pharmachologic effect
Bronchodilator, phosphodiesterase inhibitor (PDE).
It is the ethylenediamine salt of theophylline (which facilitates solubility and increases absorption). It has a bronchodilator effect, apparently due to a direct relaxing effect on the smooth muscles of the respiratory tract and blood vessels of the lungs. It is believed that this effect is caused by selective inhibition of the activity of specific PDEs, which leads to an increase in the intracellular concentration of cAMP. The results of in vitro experimental studies show that the main role appears to be played by type III and IV isoenzymes. Suppression of the activity of these isoenzymes may also cause some side effects of aminophylline (theophylline), including. vomiting, arterial hypotension and tachycardia. Blocks adenosine (purine) receptors, which may be one of the factors affecting the bronchi. Reduces airway hyperresponsiveness associated with the late phase response caused by inhaled allergens through an unknown mechanism that is not due to PDE inhibition or blockade of adenosine. There are reports that aminophylline increases the number and activity of T-suppressor cells in peripheral blood.
Increases mucociliary clearance, stimulates contraction of the diaphragm, improves the function of the respiratory and intercostal muscles, stimulates the respiratory center, increases its sensitivity to carbon dioxide and improves alveolar ventilation, which ultimately leads to a decrease in the severity and frequency of apnea episodes. By normalizing respiratory function, it helps saturate the blood with oxygen and reduce the concentration of carbon dioxide. Strengthens ventilation of the lungs in conditions of hypokalemia.
It has a stimulating effect on the activity of the heart, increases strength and heart rate, increases coronary blood flow and increases the myocardial oxygen demand. Reduces the tone of blood vessels (mainly those of the brain, skin and kidneys). It has a peripheral venodilating effect, reduces pulmonary vascular resistance, and lowers pressure in the pulmonary circulation. Increases renal blood flow and has a moderate diuretic effect. Expands extrahepatic bile ducts. Stabilizes mast cell membranes, inhibits the release of mediators of allergic reactions. Inhibits platelet aggregation (suppresses platelet activating factor and PgE2α), increases the resistance of red blood cells to deformation (improves the rheological properties of blood), reduces thrombus formation and normalizes microcirculation. It has a tocolytic effect, increases the acidity of gastric juice. In high doses it has an epileptogenic effect.
Eufillin, 10 pcs., 5 ml, 24 mg/ml, solution for intravenous administration
Ephedrine, beta-agonists, caffeine and furosemide enhance the effect of the drug. Increases the likelihood of developing side effects of glucocorticosteroids, mineralocorticosteroids (hypernatremia), and general anesthesia agents (the risk of ventricular arrhythmias increases). In combination with phenobarbital, phenytoin, rifampicin, isoniazid, carbamazepine or sulfinpyrazone, a decrease in the effectiveness of aminophylline is observed, which may require an increase in the doses of the drug. Aminoglutethimide and moracizine, being inducers of microsomal oxidation, increase the clearance of aminophylline, which may require an increase in its dose.
The clearance of the drug is reduced when prescribed in combination with macrolide antibiotics, lincomycin, allopurinol, cimetidine, isoprenaline, beta-blockers, which may require a dose reduction.
Oral estrogen-containing contraceptives, antidiarrheal drugs, intestinal sorbents weaken, and H2-histamine blockers, slow calcium channel blockers, mexiletine enhance the effect (they bind to the cytochrome P450 enzymatic system and change the metabolism of aminophylline). When used in combination with enoxacin and other fluoroquinolones, small doses of ethanol, disulfiram, recombinant interferon alpha, methotrexate, propafenone, thiabendazole, ticlopidine, verapamil, and when vaccinated against influenza, the intensity of action of aminophylline may increase, which may require a reduction in its dose.
The drug suppresses the therapeutic effects of lithium carbonate and beta-blockers. The administration of beta-blockers interferes with the bronchodilatory effect of aminophylline and can cause bronchospasm. Eufillin potentiates the effect of diuretics by increasing glomerular filtration and reducing tubular reabsorption.
With caution, aminophylline is prescribed simultaneously with anticoagulants, other theophylline or purine derivatives. It is not recommended to use aminophylline with drugs that excite the central nervous system (increases neurotoxicity). The drug cannot be used with dextrose solutions and is incompatible with fructose and levulose solutions. The pH of the solutions to be mixed must be taken into account: pharmaceutically incompatible with acid solutions.
