Nonsteroidal anti-inflammatory drugs (NSAIDs, NSAIDs) – a group of drugs that have the ability to relieve the inflammatory process, anesthetize (analgesic), relieve fever, and also perform a number of other functions, for example, inhibit blood coagulation.
The emphasis on the term “non-steroidal” is made in order to highlight their non-hormonal nature, since steroid hormones, or, as they are also called, glucocorticosteroids (HA), are more powerful means aimed at removing a strong inflammatory process. In fact, NSAIDs are synthetic analogues of hormones.
By the way, HA are more effective in relation to inflammation due to inhibition of phospholipase A2, due to which the formation of not only prostaglandins, but also another important mediator of inflammation , leukotrienes, is inhibited.
The most popular non-steroidal anti-inflammatory drugs are Aspirin, Ketanov, Diclofenac, Nimesil, Ibuprofen.
If we talk about the historical aspect of NSAIDs, the first substance is salicylic acid, isolated and synthesized from willow bark by Rafael Piria (Italian chemist) in 1829. Due to this, despite the popularity of anti-inflammatory drugs, traditional healers still use willow bark.
The mechanism of action, or how NSAIDs work
The mechanism of action of most NSAIDs is based on the inhibition (inhibition) of the production of COX enzymes (cyclooxygenase, both forms COX-1 and COX-2), which in turn take part in the production of prostaglandins. It is prostaglandins that are the substances responsible for the body’s response to infection (viruses, bacteria , etc.) and other pathogenic factors, such as fever, pain, inflammation and other symptoms of various diseases, especially of an infectious nature.
COX, and to be more specific, COX-1 is also involved in the production of thromboxane, which is one of the factors in blood coagulation. Active NSAIDs in relation to COX-1 due to inhibition of thromboxane makes the blood more liquid (angiaggregation effect). Due to this property, acetylsalicylic acid and other COX-1 inhibitors are used for the treatment and prevention of diseases of the cardiovascular system.
Thus, NSAIDs have the following effects:
- Anesthetic (analgesic);
- Immunosuppressive (moderate).
The classification of non-steroidal anti-inflammatory drugs is made according to the chemical structure, severity and mechanism of action.
The lists indicate the active substances.
By chemical structure:
- Salicylates – acetylsalicylic acid (aspirin), diflunisal, lysine monoacetylsalicylate.
- Phenylacetic derivatives – aceclofenac, diclofenac.
- Indolacetic derivatives – indomethacin, sulindac, etodolac.
- Propionic derivatives: ibuprofen, dexketoprofen, ketoprofen, naproxen, thiaprofenic acid, flurbiprofen.
- Pyrazolidines: metamizole sodium, phenylbutazone.
- Oxycams: lornoxicam, meloxicam, piroxicam, tenoxicam.
- Alkanones: Nabumeton
- Derivatives of sulfonamide: nimesulide, rofecoxib, celecoxib.
By severity of action
Location of active substances, depending on the severity of anti-inflammatory activity (from the maximum strength to the least active substance):
1. Indomethacin (Indomethacinum)
2. Flurbiprofen (Flurbiprophenum)
3. Diclofenac sodium (Sodium diclofenac)
4. Pyroxicam (Piroxicamum)
5. Ketoprofen (Ketoprophenum)
6. Naproxen (Naproxenum)
7. Ibuprofen (Ibuponhenophenum)
8. . Ustar. name – Amidopyrine 9. Acetylsalicylic acid (Acidum acetylsalicylicum).
The location of the active substances, depending on the severity of the analgesic (analgesic) effect (from the most powerful to the least active substances in this regard):
1. Ketorolac (Ketorolacum) – «Ketorolac”, “Ketanov”
2. Ketoprofen (Ketoprophenum)
3. Sodium Diclofenac (Sodium diclofenac)
4. Indomethacin (Indomethacinum)
5. Flurbiprofen (Flurbiprophenum)
6. aminophenazone (Aminophenazonum)
7. Piroxicam (Piroxicamum)
8. Naproxenum (Naproxenum)
9. Ibuprofen (Ibuprophenum)
10. Aspirin (Acidum acetylsalicylicum).
By selectivity to various COX
Depending on the severity and focus of the action, NSAIDs can be divided into 3 main groups:
1. Non-selective inhibitors with respect to COX-1 and COX-2 are the traditional and most common anti-inflammatory drugs that have high activity in all directions characteristic of NSAIDs. This includes drugs based on the following substances – amtolmethine guacyl, acetylsalicylic acid, diclofenac, ibuprofen, indomethacin, ketorolac, ketoprofen, naproxen, sulindac, etodolac.
