The basis antiplatelet action mechanism of acetylsalicylic acid (ASA) is irreversible inhibition of cyclooxygenase (COX-1), resulting in a blocked synthesis of thromboxane A2 and platelet aggregation is inhibited. Antiplatelet effect is most pronounced in platelets, because they are not able to re-synthesize cyclooxygenase. It is believed that ASA has other mechanisms of inhibition of platelet aggregation, which expands the scope of its application in various vascular diseases.
ASA also has anti-inflammatory, analgesic and antipyretic effect.
After oral administration ASA is rapidly and completely absorbed from the gastrointestinal tract (GIT). ASA partially metabolized during absorption. During and after the suction head turns into ASA metabolite – salicylic acid, which is metabolized primarily in the liver by the enzymes to form metabolites such as phenyl salicylate, and salicylate glucuronide salitsilurovaya acid, found in many tissues and urine. In women, the process of metabolism is slower (lower activity in serum enzymes). The maximum concentration of ASA in the blood plasma achieved 10-20 minutes after ingestion, salicylic acid – after 0.3-2 hours. Because acid-coated tablet shell ASA is released not in the stomach (sheath effectively blocks the dissolution of the drug in the stomach) and in an alkaline environment of the duodenum. Thus, absorption of ASA in tablet form enteric-coated delayed for 3-6 hours as compared with conventional (without a shell) tablets.
Salicylic acid ASA and strongly bind to plasma proteins (66% to 98% depending on the dose) and rapidly distributed in the organism. Salicylic acid crosses the placenta and is excreted in breast milk.
Excretion of salicylic acid is dose-dependent, since its metabolism may limit enzyme system. half-life is 2-3 hours when applied at low doses of ASA and 15 hours when using the drug in high dose (usual dose of acetylsalicylic acid as an analgesic). Unlike other salicylates, when multiple dose ASA negidrolizirovannaya drug does not accumulate in the serum. Salicylic acid and its metabolites are excreted by the kidneys. In patients with normal renal function 80-100% of a single dose of the drug is excreted by the kidneys within 24-72 hours.
- Primary prevention of acute myocardial infarction in the presence of risk factors (eg, diabetes mellitus, hyperlipidemia, hypertension, obesity, smoking, old age), and recurrent myocardial infarction;
- Unstable angina (including suspicion of acute myocardial infarction), and stable angina;
- Prevention of stroke (including patients with transient ischemic attack);
- Prevention of transient ischemic attack;
- Prevention of thromboembolism after surgery and invasive procedures on vessels (eg, coronary artery bypass grafting, carotid endarterectomy, arterio-venous bypass, angioplasty and stenting of the coronary arteries, angioplasty of the carotid arteries)
- Prevention of deep vein thrombosis and pulmonary artery and its branches (including during prolonged immobilization resulting from extensive surgery).
- Increased sensitivity to aspirin, excipients preparation and other NSAIDs
- Asthma induced by intake of salicylates and other NSAIDs; a combination of asthma, recurrent nasal polyposis, and paranasal sinuses and intolerances ASA
- Erosive and ulcerative lesions of the gastrointestinal tract (acute stage)
- Gastrointestinal bleeding
- bleeding diathesis
- The combined use with methotrexate at a dose of 15 mg or more per week
- Pregnancy (I and III trimester) and lactation
- Children and adolescence (18 years)
- Severe renal impairment (creatinine clearance (CC) of less than 30 ml / min.)
- Severe hepatic impairment (class B or higher on the scale of Child-Pugh)
- Chronic heart failure III-IV NYHA functional class classification
Use with caution:
- In gout, hyperuricemia, as ASA in low doses, reduces the excretion of uric acid; it should be borne in mind that a low dose of ASA can trigger the development of gout in predisposed patients (having a reduced excretion of uric acid)
- If you have a history of ulcerative lesions of the gastrointestinal tract or gastrointestinal bleeding
- If abnormal liver function (below class B on a scale Child-Pugh)
- If the kidney function (creatinine clearance 30 mL / min.)