Pharmacokinetics
In the body, aminophylline is metabolized at physiological pH values to release free theophylline. Bronchodilating properties appear at plasma theophylline concentrations of 10-20 mcg/ml. Concentrations above 20 mg/ml are toxic. The stimulating effect on the respiratory center is realized at a lower concentration - 5-10 mcg/ml.
Theophylline binding to plasma proteins is approximately 40%; in newborns, as well as in adults with diseases, binding decreases. Plasma protein binding in adults is about 60%, in newborns - 36%, in patients with liver cirrhosis - 36%. Penetrates the placental barrier (the concentration in the fetal blood serum is slightly higher than in the maternal serum). Excreted in breast milk.
Theophylline is metabolized in the liver with the participation of several cytochrome P450 isoenzymes, the most important of which is CYP1A2. During metabolism, 1,3-dimethyluric acid, 1-methyluric acid and 3-methylxanthine are formed. These metabolites are excreted in the urine. 10% is excreted unchanged in adults. In newborns, a significant part is excreted in the form of caffeine (due to the immaturity of the pathways for its further metabolism), unchanged - 50%.
Significant individual differences in the rate of hepatic metabolism of theophylline are the cause of pronounced variability in clearance values, plasma concentrations, and half-life. Hepatic metabolism is influenced by factors such as age, addiction to tobacco smoking, diet, diseases, and concurrent drug therapy.
T1/2 of theophylline in non-smoking patients with bronchial asthma practically without pathological changes in other organs and systems is 6-12 hours, in smokers - 4-5 hours, in children - 1-5 hours, in newborns and premature babies - 10- 45 hours
T1/2 of theophylline increases in the elderly and in patients with heart failure or liver disease.
Clearance decreases with heart failure, liver dysfunction, chronic alcoholism, pulmonary edema, chronic obstructive pulmonary disease.
Ethylenediamine does not affect the pharmacokinetics of theophylline.
Instructions for use EUPHYLLINE solution
Aminophylline has a narrow therapeutic index. Theophylline toxicity is most likely to occur at serum concentrations greater than 20 mcg/mL and becomes increasingly severe at higher serum concentrations.
Doses greater than 3 g may be serious in adults (40 mg/kg in a child). The lethal dose may be as low as 4.5 g in adults (60 mg/kg in children), but is usually higher.
Death in adults may occur when aminophylline is administered IV in large doses in patients with renal, hepatic or cardiovascular impairment, or if the injection is given quickly.
Symptoms:
tachycardia, in the absence of hypoxia, fever, or during coadministration of sympathomimetic drugs, may be a sign of theophylline toxicity.
Gastrointestinal symptoms:
anorexia, nausea, vomiting, diarrhea, vomiting blood.
Neurological symptoms:
restlessness, insomnia, irritability, headache, agitation, hallucinations, extreme thirst, slight fever, dilated pupils and tinnitus. Seizures can occur even without previous symptoms of toxicity and often lead to death. Coma can develop in very severe cases.
Cardiovascular symptoms:
palpitations, arrhythmias, arterial hypotension, supraventricular and ventricular arrhythmias.
Metabolic symptoms:
hypokalemia can develop quickly and can be serious. Hyperglycemia, albuminuria, hyperthermia, hypomagnesemia, hypophosphatemia, hypercalcemia, respiratory alkalosis, metabolic acidosis, and rhabdomyolysis may also occur.
Treatment:
Treatment of overdose is supportive and symptomatic.
Serum theophylline and potassium levels should be checked. Repeated oral administration of activated charcoal helps eliminate theophylline from the body, even after intravenous administration. Aggressive antiemetic therapy may be required to allow oral administration of activated charcoal.
Convulsions can be stopped by intravenous administration of diazepam 0.1-0.3 mg/kg to 10 mg/kg. Restoring fluid and electrolyte balance is essential. Hypokalemia should be corrected by IV infusion of potassium chloride. Sedation with diazepam may be required in agitated patients.
Propranolol can be administered IV to reverse tachycardia, hypokalemia and hyperglycemia, provided the patient does not suffer from asthma.
