Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of drugs that prevent the development or reduce the intensity of the inflammatory response. In addition to anti-inflammatory NSAIDs, they also have analgesic and antipyretic effects. NSAIDs are among the most commonly used medications; many of them are available over the counter.
treatment of inflammatory diseases of the maxillofacial area, periodontium, parodontium, and oral mucosa;
relief of acute and chronic pain;
premedication before dental surgery.
Considering that NSAIDs are one of the most used medications for dentists, as a doctor in general, it is also necessary to know other indications for their use.
Chemical properties. In terms of their chemical structure, NSAIDs are mostly weak organic acids. Some of them, such as nabumetone, are precursors of the active drug with acidic properties (prodrugs).
Classification. There are several classifications of NSAIDs. Depending on the severity of anti-inflammatory activity and chemical structure NSAIDs are classified as follows:
1. NSAIDs with pronounced anti-inflammatory activity
Salicylates
Acetylsalicylic acid (aspirin)
Diflunisal
Lysine monoacetylsalicylate
Pyrazolidines
Phenylbutazone
Indoleacetic acid derivatives
Indomethacin
Sulindak
Etodolac
Phenylacetic acid derivatives
Diclofenac
Oxycams
Piroxicam
Tenoxicam
Lornoxicam
Meloxicam
Sudoxicam
Propionic acid derivatives
Ibuprufen
Naproxen
Flurbiprofen
Ketoprofen
Tiaprofenic acid
Non-acid derivatives
Alcanons
Nabumethon
Sulfonamide derivatives
Nimesulide
Celecoxib
Rofecoxib
Valdocoxib
Lumiracoxib
Parecoxib
Etoricoxib
2. NSAIDs with weak anti-inflammatory activity
Anthranilic acid derivatives
Mefenamic acid
Etofenamate
Pyrazolones
Metamizole
Aminophenazone
Propyphenazone
Para-aminophenol derivatives
Phenacetin
Paracetamol
Heteroarylacetic acid derivatives
Ketorolac
3. Combination drugs
Arthrotec (diclofenac + misoprostol)
Another classification is based on the selectivity of NSAIDs with respect to their effect on isoforms of the cyclooxygenase enzyme (Table 21.1).
Table 21.1. Classification of NSAIDs according to selectivity for various forms of COX.
All NSAIDs have identical points of application (Brook PM, 1993), among which are:
synthesis of prostaglandins;
synthesis of leukotrienes;
formation of superoxide radicals;
release of lysosomal enzymes;
activation of cell membranes;
aggregation and adhesion of neutrophils;
lymphocyte function;
synthesis of rheumatoid factor;
cytokine synthesis;
cartilage metabolism.
Of the many mechanisms of NSAIDs, the main role belongs to the inhibition of cyclooxygenase (COX), a key enzyme of inflammation. As a result of COX inhibition, the synthesis of prostaglandins (PG) from arachidonic acid is disrupted. PGs are mediators of the inflammatory response, cause exudation and swelling, sensitize receptors to pain mediators (histamine, bradykinin) and lower the threshold of pain sensitivity. They increase the sensitivity of the hypothalamic thermoregulation centers to the action of pyrogens formed in the body under the influence of infectious agents and toxins.
There are at least two isoenzymes that regulate the synthesis of two different PG subclasses (Fig. 21.1). COX-1 is constantly present in tissues and is involved in the synthesis of PGs that regulate the physiological functions of cells: platelets, epithelium of the gastrointestinal mucosa, vascular endothelium, etc. At the same time, the amount of COX-2 in tissues is extremely small, and only during the development of the inflammatory reaction it increases sharply, which serves as one of the main pathogenetic mechanisms of inflammation. Suppression of COX-1 synthesis during the use of NSAIDs explains the nature of the main undesirable effects of these drugs. The ratio of the severity of inhibition of COX-1 and COX-2 allows us to rank NSAIDs according to their level of safety. Of the commonly used drugs, the least safe are piroxicam and indomethacin, the safer are acetylsalicylic acid, diclofenac, ketoprofen, ibuprofen. IN recent years Several selective COX-2 inhibitors have been synthesized (celecocoxib, meloxicam), which have good analgesic and anti-inflammatory activity.
Rice. 21.1. Modern cyclooxygenase concept.
The likelihood of developing undesirable effects increases in proportion to the dose of the drug (dose-dependent effect). Thus, ibuprofen in a daily dose of up to 1200 mg is relatively safe, but when the dose is increased to 2400–4800 mg, the frequency of adverse effects is comparable to that when taking other non-selective NSAIDs.
In addition to the blockade of PG synthesis, other mechanisms of action of NSAIDs are known (see above), the severity of which varies among individual agents. Metamizole sodium has been shown to inhibit conduction pain impulses V spinal cord. It has been established that the anionic properties of NSAIDs allow them to penetrate the bilayer of phospholipid membranes of immunocompetent cells and directly influence the interaction of proteins, preventing cellular activation in the early stages of inflammation. Some NSAIDs increase intracellular calcium levels in T lymphocytes, which increases proliferation and IL-2 synthesis.
Dental practice involves the use of antibacterial drugs (ABP) in the following cases:
Not applicable in the following cases: open wounds of the oral cavity with an area of less than 1 square meter. cm, no signs of inflammatory or chronic process, the wound on the mucosal surface does not contain damage to the bone tissue and periosteum, the patient has viral gingivitis without bacterial complications.
For safe therapy, it is important to take into account the patient's condition, as well as adverse reactions arising as a result of taking medications. Frequent use drug treatment can lead to suppression of the immune system, causing disorders digestive system, allergic and toxic reactions.
There are several categories of antibacterial drugs that doctors use in dental practice.