2. Selective inhibitors of COX-2 with moderate exposure to COX-1. This includes drugs based on the following substances – lornoxicam, meloxicam, nabumeton, nimesulide, tenoxicam.
3. Highly selective inhibitors in relation to COX-2, which have almost no effect on COX-1. This includes drugs based on the following substances – parecoxib, rofecoxib, celecoxib, etoricoxib.
In fact, coxibs were designed for the accented use of NSAIDs to minimize side effects from anti-inflammatory drugs. The use of coxib excludes bleeding in the digestive tract, the development of stomach ulcers and duodenal ulcers. The most famous coxibs are Valdecoxib, Lumiracoxib, Parecoxib, Rofecoxib, Firocoxib, Celecoxib, Etoricoxib.
The use of NSAIDs – for which diseases are prescribed
In what cases and diseases is it advisable to use non – steroidal anti – inflammatory drugs?
Indications for the use of NSAIDs are acute and chronic forms of diseases of various etiologies, as well as pathologies and conditions that are accompanied by pain, high body temperature, swelling, and increased blood clotting.
Most often, NSAIDs are used for the following diseases and pathologies:
- Inflammatory diseases of various localizations and etiologies, for example , acute respiratory infections, in which body temperature exceeds acceptable values for a safe course and / or does not go away for several days – tonsillitis, pharyngitis, laryngitis, tracheitis, bronchitis, pneumonia, as well as cystitis, pancreatitis, cholecystitis and others;
- Diseases of the musculoskeletal system – arthritis and arthropathy (rheumatoid, osteoarthritis, ankylosing spondylitis), osteochondrosis, myositis, tendovaginitis, gout;
- Pain of various etiologies – headache, toothache, postoperative, dysmenorrhea, traumatic nature (fractures, bruises, sprains, dislocations);
- Oncological diseases;
- Colic – renal, hepatic;
- Neurological diseases – neuralgia, rheumatism, sciatica, lumbago, sciatica;
- Fever, usually at 38.0 ° C and above in children and 38.5 ° C in adults;
- Diseases and prevention of the cardiovascular system – thrombosis, atherosclerosis, coronary heart disease (CHD), angina pectoris, heart failure, myocardial infarction.
The main contraindications to the use of NSAIDs are:
- Individual intolerance;
- The presence of erosive and / or ulcerative formations in the gastrointestinal tract;
- Diseases and pathologies of the liver, kidneys;
- Increased demand for increased care (drivers and others) – selective substances inhibit the activity of the body, such as indomethacin, phenylbutazone.
- Pregnancy (the doctor may, according to indications, prescribe a medicine with minimally pronounced activity, for example, based on acetylsalicylic acid).
With extreme caution, NSAIDs are prescribed in the following cases:
- Bronchial asthma;
- The appearance of side effects;
- Hypertension, heart failure – in this case, drugs with the least effect on blood circulation in the kidneys are prescribed;
- Old age – minimally active NSAIDs are prescribed in short courses.
After NSAIDs enter the gastrointestinal tract, it is absorbed almost completely in it, after which it binds to plasma albumin and begins to displace a number of other substances, for example, bilirubin in infants, but we will look at this in the Interaction section.
NSAID metabolism occurs in the liver, and elimination from the body through the kidneys.
In some cases, patients may experience a number of disorders in the body:
From the gastrointestinal tract – the phenomena of dyspepsia (discomfort and pain in the abdomen, nausea, flatulence), diarrhea, the development of stomach ulcers and duodenal ulcers, the formation of internal bleeding and perforation of the digestive system, as well as the so-called NSAID-gastroduodenopathy syndrome.
From the urinary system – a decrease in urine volume, edema, hypernatremia, hyperkalemia, interstitial nephritis, renal failure.