In general, theophylline is metabolized quickly and hemodialysis is not warranted. In patients with congestive heart failure or liver disease, hemodialysis may increase the clearance of theophylline by 2-fold.
Hemosorption should be considered if:
- intestinal obstruction prevents the administration of several doses of activated carbon:
- plasma theophylline concentrations >80 mg/l (acute) or >60 mg/l (chronic). In the elderly, hemosorption should be considered at theophylline concentrations >40 mg/L. Clinical signs, rather than theophylline concentration, are the best guide for treatment.
Indications
For parenteral use: status asthmaticus (additional therapy), neonatal apnea, ischemic cerebrovascular accident (as part of combination therapy), left ventricular failure with bronchospasm and Cheyne-Stokes type breathing disorder, edematous syndrome of renal origin (as part of complex therapy) ; acute and chronic heart failure (as part of combination therapy).
For oral administration: broncho-obstructive syndrome of various origins (including bronchial asthma, COPD, including emphysema, chronic obstructive bronchitis), hypertension in the pulmonary circulation, cor pulmonale, sleep apnea; acute and chronic heart failure (as part of combination therapy).
Side effect
From the side of the central nervous system:
dizziness, sleep disturbances, anxiety, tremors, convulsions.
From the cardiovascular system:
palpitations, heart rhythm disturbances; with rapid intravenous administration - the appearance of pain in the heart, decreased blood pressure, tachycardia (including in the fetus when taken in the third trimester of pregnancy), arrhythmias, decreased blood pressure, cardialgia, increased frequency of angina attacks.
From the digestive system:
nausea, vomiting, gastroesophageal reflux, heartburn, exacerbation of peptic ulcer, diarrhea; with prolonged ingestion - anorexia.
From the urinary system:
albuminuria, hematuria.
Allergic reactions:
skin rash, itching, fever.
From the side of metabolism:
rarely - hypoglycemia.
Local reactions:
compaction, hyperemia, pain at the injection site; when used rectally, irritation of the rectal mucosa, proctitis.
Other:
chest pain, tachypnea, flushing, albuminuria, hematuria, hypoglycemia, increased diuresis, increased sweating.
Modern approaches to the management of patients with back pain
P.R. Kamchatnov
Russian State Medical University, Moscow
One of the most common clinical syndromes is pain in the lumbosacral region (back pain), caused by vertebrogenic pathology. Back pain occurs in 60–80% of the adult population and is one of the most common causes of temporary disability. Episodes of back pain occur annually in half of the working population, with individuals aged 35–55 years most commonly affected. The number of such patients is extremely high, especially in outpatient neurological settings. It is believed that in the vast majority of cases (about 90%), the duration of the pain syndrome does not exceed 6 weeks, however, in other patients the pain becomes chronic. There is a tendency towards an increase in the incidence of musculoskeletal diseases. Thus, in the Russian Federation, the number of such patients over the past 10 years (1988–1997) has increased from 7.7 to 11.2 million (by more than 40%). It should be taken into account that the actual prevalence of these diseases is probably much higher.
The main causes of back pain are degenerative changes in the spine, in particular osteochondrosis, dysfunction of the facet joints, partial tear of the fibrous ring, prolapsed intervertebral discs, in some cases complicated by the formation of a disc herniation, spondylolisthesis, spinal canal stenosis, osteoporosis. It must be taken into account that in some patients the source of pain may be inflammatory changes in the vertebrae or adjacent tissues (spondylitis, osteomyelitis, epidural abscess), including those caused by the influence of a specific pathogen (for example, Koch's bacillus). The cause of pain may be a primary or metastatic tumor of the vertebrae, meninges or spinal roots. Finally, back pain may not be associated with spinal pathology, but be reflected in a wide range of somatic diseases affecting the pelvic organs, hip joint, descending aorta, etc. The variety of causes of pain requires exceptional care when making a diagnosis and developing treatment tactics. In addition to a detailed analysis of the clinical picture of the disease and radiological examination (including the use of computed tomography - CT and magnetic resonance imaging - MRI), there is often a need for an in-depth somatic examination of the patient.