They influence the synthesis of microorganisms, act on gram-positive and gram-negative microorganisms, and are effective against anaerobic bacteria.
Today, inhibitor-protected penicillins (moxicillin + clavulanic acid) are widely used. Commercial names of medications - Amoklav ®.
The drugs are well tolerated, have a wide spectrum of antimicrobial effects and rarely cause side effects.
Amoxicillin ® film-coated tablets
These drugs are used in the presence of odontogenic and periodontal inflammation, as well as during dental procedures with high risk development of bacterial complications.
There are 4 generations of cephalosporins. In dental practice, the 3rd generation () and 4th generation () are most often used.
They have a wide spectrum of action and have good absorption rates when taken orally. These include and. Prescribed for inflammatory processes in the area of soft and bone tissue, the dosage is determined by a specialist, based on the severity of the infectious-inflammatory process.
The most popular are tinidazole ® and. The principle of action is based on inhibition of DNA synthesis microbial cells. This type of antibiotics, which penetrate bone tissue, is used in the presence of large inflammatory lesions of the oral cavity. For odontogenic infections, it is prescribed in the form of gels (Metrogil-dent ®) or as part of combination therapy.
A category of drugs designed to eliminate gram-positive and gram-negative bacteria, as well as some types of anaerobes. Developed as alternative option group of beta-lactams, to which bacteria have developed resistance, and the number of allergic reactions of patients has increased.
Macrolides have low toxicity and can be used by pregnant and breastfeeding women. The group is represented by (azithromycin ®). The product has become widespread among patients who develop allergic reactions for penicillins and beta-lactams.
During a retrospective analysis of 519 outpatient records of patients with acute and chronic pulpitis, chronic generalized catarrhal gingivitis and chronic generalized periodontitis, the structure and frequency of prescription of systemic NSAIDs were studied. It was shown that drugs of this group were prescribed in 19% of cases. From huge amount Only 5 INNs were recommended for NSAIDs. The most frequently prescribed drugs were nimesulide (34%), ibuprofen (24%) and ketoprofen (16%). NSAIDs systemic action are prescribed by dental therapists mainly for analgesic purposes: patients with acute and chronic pulpitis receive them in 55% of cases. The anti-inflammatory properties of drugs are not used actively enough: for periodontal pathology they are recommended only in 15% of cases. When prescribing NSAIDs, dental therapists make mistakes: there are cases of recommending drugs to persons who have contraindications for their use (pathology of the gastrointestinal tract, liver, kidneys). Thus, the use of NSAIDs in therapeutic dentistry requires optimization: this can be achieved through intensifying educational activities (seminars, conferences, lectures, etc.) for doctors on these issues.
therapeutic dentistry
retrospective study
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2. Kamchatnov P.R. Ketoprofen: effectiveness and safety of use in patients with low back pain / P.R. Kamchatnov, G.S. Salnikova, A.V. Chugunov // Directory of a polyclinic doctor. - 2010. - No. 2. - P. 54-57.
3. Karateev A.E. Nimesulide: safety issues and opportunities long-term use// Pharmateka. - 2009. - No. 4. - P. 17-25.
4. Karateev A.E. Safety of nimesulide: emotions or balanced assessment? / A.E. Karateev, V.G. Barskova // Consilium medicum. - 2007. - T. 9. - No. 2. - P. 60-64.
5. Aggarwal V. Comparative evaluation of local infiltration of articaine, articaine plus ketorolac, and dexamethasone on anesthetic efficacy of inferior alveolar nerve block with lidocaine in patients with irreversible pulpitis / V. Aggarwal, M. Singla, A. Rizvi, S. Miglani // J. Endod. -2011. - Vol. 37. - No. 4. - R. 445-449.
6. Arslan H. Effectiveness of tenoxicam and ibuprofen for pain prevention following endodontic therapy in comparison to placebo: a randomized double-blind clinical trial / H. Arslan, H. Topcouglu, H. Aladag // J. Oral. Sci. - 2011. - Vol. 53. - No. 2. - P. 157-161.
7. Committee on the Safety of Medicines, Medicines Control Agency. Ketorolac: new restrictions on dose and duration of treatment // Current Problems in Pharmacovigilance. - 1993. - Vol. 19. - P. 5-8.
8. Garcia-Rodriguez L. Risk of hospitalization for upper gastrointestinal tract bleeding associated with ketorolac, other non-steroidal anti-inflammatory drugs, calcium antagonists, and other antihypertensive drugs / L. Garcia-Rodriguez, C. Cattaruzzi, M. Troncon, L. Agostinis // Arch.Intern.Med. - 1998. - Vol. 158. - No. 1. - P. 33-39.
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Introduction
Systemic nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in dental practice abroad in the complex treatment of endo- and periodontal diseases. In the first case, NSAIDs are used primarily to prevent pain that occurs after endodontic interventions, as well as to increase the effectiveness of blockade of the inferior alveolar nerve with local anesthetics for irreversible pulpitis. In case of periodontal pathology, NSAIDs are used in addition to mechanotherapy to improve treatment results.
In domestic dentistry there is insufficient data reflecting the use of systemic NSAIDs in such cases.
An indispensable method for gaining insight into the use of drugs in real life. clinical practice and to judge the rationality of the prescriptions made is pharmacoepidemiological analysis.
Purpose of the study: to analyze the structure and frequency of prescription of systemic NSAIDs by dental therapists in the city of Ufa.
Materials and methods. Design: Retrospective descriptive cross-sectional pharmacoepidemiological study.
An analysis of 519 outpatient records of patients (244 men and 295 women) observed in dental clinics in Ufa from 2008 to 2011 was carried out.
