British doctors have reported serious side effects from the popular painkiller ibuprofen. Experts noted that it can cause dizziness, headaches, nausea, indigestion and even poses a risk of gastrointestinal bleeding and blurred vision. But you need to be careful with any painkillers.
The side effects of ibuprofen were reported to the UK National Health Service. Doctors found that “more than one person” in 100 experienced negative symptoms after taking ibuprofen. Some had a stronger headache, others felt dizzy, felt nauseated and had indigestion.
But the biggest problems are the risk of gastrointestinal bleeding and visual impairment. In some cases, an allergic reaction is also possible.
The negative aspects of ibuprofen have been written about before. For example, in December 2022, Dr. Alexander Myasnikov said that drugs based on ibuprofen or analgin can cause stroke, heart attack or hypertension. These substances are especially contraindicated for people over 60 years of age.
In March 2020, the World Health Organization announced the dangers of self-administration of ibuprofen in the treatment of coronavirus, noting the risks of internal bleeding.
However, medical experts warned that any substance should be treated with caution. It is best not to self-medicate, but to turn to professionals.
Relevance
The results of the PRECISION-ABPM study were presented at the European Congress of Cardiology held in Barcelona.
The analysis found that ibuprofen was associated with increased blood pressure (BP) and hypertension compared with celecoxib in patients with osteoarthritis and rheumatoid arthritis. Nonsteroidal anti-inflammatory drugs (NSAIDs), both selective COX-2 inhibitors and non-selective drugs, are widely prescribed by doctors of all specialties. Thus, in developed countries, about 20% of individuals take at least one NSAID on a regular basis, and if we remember that the incidence of arterial hypertension in the general population is 40%, then the problem becomes of great importance.
Indications for use
Rheumatoid arthritis, osteoarthritis, articular syndrome with exacerbation of gout, psoriatic arthritis, ankylosing spondylitis (ankylosing spondylitis), cervical spondylosis, Barre-Lieu syndrome (cervical migraine, vertebral artery syndrome); neuralgia, myalgia, tendinitis, bursitis, tendovaginitis, neuralgic amyotrophy, sprain of the ligamentous apparatus, hematomas, radiculitis, traumatic inflammation of soft tissues and the musculoskeletal system; febrile conditions of various origins (including after immunization); symptomatic treatment of influenza and ARVI; postural hypotension when taking antihypertensive drugs; nephrotic syndrome (to reduce the severity of proteinuria). As an adjuvant: infectious and inflammatory diseases of the ENT organs (tonsillitis, pharyngitis, laryngitis, sinusitis, rhinitis), bronchitis, pneumonia, inflammatory processes in the pelvis, adnexitis, primary dysmenorrhea, algodismenorrhea, postoperative pain, headache and toothache, panniculitis.
PRECISION-ABPM Study
The PRECISION-ABPM study is part of the larger PRECISION study. The researchers assessed the effect of the NSAIDs celecoxib, naproxen and ibuprofen on blood pressure levels over a 4-month period.
PRECISION-ABPM is a double-blind, randomized, non-inferiority study. The study was conducted at 60 centers in the United States and included 444 patients, of whom 408 (92%) had osteoarthritis and 36 (8%) had rheumatoid arthritis.
Patients were randomized in a 1:1:1 ratio to receive celecoxib (100–200 mg twice daily), ibuprofen (600–800 mg three times daily), or naproxen (375–500 mg twice daily).
The primary endpoint was the change in blood pressure after 4 months of therapy (outpatient 24-hour blood pressure monitoring).
IBUPROFEN-CHEMOPHARM
Interaction
Concomitant use of ibuprofen with acetylsalicylic acid and other NSAIDs is not recommended.
When administered simultaneously, ibuprofen reduces the anti-inflammatory and antiplatelet effects of ASA (an increase in the incidence of acute coronary insufficiency in patients receiving small doses of ASA as an antiplatelet agent is possible after starting ibuprofen).
When prescribed with anticoagulant and thrombolytic drugs (alteplase, streptokinase, urokinase), the risk of bleeding simultaneously increases.
Concomitant use with serotonin reuptake inhibitors (citalopram, fluoxetine, paroxetine, sertraline) increases the risk of developing serious gastrointestinal bleeding. Cefamandole, cefaperazone, cefotetan, valproic acid, plicachycin increase the incidence of hypoprothrombinemia.
Cyclosporine and gold preparations enhance the effect of ibuprofen on the synthesis of prostaglandins in the kidneys, which is manifested by increased nephrotoxicity. Ibuprofen increases the plasma concentration of cyclosporine and the likelihood of developing its hepatotoxic effects.