Significant risk factors for the development of intervertebral disc damage are a sedentary lifestyle with a lack of physical activity or, conversely, increased physical activity with repeated microtrauma to the spine, exposure to vibration, excess body weight, high growth, and repeated pregnancies. Production factors play a major role - long stays in vehicles, frequent hypothermia, a discrepancy between the physical capabilities of the individual and the amount of stress experienced. Congenital structural features of the skeleton (asymmetry of leg length, abnormalities in the structure of the hip joints, lumbarization or sacralization, etc.) can also be considered as factors predisposing to the occurrence of degenerative lesions of the spine. There is information about the genetic determinism of intervertebral disc damage, in particular due to impaired production of type 1X collagen.
The presence of long-term chronic pain in the back or lumbar region is closely associated with the development of depression and anxiety disorders, while the frequency of depressive disorders among patients with spondylogenic dorsopathies is 3–4 times higher than in the general population. There is a relationship between the severity and duration of the pain syndrome and the severity of subsequent violations of the motor stereotype and emotional disorders. The presence of depressive and anxiety disorders, especially in combination with pain, can not only cause a decrease in the quality of life of patients, but also lead to permanent disability. Even when acute pain is relieved, emotional disorders can persist for quite a long time, causing maladaptation of the patient.
Management of the patient in the acute period
The main objectives of managing a patient in the acute period of pain as part of spondylogenic dorsopathy are pain relief, restoration of normal spinal biomechanics, and creation of conditions for a full course of rehabilitation measures. The earliest and complete relief of pain syndrome can prevent the fixation of a pathological motor stereotype and provide the opportunity for early rehabilitation measures. In addition, timely elimination of pain provides, on the one hand, the opportunity for early involvement of movement therapy and its activation, and on the other, prevents the development of emotional disorders. Currently, the advisability of choosing a therapeutic tactic that prevents the chronicization of the pathological process is beyond doubt.
In order to eliminate pathogenic physical factors that can cause increased pain, it is recommended to provide a gentle motor regimen, completely eliminate or limit physical activity (“it’s better to lie down for three days than to be treated for a week”). It is advisable to provide a gentle regimen at home or in a neurological hospital. The patient should avoid flexor or rotational movements of the lumbar spine, especially those performed at a fast pace or with additional physical activity. If hospitalization is impossible, immobilization of the corresponding part of the spine should be ensured using orthoses, fixing belts (corsets) equipped with vertical stiffeners. In the acute stage of the disease, characterized by the presence of severe pain, it is, as a rule, inappropriate to carry out active gymnastic exercises, manual massage, as well as the use of thermal procedures and manual therapy sessions. At the same time, with relatively mild exacerbations, in the case of moderate pain syndrome, with a predominance of muscle-tonic disorders, a positive effect can be achieved by performing post-isometric relaxation.
NSAIDs and analgesics
Today, there is no doubt about the advisability of using non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of patients with spondylogenic dorsopathy. The effectiveness of this approach has been established in a number of clinical studies. A characteristic feature of the pharmacological action of these drugs is the ability to inhibit the activity of cyclooxygenase-2 (COX-2), a key enzyme in the synthesis of prostaglandins, prostacyclins and thromboxanes. The role of COX-2 is known as a major catalyst in the metabolism of arachidonic acid, which is accompanied by the formation of mediators of edema and inflammation. By influencing pain endings at the site of injury, prostaglandins increase their sensitivity to bradykinin, a peptide formed in tissues during inflammation and at the same time being a stimulator of pain endings.
However, inhibition of COX-2 activity during pain syndromes associated with varying degrees of severity of the inflammatory process is not the only analgesic mechanism of NSAIDs. The different severity of the ability to suppress prostaglandin synthesis observed in drugs of this group, the dissociation between the anti-inflammatory and analgesic effects of NSAIDs suggest the existence of other mechanisms for the implementation of analgesic effects in spondylogenic dorsopathies. In addition, no direct relationship was found between the degree of suppression of the synthesis of inflammatory mediators, on the one hand, and the analgesic activity of the drugs, on the other.
The undoubted advantages of the pharmacokinetics of drugs in this group are a short half-life, lack of accumulation and enterohepatic recirculation, and long-term accumulation in the area of inflammation. Thanks to these qualities, drugs have a good benefit/risk ratio. The rapidity of onset of the analgesic effect serves as the basis for prescribing these drugs primarily for the relief of acute pain syndromes of varying intensity. The most common drugs in this group are diclofenac, ketorolac, oxicam derivatives (piroxicam, lornoxicam), propionic acid derivatives (ibuprofen, flurbiprofen, ketoprofen, naproxen).