Inclusion criteria: outpatient records of adult therapeutic patients with inflammatory endo- and periodontal diseases (acute and chronic pulpitis, chronic generalized catarrhal gingivitis and chronic generalized periodontitis).
The selection of primary medical documentation for the study was carried out by randomization using the random number method. The sample was representative (included an equal number of outpatient records of patients with the above-mentioned diagnoses from each district of the city), which made it possible to extrapolate the results obtained to the general population of persons with the designated nosologies. Grouping of data from outpatient records was carried out using Excel and Access for Windows XP.
Results and discussion. The characteristics of patients included in this study are presented in Table 1.
Table 1 - Characteristics of patients included in the study
The results obtained in our study showed that the total frequency of recommendations of systemic NSAIDs by dental therapists was 17% (90 people). The frequency of prescriptions of drugs of the group depending on the nosology is presented in Table 2.
Table 2 - Frequency of prescription of systemic NSAIDs by outpatient dental surgeons for various nosologies
|
Diagnosis |
Total quantity Human |
Number of people receiving NSAIDs |
||
|
abs. number |
% of total number of patients |
abs. number |
% of total number of patients |
|
|
Acute and chronic pulpitis |
||||
|
Chronic generalized catarrhal gingivitis |
||||
|
Chronic generalized periodontitis |
||||
As can be seen from Table 2, systemic NSAIDs are prescribed by therapeutic dentists mainly for analgesic purposes: patients with acute and chronic pulpitis receive them in 55% of cases. The anti-inflammatory properties of drugs, from our point of view, are not used actively enough: for example, in chronic generalized periodontitis, systemic NSAIDs are recommended only in 15% of cases, and in chronic catarrhal gingivitis are not assigned at all.
The full list of systemic NSAIDs prescribed in outpatient dental surgery included 10 items (ketorolac, nimesulide, ketoprofen, ibuprofen, metamizole sodium, diclofenac, indomethacin, acetaminophen, meloxicam and lornoxicam). Of these, the last 5 drugs were used in isolated cases, and therefore were combined into a separate “other” group for subsequent analysis. That is, in fact, only 5 NSAIDs are prescribed to patients, which, in our opinion, does not fully realize the potential capabilities of the class.
Identified in our previous studies low level dentists' knowledge of the pharmacology of anti-inflammatory drugs is reflected in their prescriptions. Thus, there were recommendations for NSAIDs for people with gastrointestinal, liver and kidney pathologies. The general structure of prescriptions of systemic NSAIDs by outpatient dental therapists is shown in Fig. 1.
Rice. 1. General structure of prescriptions for systemic NSAIDsoutpatient dental therapists.
The structure of NSAID prescriptions depending on nosology is shown in Table 3.
Table 3 - Structure of prescriptions of NSAIDs by therapeutic dentists depending on nosology
|
Preparation |
Frequency of drug prescription for this disease (%) |
||
|
Acute and chronic pulpitis |
Chronic generalized catarrhal gingivitis |
Chronic generalized periodontitis |
|
|
Ibuprofen |
|||
|
Ketoprofen |
|||
|
Ketorolac |
|||
|
Nimesulide |
|||
|
Metamizole sodium and metamizole-containing drugs |
|||
As can be seen from the presented images, in the structure of prescriptions of systemic NSAIDs by dental therapists, the leading drugs are nimesulide, ibuprofen and ketoprofen.
The attitude towards nimesulide in the world is ambiguous. There are many reports of hepatotoxic reactions induced by it (sometimes with fatal outcomes). Nimesulide is used in approximately 50 countries of the world; it is not registered in more than 150. These include the USA (where it was synthesized), Great Britain, Canada, Denmark, Australia, New Zealand and Japan. In 2002, Finland and Spain stopped selling the drug after reports of hepatotoxicity. Ireland and Singapore banned the use of nimesulide in 2007. The press release of the International Society of Drug Bulletins (dated December 20, 2007) states: “Nimesulide should be withdrawn from circulation worldwide due to serious liver damage that develops against its background. In cases where taking an NSAID is necessary, it is better to use a drug with an optimal benefit-risk ratio, such as ibuprofen. International Society medicinal bulletins do not accept the fact that nimesulide remains permitted in some countries in Europe and the world. This NSAID has neither therapeutic benefit nor greater gastrointestinal safety than other drugs in the group, while its use exposes patients to an increased risk of fatal liver damage."
There are also opposing opinions. So, Karateev A.E. and Barskova V.G. (2007), believe that data on the high hepatotoxicity of nimesulide are exaggerated and are based on an analysis of spontaneous reports, the number of which depends on the opinion of the medical community and external information influences. According to the results of research by Karaeev A.E. (2009), the use of nimesulide in patients with psoriatic arthritis does not cause negative dynamics of biochemical parameters indicating damage to liver cells or cholestasis.
The second place after nimesulide in frequency of prescription by dental therapists was occupied by ibuprofen (24%). The use of the drug in therapeutic dentistry, in our opinion, is justified not only by its pronounced anti-inflammatory and analgesic activity, but also by its high safety profile. Among all NSAIDs, ibtsuprofen in low doses is considered the standard of safety regarding the risk of gastrointestinal complications.
Ketoprofen was in third place in the structure of prescriptions for therapeutic dentists. The drug has a rapid and powerful analgesic effect, as well as high anti-inflammatory activity, which approaches that of the “gold standard” - diclofenac. The gastrotoxicity of the drug is low, relative risk gastric bleeding against its background is 3.2. According to many authors, ketoprofen is one of the most effective and safe modern NSAIDs.
Ketorolac was prescribed by dental therapists for acute and chronic pulpitis. The “popularity” of the drug in these situations, from our point of view, is due to the pronounced analgesic effect of the latter.
