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Mechanism of Action
US Drug Names
General dosing information
325 or 650 mg PO every 4 hours as needed, or alternatively, 975 mg PO every 6 hours, as needed. Max: 3,900 mg/day. Discontinue use if pain gets worse or lasts more than 10 days. 
300 or 600 mg PR every 4 to 6 hours, as needed. Max: 3,600 mg/day. Discontinue use if pain gets worse or lasts more than 10 days.
160 to 325 mg PO once daily starting within 24 to 48 hours of stroke symptom onset.  In patients with minor noncardioembolic ischemic stroke who did not receive a thrombolytic, use aspirin for first 21 days in combination with clopidogrel.  Aspirin is not recommended as a substitute for acute stroke treatment in patients eligible for thrombolytic therapy or mechanical thrombectomy.
1 to 5 mg/kg/dose PO once daily.   If dissection and cardioembolic causes are excluded, continue aspirin for a minimum of 2 years. Transition to clopidogrel, LMWH, or warfarin in those who have recurrent acute ischemic stroke (AIS) or transient ischemic attacks. For acute AIS due to non-Moyamoya vasculopathy, continue aspirin for 3 months; guide ongoing antithrombotic therapy with repeat cerebrovascular imaging.
1 to 5 mg/kg/dose PO once daily. Aspirin is recommended for neonates with recurrent acute ischemic stroke.
300 mg rectally once daily starting within 24 to 48 hours of stroke symptom onset.  In patients with minor noncardioembolic ischemic stroke who did not receive a thrombolytic, use aspirin for first 21 days in combination with clopidogrel.  Aspirin is not recommended as a substitute for acute stroke treatment in patients eligible for thrombolytic therapy or mechanical thrombectomy.
162.5 mg PO once daily.
75 to 100 mg PO once daily in combination with clopidogrel. 
300 to 325 mg PO loading dose, then 75 to 100 mg PO once daily plus ticagrelor for up to 30 days.
50 to 325 mg PO once daily.  Antiplatelet agents are recommended over oral anticoagulation.
50 to 150 mg PO once daily after the first trimester of pregnancy.
1 to 5 mg/kg/dose PO once daily for a minimum of 2 years.    Transition to clopidogrel, LMWH, or warfarin in those who have recurrent acute ischemic stroke or transient ischemic attacks.
150 to 325 mg PO (non-enteric coated, chewable) once as soon as possible, then 75 to 162 mg PO once daily indefinitely. Maintenance doses up to 325 mg/day have been used in special circumstances. Aspirin is the established first-line therapy in patients with NSTE-ACS and reduces the risk of recurrent MI and death. 
300 to 325 mg PO (non-enteric coated, chewable) once as soon as possible, then 75 to 100 mg PO once daily indefinitely (preferred); however, lower loading doses (162 mg) and higher maintenance doses (up to 325 mg/day) may be used. 
75 to 162 mg PO once daily. Consider in patients 40 to 70 years who are high risk ASCVD but not for bleeding. 
75 to 162 mg PO once daily indefinitely for all patients with CAD unless contraindicated.   In patients treated with dual antiplatelet therapy (DAPT) or triple therapy (aspirin, P2Y12 inhibitor, and oral anticoagulant), 81 mg PO once daily is the recommended dose.
75 to 325 mg PO preoperatively and within 6 hours after CABG; continue once daily dosing indefinitely.
75 to 325 mg PO once daily. 
75 to 325 mg PO once daily.  
1 to 5 mg/kg/dose (Max: 81 to 325 mg/dose) PO once daily. 
1 to 5 mg/kg/dose PO once daily.
1 to 5 mg/kg/dose (Max: 81 to 325 mg/day) PO once daily.             Higher doses (up to 10 mg/kg/day) have been reported. There was no significant difference in thrombosis rate at 2 years in patients receiving warfarin or aspirin (24% vs. 14%, p = 0.45) in a multicenter, randomized control trial of 111 children after Fontan surgery. Although not statistically significant, the incidence of thrombosis was 9% in patients receiving aspirin (n = 34) compared to 2% in patients receiving rivaroxaban (n = 64) for thromboprophylaxis post-Fontan procedure in a randomized, multicenter, open-label study.