The widely used diclofenac is characterized by good tolerability, combined with a pronounced analgesic effect. In clinical practice, it is convenient to use a prolonged form of diclofenac retard containing 100 mg of the active substance. Food intake does not have a clinically significant effect on the absorption of the active substance from retard tablets and its systemic bioavailability. The degree of absorption is directly dependent on the dose of the drug. The average maximum concentration of the drug in plasma is achieved on average after 4 hours and persists for 24 hours.
Propionic acid derivatives have a short half-life of about 4 hours and are well tolerated with a relatively low risk of side effects. These drugs are quickly absorbed in the intestine and quickly eliminated; they do not accumulate when metabolic processes are disrupted. They have moderate inhibitory activity on prostaglandin synthesis, and therefore are inferior in their anti-inflammatory effect to diclofenac, indomethacin and phenylbutazone. In this regard, it is advisable to use them for relatively mild dorsopathies with moderate pain.
Unfortunately, the vast majority of NSAIDs have an ulcerogenic effect, which forces the question of the appropriateness of their use and the method of administration into the body to be decided in each individual case. The absence of gastrointestinal diseases allows for oral administration. It is believed that the risk of gastropathy caused by taking NSAIDs is significantly higher in people over the age of 65 years, with long-term (more than 3 months) use of NSAIDs, especially when using two or more drugs from this group, while taking corticosteroids and indirect anticoagulants and , respectively, in patients with a history of gastric ulcer. Possible risk factors are female gender, smoking, alcohol abuse, and the presence of Helicobacter pylori infection. As preventive measures to reduce the risk of damage to the gastric mucosa, proton pump inhibitors (omeprazole 20 mg once a day) or H2-histamine receptor blockers (ranitidine 300 mg per day), as well as antacid drugs, can be used.
If NSAIDs are poorly tolerated, the presence of chronic gastritis, or previous peptic ulcer disease, the use of tablet dosage forms is excluded. In this case, parenteral (intramuscular) or rectal (in the form of suppositories) administration is possible. The use of rectal suppositories is characterized by a high absorption rate (it may correspond to that of oral administration or be slightly lower). Thus, after rectal administration of 50 mg of diclofenac, its maximum concentration in plasma is achieved on average within 1 hour. Unfortunately, the threat of exacerbation of gastrointestinal pathology is not completely excluded in this situation.
Recently, transdermal forms of NSAIDs (ointments, creams, gels) have become widespread. It is necessary to clearly understand that the bioavailability of drugs when administered locally is usually an order of magnitude lower than when administered orally. A serious disadvantage of transdermal dosage forms is the low concentration of the active substance and the limited passage of the drug directly to the pathological focus. Most researchers recognize the advisability of using transdermal forms for moderate pain syndromes, while for severe pain syndromes their effectiveness is clearly insufficient. A pronounced analgesic effect of the treatment can be achieved with repeated (at least 4-6 times a day) application of the drug.
Selective COX-2 inhibitors, which provide inhibition of the synthesis of inflammatory mediators and do not affect the production of prostanoids (celecoxib, nimesulide), attract much attention. The undoubted advantage of these drugs is the relatively low risk of damage to the mucous membrane of the stomach and duodenum. However, their analgesic effect in the acute stage of spondylogenic dorsopathy is not always sufficient, which requires prolongation of the course of therapy or increasing doses of drugs.
In accordance with modern ideas about the formation of pain syndromes, an important role in the formation and regulation of pain is assigned to opioid and non-opioid analgesic systems. Based on this, it can be assumed that one of the most specific and reliable options for pain management is to influence the central mechanisms of pain formation. To reduce the severity of pain in patients with back pain, it is extremely rare to use narcotic drugs. However, in some cases, a positive result is achieved through the use of non-narcotic analgesics. One of them is acetaminophen (paracetamol), an effective pain reliever with a complex mechanism of action. There is reason to believe that analgesia with its use is achieved by increasing the threshold of pain sensitivity, although the central effect of the drug cannot be excluded. It must be borne in mind that in large doses, acetaminophen can have nephro- and hepatotoxic effects, and the risk increases with alcohol intake and other exogenous intoxications.