However, in addition to information about the effectiveness of ketorolac, the literature is replete with information about high frequency serious side effects associated with its use, namely ulceration of the gastrointestinal tract, perforation of peptic ulcers and bleeding (including gastric and postoperative).
Following reports of 97 fatalities associated with ketorolac worldwide between 1990 and 1993, it was withdrawn from the market in some countries and its permitted dosage and maximum duration of use were reduced in others. Post-marketing studies of ketorolac revealed a relationship between gastrointestinal bleeding and the average daily dose of the drug, as well as with a duration of therapy of more than 5 days.
According to L.A. Garcia-Rodriguez et al. (1998), ketorolac is 5 times more gastrotoxic compared to other NSAIDs; the relative risk of gastric bleeding against its background is the highest among the drugs in the group and is 24.7. Increased risk These side effects are observed both with oral and intramuscular administration of ketorolac and are noted already in the first week of its administration. The results obtained, according to the authors, unfavorably characterize ketorolac from a benefit-risk point of view compared to other NSAIDs.
Positive aspects, identified during the analysis process, was, in our opinion, a low percentage of prescriptions of metamizole sodium and metamizole-containing drugs (3%), the unsafety of which can hardly be doubted by anyone.
Conclusions
Reviewers:
Today, everyone, young and old, is familiar with the rules of oral hygiene. Everyone remembers the need to brush their teeth at least twice a day, use rinses and sprays outside the home, and undergo preventive examinations at the dentist twice a year. But even the most zealous patients sometimes experience problems with their teeth and oral cavity.
Pharmacology today has the richest selection of anti-inflammatory drugs in the dental industry. These drugs have anti-inflammatory, analgesic and antipyretic effects. When getting treatment, it is still necessary to have information about what anti-inflammatory drugs in dentistry applied, and what they promise the patient.
The doctor attributes the use of anti-inflammatory drugs for toothache, periodontitis, and also in various cases of pathology of the oral mucosa. Anti-inflammatory drugs affect various stages inflammation, while either leading to a decrease in the inflammatory phase, or completely curing the inflammatory and purulent processes. Anti-inflammatory drugs are divided into steroidal and non-steroidal.
In dental practice, anti-inflammatory drugs of local and resorptive action are used (astringents, enzymes, vitamins, steroid drugs and NSAIDs, dimexide, calcium salts, heparin ointment, etc.), which differ significantly in the mechanism of action, characteristics of the chemical structure, physical and chemical properties, pharmacokinetics, pharmacodynamics, as well as on the effect on certain phases of inflammatory reactions. Despite the presence in the arsenal of a dentist of a large number of drugs of various directions of action, the main drugs used to obtain anti-inflammatory and analgesic effects are NSAIDs, the effect of which is manifested not only with resorptive action, but also with local application. The use of enzymes in medicine (enzyme therapy) is based on their selective effect on certain tissues. Enzyme preparations cause hydrolysis of proteins, polynucleotides and mucopolysaccharides, resulting in liquefaction of pus, mucus and other products of inflammatory origin. In dental practice, proteases, nucleases and lyases are most often used. Non-steroidal anti-inflammatory drugs and non-narcotic analgesics Index of drug descriptions Acetylsalicylic acid Benzidamine Diclofenac Ibuprofen Indomethacin Ketoprofen Ketorolac Lornoxicam Meloxicam Metamizole sodium Nimesulide Paracetamol Piroxicam Phenylbutazone Celecoxib No INN Cholisal The widespread use of NSAIDs in dentistry is due to their spectrum pharmacological activity, which includes anti-inflammatory, analgesic, antipyretic, and antiplatelet effects. This allows the use of NSAIDs in complex therapy inflammatory processes of the maxillofacial area, for drug preparation of patients before performing traumatic interventions, as well as to reduce pain, swelling and inflammation after them. The analgesic and anti-inflammatory activity of NSAIDs has been proven in numerous controlled trials that meet the standards of “evidence-based medicine”. The range of NSAIDs currently used in medical practice is extremely wide: from traditional groups of derivatives salicylic acid(acetylsalicylic acid (aspirin) and pyrazolone (phenylbutazone (butadione)) to modern drugs derivatives of a number of organic acids: anthranilic acid - mefenamic acid and flufenamic acid; indoleacetic - indomethacin (methindol), phenylacetic - diclofenac (ortofen, voltaren, etc.), phenylpropionic - ibuprofen (brufen), propionic - ketoprofen (artrosilene, OCI, ketonal), naproxen (naprosyn), heteroaryl acetic - ketorolac (ketalgin, ketanov, ketorol) and oxicam derivatives (piroxicam (piroxifer, hotemin), lornoxicam (xefocam), meloxicam (movalis NSAIDs have the same type of effects, but their severity varies significantly among drugs of different groups. Thus, paracetamol has a central analgesic and antipyretic effect, but its anti-inflammatory effect has not been expressed. In recent years, drugs with powerful analgesic potential have appeared, comparable in activity to tramadol. (tramal), such as ketorolac, ketoprofen and lornoxicam. high efficiency with pronounced pain syndrome different localization allows for wider use of NSAIDs in the preoperative preparation of patients. NSAIDs have also been created for topical use (based on ketoprofen, choline salicylate and phenylbutazone). Since the anti-inflammatory effect is associated with the blockade of cyclooxygenase (COX) COX-2, and many side effects are associated with the blockade of COX-1, NSAIDs have been created that primarily block COX-2 (meloxicam, nimesulide, celecoxib, etc.), which are better tolerated, especially patients at risk with a history of gastric and duodenal ulcers, bronchial asthma, kidney damage, and blood