- In bronchial asthma, chronic respiratory diseases, hay fever, nasal polyposis, drug allergy, including the group of NSAIDs (analgesics, anti-inflammatory, antirheumatic drugs)
- In the II trimester of pregnancy
- When the intended surgical procedure (including minor, such as tooth extraction) as ACK can cause bleeding propensity to develop within a few days after dosing
- The combined application with the following medicines (see “Interactions with other medicinal products” section.)
- with methotrexate for at least 15 mg per week;
- with the anticoagulant, thrombolytic and antiplatelet agents
- with NSAIDs and salicylic acid derivatives in high doses;
- with digoxin;
- with hypoglycemic agents for oral use (sulfonylurea derivatives) and insulin;
- valproic acid;
- alcohol (alcohol in particular);
- with selective serotonin reuptake inhibitors;
- with ibuprofen.
Pregnancy and lactation
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and the development of the embryo or fetus.
The use of high doses of salicylates (more than 300 mg / day; we are talking about the usual doses of 500 mg of ASA as an analgesic) in the I trimester of pregnancy is associated with an increased rate of fetal defects (split upper palate, heart defects). Appointment of salicylates in the I trimester of pregnancy is contraindicated.
In the III trimester of pregnancy salicylates in high doses (more than 300 mg / day; we are talking about the usual doses of ASA 500 mg as an analgesic) may cause inhibition of labor, premature closure of the ductus arteriosus in the fetus, increased bleeding in the mother and fetus, and destination just before birth can cause intracranial hemorrhage, especially in premature infants. Appointment of salicylates in the III trimester of pregnancy is contraindicated.
In the II trimester of pregnancy salicylates can be given only on the basis of strict risk assessment and benefit to the mother and fetus, preferably in doses not exceeding 150 mg / day and short.
salicylates and their metabolites in small amounts into breast milk. Accidental intake of salicylates during lactation is not accompanied by the development of adverse reactions in children and does not require stopping breastfeeding. However, long-term use of the drug or to appoint him to a high dose of breast-feeding should be discontinued immediately.
DOSAGE AND ADMINISTRATION
The tablets of the drug Aspirin ® CARDIO desirable to take before eating, drinking plenty of fluids. Aspirin ® CARDIO taken 1 time per day. Aspirin ® Cardio is designed for long-term use. The duration of therapy is determined by the doctor.
Primary prevention of acute myocardial infarction in the presence of risk factors: 100 mg / day or 300 mg every other day.
Prevention of re-infarction, stable and unstable angina pectoris: 100-300 mg / day.
Unstable angina (in cases of suspected development of acute myocardial infarction): initial dose of 100-300 mg (first tablet must be chewed for faster absorption) should be taken by the patient as soon as possible after suspected in the development of acute myocardial infarction. In the following 30 days after myocardial infarction should be maintained dose of 200-300 mg / day. After 30 days it is necessary to assign the appropriate therapy for the prevention of recurrent myocardial infarction.
Prevention of stroke and transient ischemic attack: 100-300 mg / day.
Prevention of thromboembolism after surgery and invasive procedures on vessels: 100-300 mg / day.
Prevention of deep vein thrombosis and pulmonary embolism and its branches: 100-200 mg / day or 300 mg every other day.
ADVERSE EFFECTS From the digestive system: most frequently reported nausea, heartburn, vomiting, abdominal pain; rarely – ulcers of the stomach and duodenum; very rarely – a perforated ulcer of the gastric mucosa and duodenal ulcers, gastrointestinal bleeding (with appropriate clinical symptoms and laboratory changes), transient liver function abnormalities with increased activity of “liver” transaminases.
From hemopoiesis system: the appointment of ASA associated with an increased risk of bleeding due to the inhibitory effect of ASA on platelet aggregation. Registered increase in the incidence of perioperative (intraoperative and postoperative) hemorrhage, hematomas (bruises), nosebleeds, bleeding gums, bleeding from the urinary tract. There are reports of serious cases of bleeding, which include gastrointestinal bleeding and bleeding in the brain (especially in patients with hypertension who have not reached target blood pressure (BP) and / or receiving concomitant therapy with anticoagulant drugs), which in some cases may be have the character (see. “Special instructions” section) life-threatening.