Drugs that block tubular secretion reduce excretion and increase plasma concentrations of ibuprofen.
Inducers of microsomal oxidation (phenytoin, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants) increase the production of hydroxylated active metabolites, increasing the risk of developing severe hepatotoxic intoxications.
Microsomal oxidation inhibitors reduce the risk of hepatotoxicity.
Reduces the hypotensive activity of vasodilators (including slow calcium channel blockers (SCBC), angiotensin-converting enzyme (ACE) inhibitors), natriuretic and diuretic activity - furosemide and hydrochlorothiazide.
Reduces the effectiveness of uricosuric drugs, enhances the effect of indirect anticoagulants, antiplatelet agents, fibrinolytics (increasing the risk of hemorrhagic complications), enhances the ulcerogenic effect with bleeding of mineralocorticosteroids (MCS) and glucocorticosteroids (GCS), colchicine, estrogens, ethanol.
Enhances the effect of oral hypoglycemic drugs (including sulfonylurea derivatives) and insulin.
Antacids and cholestyramine reduce the absorption of ibuprofen.
Increases the blood concentration of digoxin, lithium and methotrexate.
Caffeine enhances the analgesic effect.
Myelotoxic drugs increase the manifestations of hematotoxicity of the drug.
results
- The analysis showed that celecoxib reduced mean 24-hour systolic blood pressure by -0.3 mmHg. Art., while ibuprofen and naproxen increased by 3.7 and 1.6 mmHg. Art., respectively. The difference between celecoxib and ibuprofen was statistically significant (p=0.009).
- Additional analysis demonstrated that the percentage of patients with normal BP at baseline who were subsequently diagnosed with hypertension was 23.2 in the ibuprofen group, 19.0 in the naproxen group, and 10.3 in the celecoxib group (odds ratio, 0.39; p =0.004 for celecoxib ibuprofen and 0.49 p=0.03 for celecoxib vs. naproxen).
Ibuprofen and coronavirus
Ibuprofen cannot be used as a prophylactic against coronavirus. It also does not kill the virus during illness. It acts only on the symptoms, relieving inflammation, pain and fever, which alleviates the patient's condition. Ibuprofen can be used along with paracetamol. Some combination drugs contain both at the same time.
The active ingredient ibuprofen can have different forms (tablets, suspensions, suppositories, gels, ointments) and different trade names:
- Nurofen Express;
- Nurofen for children (suspension from 3 months);
- Brufen SR;
- Teraflex Advance (for joints, combination with chondroprotectors);
- Brufica Plus (suspension, combination with paracetamol for children over 2 years old);
- Nurofen Long (ibuprofen + paracetamol from 12 years);
- Ibuprofen suppositories (for children).
Other traditional NSAIDs will be analogues of ibuprofen.
However, paracetamol is not an absolutely safe medicine. It is a common cause of acute high-dose poisoning with subsequent hospitalization in the USA and Great Britain1.
It is not recommended to lower the temperature until it is above 38.5 C and is comfortably tolerated by the body.
Discussion
The principal investigator, Prof Ruschitzka (Switzerland, Zurich) noted that the increase in cardiovascular risk during NSAID therapy is in particular associated with drug-mediated increases in blood pressure. This position challenges the well-known hypothesis that the adverse cardiovascular effects of NSAIDs are directly related to effects on platelets and endothelial cells.
It is important to remember that the decrease in systolic blood pressure is only 2 mmHg. Art. is associated with a 10% reduction in mortality from stroke and a 7% reduction in mortality from coronary heart disease.
Source:
European Society of Cardiology Congress. August 28, 2022.
The use of ibuprofen in gynecological practice
Probably, almost every woman at least once in her life has encountered such a condition as painful menstruation. For some, pain during menstruation is so severe that it can render a woman completely incapacitated. In other words, pain is not uncommon in a woman’s life. At the same time, in gynecological practice we often have to perform all sorts of invasive interventions, accompanied by pain, sometimes quite severe, for which it is usually not customary to use general anesthesia. In this situation, you have to resort to non-narcotic analgesics, the effectiveness of which can vary quite a lot. In this article we want to touch upon the issue of pain in gynecological practice and offer treatment options for this condition.
Dysmenorrhea or painful menstruation
are one of the most common reasons why women miss work or school. In many state-owned enterprises, there is still such a thing as “women’s day,” which allows a woman to experience “critical days” outside of the workplace once a month.