clotting disorders. Mechanism of action and pharmacological effects of NSAIDs inhibit COX, a key metabolic enzyme arachidonic acid, regulating its conversion to prostaglandins (PG), prostacyclin (PGI2) and thromboxane TxA2. PGs are involved in the processes of pain, inflammation and fever. By inhibiting their synthesis, NSAIDs reduce the sensitivity of pain receptors to bradykinin, reduce tissue swelling at the site of inflammation, thereby weakening the mechanical pressure on nociceptors. In recent years, it has been shown that the anti-inflammatory effect of these drugs is related to the prevention of activation of immunocompetent cells in the early stages of inflammation. NSAIDs increase the content of intracellular Ca2+ in T lymphocytes, which promotes their proliferation, the synthesis of interleukin-2 (IL-2) and the suppression of neutrophil activation. A relationship has been established between the severity of the inflammatory process in tissues maxillofacial area and changes in the content of arachidonic acid, PG, especially PGE2 and PGF2a, lipid peroxidation products, IL-1β and cyclic nucleotides. The use of NSAIDs in these conditions reduces the severity of hyperergic inflammation, swelling, pain, and the degree of tissue destruction. NSAIDs act primarily on two phases of inflammation: the exudation phase and the proliferation phase. The analgesic effect of NSAIDs is especially pronounced for pain inflammatory in nature, which is due to a decrease in exudation, prevention of the development of hyperalgesia, and a decrease in the sensitivity of pain receptors to pain mediators. Analgesic activity is higher for NSAIDs whose solutions have a neutral pH. They accumulate less at the site of inflammation, penetrate the blood-brain barrier faster, and affect the thalamic centers pain sensitivity, suppressing COX in the central nervous system. NSAIDs reduce the level of PG in brain structures involved in the conduction of pain impulses, but do not affect the mental component of pain and its assessment. The antipyretic effect of NSAIDs is mainly associated with an increase in heat transfer and appears only at elevated temperatures. This is due to inhibition of PGE1 synthesis in the central nervous system and inhibition of their activating effect on the thermoregulation center located in the hypothalamus. Inhibition of platelet aggregation is due to blockade of COX and inhibition of thromboxane A2 synthesis. For a long time use of NSAIDs a desensitizing effect develops, which is caused by a decrease in the formation of PGE2 in the site of inflammation and leukocytes, inhibition of blast transformation of lymphocytes, and a decrease in the chemotactic activity of monocytes, T-lymphocytes, eosinophils, and polymorphonuclear neutrophils. PGs are involved not only in the implementation of inflammatory reactions. They are necessary for normal course physiological processes, perform a gastroprotective function, regulate renal blood flow, glomerular filtration, platelet aggregation.
Place in therapy In dental practice, NSAIDs are widely used for inflammatory diseases maxillofacial region and oral mucosa, inflammatory swelling after injuries, operations, pain syndrome, arthrosis and arthritis of the temporomandibular joint, myofascial pain syndrome of the maxillofacial region, neuritis, neuralgia, postoperative pain, feverish conditions. Tolerance and side effects NSAIDs are widely and uncontrolledly used as anti-inflammatory, analgesic and antipyretic drugs, but their potential toxicity is not always taken into account, especially in patients at risk with a history of diseases of the gastrointestinal tract, liver, kidneys, cardiovascular system, and bronchial asthma. and prone to allergic reactions. When using NSAIDs, especially a course, complications from many systems and organs are possible. From the gastrointestinal tract: stomatitis, nausea, vomiting, flatulence, pain in the epigastric region, constipation, diarrhea, ulcerogenic effect, gastrointestinal bleeding, gastroesophageal reflux, cholestasis, hepatitis, jaundice. From the central nervous system and sensory organs: headache, dizziness, irritability, increased fatigue, insomnia, tinnitus, decreased hearing acuity, sensory impairment, hallucinations, convulsions, retinopathy, keratopathy, neuritis optic nerve. Hematological reactions: leukopenia, anemia, thrombocytopenia, agranulocytosis. From the urinary system: interstitial nephropathy, edema. Allergic reactions: bronchospasm, urticaria, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), allergic purpura, Quincke's edema, anaphylactic shock. From the outside skin and subcutaneous fat: rash, bullous rashes, polymorphic erythema, erythroderma (exfoliative dermatitis), alopecia, photosensitivity, toxicoderma. The most common complications are those caused by the inhibition of COX-1 (damages to the gastrointestinal tract, impaired renal function and platelet aggregation, effects on the circulatory system). Contraindications Hypersensitivity to drugs of this group. Course therapy with NSAIDs is contraindicated: - for gastric and duodenal ulcers; - with leukopenia; - with severe damage to the kidneys and liver; - in the first trimester of pregnancy; - during lactation; - children under 6 years of age (meloxicam - up to 15 years, ketorolac - up to 16 years). Cautions: NSAIDs should be used with caution in patients with bronchial asthma, arterial hypertension and heart failure. In elderly patients, low doses and short courses of NSAIDs are recommended. Interaction When taken together with anticoagulants, antiplatelet agents and fibrinolytics, the risk of developing gastrointestinal bleeding. When combined with beta-blockers or angiotensin-converting enzyme (ACE) inhibitors, the antihypertensive effect may be reduced. NSAIDs increase the side effects of corticosteroids and estrogens. Deterioration of renal function can be observed when NSAIDs are combined with potassium-sparing diuretics (triamterene), ACE inhibitors, and cyclosporine. When paracetamol is combined with barbiturates, anticonvulsants and ethyl alcohol the risk of hepatotoxicity increases. The use of paracetamol together with ethanol contributes to the development of acute pancreatitis.