From the cardiovascular system – high blood pressure.
From the circulatory system – agranulocytosis, aplastic anemia.
Extension of the period of bearing a child.
Other complications are dizziness, impaired coordination of motion, confusion, allergies, skin rash, jaundice, hepatitis, Quincke’s edema, anaphylactic shock, Stevens-Johnson syndrome, Lyell’s syndrome, Reye’s syndrome.
The main factors of undesirable effects:
- Exceeding the dosage of drugs and prolonged therapy with these drugs;
- Simultaneous intake of more than 1 agent from the NSAID group, as well as when combined with the use of hormonal drugs (HA);
- Bad habits – alcohol abuse, smoking;
- The presence of severe diseases of the cardiovascular system;
- Reception of anticoagulants, immunosuppressants;
- Cirrhosis of the liver;
- Large blood loss;
- Age up to 10-12 years, as well as 65 years and older.
How to take NSAIDs
To better reschedule NSAIDs, it is recommended:
- Take another remedy that protects the gastrointestinal mucosa from side effects and damage – misoprostol, omeprazole;
- Observe clear dosages and medication;
- Take the medicine an hour or two after eating, drink plenty of clean water;
- With prolonged therapy, consult a doctor to monitor the health of the liver, kidneys, blood counts;
- In case of external use (gel, ointment), wait for the complete absorption of the product, and also avoid water procedures after this for several hours.
Interaction of NSAIDs with other substances
- It can increase the activity of oral hypoglycemic drugs, indirect coagulants;
- May weaken the effect of antihypertensive, diuretic (diuretic) drugs;
- Increases toxic effects on the body of aminoglycosides (antibiotics);
- Absorption in the digestive tract is weakened in the case of simultaneous administration with cholestyramine, aluminum-containing antacids (“Maalox”, “Almagel”) – make at least the minimum intervals between doses of 4 hours;
- Absorption in the digestive tract is enhanced with the addition of sodium bicarbonate;
- Anti-inflammatory activity is enhanced if glucocorticoids and other NSAIDs are additionally taken (aminoquinolines, gold preparations);
- Anesthetic activity increases if sedatives, narcotic analgesics are additionally taken;
Try to avoid the following combinations:
- Indirect Coagulants + Oxyphenbutazone, Phenylbutazone, Aspirin
- Sulfonylurea derivatives + Oxyphenbutazone, Phenylbutazone, Aspirin
- Phenytoin + Phenylbutazone, Oxyphenbutazone
- Digoxin + all NSAIDs.
Combinations are contraindicated
- Diuretics + all NSAIDs (at least sulindac)
- Indomethacin + Triamteren
- Methotrexate + all NSAIDs.
NSAID List – New and Old
The list shows the active substances and trade names of the drugs.
Aminophenazone (Aminophenazonum), amidopyrine – is banned in many countries due to the ability to cause a carcinogenic effect in contact with nitrates, which are often present in modern food products. However, small doses of this substance are present in the following medicines – Anapirin, Omazol, Pentalgin, Piranal, Reopyrin, Theofedrine N.
Acetylsalicylic acid (Acidum acetylsalicylicum) – Anopyrin, Askopyrin, Aspikard, Aspikor, Aspinat, Aspirin, Acecardol, Acenterin, Acetylsalicylic acid, Acylperin ”,“ CardiASK ”,“ Colfarit ”,“ Mikristin ”,“ Plidol ”,“ Taspir ”,“ Trombo ACC ”,“ Trombogard ”,“ Trombopol ”,“ Trombosten ”,“ Upsarin UPSA ”.
Diclofenac (Diclophenacum) – Argette, Artrex, Veral, Voltaren, Dialrapid, Diclac, Diclobene, Dicloberl, Diclovit, Diclogen, Diclomax, Diclomelan, Diclonac, Diclonat, Dicloran, Diclorium, Diclofarm, Diclofen, Diclofenac, Diphen, Dorosan, Naklof, Naklofen, Sodium Diclofenac ”,“ Ortofen ”,“ Ortofer ”,“ Ortofleks ”,“ Penside ”,“ Rapten ”,“ Revmavek ”,“ Revodina retard ”,“ Remetan ”,“ Sanfinak ”,“ Feloran ”,“ Flektor ”,“ Flotak ” .