1 to 5 mg/kg/dose PO once daily.          Higher doses (up to 15 mg/kg/day) have been reported.    A flat dose of 40 mg/day PO was described in a retrospective review evaluating thrombosis after modified BT shunt placement in 207 patients, 162 (78%) which were neonates, with a mean weight of 3.1 +/- 0.8 kg.
1 to 5 mg/kg/dose (Max: 81 to 325 mg/dose) PO once daily; begin 1 to several days before device implantation and continue for at least 6 months. Higher doses (up to 10 mg/kg/day) have been reported.
1 to 5 mg/kg/dose PO once daily; begin within 72 hours of VAD placement. Use in combination with heparin (begun 8 to 48 hours after implantation) and with or without dipyridamole.
75 to 325 mg PO once daily. 
300 to 325 mg PO (non-enteric coated) at least 2 hours (preferably 24 hours) before PCI; for patients already on daily aspirin, 75 to 325 mg PO before PCI. Continue 75 to 81 mg PO once daily indefinitely.   Lower loading doses (150 to 162 mg) and higher maintenance doses (up to 325 mg/day) may be used. 
75 to 100 mg PO once daily indefinitely.
81 mg PO once daily for patients who have a 10% or more 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years.
325 or 650 mg PO every 4 hours as needed, or alternatively, 975 mg PO every 6 hours, as needed. Max: 3,900 mg/day. Discontinue use if fever gets worse or lasts more than 3 days. 
300 or 600 mg PR every 4 to 6 hours, as needed. Max: 3,600 mg/day. Discontinue use if fever gets worse or lasts more than 3 days.
81 mg PO once daily starting at 12 weeks gestation.    In pregnant women with pre-existing diabetes mellitus, 162 mg PO once daily may be appropriate.
Dosage not established. 65 to 100 mg PO once daily initiated at various times during pregnancy (e.g., 12 weeks) and continued until 34 weeks or delivery has been used.  
80 to 100 mg/kg/day PO in 4 divided doses during the acute phase, then decrease dose to 3 to 5 mg/kg/day PO once daily (Max: 325 mg/day) for at least 4 to 6 weeks after the onset of illness.     Duration of high-dose aspirin varies in clinical practice; while many clinicians reduce the aspirin dose after the patient is afebrile for 24 to 72 hours, others continue high-dose aspirin until day 14 of illness and at least 48 to 72 hours after cessation of fever.  There is also debate over the optimal dose of aspirin in the acute phase of treatment. High-dose is recommended in guidelines. However, moderate doses are commonly used during the acute phase to minimize aspirin toxicity. There are no data to suggest either dose is superior.       Additionally, some data suggest low-dose aspirin is not inferior to high-dose aspirin in reducing the risk of coronary artery aneurysms when given concomitantly with IVIG during the acute phase. 
30 to 50 mg/kg/day PO in 4 divided doses during the acute phase, then decrease dose to 3 to 5 mg/kg/day PO once daily (Max: 325 mg/day) for at least 4 to 6 weeks after the onset of illness.         There is debate over the optimal dose of aspirin in the acute phase of treatment. High-dose is recommended in the guidelines. However, moderate doses are commonly used during the acute phase to minimize aspirin toxicity. There are no data to suggest either dose is superior.      
3 to 10 mg/kg/day PO once daily (Max: 325 mg/day) for at least 4 to 6 weeks after the onset of illness. For those who develop coronary abnormalities, low-dose therapy may continue indefinitely.      Some data suggest low-dose aspirin is not inferior to high-dose aspirin in reducing the risk of coronary artery aneurysms when given concomitantly with IVIG during the acute phase. 
750 to 1,000 mg PO every 8 hours for 1 to 2 weeks, then decrease dose by 250 to 500 mg/day every 1 to 2 weeks in combination with colchicine.
