Not long ago, our gynecologists attended the XXVI European Congress of Perinatal Medicine (ECPM 2018). We, together with Svetlana Silenko, Deputy Head of the Center for Obstetrics and Gynecology GMS Clinic, decided to share with you the most interesting facts heard and seen at the congress.
National Institute of Health (NICE) guidelines
Aspirin 75 mg is recommended from 12 weeks of pregnancy if there is at least one high risk:
- arterial hypertension in a previous pregnancy;
- chronic renal pathology;
- autoimmune diseases (such as APS);
- diabetes;
- chronic arterial hypertension.
Aspirin 75 mg is recommended from 12 weeks if there are two or more moderate risks:
- first pregnancy;
- age over 40 years;
- the interval between pregnancies is more than 10 years;
- family history of preeclampsia;
- multiple pregnancy;
- BMI>35.
Aspirin Complex, 10 pcs., effervescent powder for the preparation of solution for oral administration
Acetylsalicylic acid Combination with Methotrexate at a dose of > 15 mg per week is contraindicated. Combinations of drugs that are used with caution: Methotrexate at a dose of less than 15 mg/week: With simultaneous use of drugs, the hematological toxicity of methotrexate increases due to the fact that NSAIDs in general reduce the renal clearance of methotrexate, and salicylags, in particular, displace it from association with plasma proteins . Anticoagulants (coumarin, heparin): when taking ASA and indirect anticoagulants simultaneously, the risk of bleeding increases due to suppression of platelet function, damage to the mucous membrane of the stomach and duodenum and displacement of oral anticoagulants from their connection with plasma proteins. Other NSAIDs with salicylates in high doses (at a dose of 3 g/day or more): with simultaneous use of drugs due to the synergistic effect, the risk of ulcers of the gastrointestinal mucosa and bleeding increases. Uricosuric drugs (probenecid, sulfinpyrazone): the therapeutic effect of uricosuric drugs is reduced due to competitive tubular elimination of uric acid. Digoxin: with simultaneous use of drugs, the concentration of digoxin in plasma increases due to a decrease in its excretion. Antidiabetic drugs (insulin, sulfonylurea): the hypoglycemic effect is enhanced due to the fact that ASA in a high dose has hypoglycemic properties and displaces sulfonylurea from binding to plasma proteins. Thrombolytics/antiplatelet drugs of other classes (ticlopidine): increased risk of bleeding. Diuretics in combination with ASA at a dose of 3 g/day or more: glomerular filtration is reduced due to a decrease in the synthesis of prostaglandins in the kidneys. Systemic glucocorticosteroids (GCS), with the exception of hydrocortisone (used to treat Addison's disease): with simultaneous use of drugs, the concentration of salicylates in the blood decreases, since GCS enhances the elimination of salicylates. Angiotensin-converting enzyme (ACE) inhibitors: with simultaneous use of ACE inhibitors and ASA at a dose of 3 g/day or more, a decrease in the hypotensive effect of ACE inhibitors is observed due to a decrease in glomerular filtration. Valproic acid: ASA disrupts the binding of valproic acid to plasma proteins, resulting in increased toxicity. Alcohol: when combined with ASA, the damaging effect on the mucous membrane of the gastrointestinal tract increases and bleeding time prolongs. Phenylephrine Monoamine oxidase inhibitors (MAO inhibitors): with the simultaneous use of phenylephrine and MAO inhibitors (antidepressants - tranylcypromine, moclobemide; antiparkinsonian drugs - selegiline), severe side effects are possible in the form of intense headache, increased blood pressure and body temperature. Beta-blockers - with simultaneous use, an increase in blood pressure (arterial hypertension) and severe bradycardia is possible. Sympathomimetics: with simultaneous use, the effect of sympathomimetics on the central nervous system and cardiovascular system is enhanced. Possible agitation, irritability, insomnia. Inhalational anesthetics: The use of filephrine before inhalational anesthesia increases the risk of cardiac arrhythmias. Treatment with phenylephrine should be discontinued several days before elective surgery. Rauwolfia alkaloids - with simultaneous use, the therapeutic effect of phenylephrine may be reduced. Caffeine: Concomitant use may increase the therapeutic and toxic effects of caffeine. Indomethacin, bromocriptine: in isolated cases, when phenylephrine is used concomitantly with indomethacin or bromocriptine, severe arterial hypertension is possible. Selective serotonin reuptake inhibitors: when used simultaneously with antidepressants of this group (fluvoxamine, paroxetine, sertraline), both the body's sensitivity to sympathomimetics and the risk of developing a serotonergic effect may increase. Antihypertensive drugs from the sympatholytic group, such as reserpine, guanethidine: phenylephrine reduces the hypotensive effect of these drugs. Chlorphenamine Alcohol, hypnotics, tranquilizers, antipsychotics (neuroleptics), neutral analgesics: chlorphenamine may enhance the depressant effect of these drugs on the central nervous system. Anticholinergic drugs (atropine, antispasmodics, tricyclic antidepressants, MAO inhibitors, antiparkinsonian drugs): chlorphenamine enhances the anticholinergic effect of these drugs.