The timing of use of NSAIDs and analgesics is determined by the intensity of the pain syndrome; the course of their use is stopped as the effect is achieved. It should be noted that the “prophylactic” use of NSAIDs in patients with spondylogenic dorsopathies in the absence of pain is inappropriate - no convincing evidence of a preventive effect has been obtained, while the risk of complications increases significantly.
Increasing the effectiveness of the use of NSAIDs can be achieved by combining drugs that affect various parts of the pathogenesis of pain. The observed potentiation of the effect makes it possible to use relatively low doses of drugs and minimize the pharmacological load on the patient’s body. For this purpose, in some patients, intravenous drip administration of a mixture of painkillers, sedatives, and diuretics can be used. In addition to the mutually potentiating effect of adequately selected components of the “cocktail,” the psychotherapeutic effect of this method of treatment cannot be excluded.
Muscle relaxants
A combination of painkillers with muscle relaxants that reduce the severity of muscle-tonic manifestations has a good therapeutic effect. This complex can be effective for both compression and reflex syndromes. Benzodiazepine derivatives (diazepam, tetrazepam), tolperisone, and tizanidine are used as drugs that reduce increased muscle tone. Tizanidine, in addition to its relaxing effect on striated muscles, has a moderate gastroprotective effect. The mechanism of this effect is not entirely clear, although there is evidence that the drug, acting through central alpha-adrenergic pathways, inhibits the production of gastric secretions, prevents changes in glycoproteins caused by the action of acetylsalicylic acid or NSAIDs, and damage to the gastric mucosa. Considering that almost all muscle relaxants have a sedative effect to one degree or another, the patient should be informed about possible side effects - drowsiness, decreased concentration, lethargy. Often the severity of these effects limits the use of this group of drugs in outpatient settings.
Decongestant therapy
In some cases, compression syndrome is accompanied by local venous congestion, swelling of the root and surrounding tissues, which makes it advisable to include diuretics (saluretics or osmotic) and, in some severe cases, corticosteroids in the therapeutic complex. Hormonal drugs usually use prednisolone (40–60 mg per day) or dexamethasone (4–8 mg per day) for 3–5 days, followed by rapid withdrawal. The increased risk of gastrointestinal complications must be taken into account when corticosteroids and NSAIDs are used concomitantly. Epidural corticosteroids are used in a number of countries. Data were obtained on the effectiveness of this method of treatment in patients with acutely developed pain syndrome. Less justified is the epidural administration of drugs for moderate pain in the lower back and lower back, as well as for their chronic or subacute nature.
Combination drugs
A successful combination of drugs that have analgesic and anti-edematous effects, which have a positive effect on metabolism in the peripheral nerve and surrounding tissues, is the drug “Ambene”. Available in the form of a ready-to-use two-chamber syringe for injection, the first chamber of which contains 2 ml of phenylbutazone solution (375 mg) and 3.5 mg of dexamethasone, the second - 1 ml of cyanocobalamin (2.5 mg). In addition, Ambene contains lidocaine, the addition of which reduces pain directly at the injection site. Solutions are mixed immediately before use. The therapeutic effects of the components included in Ambene are potentiated, thereby ensuring a quick and lasting analgesic effect.
Phenylbutazone is a pyrazolone-type NSAID, which, by inhibiting COX activity, reduces the production of prostaglandins and has an analgesic and anti-inflammatory effect. The pronounced analgesic effect is combined with good tolerability, so the daily dose can be up to 1200–1600 mg. Dexamethasone is a synthetic glucocorticoid with powerful anti-inflammatory, antiallergic, desensitizing, and anti-edematous effects. The main clinical effects are realized due to inhibition of the release of inflammatory mediators by eosinophils, membrane-stabilizing effects, and a decrease in the number of mast cells. Cyanocobalamin (vitamin B12) is involved in the metabolism of a number of biologically active substances and has high biological activity, including in relation to metabolic processes in the peripheral nervous system.