The dentist has every right to prescribe the use of anti-inflammatory drugs in the following cases: The occurrence of toothache; Presence of periodontitis; Manifestation of pathology of the oral mucosa
Non-steroidal anti-inflammatory drugs The category of non-steroidal anti-inflammatory drugs is most often used in the field of periodontics. The main effect of these drugs is the normalization of the working process of capillaries, as well as the establishment of microcirculation. They are used to treat diseases such as gingivitis and periodontitis. Often in dentistry, non-steroidal anti-inflammatory drugs are used to apply special therapeutic dressings. This creates periodontal pockets. This type of drugs primarily includes paracetamol, ortofen, ketorod and many others. The main pharmacological effect of these drugs is to relieve the inflammatory process, and only then an anesthetic effect, antipyretic and general anesthesia. Minor side effects often occur: mainly allergic reactions, or attacks of anemia. Taking absolutely any anti-inflammatory drugs is contraindicated during the first trimester of pregnancy, as well as in the presence of certain types of chronic diseases. It is also worth knowing about personal intolerance to certain types of drugs or their components. The use of medications is possible only after examination by the attending physician and on his direct recommendation. Just in case, we recommend that you read about the symptoms of cancer.
The use of non-steroidal anti-inflammatory drugs (NSAIDs) in dental practice is due to their pharmacological effects: analgesic, anti-inflammatory and hypothermic. In recent years, the number of NSAIDs has increased significantly and includes many drugs that differ in their characteristics of action and use. They all have similar effects, but their severity varies significantly among different drugs. In this regard, it remains current choice effective and safe NSAID.
The analgesic effect of NSAIDs is due to the suppression of cyclooxygenase (COX) activity and a decrease in the production of prostaglandins E2 and F2a, which increase the sensitivity of nociceptors both during inflammation and tissue damage. A more pronounced analgesic than anti-inflammatory effect is exerted by those NSAIDs that, due to their chemical structure, are neutral, accumulate less in inflammatory tissue, quickly penetrate the blood-brain barrier and suppress COX in the central nervous system, and also affect the thalamic centers of pain sensitivity. These drugs are classified into a separate group - non-narcotic analgesics.
Along with the central analgesic effect of NSAIDs, their peripheral action, associated with an anti-exudative effect, which leads to a decrease in the accumulation of pain mediators and a decrease in mechanical pressure on pain receptors in tissues.
The results of numerous foreign and domestic studies allow us to consider ketorolac as the drug of choice in the group of non-narcotic analgesics.
Ketorolac has a pronounced analgesic effect, has anti-inflammatory and moderate antipyretic effects. The mechanism of action is associated with non-selective inhibition of COX activity (COX-1 and COX-2), which catalyzes the formation of prostaglandins from arachidonic acid, which play an important role in the pathogenesis of pain, inflammation and fever.
The strength of the analgesic effect is comparable to morphine, significantly superior to most NSAIDs, such as diclofenac, ibuprofen, ketoprofen and many others; also has moderate anti-inflammatory properties; has an antipyretic effect.
The drug does not affect opioid receptors, does not depress respiration, does not cause drug dependence, does not have a sedative or anxiolytic effect, and does not cause euphoria or spasm of the smooth muscles of internal organs.
Ketorolac is taken orally in a single dose of 10 mg. In case of severe pain syndrome (PS), the drug is taken repeatedly at 10 mg up to 4 times a day, depending on the severity of pain. The maximum daily dose for oral administration is 40 mg. The minimum effective dose should be used. When taken orally, the duration of treatment should not exceed 5 days.
Solution for intravenous or intramuscular injection used in the minimum effective dose, selected in accordance with the intensity of pain. For patients aged 16 to 64 years with a body weight of more than 50 kg, the drug is administered intramuscularly in a single dose of no more than 60 mg (including oral administration); usually 30 mg every 6 hours. Intramuscular injection is carried out slowly, deep into the muscle. When administered intravenously, the dose must be administered at least 15 seconds before single dose is 30 mg, no more than 15 doses in 5 days.
Adults weighing less than 50 kg or with chronic renal failure a single dose for intramuscular administration is no more than 30 mg (including oral administration), usually 15 mg (no more than 20 doses in 5 days); intravenously - no more than 15 mg every 6 hours, no more than 20 doses in 5 days. The duration of therapy should not exceed 5 days.
When switching from parenteral administration of the drug to oral administration, the total daily dose of both dosage forms on the day of transfer should not exceed 90 mg for patients aged 16 to 65 years and 60 mg for patients over 65 years of age or with impaired renal function. In this case, the dose of the drug in tablets on the day of transition should not exceed 30 mg.
Surgical practice is one of the widest areas of application of ketorolac in medicine. In the postoperative period, despite the use wide range drug and non-drug analgesia, 1/3–3/4 patients have BS. The use of opioid analgesics for pain relief is often accompanied by nausea, vomiting, restlessness, severe sedation, respiratory depression, urticaria, and skin itching. The analgesic effectiveness of ketorolac is comparable to morphine and significantly superior to placebo. Ketorolac, when administered parenterally or orally, is a safe and effective analgesic for the short-term treatment of acute postoperative pain and can be used as an alternative to opioid therapy.
Dental procedures performed as part of modern surgical procedures in dental healthcare institutions are characterized by a large volume and duration. And in these modern realities, it is important to provide complete pain relief to the patient not only during surgical procedures, but also in the postoperative period. Thus, important points The choice of NSAIDs is: adequate analgesic effect, short time of onset of analgesic effect, long period of action in the postoperative period. Ketorolac meets these requirements.