Recommendations of the International Federation of Gynecology and Obstetrics
Women at risk should start taking aspirin 75-150 mg as soon as possible from at least 12 weeks (up to 16 weeks) and continue until 37 weeks of pregnancy or two weeks before an earlier planned birth.
Take at night, as it has been found to be more effective when taken this way. Monitoring platelet levels or bleeding time is not advisable unless there are complaints of any bleeding. In these cases, aspirin is discontinued.
Enteric forms are used if there is a history of indications of a gastric ulcer. Low doses of Aspirin were not associated with a higher risk of bleeding and do not affect the tactics of delivery, labor management, or the choice of pain relief method
The recommended dose of aspirin by professional societies is 75-80 mg per day, but a recent meta-analysis suggests that the dose of aspirin should be 100 mg or more per day, and started before 16 weeks of gestation. Therapy should be completed at 36 weeks or if labor begins.
Aspirin Cardio, 56 pcs., 100 mg, enteric-coated tablets
With simultaneous use, ASA enhances the effect of the drugs listed below; If it is necessary to simultaneously prescribe ASA with the listed drugs, the need to reduce the dose of these drugs should be considered:
- methotrexate - by reducing renal clearance and displacing it from protein binding; the combination of ASA with methotrexate is accompanied by an increased incidence of side effects from the hematopoietic organs; the use of Aspirin® Cardio together with methotrexate is contraindicated if the dose of the latter exceeds 15 mg per week (see section “Contraindications”); and possibly with caution - with a dose of methotrexate less than 15 mg per week;
- heparin and indirect anticoagulants - due to disruption of platelet function and displacement of indirect anticoagulants from binding with proteins; when used simultaneously with anticoagulants, thrombolytic and antiplatelet agents (ticlopidine), there is an increased risk of bleeding as a result of the synergism of the main therapeutic effects of the drugs used and increased damaging effects on the gastrointestinal mucosa;
- selective serotonin reuptake inhibitors, because possible increased risk of bleeding from the upper gastrointestinal tract (synergism with ASA);
- digoxin - due to a decrease in its renal excretion, which can lead to an overdose;
- hypoglycemic agents for oral administration (sulfonylurea derivatives) and insulin - due to the hypoglycemic properties of ASA itself in high doses and displacing sulfonylurea derivatives from communication with blood plasma proteins; this must be kept in mind when prescribing ASA to patients with diabetes mellitus receiving the listed drugs;
- simultaneous use with valproic acid increases its toxicity due to displacement from the connection with blood plasma proteins;
- NSAIDs, incl. derivatives of salicylic acid in high doses (increased risk of ulcerogenic effect and bleeding from the gastrointestinal tract as a result of synergistic action);
- ethanol (alcoholic drinks) - increased risk of damage to the gastrointestinal mucosa and prolongation of bleeding time as a result of the mutual enhancement of the effects of ASA and ethanol.
Simultaneous administration of ASA in high doses may weaken the effect of the drugs listed below. If it is necessary to simultaneously prescribe ASA with the listed drugs, you should consider the need to adjust the dose of the drugs listed below:
- any diuretics (when used together with ASA in high doses, a decrease in glomerular filtration rate is observed as a result of a decrease in PG synthesis in the kidneys);
- ACE inhibitors - there is a dose-dependent decrease in glomerular filtration rate (GFR) as a result of inhibition of PGs that have a vasodilatory effect, and, accordingly, a weakening of the hypotensive effect. The clinical significance of a decrease in GFR is observed when the daily dose of ASA is more than 160 mg. In addition, there is a decrease in the positive cardioprotective effect of ACE inhibitors prescribed to patients for the treatment of chronic heart failure. This effect also occurs when used in combination with ASA in large doses;
- drugs with uricosuric action - benzbromarone, probenecid - a decrease in the uricosuric effect due to competitive suppression of renal tubular excretion of uric acid.
When used simultaneously with ibuprofen, antagonism is observed against the irreversible platelet inhibition caused by the action of ASA, which leads to a decrease in the cardioprotective effects of ASA. Therefore, the combination of ASA with ibuprofen is not recommended in patients with an increased risk of cardiovascular disease.
When used simultaneously with systemic corticosteroids (with the exception of hydrocortisone or other corticosteroids used for replacement therapy of Addison's disease), there is an increase in the elimination of salicylates and, accordingly, a weakening of their effect. When using GCS and salicylates in combination, it should be remembered that the level of salicylates in the blood is reduced, and after discontinuation of GCS, an overdose of salicylates is possible.
Triple effect
How did it happen that a medicine with a triple effect - analgesic, antipyretic and anti-inflammatory - became the best friend of heart patients? Aspirin was created in 1897 in Germany, and it was a new word in the treatment of rheumatism. Its triple effect was ideal for this disease. Naturally, the drug was used for various pains, high fevers and colds.
Related article The era of aspirin: the history of the creation of a drug for pain, fever and cancer Everything changed in 1971, when the English pharmacologist
John Vane deciphered the mechanism of action of aspirin. Before this, the drug was like a “black box”: its three effects were known, but it was not clear how it did it. Professor Wayne has proven that aspirin inhibits the synthesis of prostaglandins (PGs), which are widely involved in inflammation, pain and temperature regulation, and also, which is especially important for heart patients, in blood clotting.
