptors that various endogenous (produced in the body itself) peptides that have high analgesic activity normally interact. Endogenous peptides have a very high affinity (affinity) for these opiate receptors. The latter, as it has become known, are located and function in various parts of the central nervous system and in peripheral tissues. Due to the fact that endogenous peptides have high affinity, in the literature they are also called LIGANDS in relation to opiate receptors, that is (from the Latin - ligo - I bind) directly binding to the receptors.
There are several endogenous ligands; they are all oligo-peptides containing different quantities amino acids and united under the name "ENDORPHINS" (that is, endogenous morphines). Peptides containing five amino acids are called enkephalins (methionine-enkephalin, lysine-enkephalin). Currently, this is a whole class of 10-15 substances containing from 5 to 31 amino acids in their molecules.
Enkephalin, according to Hughes, Kosterlitz, is “a substance in the head.”
Pharmacological effects of enkephalins:
Release of pituitary hormones;
Memory change;
Regulation of breathing;
Modulation of the immune response;
Anesthesia;
Catatonic-like state;
Convulsive seizures;
Regulation of body temperature;
Appetite control;
Reproduction functions;
Sexual behavior;
Reactions to stress;
Decreased blood pressure.
MAIN BIOLOGICAL EFFECTS OF ENDOGENOUS OPIATES
The main effect, role, biological function endorphins is the inhibition of the release of “pain neurotransmitters” from the central endings of afferent unmyelinated C-fibers (including norepinephrine, acetylcholine, dopamine).
As is known, these pain mediators can be, first of all, substance P (a peptide of amino acids), cholecystokinin, somatostatin, bradykinin, serotonin, histamine, prostaglandin. Pain impulses travel along the C- and A-fibers (A-delta fibers) and enter the dorsal horns of the spinal cord.
When pain occurs, a special system of enkephalinergic neurons, the so-called antinociceptive (antipain) system, is normally stimulated, neuropeptides are released, which has an inhibitory effect on the pain system (nociceptive) neurons. The end result The effect of endogenous peptides on opiate receptors is to increase the threshold of pain sensitivity.
Endogenous peptides are very active, they are hundreds of times more active than morphine. Currently, they are isolated in pure form, but in very small quantities, they are very expensive, and so far they are mainly used in experiments. But there are already results in practice. For example, the domestic peptide DALARGIN has been synthesized. The first results have been received, and already in the clinic.
In case of insufficiency of the antinoceceptive system (antipain enkephalinergic), and this happens with excessively pronounced or prolonged damaging effects, pain must be suppressed with the help of painkillers - analgesics. It turned out that the site of action of both endogenous peptides and exogenous drugs are the same structures, namely the opiate receptors of the nociceptive (pain) system. In this regard, morphine and its analogues are opiate receptor agonists. Individual endo- and exogenous morphines act at different opiate receptors.
In particular, morphine acts predominantly on mu receptors, enkephalins on delta receptors, etc. (“responsible” for pain relief, respiratory depression, reduction in the frequency of cardiovascular events, immobility).
Thus, narcotic analgesics, in particular morphine, playing the role of endogenous opiate peptides, being essentially imitators of the action of endogenous ligands (endorphins and enkephalins), increase the activity of the antinociceptive system and enhance its inhibitory effect on the pain system.
In addition to endorphins, serotonin and glycine, which are synergists of morphine, function in this antinociceptive system. By acting predominantly on mu receptors, morphine and other drugs of this group primarily suppress aching, nagging pain associated with the summation of nociceptive impulses coming from the spinal cord along a nonspecific path to the nonspecific nuclei of the thalamus, disrupting its spread to the superior frontal, parietal gyri of the cortex big brain(that is, the perception of pain), as well as to its other parts, in particular, to the hypothalamus, the amygdala complex, in which autonomic, hormonal, and emotional reactions to pain are formed.
By suppressing this pain, drugs inhibit the emotional reaction to it, as a result of which narcotic analgesics prevent dysfunction of the cardiovascular system, the occurrence of fear, and suffering associated with pain. Strong analgesics (fentanyl) can suppress the conduction of excitation along a specific nociceptive pathway.
By stimulating enkephalin (opiate) receptors in other structures of the brain, endorphins and narcotic analgesics affect sleep, wakefulness, emotions, sexual behavior, convulsive and epileptic reactions, and autonomic functions. It turned out that almost all known neurotransmitter systems are involved in the implementation of the effects of endorphins and morphine-like drugs.
Hence various other pharmacological effects of morphine and its drugs. So, the second effect of morphine is a sedative and hypnotic effect. The sedative effect of morphine is very clearly expressed. Morpheus is the son of the god of sleep. The sedative effect of morphine is the development of drowsiness, some darkening of consciousness, and impaired logical thinking. Patients are easily awakened from morphine-induced sleep. The combination of morphine with hypnotics or other sedatives makes the central nervous system depression more pronounced.
The 3rd effect is the effect of morphine on mood. The influence here is twofold. Some patients, and more often healthy individuals, after a single injection of morphine experience a feeling of dysphoria, anxiety, negative emotions, no pleasure, and decreased mood. As a rule, this occurs in healthy individuals who do not have an indication for the use of morphine.
With repeated administration of morphine, especially if there are indications for the use of morphine, the phenomenon of euphoria usually develops: an increase in mood occurs with a feeling of bliss, lightness, positive emotions, pleasantness throughout the body. Against the background of drowsiness, decreased physical activity, difficulty concentrating, and a feeling of indifference to the world around us arises.
A person’s thoughts and judgments lose their logical consistency, the imagination becomes fantastical, bright colorful pictures and visions arise (dream world, “high”). The ability to engage in art, science, and creativity is lost.
The occurrence of these psychotropic effects is due to the fact that morphine, like other analgesics of this group, directly interact with opiate receptors localized in the cerebral cortex, hypothalamus, hippocampus, and amygdala complex.
The desire to experience this state again is the cause of a person’s mental dependence on the drug. Thus, it is euphoria that is responsible for the development of drug addiction. Euphoria can occur even after one injection.
The fourth pharmacological effect of morphine is associated with its effect on the hypothalamus. Morphine inhibits the thermoregulatory center, which can lead to sharp decline body temperature in morphine poisoning. In addition, the effect of morphine on the hypothalamus is also related to the fact that it, like all narcotic analgesics, stimulates the release of antidiuretic hormone, which leads to urinary retention. In addition, it stimulates the release of prolactin and somatotropin, but delays the release of luteinizing hormone. Under the influence of morphine, appetite decreases.