Ambene has a pronounced analgesic effect in patients with spondylogenic dorsopathy, and is well tolerated. The drug is administered intramuscularly once a day, no more than once every 2–3 days. It should be borne in mind that individual components of the drug can cause unwanted side effects. Like other NSAIDs, phenylbutazone has an ulcerogenic effect; skin manifestations (urticaria, dry eczema) are relatively rare. Dexamethasone is characterized by a low incidence of side effects, however, it is necessary to keep in mind the possibility of reducing glucose tolerance and increasing the risk of developing erosive and ulcerative lesions of the stomach and duodenum. Based on this, Ambene should not be used in patients with acute diseases of the stomach and duodenum, impaired carbohydrate metabolism (decreased glucose tolerance), or individual intolerance to its individual components.
Relief of both compression and reflex pain syndromes can be achieved by blocking painful muscle groups or trigger points. Technically correctly performed, these manipulations are quite effective and do not cause significant complications. Care is required when performing paravertebral blocks to avoid trauma to the spinal roots. Combinations of anesthetic solution (novocaine, lidocaine) and a small dose of corticosteroid (hydrocortisone suspension, betamethasone dipropionate) are used. Local administration of drugs that have a systemic rather than local effect (antiplatelet agents, vasoactive drugs, muscle relaxants, etc.), and also do not have the ability to be deposited in tissue, is impractical. Unfortunately, the effect of blockades on pain is not lasting, and therefore there is a need for repeated manipulations.
In some cases, the use of NSAIDs, even in combination with muscle relaxants, does not have the desired positive effect. Chronic pain syndrome is accompanied by emotional disorders, in particular with a predominance of depressive reactions, which dictates the need to expand the pharmacotherapeutic arsenal. Research in recent years has convincingly demonstrated that the chronicity of pain in patients with lumbar pain is due to psychological rather than biomechanical reasons (i.e., directly related to the pathology of the spine and roots). The consequence of this is an increase in the recovery process, a sharp limitation in the possibility of motor rehabilitation of patients, and disruption of interaction in the “doctor-patient” system. The reasons that complicate the recovery process are the patient’s belief in the presence of progressive organic damage to the spine, the need to completely limit physical activity, impairment of social functions associated with the disease, orientation towards passive (medicinal, physiotherapeutic) but not active treatment (dosed physical activity, special exercises). A powerful therapeutic tool in this situation is conducting explanatory psychotherapy, developing optimistic views in the patient about the prospects for treatment, developing a behavior strategy for the future (optimal volume and nature of work and household stress, carrying out preventive measures, etc.).
Antidepressants and anticonvulsants
In this situation, antidepressants can be added to treatment, and it is advisable to use drugs that have a sedative and muscle relaxant effect (for example, amitriptyline). Carbamazepine, an effective anticonvulsant from the group of iminostilbene derivatives, has an analgesic effect. The drug inactivates sodium channels, inhibits the release of excitatory neurotransmitters into the synaptic cleft, causing a decrease in synaptic transmission. In addition to the main anticonvulsant and analgesic effect, the drug has antipsychotic and antimanic effects. It has been suggested that the positive effect of carbamazepine in patients with spondylogenic dorsopathies may be mediated by its effect on central nociceptive mechanisms and normalization of muscle tone. Dosing of the drug is carried out individually, depending on tolerability, as well as on the nature of the motor mode. Side effects (primarily drowsiness, impaired concentration) require care in selecting the dose of the drug, especially in an outpatient setting. The likelihood of these disorders increases with the simultaneous prescription of sedatives, antidepressants, and some muscle relaxants. Convincing data on the advisability of using other anticonvulsants has not been obtained, although studies of this kind are being conducted.
The complex of therapeutic measures should also include non-drug treatment methods - physiotherapy (phono- or electrophoresis of drugs, exposure to electric currents of a specially selected configuration, frequency and voltage, low-energy laser radiation). Reflexology in various modifications (traditional acupuncture, electro- and laser puncture) has an analgesic effect. It should be noted that there are significant difficulties in comparing the results of using various physiotherapeutic treatment methods, and the obvious lack of research on their effectiveness that meets the requirements of evidence-based medicine.
Currently available data indicate the existence of a significant arsenal of pharmacotherapeutic and non-drug methods for relieving pain in patients with spondylogenic dorsopathies. It seems desirable to make an individual choice of therapeutic tactics using a combination of different drugs, their dosages and routes of administration. The combined use of various treatment methods can increase the effectiveness of treatment and reduce the pharmacological load on the body. As the pain syndrome is relieved, it is absolutely necessary to use methods of restorative therapy, therapeutic exercises aimed at forming a muscle corset, strengthening the muscles of the abdominal wall and back. Equally important is teaching the patient the skills of daily physical activity - the formation of a motor stereotype that prevents the occurrence of pain.