Dysmenorrhea is divided into primary and secondary. Under primary dysmenorrhea
understand painful menstruation in the absence of pathological changes in the genital organs.
With secondary dysmenorrhea,
painful menstruation is caused by the presence of gynecological diseases. Most often these include endometriosis, inflammatory diseases of the genital organs, uterine fibroids and others. According to various authors, the incidence of dysmenorrhea depending on age ranges from 60 to 92%. It is obvious that primary dysmenorrhea occurs mainly in adolescents, while secondary dysmenorrhea is typical for older age groups.
Primary dysmenorrhea usually develops 6–12 months after menarche, when the first ovulatory cycles appear. Symptoms of dysmenorrhea usually occur with the onset of menstruation, rarely the day before, and are characterized by cramping, aching, jerking, bursting pain that can radiate to the rectum, appendages and bladder. In addition, nausea, vomiting, headache, irritability, bloating and other autonomic phenomena may occur.
Among adolescents, the peak incidence of dysmenorrhea occurs at 17–18 years of age, that is, at the time of the final formation of menstrual function and the formation of the ovulatory menstrual cycle. This pattern, in particular, indicates the significant role of ovulation in the pathogenesis of primary dysmenorrhea.
Although there is still no clear idea about the etiology of primary dysmenorrhea, most researchers agree that the leading role in the development of this disease is played by an imbalance of prostaglandins in the uterus
.
As early as 1978, it was shown that prostaglandin F2a (PGF2a) and prostaglandin E2 (PGE2) accumulate in the endometrium during menstruation and cause symptoms of dysmenorrhea [1]. Prostaglandin F2a and PGE2 are synthesized from arachidonic acid through the so-called cyclooxygenase pathway. The activity of this enzyme pathway in the endometrium is regulated by sex hormones, more precisely, by sequential stimulation of the endometrium, first with estrogens and then with progesterone. By the time of menstruation, a large concentration of prostaglandins accumulates in the endometrium, which are released due to lysis of endometrial cells. Prostaglandins released from the cells act on the myometrium, which leads to alternating constriction and relaxation of smooth muscle cells. Uterine contractions caused by prostaglandins can last several minutes, and the pressure developed in the uterus can reach 60 mm Hg. Prolonged contractions of the uterus lead to the development of ischemia and, as a consequence, to the accumulation of anaerobic metabolic products, which, in turn, stimulate C-type pain neurons. In other words, primary dysmenorrhea can be called “uterine angina.”
The role of prostaglandins in the development of primary dysmenorrhea is confirmed by a study that found that the concentration of prostaglandins in the endometrium correlates with the severity of symptoms, that is, the higher the concentration of PGF2a and PGE2 in the endometrium, the more severe the dysmenorrhea [2].
Many factors can modulate the effect of prostaglandins on the uterus. For example, vigorous exercise may increase uterine tone, possibly by reducing uterine blood flow. Many female athletes note that intense training during menstruation significantly increases the symptoms of dysmenorrhea. In addition to affecting the uterus, PGF2a and PGE2 can cause bronchoconstriction, diarrhea and hypertension, so, in particular, diarrhea most often accompanies primary dysmenorrhea.
For high production of prostaglandins in the endometrium, sequential exposure to estrogens and then progesterone
. It is obvious that women with an anovulatory menstrual cycle extremely rarely suffer from primary dysmenorrhea due to their lack of sufficient progesterone secretion. In this regard, the presence of ovulation is one of the factors causing the symptoms of dysmenorrhea.
The most common drugs for treatment
primary dysmenorrhea are
oral contraceptives and non-steroidal anti-inflammatory drugs
(NSAIDs). The prescription of oral contraceptives is mainly aimed at stopping ovulation, since, as noted above, it is the ovulatory menstrual cycle that provides cyclic stimulation of the endometrium, which contributes to the accumulation of prostaglandins responsible for the development of symptoms of dysmenorrhea. This method of treatment is quite effective, but when choosing it it is necessary to take into account a number of factors. Firstly, the majority of patients with primary dysmenorrhea are adolescents who are not sexually active, for whom the problem of contraception accompanying the treatment is not so relevant, and the belief in the inevitable gain of excess weight “from hormones” is extremely strong. Secondly, it is not possible to prescribe oral contraceptives in all cases, since they have a number of contraindications. Thirdly, the therapeutic effect from the prescription of oral contraceptives develops only after 2–3 months from the start of their use, which makes their use irrational in cases of particularly severe disease. Thus, the use of oral contraceptives for the treatment of primary dysmenorrhea is optimal in cases where the patient, in addition to treatment, requires reliable contraception, as well as in cases of mild to moderate symptoms.