5th effect - morphine, like all other drugs in this group, has a pronounced effect on the centers of the medulla oblongata. This action is ambiguous, since it excites a number of centers, and depresses a number.
Depression of the respiratory center most easily occurs in children. Inhibition of the respiratory center is associated with a decrease in its sensitivity to carbon dioxide.
Morphine inhibits the central links cough reflex and has pronounced antitussive activity.
Narcotic analgesics, like morphine, can stimulate the neurons of the chemoreceptor trigger zone of the fundus of the fourth ventricle, causing nausea and vomiting. Morphine in large doses depresses the vomiting center itself, so repeated administration of morphine does not cause vomiting. In this regard, the use of emetics for morphine poisoning is useless.
The 6th effect is the effect of morphine and its drugs on blood vessels. Therapeutic doses have little effect on blood pressure and the heart; toxic doses can cause hypotension. But morphine causes dilation of peripheral blood vessels, especially capillaries, partly by direct action and partly by the release of histamine. Thus, it can cause redness of the skin, increased temperature, swelling, itching, and sweating.
INFLUENCE OF MORPHINE ON THE GASTROINTESTINAL TRACT AND OTHER SMOOTH MUSCLE ORGANS
The effect of narcotic analgesics (morphine) on the gastrointestinal tract is attributed mainly to their increase in the activity of neurons in the center n. vagus, and to a lesser extent due to a direct effect on the nerve elements of the wall of the gastrointestinal tract. In this regard, morphine causes severe spasm smooth muscles of the intestine, imocecal and anal sphincters and at the same time reduces motor activity, reducing peristalsis (gastrointestinal tract). The spasmogenic effect of morphine is most pronounced in the duodenum and large intestine. The secretion of saliva, hydrochloric acid of gastric juice and the secretory activity of the intestinal mucosa decreases. The passage of feces slows down, the absorption of water from them increases, which leads to constipation (morphine constipation - increased tone of all 3 muscle groups). Morphine and its analogues increase the tone of the gallbladder and promote the development of spasm of the sphincter of Oddi. Therefore, although the analgesic effect alleviates the patient’s condition with biliary colic, the course of the pathological process itself is aggravated.
EFFECT OF MORPHINE ON OTHER SMOOTH MUSCLE FORMS
Morphine increases uterine tone and Bladder, ureters, which is accompanied by “urinary haste”. At the same time, the visceral sphincter contracts, which, if there is insufficient response to the urge from the bladder, leads to urinary retention.
Morphine increases the tone of the bronchi and bronchioles.
INDICATIONS FOR MORPHINE USE
1) Acute pain that threatens the development of painful shock. Examples: severe trauma (tubular bone fractures, burns), relief of the postoperative period. In this case, morphine is used as an analgesic and anti-shock agent. For the same purpose, morphine is used for myocardial infarction, embolism pulmonary artery, acute pericarditis, spontaneous pneumothorax. To relieve sudden onset pain, morphine is administered intravenously, which quickly reduces the risk of shock.
In addition, morphine as an analgesic is used for colic, for example, intestinal, renal, hepatic, etc. However, it must be clearly remembered that in this case morphine is administered together with the antispasmodic atropine, and only when the doctor is absolutely sure of the correct diagnosis .
2) Chronic pain in hopeless dying patients with a humane purpose (example: hospices - hospitals for hopeless cancer patients; appointments by the hour). In fact, chronic pain is a contraindication to the use of morphine. Only in hopeless, dying tumor carriers, doomed, the administration of morphine is mandatory.
3) As a means of premedication during anesthesia, before anesthesia, that is, in anesthesiology.
4) As an antitussive for coughs that threaten the patient’s life. By this indication morphine is prescribed, for example, for extensive operations, chest injuries.
5) In acute left ventricular failure, that is, in cardiac asthma. In this case, the effect is due to a decrease in the excitability of the central nervous system and pathological shortness of breath. It causes dilatation of peripheral vessels, as a result of which blood is redistributed from the pulmonary artery system into dilated peripheral vessels. This is accompanied by a decrease in blood flow and a decrease in pressure in the pulmonary artery and central venous pressure. This reduces the work of the heart.
6) For acute pulmonary edema.
SIDE EFFECTS OF MORPHINE
The breadth of pharmacological effects of morphine also determines its numerous adverse reactions. These are, first of all, dysphoria, constipation, dry mouth, foggy thinking, dizziness, nausea and vomiting, respiratory depression, headache, increased fatigue, paresthesia, bradycardia. Sometimes intolerance occurs in the form of tremors and delirium, as well as allergic reactions.
CONTRAINDICATIONS TO THE USE OF MORPHINE
There are no absolute ones, but there is a whole group of relative contraindications:
1) early childhood(up to 3 years) - risk of respiratory depression;
2) in pregnant women (especially at the end of pregnancy, during childbirth);
3) for various types of respiratory failure (emphysema, bronchial asthma, kyphoscoliosis, obesity);
4) when severe injuries head (increased intracranial pressure; in this case, morphine further increases intracranial pressure, causes vomiting; vomiting, in turn, increases intracranial pressure and thus a vicious circle is formed).
In our country, a very powerful analgesic with long-term action has been created on the basis of morphine - MORPHYLONG. He represents a new medicine, containing morphine hydrochloride and narrowly fractionated polyvinylpyrrolidone. Morphilong as a result acquires a longer duration of action (22-24 hours its analgesic effect) and greater intensity of the effect. Less pronounced side effects. This is its advantage over morphine (the duration is 4-6 times longer than the duration of action of morphine). Used as a long-lasting pain reliever:
1) in the postoperative period;
2) with pronounced pain syndrome.
OMNOPON (Omnoponum in amp. 1 ml - 1% and 2% solution). Omnopon is a new galenic opium preparation in the form of a mixture of 5 opium alkaloids. It contains 48-50% morphine and 32-35% other alkaloids of both the phenanthrene and isoquinoline series (papaverine). In this regard, omnopon has a less spasmogenic effect. In principle, the pharmacodynamics of omnopon are similar to those of morphine. However, omnopon is still used together with atropine. Indications for use are almost the same.
In addition to morphine, omnopon in medical practice Many synthetic and semi-synthetic drugs have found use. These drugs were created for 2 purposes:
1) to get rid of poppy plantations;
2) so that patients do not develop an addiction. But this goal failed, since all narcotic analgesics general mechanisms actions (via opiate receptors).
Of significant interest is PROMEDOL, which is a synthetic drug derived from piperidine.