500 to 1,000 mg PO every 6 to 8 hours for at least 2 to 4 weeks, then decrease dose by 250 to 500 mg/day every 1 to 2 weeks in combination with colchicine. Dose range: 1.5 to 4 g/day. 
100 or 325 mg PO every other day, or alternately, 300 mg PO once daily.   Clinical practice guidelines classify aspirin as having inadequate or conflicting data to support or refute use for migraine prophylaxis.
500 mg PO as a single dose. Guidelines classify aspirin as having established efficacy for the treatment of acute migraine. 
3 to 5 mg/kg/dose (Max: 81 mg) PO once daily for all patients without risk factors for bleeding.   Continuation is recommended until platelet count is normalized and normal coronary arteries are confirmed at least 4 weeks after diagnosis. Avoid use in patients with active bleeding, significant bleeding risk, and/or a platelet count of 80,000/microliter or less. Patients with coronary artery aneurysms and a maximal z-score of 2.5 to 10 should be treated with low dose aspirin, whereas patients with a z-score of 10 or more should be treated with low dose aspirin and therapeutic anticoagulation with enoxaparin for at least 2 weeks before transitioning to warfarin. Patients with an ejection fraction (EF) less than 35% should receive low dose aspirin and therapeutic anticoagulation until EF exceeds 35%. Patients with documented thrombosis should receive low dose aspirin and therapeutic anticoagulation for 3 months, pending thrombosis resolution.
Most patients experience signs of acute salicylate toxicity when the total salicylate concentration is more than 300 mcg/mL. In chronic salicylism, signs of toxicity may occur at lower concentrations (150 mcg/mL or more).
Avoid aspirin in patients with severe hepatic insufficiency. Patients with any degree of hepatic disease are at increased risk of salicylate-induced adverse reactions.
CrCl less than 10 mL/minute: Avoid analgesic doses. Use of low-dose aspirin for primary and secondary prevention of atherosclerotic events in patients with cardiovascular disease is recommended.
Avoid analgesic doses. Use of low-dose aspirin for primary and secondary prevention of atherosclerotic events in patients with cardiovascular disease is recommended. If use is necessary, doses should be administered after hemodialysis; aspirin is 50% to 100% dialyzable.
Continuous ambulatory peritoneal dialysis (CAPD)
Avoid analgesic doses. Use of low-dose aspirin for primary and secondary prevention of atherosclerotic events in patients with cardiovascular disease is recommended.
Continuous renal replacement therapy (CRRT)
No dosage adjustment needed; monitor serum salicylate concentrations if possible.
Aspirin is an oral and rectal nonsteroidal antiinflammatory drug (NSAID) indicated for the temporary relief of minor aches and pains associated with headache, backache, muscular aches, a cold, toothache, minor pain of arthritis, premenstrual and menstrual cramps, to reduce the risk of death and myocardial infarction (MI) in patients with chronic coronary artery disease, such as patients with a history of MI or angina pectoris or chronic stable angina, and to reduce the risk of death and recurrent stroke in patients who have had an ischemic stroke or transient ischemic attack (TIA). Aspirin increases the risk of bleeding and may cause gastric ulceration and bleeding. Reye's syndrome, a potentially fatal disease, has been associated with aspirin use after active varicella infection or other viral illnesses in children; hence, aspirin use is children is primarily limited to the treatment of Kawasaki disease, for thrombosis prophylaxis, particularly in those with congenital heart disease after cardiac surgery, and for the treatment and secondary prevention of arterial ischemic stroke. Guidelines for the treatment of juvenile idiopathic arthritis in children no longer recommend aspirin as a treatment option due to the availability of other NSAIDs (i.e., ibuprofen, naproxen) that are just as effective, safer, and better tolerated. Observational studies have suggested that aspirin reduces the risk of colorectal cancer. However, long-term follow-up of the randomized Physicians' Health Study found no association between aspirin use and colorectal cancer. In contrast, randomized trials have shown that aspirin reduces the risk of recurrent adenomas in persons with a history of colorectal cancer or adenomas. The role of aspirin in the chemoprevention of colorectal cancer, either as primary or secondary prophylaxis, has not been determined.