Ibuprofen (Ibuprophenum) – “Advil”, “ArtroKam”, “Baralgin”, “Bonifen”, “Brudol”, “Brufen”, “Bumidol”, “Burana”, “Deblock”, “Dolgit”, “Ibuprom”, “ Ibuprofen ”,“ Ibusan ”,“ Ibutop gel ”,“ Ibufen ”,“ Ipren ”,“ Maxikold ”,“ MIG ”,“ Nebolin ”,“ Nurofactor ”,“ Nurofast ”,“ Nurofen ”,“ Pedea ”,“ Sedalgin “,” Solpafleks “,” Faspik “.
Indomethacinum (Indomethacinum) – Indobene, Indovis, Indocollyr, Indomethacin, Indotard, Indocide, Metindol.
Ketorolac (Ketorolacum) – “Adolor”, “Dolak”, “Dolomin”, “Ketalgin”, “Ketanov”, “Ketokam”, “Ketolak”, “Ketorol”, “Ketorolak”, “Ketorolac tromethamine”, “Ketofril”, “Toradol”, “Torolak”.
Ketoprofen (Ketoprophenum) – Arketal, Arthrosilen, Artrum, Bystrum Forte, Bystrumgel, Bystrumkaps, Valusal, Ketonal, Ketoprovel, Ketoprofen, Oki, “Oruvel”, “Pentalgin”, “Profenid”, “Spazgel”, “Fastum”, “Febrofid”, “Flamax”, “Flexen”.
Lornoxicamum (Lornoxicamum) – “Zornika”, “Xefocam”, “Lornoxicam”.
Meloxicamum (Meloxicamum) – Ameloteks, Arthrosan, Genitron, Lem, Liberum, Mataren, Medsikam, Melbek, Melokvitis, Meloks, Meloksam, Meloxicam ”,“ Meloflex ”,“ Mesipol ”,“ Mirlox ”,“ Movagain ”,“ Movalis ”,“ Movasin ”,“ Movix ”,“ Oksikamoks ”,“ Revmart ”,“ Flexibon ”,“ Exen-Sanovel ”.
Metamizole sodium (Metamizolum natrium) – “Analgin”, “Baralgin”, “Metamizole sodium”, “Optalgin”, “Spazdolzin”.
Nabumetonum (Nabumetonum) – “Relafen”.
Naproxenum (Naproxenum) – “Algezir”, “Olive”, “Apranax”, “Motrin”, “Nalgezin”, “Naprios”, “Naprobene”, “Naproxen”, “Naproxen sodium”, “Pentalgin”, “Pronaxen”, “Sanaprox”, “Theraliv”.
Nimesulid (Nimesulidum) – Aktasulid, Aponil, Aulin, Mesulid, Nise, Naysulid, Nemuleks, Nimegesik, Nimesan, Nimesil, Nimesulid Nimika ”,“ Nimulid ”,“ Prolide ”,“ Sulaydin ”,“ Flolid ”.
Parecoxib (Parecoxibum) – “Dynastat”.
Piroxicamum (Piroxicamum) – “Vero-Pyroxicam”, “Kalmopyrol”, “Pirokam”, “Pyroxicam”, “Pyroxifer”, “Revmador”, “Remoxicam”, “Sanikam”, “Feldoral”, “Felden”, “Final gel” , Hotemin.
Rofecoxib (Rofecoxibum) – “Vioks”.
Sulindak (Sulindacum) – “Clinoril”.
Tenoxicam (Tenoxicamum) – Artoxan, Texamen, Texared, Tenikam, Tenoktil, Tilkotil, Tobitil.
Flurbiprophenum (Flurbiprophenum) – “Rakstan-Sanovel”, “Strepsils Intensive”, “Flugalin”.
Celecoxibum (Celecoxibum) – Dilaxa, Coxib, Rouxoxib, Simcoxib, Celebrex, Celecoxib.
Etodolac (Etodolacum) – “Nobedolac”, “Elderin”.
Etoricoxibum (Etoricoxibum) – Arkoxia, Atorika, Bixitor, Kostaroks, Riksia, Strega, Etorelex, Etoriaks, Etorikoksib.