Promedolum (table - 0.025; amp. 1 ml - 1% and 2% solution). In terms of analgesic activity, it is 2-4 times inferior to morphine. Duration of action is 3-4 hours. Less likely to cause nausea and vomiting, less depressing respiratory center. Unlike morphine, promedol reduces the tone of the ureters and bronchi, relaxes the cervix and slightly increases contractions of the uterine wall. In this regard, promedol is preferred for colic. In addition, it can be used during childbirth (according to indications, since it depresses fetal breathing to a lesser extent than morphine, and also relaxes the cervix).
In 1978, a synthetic analgesic appeared - MORADOL, which is a derivative of phenanthrene in its chemical structure. A similar synthetic drug is TRAMAL. MORADOL (butorphanol tartrate) with intramuscular and intravenous administration provides a high degree of analgesic effectiveness, and analgesia occurs faster than with the administration of morphine (after 30-60 minutes, morphine - after 60 minutes). The action lasts 3-4 hours. At the same time, it has significantly fewer side effects and, most importantly, a very low risk of developing physical dependence even with long-term use, since moradol rarely causes euphoria (it acts primarily on other delta opiate receptors). In addition, it has a limited respiratory depressant effect, even in large doses. Use: for the same indications as morphine, but in case of long-term need for use. In therapeutic doses it does not depress the respiratory center and is safe for the mother and fetus.
Another synthetic representative of piperidine-phenanthrene derivatives is FENTANYL. Fentanyl has very high analgesic activity, exceeding the activity of morphine (100-400 times). A distinctive feature of fentanyl is the short duration of pain relief it causes (20-30 minutes). The effect develops within 1-3 minutes. Therefore, fentanyl is used for neuroleptanalgesia together with the antipsychotic droperidol (talomonal).
This type of analgesia is used when the patient must be conscious, for example, during myocardial infarction. The form of anesthesia itself is very convenient, since the patient does not react to painful stimulation (analgesic effect) and is completely indifferent to everything that happens (neuroleptic effect, consisting of a supersedative and a strong tranquilizing effect).
The opium alkaloid CODEINE (Codeinum in the table of 0.015) stands apart. As an analgesic it is much weaker than morphine. Has a weaker affinity for opiate receptors. The antitussive effect of codeine is weaker than that of morphine, but quite sufficient for practice.
Advantages of codeine:
1) unlike morphine, it is well absorbed when taken orally;
2) codeine depresses breathing less;
3) causes less drowsiness;
4) has less spasmogenic activity;
5) addiction to codeine develops more slowly.
INDICATIONS FOR CODEINE USE:
1) with a dry, raw, unproductive cough;
2) the second stage of the fight against chronic pain in a cancer patient (WHO), according to a three-stage scheme. Codeine (50-150 mg every 5 hours) plus non-narcotic analgesic, plus aids(glucocorticoids, antidepressants, anticonvulsants, psychotropics, etc.).
ACUTE POISONING WITH MORPHINE AND MORPHINE-LIKE DRUGS
Acute morphine poisoning can occur with an overdose of the drug, as well as with accidental ingestion of large doses in addictive patients. In addition, morphine can be used for suicidal purposes. For adults, the lethal dose is 250 mg.
In acute morphine poisoning clinical picture characteristic. The patient's condition is very serious. First, sleep develops, passing into the stage of anesthesia, then coma, leading to paralysis of the respiratory center.
The clinical picture consists primarily of respiratory depression and slowdown. The skin is pale, cold, cyanotic. There is a decrease in body temperature and urination, and at the end of poisoning there is a decrease in blood pressure. Bradycardia develops, a sharp constriction of the pupil (spot pupil size), and in the end the pupil dilates due to hypoxia. Death occurs due to respiratory depression or shock, pulmonary edema and secondary infection.
TREATMENT of patients with acute morphine poisoning is based on the same principles as the treatment of acute intoxication with barbiturates. Help measures are divided into specific and non-specific.
SPECIFIC MEASURES OF ASSISTANCE are associated with the administration of specific morphine antagonists. The best antagonist is NALOXONE (Narcan). In our country there is practically no naloxone, and therefore a partial antagonist, NALORPHINE, is used more often.
Naloxone and nalorphine eliminate the effect of morphine and its drugs on opiate receptors and restore normal function CNS.
Nalorphine, a partial antagonist of morphine, in its pure form (monomedicine) acts like morphine (causes an analgesic effect, but weaker, depresses breathing, causes bradycardia, constricts the pupils). But against the background of administered morphine, nalorphine manifests itself as its antagonist. Nalorphine is usually used intravenously in a dose of 3 to 5 mg, repeating the injection after 30 minutes if necessary. Its effect literally appears at the “tip of the needle” - within the first minute of administration. With an overdose of these drugs, a person poisoned with morphine can quickly develop withdrawal syndrome.
NON-SPECIFIC HELP MEASURES are associated with the removal of unabsorbed poison. Moreover, gastric lavage must be done even with parenteral administration morphine, since it is partially released from the gastrointestinal mucosa into the intestinal lumen. It is necessary to warm the patient; if convulsions occur, anticonvulsants are used.
In case of deep respiratory depression, artificial ventilation of the lungs is performed.
CHRONIC MORPHINE POISONING is usually associated with the development of dependence on it. The development of addiction and drug addiction is naturally accompanied by repeated administration of narcotic analgesics. There are physical and mental dependence.
A manifestation of established PHYSICAL DEPENDENCE on narcotic analgesics is the occurrence of withdrawal or abstinence syndrome when repeated administration of morphine is stopped. Withdrawal syndrome consists of a number of characteristic features: 6-10-12 hours after the last morphine injection, the morphine user experiences rhinorrhea, lacrimation, terrible yawning, chills, goose bumps, hyperventilation, hyperthermia, mydriasis, muscle pain, vomiting, diarrhea, tachycardia, weakness, sweating, disorders sleep, hallucinations, anxiety, restlessness, aggressiveness. These symptoms continue for 2-3 days. To prevent or eliminate these phenomena, the addict is ready to do anything, even commit a crime. Constant use of the drug leads a person to physical and mental degradation.
The mechanism of development of withdrawal is associated with the fact that narcotic analgesics, activating opiate receptors according to the principle feedback(as in endocrinology), inhibit the release, and perhaps the synthesis, of endogenous opiate peptides, gradually replacing their activity. As a result of the withdrawal of analgesics, a deficiency of both the previously administered analgesic and the endogenous peptide occurs. Withdrawal syndrome develops.