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Central nervous system adverse effects reported with aspirin include agitation, cerebral edema, coma, confusion, dizziness, headache, lethargy, and seizures. Tinnitus and hearing loss may occur in patients receiving high-dose and/or long-term aspirin therapy. Discontinue aspirin if tinnitus or hearing loss occurs. These effects are early manifestations of salicylate toxicity. However, hearing loss has occurred in patients at low serum salicylate concentrations. Tinnitus and hearing loss are usually dose-related and reversible upon dose reduction or discontinuation. Tinnitus is commonly associated with salicylate concentrations more than 200 to 300 mcg/mL. Maximum hearing loss occurs most frequently at salicylate concentrations of 400 mcg/mL or more.  The association of hearing loss and regular analgesic therapy (including aspirin) was prospectively assessed over 18 years in a study of 26,917 males age 40 to 74 years at study enrollment. During 369,079 person-years of follow-up, 3,488 cases of hearing loss were reported. After adjustment for confounders, the hazard ratio (HR) for aspirin associated hearing loss was 1.12 (95% CI 1.04 to 1.2, p = 0.005) in patients who were regular users of the drug (2 times weekly or more) compared to those with less use. Men who used aspirin regularly for 1 to 4 years were 28% (17% to 40%) more likely to develop hearing loss than those without regular use; the risk of hearing loss did not further increase with longer duration of use. Regular users of aspirin younger than 60 years were 33% more likely to experience hearing loss compared to non-regular users; no association occurred in those 60 years and older. This study does suggest association; however, data are based on patient reporting of the outcomes. Information regarding noise exposure and analgesic doses was not provided. Conversely, a similar prospective analysis conducted over 14 years in 62,261 women did not demonstrate an independent association of aspirin therapy with hearing loss. Salicylate ototoxicity may result from damage to the cochlea or auditory nerve through multiple mechanisms, including reduced cochlear blood flow, impairment of outer hair cell function, or inhibition of prostaglandin-forming cyclooxygenase.
Gastrointestinal adverse effects reported with aspirin include abdominal pain, anorexia, dyspepsia, elevated hepatic enzymes, gastritis, GI bleeding, hepatitis, nausea, and vomiting. Aspirin may cause peptic ulcer. 
Reye's syndrome has been reported with aspirin use. Aspirin may increase the risk of developing Reye's syndrome, a rare but serious disease which can follow flu or chicken pox in children and adolescents.  Reye's syndrome has been reported in children of all ages; however, most of the reported cases have occurred in children 5 to 10 years. Data are not strong to support a dose-dependent association with Reyes's syndrome; however, a case-controlled study reported that patients who developed Reye's syndrome (n = 27) had received larger doses for a longer duration compared with controls who did not develop Reye's syndrome. Of the patients who developed Reye's syndrome, 67% were receiving more than 20 mg/kg/day of salicylates compared with only 22% of controls.  Reye's syndrome is a multisystem disorder evidenced by persistent vomiting, altered sensorium, elevated hepatic enzymes, hypoprothrombinemia, hyperammonemia, convulsions, and encephalopathy.  
Renal adverse effects reported with aspirin include interstitial nephritis, renal papillary necrosis, proteinuria, renal insufficiency and acute renal failure. 
Dermatologic adverse reactions reported with aspirin include rash, pruritus, and purpura.
Salicylates, such as aspirin, have dose-dependent effects on plasma uric acid concentrations. At low doses (1 to 2 g/day) decreased urate excretion and hyperuricemia may be seen. Intermediate salicylate doses (2 to 3 g/day) usually do not alter urate excretion, and high doses of salicylates (more than 3 g/day) induce uricosuria and lower plasma uric acid concentrations.
Intracranial bleeding has been reported with aspirin use.
