Indomethacin

Like NSAIDs, indomethacin is analgesic, anti-inflammatory and antipyretic. Clinical indications for indomethacin include:

Joint diseases

• rheumatoid arthritis ^[1]
• ankylosing spondylitis ^[1]
• osteoarthritis ^[1]
• gouty arthritis ^[1]
• acute painful brachial bursitis or tendonitis ^[1]

Headaches

• Trigeminal vegetative cephalias ^[2]
• Paroxysmal hemicrania ^[2]
• Chronic paroxysmal hemicrania ^[2]
• Episodic paroxysmal hemcrania ^[2]
• Hemicrania continua ^[2]
• Valsalva-induced headaches ^[2]
• Primary cough headache ^[2]
• Primary Tense Headache ^[2]
• Primary headache associated with sexual activity (preorgasm and orgasm) ^[2]
• Primary headache (shock and jolt syndrome) ^[2]
• Hypnotic headache ^[2]

Other

• Open arterial duct ^[3]

Indomethacin has also been used clinically to delay preterm labor , reduce amniotic fluid in polyhydramnios, and close an open arterial duct .

Indomethacin is a potent drug with many serious side effects and should not be considered an analgesic for minor pains and fever. The drug is better described as anti-inflammatory rather than analgesic. Indomethacin can also affect warfarin and subsequently increase the prothrombin time .

Extensive evidence implies inflammatory processes in the pathogenesis of Alzheimer's disease. Nonsteroidal anti-inflammatory drugs, such as indomethacin, have been proposed for the treatment of patients with Alzheimer's disease. Only one study met the inclusion criteria. In this selected trial, the authors did not perform a statistical analysis of the absolute change from the baseline, but on a percentage change from the baseline. Given the difficulties in evaluating a single trial, there is currently no indication for the treatment of mild to moderate Alzheimer's disease with indomethacin. ^[four]

Indomethacin for very premature or small children with signs of open arterial duct (OAD), but no symptoms can prevent OAD, but more research is needed for long-term results. A common complication for very premature (premature) or very young children is a PDA (open arterial duct). OAP is an open channel between the lungs and the heart, which was supposed to close after birth, and can cause life-threatening complications. Indomethacin is often given to all babies who are at risk from OAD, but this can cause adverse effects. It can also be given only to babies who have early signs of PDA, but who still do not have symptoms. A review of research has shown that this selective use of indomethacin can prevent PDA and has short-term benefits, but more research is needed for long-term results. ^[five]

Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) used to treat postoperative pain. Only one small study of women with posepiomyotomicheskoy pain was found, when the effectiveness of the drug (taken orally) was compared with placebo. Conclusions regarding the efficacy of oral administration of indomethacin cannot be made until further studies have been carried out. ^[6]

• Joint peptic ulcer or ulcers in the history of the disease
• Allergy to indomethacin, aspirin or other NSAIDs
• Roux-en-Y gastric shunt and gastric sleeve
• Patients with nasal polyps that react with angioedema other NSAIDs
• Children under 2 years old (except for newborns with duct atherosclerosis)
• Pre-existing severe kidney and liver damage

Take with caution

• Pre-existing bone marrow damage (indicated are frequent blood cell counts)
• Tendency to bleed of unknown origin (indomethacin inhibits platelet aggregation)
• Parkinson's disease , epilepsy , psychotic disorders (indomethacin can worsen these conditions) ^[7]
• In parallel with potassium-sparing diuretics
• Patients who have a defect of the heart defect associated with the arterial duct (for example, the transfer of large vessels)
• Significant hypertension (high blood pressure)
• Concomitant administration of lithium salts (such as lithium carbonate)

In general, the side effects observed with indomethacin are similar to all other NSAIDs. For example, indomethacin inhibits both cyclooxygenase-1 and cyclooxygenase-2, which then inhibits the production of prostaglandins in the stomach and intestines , which are responsible for maintaining the mucous membrane of the gastrointestinal tract . Thus, indomethacin, like other non-selective inhibitors of MOR, can cause peptic ulcers . These ulcers can lead to serious bleeding and / or perforation, requiring the patient to be hospitalized.

To reduce the likelihood of ulcers in the peptic region, indomethacin should be administered with the minimum dose necessary to achieve a therapeutic effect, usually from 50 to 200 mg / day. It should always be taken with food. Almost all patients receive medication for ulcers (for example, high-dose antacids, ranitidine 150 mg at bedtime or omeprazole 20 mg at bedtime). Other common gastrointestinal complaints, including dyspepsia , heartburn, and mild diarrhea, are less serious and rarely require discontinuation of indomethacin.

Many NSAIDs, but especially indomethacin, cause lithium retention by reducing its excretion by the kidneys. Thus, users of indomethacin have an increased risk of lithium toxicity. For patients taking lithium (for example, to treat depression or bipolar disorder ), less toxic NSAIDs such as sulindac or aspirin are preferred.