Mental dependence develops before physical dependence. The basis for the emergence of mental dependence is euphoria, sedation and an indifferent attitude towards disturbing influences. external environment. In addition, repeated administration of morphine causes very pleasant sensations for the morphine user. abdominal cavity, sensations of unusual warmth in the epigastric region and lower abdomen, reminiscent of those during an intense orgasm.
In addition to mental and physical dependence, there is a third sign of drug addiction - the development of tolerance, stability, addiction. In this regard, the drug addict is constantly forced to increase the dose of the analgesic.
Treatment of addiction to morphine is not fundamentally different from treatment of addiction to alcohol or barbiturates. Treatment of drug addicts is carried out in special institutions, but the results are not yet encouraging (a few percent). The development of deprivation syndrome (abstinence) and relapses of addiction are common.
There is none special means. They use general strengthening vitamins. It is easier to prevent drug addiction than to treat it. The danger of developing drug addiction is the main reason for limiting the use of these drugs in medicine. They are released from pharmacies only with special prescriptions; the drugs are stored according to list “A”.
NON-NARCOTIC ANALGESICS are painkillers and analgesics that do not have a significant effect on the central nervous system and do not cause drug addiction or anesthesia. In other words, unlike narcotic analgesics, they do not have a sedative and hypnotic effect; euphoria, addiction and drug dependence do not occur with their use.
Currently, a large group of drugs has been synthesized, among which are the so-called:
1) old or classic non-narcotic analgesics
2) new, more modern and more anti-inflammatory drugs - the so-called non-steroidal anti-inflammatory drugs - NSAIDs.
According to their chemical structure, old or classic non-narcotic analgesics are divided into 3 main groups:
1) derivatives of salicylic acid (ortho-hydroxybenzoic acid) - salicylates:
a) Acetylsalicylic acid - (aspirin, Acidum acetylsalicylicum);
b) sodium salicylate (Natrii salicylas).
Other drugs in this group: salicylamide, methyl salicylate, as well as diflunisal, benortan, tosiben.
2) pyrazolone derivatives:
a) amidopyrine (Amidopyrinum, in the table 0.25) - discontinued as a single drug, used in combination products;
b) analgin (Analginum, in the table 0.5; amp. 1; 2 ml - 25% and 50% solution);
c) butadione (Butadionum, in the table 0.15);
3) aniline derivatives:
a) phenacetin (Phenacetinum - in combined tablets);
b) paracetamol (Paracetamolum, in tables 0, 2).
Non-narcotic analgesics have 3 main pharmacological effects.
1) Analgesic or analgesic effect. The analgesic activity of non-narcotic analgesics manifests itself when certain types pain: mainly with neuralgic, muscle, joint pain, as well as with headaches and toothaches.
For severe pain associated with injuries, abdominal surgical interventions, malignant formations they are practically ineffective.
2) Antipyretic or antipyretic effect, manifested in febrile conditions.
3) Anti-inflammatory, action expressed in varying degrees for various compounds of this group.
Let's start with salicylates. The main drug of this group is acetylsalicylic acid or ASPIRIN (Acidum acetylsalicylicum in tables 0, 1 - children's; 0, 25; 0, 5) (AA).
Salicylates have been known for a long time, they are more than 130 years old, they were the first drugs that have a specific anti-inflammatory effect, which is considered to have an analgesic and antipyretic effect. The complete synthesis of acetylsalicylic acid was carried out in 1869. Salicylates have since become widespread in medical practice.
Salicylates, including AA (aspirin), have 3 main pharmaceutical effects.
1) Analgesic or analgesic effect. This effect is somewhat less pronounced, especially with visceral pain, than with morphine. AA acid turns out to be an effective drug for the following types of pain: headaches; toothache; pain emanating from muscle and nervous tissue (myalgia, neuralgia), with joint pain (arthralgia), as well as with pain emanating from the pelvis.
The analgesic effect of non-narcotic analgesics, in particular salicylates, is especially pronounced during inflammation.
2) The second effect of AA is antipyretic (antipyretic). This effect is to reduce febrile, but not normal, body temperature. Typically, salicylates are indicated as antipyretic drugs starting at a temperature of 38.5-39 degrees, that is, at a temperature that violates general state sick. This provision especially applies to children.
At lower body temperatures, salicylates are not recommended as antipyretics, since fever is one of the manifestations of the body's protective reaction to infection.
3) The third effect of salicylates, and therefore AA, is anti-inflammatory. The anti-inflammatory effect manifests itself in the presence of inflammation in the connective tissue, that is, with various disseminated systemic diseases tissue or collagen diseases (rheumatism, rheumatoid arthritis, ankylosing spondylitis, arthralgia, systemic lupus erythematosus).
The anti-inflammatory effect of AA begins after a constant level of salicylates is reached in the tissues, and this occurs after 1-2 days. The patient's intensity decreases pain reaction, exudative phenomena are reduced, which is clinically manifested by a decrease in swelling and puffiness. Usually the effect persists during the period of use of the drug. The reduction of inflammatory phenomena associated with the limitation (inhibition) of the exudative and proliferative phases of inflammation by salicylates is the causative element of the analgesic effect, that is, the anti-inflammatory effect of salicylates also enhances their analgesic effect.
It should be said that for salicylates, all 3 listed pharmacological effects are approximately equal in severity.
In addition to the listed effects, salicylates are also characterized by an antiaggregation effect on blood platelets, and when long-term use Salicylates also have a desensitizing effect.
MECHANISM OF ACTION OF SALICYLATES
The action of salicylates is associated with inhibition (inhibition) of the synthesis of prostaglandins of various classes. These highly active compounds were discovered in 1930 by Swedish scientists. Prostaglandins are normally present in trace amounts in tissues, but even with minor exposures (toxic substances, some hormones), their concentration in tissues increases sharply. Prostaglandins are basically cyclic fatty acids with 20 carbon atoms in the chain. They arise from free fatty acids, primarily from arachidonic acid, that enter the body with food. They are also formed from linoleic and linolenic acids after their conversion to arachidonic acid. These unsaturated acids are part of phospholipids. They are released from phospholipids under the action of phospholipase 2 or phospholipase A, after which they become a substrate for the biosynthesis of prostaglandins. Calcium ions take part in the activation of prostaglandin synthesis.
Prostaglandins are cellular, local hormones.