Bleeding can lead to acute or chronic post-hemorrhagic / iron deficiency anemia (eg due to hidden bleeding) with relevant clinical and laboratory signs and symptoms (fatigue, pallor, hypoperfusion).
Allergic reactions: hypersensitivity reactions with respective laboratory and clinical signs, such as asthmatic syndrome (bronchospasm), the reaction mild to moderate side of the skin, respiratory tract, gastrointestinal tract and the cardiovascular system, including symptoms such as skin rash , pruritus, urticaria, angioedema, rhinitis, swelling of nasal mucosa, rhinitis, cardio-respiratory distress syndrome, and severe reactions, including anaphylactic shock.
On the part of the central nervous system (CNS) have been reported cases of dizziness, hearing loss, headache, tinnitus, which can be a sign of overdose (see “Overdose” section.).
salicylate intoxication (developed with ASA in a dose of 100 mg / kg / day for more than 2 days) may result from prolonged use of toxic doses of the drug within the wrong therapeutic use of the drug (chronic toxicity), or a single accidental or intentional receive a toxic dose drug or an adult child (acute intoxication).
Symptoms of chronic intoxication with salicylic acid derivatives are non-specific and are often diagnosed with difficulty. Mild intoxication usually develop only after repeated use of high doses of the drug and is manifested by dizziness, tinnitus, hearing loss, increased sweating, nausea and vomiting, headache and confusion. The above symptoms disappear after reducing the dose. Tinnitus may occur if plasma levels of ASA from 150 to 300 pg / ml. More severe symptoms when the concentration of ASA in the blood plasma levels above 300 micrograms / ml.
The main manifestation of acute intoxication is severe disturbance of acid-base status, the manifestations of which may vary depending on the patient’s age and the degree of severity of intoxication. In children, the most common is the development of metabolic acidosis. Intoxication Treatment is carried out in accordance with accepted standards and depends on the severity of poisoning and the clinical picture and should be aimed mainly at accelerating the excretion of the drug and the restoration of water and electrolyte balance and acid-base status.
• Overdose symptoms of mild to moderate severity:
Vertigo, tinnitus, hearing loss, increased sweating, nausea, vomiting, headache, confusion, profuse sweating, tachypnea, hyperventilation, respiratory alkalosis.
Treatment: gastric lavage, repeated administration of activated charcoal, forced alkaline diuresis, restoring fluid and electrolyte balance and acid-base status.
• Overdose symptoms from mild to severe:
- respiratory alkalosis with compensatory metabolic acidosis;
- hyperpyrexia (extremely high body temperature);
- disordered breathing: hyperventilation, non-cardiogenic pulmonary edema, respiratory depression, apnea;
- disorders of the cardiovascular system: cardiac arrhythmias, hypotension, depression of cardiac activity;
- violations of water-electrolyte balance: dehydration (dehydration), renal dysfunction by oliguria until the development to kidney failure, characterized by hypokalemia, hypernatremia, hyponatremia;
- impaired glucose metabolism: hyperglycemia, hypoglycemia (especially in children), ketoacidosis;
- tinnitus, deafness;
- gastrointestinal bleeding;
- haematological disorders from platelet aggregation inhibition to coagulopathy, prolonged prothrombin time, hypoprothrombinemia;
- neurological disorders: toxic encephalopathy and central nervous system depression (drowsiness, confusion, coma, convulsions).
Treatment: immediate hospitalization in specialized departments for emergency therapy – gastric lavage, repeated administration of activated charcoal, forced alkaline diuresis “hemodialysis, restoring fluid and electrolyte primobolan enanthate balance and acid-base status, symptomatic therapy.