Another equally effective approach to the treatment of primary dysmenorrhea is the prescription of NSAIDs, in particular the drug ibuprofen
(Nurofen)
, which is most widely used in world clinical practice.
Nurofen (ibuprofen) is a derivative of phenylpropionic acid. Nurofen inhibits the synthesis of prostaglandins by inhibiting the activity of cyclooxygenase. After oral administration, ibuprofen is rapidly absorbed from the gastrointestinal tract, its maximum concentration in the blood plasma is determined after 1–2 hours. Ibuprofen is metabolized in the liver, excreted by the kidneys unchanged and in the form of conjugates, the half-life is 2 hours. Unlike other NSAIDs, side effects are extremely rarely observed when using Nurofen, which are mainly characterized by mild digestive disorders. For the treatment of primary dysmenorrhea, Nurofen is prescribed at an initial dose of 400 mg, then the drug is prescribed at a dose of 200–400 mg every 4 hours, the maximum daily dose of Nurofen is 1200 mg. Obviously, the dose of Nurofen should be selected depending on the severity of the symptoms of the disease.
If the analgesic effect of Nurofen is not enough, it is possible to use the combination drug Nurofen Plus
. This drug combines ibuprofen with codeine, an analgesic that acts on opiate receptors in the central nervous system. This combination gives a more pronounced analgesic effect.
In general, the use of NSAIDs for the treatment of primary dysmenorrhea has a number of advantages over the use of oral contraceptives. Unlike oral contraceptives, which should be taken for several months, NSAIDs are prescribed only for 2-3 days a month, which, on the one hand, is more convenient, and on the other, more cost-effective. In addition, NSAIDs not only effectively neutralize the negative effects of prostaglandins on the uterus, but also eliminate other symptoms of dysmenorrhea, such as nausea, vomiting and diarrhea.
Objectively speaking, it was the high effectiveness of NSAIDs in treating not only the main but also accompanying symptoms of primary dysmenorrhea that confirmed the hypothesis about the role of prostaglandins in the pathogenesis of this disease, and therefore it is obvious that NSAIDs are first-line drugs in the treatment of primary dysmenorrhea
.
Although primary dysmenorrhea is one of the most common gynecological diseases accompanied by pain, a number of other gynecological pathologies often require the use of effective analgesics.
Secondary dysmenorrhea
, as noted above, is due to the presence of organic disorders of the genitals (Table 1).
There are a number of factors that help distinguish secondary dysmenorrhea from primary.
1. Symptoms of dysmenorrhea appear during the first or second menstrual cycle after menarche (congenital obstructive malformations).
2. Symptoms of dysmenorrhea first appear after the age of 25 years.
3. Presence of gynecological diseases: infertility (endometriosis, inflammatory diseases of the pelvic organs or other causes of adhesions are assumed), heavy menstruation or intermenstrual bleeding (adenomyosis, uterine fibroids, polyps are assumed), dyspareunia.
4. Lack of effect or its insignificant severity from therapy with NSAIDs and/or oral contraceptives.
The most common cause of secondary dysmenorrhea is endometriosis
. Characteristic symptoms of endometriosis are: the appearance of progressively increasing pain that occurs immediately before or during menstruation; dyspareunia, painful bowel movements, premenstrual spotting and polymenorrhea; pain over the pubis, dysuria and hematuria; infertility. A number of patients may not identify pain as an acquired phenomenon, but simply note that they have painful menstruation, although most indicate increased pain during menstruation. The pain is most often bilateral and ranges in intensity from mild to extremely severe; pain is often associated with a feeling of pressure in the rectum and can radiate to the back and leg. Constant “unpleasant sensations” throughout the menstrual cycle, intensifying before menstruation or during coitus, may be the only complaint presented by a patient with endometriosis. The cause of the pain has not been fully established; it is assumed that it may be associated with the phenomenon of “miniature menstruation” of endometriotic explants, which leads to irritation of the nerve endings. The disappearance of pain during the induction of amenorrhea in patients with endometriosis, that is, the elimination of cyclic hormonal effects on endometrioid explants, in fact, proves the mechanism of pain syndrome.
However, pain is not always associated with endometriosis, even in cases where the disease is severe. For example, bilateral large endometrioid ovarian cysts are most often asymptomatic unless they rupture, while severe discomfort may be a consequence of a minimal number of active endometrioid heterotopias.