The first step in prostaglandin (PG) biosynthesis is the oxidation of arachidonic acid, carried out by the PG-cyclogenase-peroxidase complex associated with microsomal membranes. A circular structure of PGG-2 appears, which, under the action of peroxidase, transforms into PGH-2. From the resulting products - cyclic endoperoxides - under the influence of PG isomerase, "classical" prostaglandins are formed - PGD-2 and PGE-2 (the two in the index means the presence of two double bonds in the chain; the letters indicate the type and position of the side radicals of the cyclopentane ring).
Under the influence of PG reductase, PGF-2 is formed.
Enzymes have been discovered that catalyze the synthesis of other PGs; having special biological properties: PG-I-isomerase, -oxocyclase, which catalyzes the formation of prostacyclin (PG I-2) and PG-thromboxane-A-isomerase, which catalyzes the synthesis of thromboxane A-2 (TxA-2).
The reduction and suppression of prostaglandin synthesis under the influence of salicylates is associated primarily with inhibition of PG synthesis enzymes, namely inhibition of cyclooxygenases (COX). The latter leads to a decrease in the synthesis of pro-inflammatory prostaglandins (especially PGE-2) from arachidonic acid, which potentiate the activity of inflammatory mediators - histamine, serotonin, bradykinin. Prostaglandins are known to cause hyperalgesia, that is, they increase the sensitivity of pain receptors to chemical and mechanical stimuli.
Thus, salicylates, by inhibiting the synthesis of prostaglandins (PGE-2, PGF-2, PGI-2), prevent the development of hyperalgesia. The threshold of sensitivity to painful stimuli increases. The analgesic effect is most pronounced during inflammation. Under these conditions, prostaglandins and other “inflammatory mediators” are released and interact at the site of inflammation. Prostaglandins cause dilation of arterioles at the site of inflammation and hyperemia, PGF-2 and TxA-2 - narrowing of venules - stasis, both prostaglandins increase the permeability of the vascular wall, promoting the exudation of fluid and white blood elements, and enhance the effect of other inflammatory mediators on the vascular wall. TxA-2 promotes the formation of platelet blood clots, endoperoxides initiate free radical reactions that damage tissue. Thus, Pg contribute to the implementation of all phases of inflammation: alteration, exudation, proliferation.
Suppression of the participation of inflammatory mediators in the development of the pathological process by non-narcotic analgesics, in particular salicylates, leads to the utilization of arachidonic acid through the lipoxygenase pathway and to increased formation of leukotrienes (LTD-4, LTS-4), including the slow-reacting substance of anaphylaxis, causing vasoconstriction and limiting exudation. The inhibition of prostaglandin synthesis by salicylates explains their ability to suppress pain and reduce inflammatory reaction, as well as feverish body temperature. The antipyretic effect of salicylates is to reduce febrile, but not normal body temperature. Fever is one of the manifestations of the body's protective reaction to infection. Fever is a consequence of an increase in the concentration of PgE-2 in the cerebral fluid, which is manifested by an increase in heat production and a decrease in heat transfer. Salicylates, by inhibiting the formation of PGE-2, restore the normal activity of neurons in the thermoregulation center. As a result, heat transfer increases by radiating heat from the surface of the skin and evaporation copious amounts sweat. The heat generation remains practically unchanged. The hypothermic effect of salicylates is quite distinct only if they are used against the background of fever. With normothermia, they practically do not change body temperature.
INDICATIONS FOR USE of salicylates and acetylsalicylic acid (Aspirin)
1) AA is used as an analgesic for neuralgia, myalgia, arthralgia (joint pain). Typically, acetylsalicylic acid is used for the symptomatic treatment of aching and chronic pain. The drug is effective for many types of pain (for shallow, moderate intensity postoperative and postpartum pain, as well as for pain caused by soft tissue injuries, for thrombophlebitis of the superficial veins, for headaches, for dysmenorrhea, algomenorrhea).
2) As an antipyretic for fever, for example, of rheumatic etiology, for fever of infectious-inflammatory origin. Prescribing salicylates to reduce body temperature is advisable only at very high temperatures, which adversely affect the patient’s condition (39 degrees or more); i.e. during febrile fever.
3) As an anti-inflammatory agent for the treatment of patients with inflammatory processes, in particular with arthritis and myositis, acetylsalicylic acid is mainly used. It reduces the inflammatory response, but does not interrupt it.
4) As an antirheumatic agent for collagenosis (rheumatism, rheumatoid arthritis, SLE, etc.), i.e., for systemic diffuse connective tissue diseases. In this case, all effects are used, including the desensitizing effect.
When used in high doses, salicylates over a period of 24-48 hours dramatically reduce signs of inflammation. Pain, swelling, immobility, increased local temperature, and redness of the joint are reduced.
5) As an antiaggregating agent to prevent the formation of lamellar fibrin thrombi. For this purpose, aspirin is used in small doses, approximately 150-300 mg/day. Daily intake of such doses of the drug has proven itself to be effective for the prevention and treatment of intravascular coagulation and for the prevention of myocardial infarction.
6) Small doses of ASA (600-900 mg) - when used prophylactically, they prevent symptoms of food intolerance. In addition, AA is effective for diarrhea, as well as for radiation sickness.
SIDE EFFECTS
1) The most common complication when using ASA is irritation of the gastric mucosa (a consequence of suppression of the synthesis of cytoprotective prostaglandins, in particular PGI-2 prostacyclin), the development of erosions, sometimes with bleeding. Dual nature this complication: AA is an acid, which means it irritates the mucous membrane; inhibition of the synthesis of prostaglandins in the mucosa, prostacyclin, is the second contributing factor.
In patients, salicylates cause dyspepsia, nausea, vomiting, and with prolonged use they can have an ulcerogenic effect.
2) A common complication when taking salicylates, hemorrhages (hemorrhages and bleeding) are caused by salicylates inhibiting platelet aggregation and antagonism of vitamin K, which is necessary for the activation of prothrombin, proconvertin, coagulation factors IX and X, as well as for maintaining the normal structure of the vascular wall. Therefore, when using salicylates, not only blood clotting is disrupted, but the fragility of blood vessels also increases. To prevent or eliminate this complication, vitamin K preparations are used. Most often, vikasol, but it is better to prescribe phytomenadione, an analogue of vitamin K, which is absorbed faster, more effective and less toxic.
3) In large doses, AA causes cerebral symptoms, manifested by tinnitus, ringing in the ears, decreased hearing, anxiety, and in more severe cases, hallucinations, loss of consciousness, convulsions, and respiratory failure.
4) In persons suffering bronchial asthma or obstructive bronchitis, salicylates can cause an increase in bronchospasm attacks (which is a consequence of suppression of the synthesis of antispasmodic prostaglandins and the predominant formation of leukotrienes, including the slow-reacting substance of anaphylaxis from their common precursor - arachidonic acid).