Ketorolac is currently widely used for pain relief in maxillofacial surgery and surgical dentistry. Ketorolac provides fairly reliable and adequate pain relief in the postoperative period, which allows it to be considered an effective analgesic. The drug is trouble-free, and when prescribed prophylactically (i.e. before BS), it contributes to a painless course of the postoperative period.
In the group of patients who received under intravenous anesthesia third molars lower jaw 30 mg ketorolac intravenously, a decrease in pain intensity, measured using a visual analogue pain scale, was noted in the postoperative period.
The high analgesic potential of ketorolac has been noted in a number of studies in patients after periodontal surgery. Preoperative administration of ketorolac 10 mg in periodontal surgery significantly reduces the intensity of initial surgical pain compared with placebo. In comparative studies in dental patients, it was noted that ketorolac has a stronger and longer-lasting analgesic effect compared to dexketoprofen and tramadol.
Postoperative pain is also a serious problem for patients in aesthetic surgery clinics. The use of ketorolac in this category of people reduces the incidence of postoperative nausea and vomiting, which leads to a more favorable course of the postoperative period.
In the Russian Federation, among drugs with international non-proprietary name“Ketorolac”, the best known drug is Ketorol® (Dr. Reddy’s Laboratories Ltd., India). The drug Ketorol® is available in following forms: 1) solution for parenteral administration in ampoules of 30 mg/ml;
2) tablets for oral administration, 10 mg; 3) 2% gel for topical use (contains 20 mg of active substance).
Ketorol® has many years of positive experience in use in surgical, traumatological, oncological, neurological, therapeutic, dental and other hospitals, as well as in outpatient and emergency practice.
The presence of the drug Ketorol® in the arsenal of a dental surgeon allows for effective and safe therapy pain at all stages of surgical treatment.
Anti-inflammatory tablets for toothache are, strictly speaking, not a treatment, but only a relief of symptoms, alleviation of the condition of a patient suffering from toothache. Since dentistry is the only area in medicine that uses completely different means as treatment. Tablets help you endure the pain, but you still have to go to the dentist. In addition, if you suppressed the pain with pills and it went away within a day, this does not mean that the problem has been resolved - a new exacerbation cannot be avoided, because dental inflammation don't go away on their own.
So, what anti-inflammatory pills can help you temporarily cope with toothache on your own - before visiting the dentist?
Anti-inflammatory drugs include Nurofen, Ibuprofen, Ketorol, Ketanov, Brufen, Nise, Actasulide, Aspirin-S and others. Let's look at some of them in a little more detail.
Axatulide. This non-steroidal anti-inflammatory drug belongs to the nimesulide group. Axatulide has a strong analgesic and anti-inflammatory effect. It is used in dental practice for pulpitis, periodontitis and other dental diseases. The drug has contraindications: it cannot be used if there is peptic ulcer stomach and duodenum, as well as for diseases of the liver, kidneys, diabetes mellitus, hypertension, heart failure. Children under 12 years of age are also contraindicated.
Nise. Also belongs to the group of nimesulides. It has a pronounced anti-inflammatory and less pronounced analgesic effect. It is usually used for pain during the post-filling period, as well as for pulpitis, etc.
Aspirin-S. This non-steroidal anti-inflammatory drug belongs to the group of salicylates. Action – analgesic, anti-inflammatory, antipyretic. It is usually used for pain of various etiologies - headache, toothache, migraine, neuralgic pain, etc. Contraindications: ulcerative-erosive lesions gastrointestinal tract(in the acute stage), bleeding in the gastrointestinal tract, renal dysfunction.
Ketorol. It has a pronounced analgesic with a slight anti-inflammatory effect. It is used for very severe toothache when other anti-inflammatory drugs have no longer helped.
Sologova Diana Igorevna
Poundovaya Kristina Dmitrievna
Federal State Autonomous Educational Institution of Higher Education “First Moscow State Medical University named after. THEM. Sechenov Ministry of Health of Russia" (Sechenov University)
EFFECTIVENESS OF NSAID USE
In terms of the strength of the analgesic effect, Ketorolac is significantly superior to other NSAIDs. The drug does not depress respiration, does not affect opioid receptors, does not cause drug dependence, and does not have a sedative or anxiolytic effect. It is also important that the drug begins to have an analgesic effect after 15-30 minutes. after reception. The drug is recommended for use as a pathogenetic and symptomatic therapy with conservative and surgical treatment generalized periodontitis. With its use, earlier relief of pain and signs of local inflammatory reaction (swelling and bleeding of the gums) are recorded. The drug is also capable of reducing the rate of bone tissue resorption, incl. and in the presence of microorganisms, which is a significant factor in favor of including the drug in the pharmacotherapy regimen for periodontitis.
In addition, because Ketorolac has high analgesic activity; it is used as an alternative to narcotic analgesics for moderate or severe pain after surgery in the maxillofacial area.
It relieves pain well and helps with most of these symptoms, and also relieves the inflammatory process in soft tissues. In addition, ketoprofen helps lower the temperature if it is elevated due to some serious pathology. It is used in the form of a rinse solution - symptomatic treatment of inflammatory diseases of the oral cavity, such as stomatitis, glossitis, gingivitis, periodontitis, periodontal disease, for analgesia during the treatment and extraction of teeth (as an auxiliary drug). Ketoprofen relieves pain quite quickly, but this is not enough. It does not affect the cause of the disease (caries, pulpitis or periodontitis). The main danger of the drug is that a person can suppress the pain for a very long time and not go to the doctor, and this will lead to complications both for dental diseases and for the whole body (possible development of dizziness, lethargy, vomiting, nausea, abdominal pain) .