All NSAIDs, including indomethacin, also increase plasma renin activity and aldosterone levels, and increase sodium and potassium retention. Also increases the activity of vasopressin . Together they can lead to:

• Edema (swelling due to fluid retention)
• Hyperkalemia (high potassium levels) ^[8]
• Hypernatremia (high sodium)
• Increased blood pressure

Elevated serum creatinine levels and more serious kidney damage are also possible, such as acute renal failure , chronic nephritis and nephrotic syndrome . These conditions also often begin with edema and hyperkalemia.

Paradoxically, but unusually, indomethacin can cause a headache (from 10 to 20%), sometimes with dizziness, hearing loss, tinnitus, blurred vision (with or without retinal damage). There are unsubstantiated reports of worsening Parkinson's disease, epilepsy, and mental disorders. Cases of life-threatening shock have been reported (including angioedema, sweating, severe hypotension and tachycardia, as well as acute bronchospasm), severe or lethal hepatitis, and severe bone marrow damage. Skin reactions and photosensitivity are also possible side effects.

The frequency and severity of side effects and the availability of more portable alternatives make today indomethacin the drug of the second choice. Its use in acute attacks of gout and in dysmenorrhea is well established, because according to these indications the duration of treatment is limited to only a few days, so serious side effects are unlikely to occur.

People should undergo a regular physical examination to detect edema and signs of central-nervous side effects. A blood pressure check will show the development of hypertension. It is necessary to conduct periodic measurements of electrolytes (sodium, potassium, chloride), complete analysis of blood cells and evaluation of liver enzymes, as well as creatinine (renal function). This is especially important if indomethacin is administered with an ACE inhibitor or with potassium-sparing diuretics, since these combinations can lead to hyperkalemia and / or serious renal failure. No examinations are needed if only topical preparations are used (spray or gel).

Rare cases have shown that the use of this medication by pregnant women can affect the heart of the fetus, which can lead to the death of the fetus with premature closure of the arterial duct . ^[9]

Indomethacin has a high acute toxicity for animals (in rats, 12 mg / kg) and for humans. Accurate human data does not exist, but some deaths in humans, especially in children and adolescents, have been observed.

As a rule, overdose in people causes drowsiness, dizziness, severe headache, mental confusion, paresthesia , numbness of the limbs, nausea and vomiting. Severe gastrointestinal bleeding is also possible. Osteochondrosis and cardiac arrest were observed in children.

The treatment is symptomatic and pretty much the same as that of diclofenac . Nevertheless, it should be noted the possibility of serious symptoms of the gastrointestinal tract.

The risk of overdose after exaggerated local gel or spray therapy is very limited.

Pharmacological action: anti-inflammatory, antipyretic, analgesic. Inhibits cyclooxygenase (COX-1 and COX-2), reduces the synthesis of prostaglandins (Pg), causing pain in the inflammation focus, fever, and an increase in tissue permeability. It has an antiplatelet effect ^[10] .

Causes the weakening or disappearance of rheumatic and non-rheumatic pain syndrome (including pain in the joints at rest and during movement, reduces morning stiffness and swelling of the joints, increases the volume of movements; during inflammatory processes that occur after surgery and injuries, quickly alleviates both spontaneous pain and pain when moving, reduces inflammatory swelling at the wound site).

After ingestion of a single dose of 25 or 50 mg is rapidly absorbed, Tmax - about 2 hours; with rectal use, the absorption rate is higher. When taken orally, bioavailability is 90–98%, with rectal use it is slightly less — 80–90%, which is probably due to insufficient suppository retention time (less than 1 hour) to ensure complete absorption. Plasma protein binding is 90–98%. T1 / 2 - 4–9 hours. With 25 or 50 mg daily of indomethacin three times a day, the equilibrium concentration is 1.4 times higher than the concentration after a single dose. Biotransforming mainly in the liver. In the blood plasma is in the form of an unchanged substance and desmethyl-, disbenzoyl- and desmethyl-disbenzoylmetabolites, present in the unconjugated form. Excreted primarily by the kidneys - 70% (30% - unchanged) and the gastrointestinal tract - 30%. Passes through the hemato-encephalic barrier , the placenta, penetrates into breast milk. Not removed during hemodialysis.

When instillation of eye drops penetrates into the anterior chamber of the eye. After a single instillation is determined in the moisture of the anterior chamber for several hours.

Indomethacin suppositories are prescribed for prostatitis to relieve symptoms. The main therapeutic properties of indomethacin for prostatitis are:

• analgesic effect
• antimicrobial action
• decrease in prostaglandin synthesis
• size reduction of the inflamed prostate

The medicine is prescribed by doctors usually in the case of chronic prostatitis as an adjuvant. Apply candles can be no more than 2 times a day. Usually, doctors recommend patients to install them in the early morning and evening, before going to bed. The duration of the course of therapy in this way can be 25-30 days. ^[eleven]