5) Some patients may have hypoglycemic conditions - a consequence of suppressing the synthesis of PGE-2 and thereby eliminating its inhibitory effect on the release of insulin from the beta cells of the islet tissue of the pancreas.
6) When using AA at the end of pregnancy, labor may be delayed by 3-10 days. Newborns whose mothers took salicylates (SA) at the end of pregnancy according to indications may develop severe vascular pulmonary diseases. In addition, salicylates (AA) taken during pregnancy can disrupt the course of normal organogenesis, in particular lead to patent ductus botalus (due to inhibition of the synthesis of prostaglandins necessary for normal organogenesis).
7) Rarely (1: 500), but allergic reactions to salicylates occur. Intolerance may manifest as skin rashes, urticaria, itching, angioedema, thrombocytopenic purpura.
Salicylic acid is an ingredient in many substances, including fruits (apples, grapes, oranges, peaches, plums), and is found in some soaps, fragrances and drinks (especially birch sap).
Of the salicylates, in addition to AA, SODIUM SALICYLATE is used - this drug gives an analgesic effect that is only 60% of that of Aspirin; Its analgesic and anti-inflammatory effects are even weaker, so it is used relatively rarely. They are used mainly for systemic diffuse tissue diseases, collagenosis (RA, rheumatism). Similar drug- methyl salicylate.
The second group of non-narcotic analgesics are pyrazolone derivatives. This group of drugs includes AMIDOPYRINE, BUTADIONE, and ANALGIN.
AMIDOPYRINE (PYRAMIDON) (Amidopyrinum powder; table 0, 25). Pyros - fire. It is a powerful analgesic and antipyretic.
The drug is completely and quickly absorbed from the intestines and is almost completely metabolized in the body. However, due to its high toxicity, in particular its pronounced inhibitory effect on hematopoiesis, amidopyrine is practically not used in the clinic; excluded from use as an independent remedy and is included only in some combination drugs.
ANALGIN (Analginum; powder; in tables of 0.5; in amps of 1 and 2 ml - 25% and 50% solution). Analgin is chemically and pharmacologically similar to amidopyrine. Analgin is highly soluble in water, so it can also be administered parenterally. Just like amidopyrine, this drug has an analgesic effect that is more pronounced than its antipyretic, and especially anti-inflammatory effects.
Analgin is used to obtain short-term analgesic and antipyretic effects for neuralgia, myositis, headache, and toothache. In this case, as a rule, tablet form is used. In more pronounced cases, when it is necessary to quickly produce an effect, injections of analgin are used. In this case, analgin quickly reduces elevated body temperature. Analgin is prescribed as an antipyretic only in the case of febrile fever, when the drug is the first aid remedy. Administered intramuscularly. A child should It is good to remember that you cannot administer 1 ml or more, as there may be a lytic drop in temperature, which will lead to temperature collapse. The child is administered 0.3-0.4 ml. As a rule, in this case, dimed is added to the analgin solution
roll Treatment with analgin is associated with the risk of complications (primarily from the blood) and therefore its use as an analgesic and antipyretic is not justified, when salicylates or other agents are equally effective.
BARALGIN (Baralginum) - developed in Germany. A drug very close to analgin. In tablet form it comes from Bulgaria as SPAZMOLGON. Baralgin consists of analgin, to which 2 more synthetic substances have been added (one of which has a papaverine-like effect, the second a weak ganglion-blocking effect). From this it is clear that baralgin is indicated primarily for renal, hepatic, and intestinal colic. It is also used for cerebral vascular spasms, headaches, and migraines. They are produced both in tablets and in injection form.
Currently, a whole series of combination drugs containing analgin (Maxigan, Spazmalgin, Spazgan, Veralgan, etc.) is entering the Russian drug market.
BUTADIONE (Butadionum; in the table 0, 15). It is believed that butadione is approximately equal in analgesic activity to analgin, and in anti-inflammatory activity is significantly higher than it. It is therefore used as an anti-inflammatory drug. According to this indication, butadione is prescribed for lesions of extra-articular tissues (bursitis, tendinitis, synovitis) of rheumatic and non-rheumatic origin. Indicated for ankylosing spondylitis, rheumatoid arthritis, osteoarthritis.
The maximum concentration of butadione in the blood, as well as other pyrazolone derivatives, is achieved after approximately 2 hours. The drug actively binds to plasma proteins (98%). Long-term treatment butadione leads to stimulation of liver microsomal enzymes. Due to this, butadione is sometimes used in small doses (0.005 g/kg per day) in children with hyperbilirubinemia. Butadione reduces the reabsorption of urate in the terminal tubules, which promotes the excretion of these salts from the body. In this regard, it is used for gout.
The drug is toxic, hence the side effects:
1) like all pyrazolone derivatives, long-term use can cause anorexia, heaviness in the epigastrium, heartburn, nausea, vomiting, diarrhea, and the formation of peptic ulcers. Can cause hepatitis, so it is prescribed only for 5-7 days;
2) like all pyrazolone drugs, butadione inhibits hematopoiesis (leukopenia, anemia, thrombocytopenia) to the point of agranuloditis;
3) when treated with butadione, swelling may develop, since it retains sodium ions in the body, and therefore water (reduces natriuresis); this may lead to congestive failure heart disease or even pulmonary edema.
REOPYRIN (Rheopyrinum) is a drug that is a combination of amidopyrine and butadione, has pronounced anti-inflammatory and analgesic activity. It is used only as an anti-inflammatory agent for arthritis, rheumatic lesions, lumbago, adnexitis, parametritis, neuralgia. In addition, it is prescribed for gout by promoting the removal of urate salts from the body. Available in both tablet and injection forms dosage forms(Gedeon Rihter).
IN Lately a group of new analgesics was synthesized, which were called non-steroidal anti-inflammatory drugs - NSAIDs.
ANILINE DERIVATIVES (or more precisely, para-aminophenol).
Two drugs should be mentioned here: phenacetin and paracetamol.