Despite the fact that there is a completely definite pathogenetic therapy for endometriosis, including the use of GnRH agonists and 19-norsteroid derivatives, quite often in the first stages of treatment, and sometimes over longer periods, it is necessary to add analgesics to the main drugs. This is due to the fact that the basic drugs do not have their maximum effect immediately, and in some cases the basic drugs are not able to completely eliminate the pain syndrome. Thus, the drug Nurofen or Nurofen Plus also finds its place in the treatment of endometriosis.
Everyday gynecological practice
cannot do without procedures such as the introduction and removal of intrauterine devices, treatment of cervical pathology, endometrial biopsy, hysterosalpingography, etc. Of course, in most cases, these interventions do not require the use of pain medications at all. The era of abortions performed without any anesthesia has not yet been forgotten. One could simply shout at the patient - “be patient, they didn’t tolerate this during the war” - and that would be the end of it, but in modern conditions this is completely unacceptable. Moreover, all of the above procedures can be quite well anesthetized and thereby achieve good emotional tolerance of these interventions. For this purpose, it is also possible to use Nurofen Plus, preferably 20–30 minutes before the procedure and subsequently after its completion. Taking this drug once or twice, depending on the severity of the pain syndrome, will provide the patient with pleasant memories of a caring doctor.
We would like to touch upon one more, fairly common pain syndrome within the framework of this story. We are talking about the so-called pelvic ganglioneuritis
. This is a variant of radiculitis, in which the nerve trunks exiting in the pelvic area are pinched. Patients with this disease most often complain of recurrent pain in the iliac regions. As a rule, the examination fails to reveal any signs of an inflammatory process in the uterine appendages or any other pathological changes. The pain syndrome in such patients is quite well controlled by taking analgesics from the NSAID group, in particular Nurofen.
Since 2001, in our clinic for the treatment of patients with uterine fibroids
We began to use the method of uterine artery embolization. After the procedure, patients usually experience pain of varying severity. The duration of this syndrome also varies, but on average it is 8 days. We used various pain relief regimens in this category of patients and settled on a regimen that included the use of Nurofen and Nurofen Plus. In particular, we were able to note a more pronounced analgesic effect of this drug, a rapid onset of effect and good tolerability.
Thus, Nurofen and Nurofen Plus are widely used in gynecological practice, effectively relieving women of pain.
Literature:
1. Ylikorkala O, Dawood MY New concept in dysmenorrhea. Am J Obstet Gynecol 1978; 130:833
2. Chan WY, Dawood MY, Fuchs F. Relief of dysmenorrhea with the prostaglandin synthetase inhibitor ibuprofen: effect of prostaglandin levels in menstrual fluid. Am J Obstet Gynecol 1979; 135:102.
Side effect
From the gastrointestinal tract: nausea, vomiting, abdominal pain, heartburn, anorexia, diarrhea, flatulence, NSAID gastropathy.
From the nervous system: headache, dizziness, hearing loss, tinnitus, insomnia, agitation, drowsiness, depression.
From the cardiovascular system: heart failure, tachycardia, increased blood pressure.
From the urinary system: edema syndrome, impaired renal function.
Allergic reactions: skin rash, itching, urticaria, angioedema, rarely, aseptic meningitis (more often in patients with autoimmune diseases), bronchospasm.
From the hematopoietic organs: anemia, thrombocytopenia, agranulocytosis, leukopenia.
Other: increased sweating.
With long-term use in large doses - ulceration of the gastrointestinal mucosa, bleeding (gastrointestinal, gingival, uterine, hemorrhoidal), visual impairment (impaired color vision, scotoma, amblyopia).
Overdose
Symptoms: abdominal pain, nausea, vomiting, lethargy, drowsiness, depression, headache, tinnitus, metabolic acidosis, coma, acute renal failure, decreased blood pressure, bradycardia, tachycardia, atrial fibrillation, respiratory arrest.
Treatment: gastric lavage (only within an hour after administration), activated charcoal, alkaline drinking, forced diuresis, symptomatic therapy (correction of acid-base status, blood pressure).
special instructions
During treatment, monitoring of the peripheral blood picture and the functional state of the liver and kidneys is necessary.
When symptoms of gastropathy appear, careful monitoring is indicated, including esophagogastroduodenoscopy, a blood test to determine Hb, hematocrit, and a stool test for occult blood.
To prevent the development of NSAID gastropathy, it is recommended to combine it with prostaglandin preparations.
If it is necessary to determine 17 - ketosteroids, the drug should be discontinued 48 hours before the study.
Patients should refrain from all activities that require increased attention, rapid mental and motor reactions.
During the treatment period, ethanol intake is not recommended.