Source: https://www.consilium-medicum.com/media/consilium/04_08/557.shtml :: Wednesday, 10-Nov-2004 21:25:33 MSK
Use during pregnancy and breastfeeding
Theophylline penetrates the placental barrier. The use of aminophylline during pregnancy may result in potentially dangerous concentrations of theophylline and caffeine in the blood plasma of the newborn. Newborns whose mothers received aminophylline during pregnancy (especially in the third trimester) require medical supervision to monitor possible symptoms of theophylline intoxication.
Theophylline is excreted in breast milk. When using aminophylline in a nursing mother during lactation, irritability may occur in the child.
Thus, the use of aminophylline during pregnancy and lactation (breastfeeding) is possible in cases where the expected benefit of therapy for the mother outweighs the potential risk for the fetus or child.
special instructions
Use with caution in severe coronary insufficiency (acute phase of myocardial infarction, angina pectoris), widespread atherosclerosis, hypertrophic obstructive cardiomyopathy, frequent ventricular extrasystoles, increased convulsive readiness, liver and/or renal failure, gastric and duodenal ulcers (history), with recent bleeding from the gastrointestinal tract, uncontrolled hypothyroidism (possibility of cumulation) or thyrotoxicosis, with prolonged hyperthermia, gastroesophageal reflux, prostatic hypertrophy, in elderly patients, in children (especially orally).
Correction of the aminophylline dosage regimen may be required for heart failure, liver dysfunction, chronic alcoholism, fever, and acute respiratory infections.
In elderly patients, a dose reduction may be required.
When replacing the used dosage form of aminophylline with another, clinical observation and monitoring of the concentration of theophylline in the blood plasma is necessary.
Aminophylline is not used simultaneously with other xanthine derivatives. During the treatment period, you should avoid eating foods containing xanthine derivatives (strong coffee, tea).
Use with caution simultaneously with anticoagulants, with other theophylline or purine derivatives.
Concomitant use with beta-blockers should be avoided.
Aminophylline should not be used simultaneously with glucose solution.
Do not use rectally in children.
Euphyllin (Euphyllini)
Ephedrine, beta-agonists, caffeine and furosemide enhance the effect of the drug. Increases the likelihood of developing side effects of glucocorticosteroids, mineralocorticosteroids (hypernatremia), and general anesthesia agents (the risk of ventricular arrhythmias increases). In combination with phenobarbital, phenytoin, rifampicin, isoniazid, carbamazepine or sulfinpyrazone, a decrease in the effectiveness of aminophylline is observed, which may require an increase in the doses of the drug. Aminoglutethimide and moracizine, being inducers of microsomal oxidation, increase the clearance of aminophylline, which may require an increase in its dose.
The clearance of the drug is reduced when prescribed in combination with macrolide antibiotics, lincomycin, allopurinol, cimetidine, isoprenaline, beta-blockers, which may require a dose reduction.
Oral estrogen-containing contraceptives, antidiarrheal drugs, intestinal sorbents weaken, and H2-histamine blockers, slow calcium channel blockers, mexiletine enhance the effect (they bind to the cytochrome P450 enzymatic system and change the metabolism of aminophylline). When used in combination with enoxacin and other fluoroquinolones, small doses of ethanol, disulfiram, recombinant interferon alpha, methotrexate, propafenone, thiabendazole, ticlopidine, verapamil, and when vaccinated against influenza, the intensity of action of aminophylline may increase, which may require a reduction in its dose. The drug suppresses the therapeutic effects of lithium carbonate and beta-blockers. The administration of beta-blockers interferes with the bronchodilatory effect of aminophylline and can cause bronchospasm. Eufillin potentiates the effect of diuretics by increasing glomerular filtration and reducing tubular reabsorption. With caution, aminophylline is prescribed simultaneously with anticoagulants, other theophylline or purine derivatives. It is not recommended to use aminophylline with drugs that excite the central nervous system (increases neurotoxicity). The drug cannot be used with dextrose solutions and is incompatible with fructose and levulose solutions. The pH of the solutions to be mixed must be taken into account: pharmaceutically incompatible with acid solutions.