Paracetamol as an active analgesic and antipyretic substance was discovered in 1893 by von Mehring. In 1995, it was suggested that paracetamol is a metabolite of phenacetin, and in 1948, Brody and Axelrod demonstrated the role of paracetamol as the main metabolite of phenacetin. Nowadays, paracetamol is widely used as an antipyretic and analgesic at the stage of pre-medical pharmacological care for the patient. In this regard, paracetamol is one of the characteristic drugs OTC market (OTC - jver the counter), i.e. drugs sold without a doctor's prescription. One of the first pharmaceutical companies to officially present OTC drugs, and in particular paracetamol (Panadol in various dosage forms), is the Sterling Health company. Despite the fact that the drug paracetamol is currently produced by many pharmaceutical companies under various names (Acetaminophen, Watsou, USA; Dolipran, USA-France; Miralgan, Yugoslavia; Calpol, Wellcome England; Dofalgan, France, etc.), certain conditions are required to obtain a pure product. Otherwise, the medicine will contain phenacetin and 4-p-aminophenol. It was these toxic components that prevented paracetamol long time take its rightful place in the medicinal arsenal of doctors. Western companies, in particular the Sterling Health company, produce paracetamol (Panadol) under GMP conditions and contain a highly purified active ingredient.
MECHANISM OF ACTION OF PARACETAMOL.
It has been established that paracetamol is a weak inhibitor of prostaglandin biosynthesis, and its blocking effect on the synthesis of prostaglandins - mediators of pain and temperature reaction - occurs to a greater extent in the central nervous system than in the periphery. This explains the presence of a pronounced analgesic and antipyretic effect of paracetamol and a very weak anti-inflammatory effect. Paracetamol practically does not bind to plasma proteins, easily penetrates the blood-brain barrier, and is almost evenly distributed in the brain. The drug begins to have a rapid antipyretic and analgesic effect after about 20-30 minutes and continues to act for 4 hours. The period of complete elimination of the drug averages 4.5 hours.
The drug is primarily excreted by the kidneys (98%), the main part of the administered dose is biotransformed in the liver. Due to the fact that paracetamol has virtually no effect on the gastric mucosa, i.e. it does not cause an ulcerogenic effect. This also explains the absence of bronchospasm when using paracetamol, even in people suffering from bronchial asthma. The drug does not affect, unlike aspirin, the hematopoietic system and the blood coagulation system.
These advantages, as well as the wide range of therapeutic effects of paracetamol, have now allowed it to take its rightful place among other non-narcotic analgesics. Preparations containing paracetamol are used for the following indications:
1) Pain syndrome of minor and medium intensity of various origins (headache, toothache, neuralgia, myalgia, pain from injuries, burns).
2) Febrile fever in infectious and inflammatory diseases. It is best used as an antipyretic in pediatric practice.
Sometimes aniline derivatives (phenacetin, for example) are combined in one tablet with other non-narcotic analgesics, thus obtaining combined agents. Most often, phenacetin is combined with AA and codeine. The following are known combination drugs: asphen, sedalgin, citramon, pirkofen, panadeine, solpadeine.
Side effects are few and are more due to the administration of phenacetin than paracetamol. Reports of serious adverse reactions to paracetamol are rare and are usually associated with either an overdose of the drug (more than 4.0 per day) or with prolonged use (more than 4 days). Only a few cases of thrombocytopenia and hemolytic anemia associated with taking the drug have been described. The most frequently reported development of methemoglobinemia with the use of phenacetin, as well as the hepatotoxic effect.
As a rule, modern non-narcotic analgesics primarily have a pronounced anti-inflammatory effect, which is why they are most often called NSAIDs.
These are chemical compounds of various groups, mainly salts of various acids:
a) derivatives of acetic acid: indomethacin, sulindac, ibufenac, sofenac, pranoprofen;
b) derivatives of propionic acid: ibuprofen, naproxen, ketoprofen, surgam, etc.;
c) anthranilic acid derivatives: flufenamic acid, mephenanoic acid, voltaren;
d) derivatives nicotinic acid: niflumic acid, clonixin;
e) oxicams (enolic acids): piroxicam, isoxicam, sudoxicam.
Indomethacin (Indometacinum; capsules and dragees 0.025; suppositories - 0.05) is a non-steroidal anti-inflammatory drug (NSAID), which is a derivative of indoleacetic acid (indole). It has anti-inflammatory, analgesic and antipyretic activity. This is one of the most powerful NSAIDs and is the standard NSAID. NSAIDs, unlike salicylates, cause reversible inhibition of prostaglandin synthetase (COX).
Its anti-inflammatory effect is used for exudative forms of inflammation, rheumatism, disseminated (systemic) connective tissue diseases (SLE, scleroderma, periarthritis nodosa, dermatomyositis). The drug is most effective for inflammatory processes accompanied by degenerative changes in the joints of the spine, with deforming osteoarthritis, with psoriatic arthropathy. Used for chronic glomerulonephritis. Very effective in acute attacks of gout, the analgesic effect lasts for 2 hours.
In premature babies, it is used (1-2 times) to close the functioning ductus arteriosus.
It is toxic, therefore, in 25-50% of cases, pronounced side effects occur (cerebral: headache, dizziness, ringing in the ears, confusion, blurred visual perceptions, depression; from the gastrointestinal tract: ulcers, nausea, vomiting, dyspepsia; skin: rashes; blood: dyscrasia; sodium ion retention; hepatotoxic). Children under 14 years old are not recommended.
The next NSAID - IBUPROFEN (Ibuprofenum; in tables 0, 2) - was synthesized in 1976 in England. Ibuprofen is a derivative of phenylpropionic acid. In terms of anti-inflammatory activity, analgesic and antipyretic effect, it is close to salicylates and even more active. Well absorbed from the gastrointestinal tract. Better tolerated by patients than AA. When taken orally, the frequency of adverse reactions is lower. However, it also irritates the gastrointestinal tract (to the point of ulceration). In addition, if you are allergic to penicillin, patients will also be sensitive to brufen (ibuprofen), especially patients with SLE.
92-99% bound to plasma proteins. It slowly penetrates into the joint cavity, but lingers in the synovial tissue, creating higher concentrations in it than in the blood plasma and slowly disappearing from it after withdrawal. It is quickly eliminated from the body (T 1/2 = 2-2.5 hours), and therefore frequent administration of the drug is necessary (3-4 times a day - the first dose before meals, and the rest after meals to prolong the effect).
Indicated for: treatment of patients with RA, deforming osteoarthritis, ankylosing spondylitis, and rheumatism. It has the greatest effect in the initial stage of the disease. In addition, ibuprofen is used as a strong antipyretic.
A drug close to brufen is NAPROXEN (naprosyn; table 0.25) - a derivative of naphthylpropionic acid. Rapidly absorbed from the gastrointestinal tract, maximum concentration in the blood is after 2 hours. 97-98% bound to plasma proteins. Penetrates well into tissues and synovial fluid. Has a good analgesic effect. The anti-inflammatory effect is approximately the same as butadione (even higher). The antipyretic effect is higher than that of aspirin and butadione. It has a long-lasting effect, so it is prescribed only 2 times a day. Well tolerated by patients.