INTERACTION WITH OTHER DRUGS
In an application of ASA enhances the action of drugs listed below, if necessary, co-administration of ASA with transfer of funds should consider the need to reduce the dose of these drugs:
- methotrexate by reducing renal clearance and displacement of its association with proteins; ASA combination with methotrexate is accompanied by an increased incidence of side effects of hematopoiesis; Aspirin use of the drug ® Cardio together with methotrexate is contraindicated if the last dose greater than 15 mg per week (see section “Contraindications”.) and possibly with caution – with a dose of methotrexate for at least 15 mg per week;
- heparin and indirect anticoagulants due to dysfunction of platelets and displacing anticoagulants from binding with proteins;
- while the use of an anticoagulant, thrombolytic and antiplatelet agents (ticlopidine), there is an increase risk of bleeding as a result of synergies major therapeutic effects of the drugs;
- while the use of drugs that possess anticoagulant, thrombolytic and antiplatelet effect has increased, damaging effect on the mucous membrane of the gastrointestinal tract;
- selective serotonin reuptake inhibitors, which may lead to increased risk of bleeding from the upper gastrointestinal tract (synergy with ASA)
- digoxin consequence reduce its renal excretion, which may lead to overdose
- hypoglycemic agents for oral use (sulfonylurea derivatives) and insulin hypoglycemic properties by itself in high doses of ASA and sulfonylurea derivatives of displacement due to plasma protein; it must be borne in mind when assigning the primobolan enanthate ASA in patients with diabetes receiving medications listed
- while the use of valproic acid increases its toxicity due to displacement from its association with plasma proteins;
- NSAID derivatives and salicylic acid in high doses (increased risk ulcerogenic effects and bleeding from the gastrointestinal tract as a result of synergism of action);
- Ethanol (alcohol) (increased risk of damage to the mucosa of the gastrointestinal tract and prolongation of bleeding time as a result of mutual reinforcement effects of ASA and ethanol).
Co-administration of ASA in high doses can impair the action of drugs listed below. If necessary, co-administration of ASA with these drugs should consider the need for dose adjustment tools listed below:
- any diuretics (when combined with high doses of ASA in a decline in glomerular filtration rate due to a decrease in renal prostaglandin synthesis);
- angiotensin-converting enzyme (ACE) inhibitors (marked dose-dependent decrease in glomerular filtration rate (GFR) by inhibiting prostatlandinov having a vasodilating action, consequently weakening of hypotensive effect. The clinical significance of GFR decline observed at a daily dose of ASA 160 mg. In addition, there is a decrease of positive cardioprotective . ACE inhibitors steps assigned to patients to treat chronic heart failure this effect is also evident when used in conjunction with ASA in high doses);
- drugs with uricosuric action – benzbromaron, probenecid (urikozuricheskogo reduction effect due to competitive suppression of renal tubular excretion of uric acid).
While the use of ibuprofen observed antagonism of irreversible platelet inhibition caused by the action of ASA, which reduces the cardioprotective effects of ASA, it is not advisable combination of ASA with ibuprofen at patsentov with an increased risk of cardiovascular disease.
While the use of systemic glucocorticosteroids (GCS) (except hydrocortisone or other corticosteroids used for replacement therapy of disease Adtsisona) noted increased elimination of salicylates and thus weakening their actions. If concomitant use of corticosteroids and salicylates should be remembered that during treatment the level of salicylate in the blood is reduced, and after the abolition of GCS possible overdose of salicylates.
- The drug should be used by a physician.
- ASA may provoke bronchospasm and induce asthma attacks or other hypersensitivity reactions. Risk factors are the presence of a history of asthma, hay fever, nasal polyposis, chronic respiratory diseases and allergic reactions primobolan enanthate to other drugs (eg, skin reactions, pruritus, urticaria).
- The inhibitory effect of ASA on platelet aggregation is maintained for a few days after administration, and therefore, may increase the risk of bleeding during surgery or postoperatively. If necessary, the absolute exclusion of bleeding during surgery should be possible to completely abandon the use of ASA in the preoperative period.
- Exceeding the dose ASA carries a risk of gastrointestinal bleeding.
- Overdose is especially dangerous in elderly patients.
Effects on ability to drive / moving mechanisms
The drug Aspirin ® Cardio does not affect the ability to drive / moving mechanisms. clebol