Ketoprofen in the form of a 1% cream, when applied 1.8 ml once a day for 6 months to the gum area of rhesus monkeys with periodontitis, promoted the restoration of alveolar bone and significantly reduced the levels of PGE2 and LT B4 in the periodontal fluid (after 2 and 3 months of treatment ). The drug in the form of a 2% gel, when applied to the gums of patients with chronic periodontitis in addition to instrumental therapy, contributed to a significant reduction in probing depth.
The drug is used primarily for rheumatic diseases, affecting joints and surrounding tissues. The action of the medicine is aimed at eliminating the symptoms of inflammation, which include pain, incl. and dental. But it must be remembered that the effectiveness of Nimesulide depends on the reason for the toothache. In severe dental pathologies, even potent analgesics cannot eliminate the symptom.
It is effective to use the drug for gingivitis, because it eliminates swelling and helps normalize local temperature. The effect after administration is observed quite quickly; on average, it begins to act after 25-30 minutes. The analgesic effect lasts for a fairly long period of time - up to 10 hours.
Important! The medicine is also characterized by a number of disadvantages: it cannot be used during pregnancy and children; it is not intended for long-term use; there is a possibility of addiction; toxic effects on the liver; potential - overdose and poisoning.
Due to this, pain is reduced, but the effect is temporary (lasts up to 12 hours). You can take the drug for toothache, but no more than 5 days in a row.
The administration of Ibuprofen to patients with chronic periodontitis after 14 days was accompanied by a significantly more pronounced reduction in bleeding and hyperemia of the gums, as well as the depth of periodontal pockets compared to the group without pharmacotherapy.
Use of NSAIDs:
You should not take NSAIDs if:
To avoid intoxication and negative impact on the gastric mucosa, you must take the drug after meals.
NSAIDs. GENERAL CHARACTERISTICS
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of medications that are widely used in clinical practice, many of which can be purchased without a prescription. More than thirty million people worldwide take NSAIDs daily, with 40% of these patients over 60 years of age. The great popularity of NSAIDs is explained by the fact that they have anti-inflammatory, analgesic and antipyretic effects and bring relief to patients with corresponding symptoms (inflammation, pain, fever), which are observed in many diseases. The use of the term “non-steroidal” emphasizes their difference from glucocorticoids, which have not only an anti-inflammatory effect, but also other, sometimes undesirable properties of steroids.
Over the past 30 years, the number of NSAIDs has increased significantly, and currently this group includes large number drugs that differ in their characteristics of action and use.
More than 60 million packages of Ibuprofen and Ketorolac, more than 25 million packages of Diclofenac, and almost 20 million packages of Nimesulide are sold annually in Russia.
The main mechanism of action of NSAIDs is the suppression of the activity of cyclooxygenase (COX), an enzyme that regulates the conversion of arachidonic acid into prostaglandins (PG), prostacyclin (PG12) and thromboxane (TxAg). Especially great value has the effect of NSAIDs on the COX isoforms - COX-1 and COX-2. COX-1 is constantly present in most tissues (albeit in varying quantities) and belongs to the category of “constitutive” (“structural”) enzymes that regulate physiological effects PG. COX-2 plays the role of a “structural” enzyme only in some organs (brain, kidneys, bones, reproductive system in women), and is not normally found in other organs. However, the expression of COX-2 increases significantly under the influence of immune mediators (cytokines) involved in the development of the immune response, inflammation, cell proliferation, etc.
Inhibition of COX-2 is one of the important mechanisms of anti-inflammatory and analgesic activity, and COX-1 of the toxicity of NSAIDs. Non-selective NSAIDs inhibit the activity of both COX isoforms to the same extent and therefore have approximately similar effectiveness. This discovery served as the basis for the creation new group NSAIDs that primarily inhibit COX-2 (selective COX-2 inhibitors). They have all the positive properties of non-selective NSAIDs, but are less toxic, at least in relation to the gastrointestinal tract. Based on their selectivity of action against COX isoforms, NSAIDs are divided into 4 groups ( table 1).
Table 1 Classification of NSAIDs by selectivity of action on COX isoforms
In addition, NSAIDs are classified depending on the severity of their anti-inflammatory activity and chemical structure. The first group includes drugs with a pronounced anti-inflammatory effect. NSAIDs of the second group, which have a weak anti-inflammatory effect, are often referred to as “non-narcotic analgesics” or “analgesics-antipyretics” ( table 2).
Table 2Classification of NSAIDs depending on severity
anti-inflammatory activity and chemical structure
|
NSAIDs with pronounced anti-inflammatory activity |
|
|
Salicylates |
Acetylsalicylic acid |
|
Pyrazolidines |
Phenylbutazone |
|
Indoleacetic acid derivatives |
Indomethacin |
|
Phenylacetic acid derivatives |
Diclofenac |
|
Oxycams |
Piroxicam |
|
Propionic acid derivatives |
Ibuprofen |
|
Non-acid derivatives |
|
|
Alcanons |
Nabumethon |
|
Sulfonamide derivatives |
Nimesulide |
|
NSAIDs with weak anti-inflammatory activity |
|
|
Anthranilic acid derivatives |
Mefenamic acid |
|
Pyrazolones |
Metamizole |
|
Para-aminophenol derivatives |
Phenacetin |
|
Heteroarylacetic acid derivatives |
Ketorolac |
NSAIDS IN DENTISTRY
According to Orenburg state university, the list of the most commonly used non-steroidal anti-inflammatory drugs in dental practice in tablet form according to data for 2015 was as follows ( rice.):
In dental practice, NSAIDs are widely used for inflammatory diseases of the maxillofacial region and oral mucosa, inflammatory swelling after injuries, operations, pain syndrome, arthrosis and arthritis of the temporomandibular joint, myofascial pain syndrome of the maxillofacial region, neuritis, neuralgia, postoperative pain, feverish conditions.