Apply it:
1) as an antipyretic; in this regard, it is more effective than aspirin;
2) as an anti-inflammatory and analgesic agent for RA, chronic rheumatic diseases, and myositis.
Adverse reactions are rare and occur in the form of dyspeptic symptoms (heartburn, abdominal pain), headache, sweating, and allergic reactions.
The next modern NSAID is SURGAM or thioprofenic acid (tables 0, 1 and 0, 3) - a derivative of propionic acid. Has analgesic and anti-inflammatory effects. The antipyretic effect of the drug was also noted. The indications and side effects are the same.
DICLOFENAC-SODIUM (voltaren, ortofen) is a derivative of phenylacetic acid. This is one of the most active anti-inflammatory drugs today; its potency is approximately equal to indomethacin. In addition, it has a pronounced analgesic and antipyretic effect. In terms of anti-inflammatory and analgesic effect, it is more active than aspirin, butadione, and ibuprofen.
It is well absorbed from the gastrointestinal tract; when taken orally, the maximum concentration in the blood occurs after 2-4 hours. It is intensively subjected to presystemic elimination, and only 60% of the dose taken enters the circulatory system. 99% bound to plasma proteins. Quickly penetrates into the synovial fluid.
It has low toxicity, but a significant breadth of therapeutic action. It is well tolerated, sometimes only causing dyspeptic and allergic reactions.
Indicated for inflammation of any location and etiology, but it is mainly used for rheumatism, RA and other connective tissue diseases (ankylosing spondylitis).
PIROXICAM (isoxicam, sudoxicam) is a new non-steroidal anti-inflammatory drug, different from other NSAIDs, a derivative of oxicam.
Satisfactorily absorbed from the gastrointestinal tract. The maximum concentration in the blood occurs after 2-3 hours. When taken orally, it is well absorbed, its half-life is about 38-45 hours (this is for short-term use, and for long-term use - up to 70 hours), so it can be used once a day.
SIDE EFFECTS: dyspepsia, occasionally hemorrhages.
Piroxicam inhibits the formation of interleukin-1, which stimulates the proliferation of synovial cells and their production of neutral proteolytic enzymes (collagenase, elastase) and prostaglandin E. IL-1 activates the proliferation of T-lymphocytes, fibroblasts and synovial cells.
In blood plasma it is 99% bound to proteins. In patients with rheumatoid arthritis, it penetrates well into the synovial fluid. Doses of 10 to 20 mg (1 or 2 tablets) cause analgesic (30 minutes after administration) and antipyretic effects, and higher doses (20-40 mg) cause anti-inflammatory effects (by the end of 1 week of continuous use). Unlike aspirin, it is less irritating to the gastrointestinal tract.
The drug is used for RA, ankylosing spondylitis, osteoarthritis and exacerbation of gout.
All of the above agents, with the exception of salicylates, have a more pronounced anti-inflammatory effect than other agents.
They suppress well exudative inflammation and the accompanying pain syndrome and have a significantly less active effect on the alterative and proliferative phases.
These drugs are better tolerated by patients than aspirin and salicylates, indomethacin, butadione. This is why these drugs began to be mainly used as anti-inflammatory drugs. Hence they received the name - NSAIDs (non-steroidal anti-inflammatory drugs). However, in addition to these new NSAIDs, non-steroidal PVS also largely include old drugs - non-narcotic analgesics.
All new NSAIDs less toxic than salicylates and indomethacin.
On destructive processes in cartilage and bone tissue NSAIDs not only do not have an inhibitory effect, but in some cases they can even provoke them. They disrupt the ability of chondrocytes to synthesize protease inhibitors (collagenase, elastase) and thereby increase damage to cartilage and bones. By inhibiting the synthesis of prostaglandins, NSAIDs inhibit the synthesis of glycoproteins, glycosaminoglycans, collagen and other proteins necessary for cartilage regeneration. Fortunately, deterioration is observed only in some patients; in the majority, limiting inflammation can prevent further development of the pathological process.
ANALGESICS(analgesics), medications that reduce or eliminate the feeling of pain. Analgesic (pain-relieving) effects are exerted by drugs of various pharmacological groups. It is most pronounced in narcotic, opioid A.s., which interact with opioid receptors. They are used in anesthesiology. arr. For general anesthesia and postoperative pain relief; for injuries and diseases with severe pain (malignant neoplasms, myocardial infarction, etc.). The main representatives of this group are A. s. – morphine, fentanyl (remifentanil), omnopon, promedol, trimeperidine, prosidol, butorphanol, moradol, stadol, nalbuphine, tramadol. Narcotic A. s. have strong analgesic activity, can cause drug dependence, withdrawal syndrome, in case of an overdose, deep sleep develops, turning into the stage of anesthesia, then coma, leading to paralysis of the respiratory center.
Buprenorphine (a semi-synthetic derivative of the alkaloid thebaine) is 20–50 times more analgesic than morphine; prescribed for the relief of intense pain after minor abdominal operations; Thanks to its tablet form, it is indispensable for emergency medicine in case of mass traumatic injuries.
A universal antagonist of opioid A. s. is naxolone, which blocks their binding or displaces them from all types of opioid receptors. It is used to quickly stop the effects of opioids, including in case of overdose (post-anesthesia respiratory depression, acute poisoning opioids, etc.).
To non-narcotic A. s. include derivatives of pyrazolone (amidopyrine, analgin, antipyrine, baralgin, butadione, reopirine), aniline (antifebrine, paracetamol, phenacetin), salicylic acid (acetylsalicylic acid, sodium salicylate, salicylamide, diflunisal, tosiben). In terms of analgesic activity, they are significantly inferior to narcotic drugs and have an antipyretic effect in febrile conditions. Compounds of various groups have a pronounced anti-inflammatory effect, Ch. arr. salts of various acids: derivatives of acetic acid (indomethacin, ibufenac, sulindac, sofenac, pranoprofen); propionic acid (ibuprofen, ketoprofen, naproxen, etc.); anthranilic acid (voltaren, etc.); nicotinic acid (clonixin); oxicams (piroxicam). In addition, they are effective only for certain types of pain (neuralgic, headache, dental, muscle, joint). Non-narcotic A. s. do not have a hypnotic effect, do not affect the respiratory and cough centers, conditioned reflex activity, do not cause euphoria and drug dependence.
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