At therapeutic doses, salicylates such as aspirin cause changes in acid/base balance and electrolytes resulting in respiratory alkalosis. In patients with normal renal and respiratory function, this is usually compensated for appropriately. Severe acid/base disturbances may occur during salicylate toxicity. Infants and children with salicylate toxicity rarely present clinically with respiratory alkalosis. As salicylate toxicity progresses, changes resembling metabolic acidosis are present (e.g., low blood pH, low plasma bicarbonate concentrations, and normal or nearly normal plasma PaCO2). In reality, a combination of respiratory acidosis and metabolic acidosis is present. Alterations in water and electrolyte balance also occur in salicylate toxicity. Dehydration due to salicylate-induced diaphoresis and hyperventilation occurs. Since more water than electrolytes are lost, dehydration is associated with hypernatremia. Other laboratory changes noted in salicylate toxicity include hyperglycemia or hypoglycemia (especially in children), ketonuria, hypokalemia, and proteinuria. Prolonged exposure to high doses of salicylates also causes hypokalemia through both renal and nonrenal losses. Hyperventilation occurs due to direct stimulation of the respiratory center in the medulla. At high salicylate plasma concentrations (350 mcg/mL or more), marked hyperventilation will occur, and at serum concentrations of about 500 mcg/mL, hyperpnea will be seen. At high or prolonged doses, salicylates also have a depressant effect on the medulla. Toxic doses of salicylates cause central respiratory depression as well as cardiovascular collapse secondary to vasomotor depression. Since enhanced CO2 production continues, respiratory acidosis occurs.  
Overuse of drugs for treating acute headaches, including aspirin, may lead to medication overuse headache. Patients may experience migraine-like daily headaches or a significant increase in migraine attack frequency. Discontinuation of the overused drug and treatment of withdrawal symptoms (e.g., transient worsening of headache) may be necessary. Advise patients about the risks of medication overuse (e.g., use of aspirin for at least 15 days/month or any combination of therapy for at least 10 days/month) and encourage them to keep a written record of headache frequency and drug use. 
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), a multi-organ hypersensitivity reaction, has occurred with NSAIDs. Some of these events have been life-threatening or fatal. DRESS typically presents as fever, rash, and/or lymphadenopathy in conjunction with other organ system involvement including hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. Early manifestations such as fever and lymphadenopathy may be present without evidence of a rash. Discontinue the NSAID in patients presenting with such signs and symptoms in whom an alternative etiology cannot be identified.
Aspirin is contraindicated in patients with salicylate hypersensitivity or NSAID hypersensitivity. Aspirin is also contraindicated in patients with the syndrome of asthma, rhinitis, and nasal polyps; aspirin may cause severe urticaria, angioedema, or bronchospasm in these patients.
Aspirin is contraindicated in infants and children for viral infection, with or without fever, because of the risks of Reye's syndrome. Do not use aspirin in children recovering from varicella infection or influenza.    If children are receiving chronic aspirin therapy, aspirin should be discontinued immediately if a fever develops, and not resumed until diagnosis confirms that the febrile viral illness has run its course and the absence of Reye's syndrome. Following varicella vaccination, aspirin use should generally be avoided for 6 weeks. Children receiving long-term aspirin therapy should receive the annual influenza vaccine.
Avoid aspirin in patients with active peptic ulcer disease due to the risk for gastric ulceration and bleeding. Aspirin increases bleeding risk; risk factors for bleeding include the use of other drugs that increase the risk of bleeding (e.g., anticoagulant therapy, antiplatelet agents, NSAID therapy), inherited (hemophilia, von Willebrand's disease) or acquired (liver disease) coagulopathy, alcoholism, and age 60 years and older.   Neonates have a slower clearance of aspirin and therefore are at higher risk for bleeding.
Avoid aspirin in patients with severe hepatic insufficiency. Hepatic disease increases the risk for bleeding.
Avoid aspirin in patients with severe renal failure (i.e., GFR less than 10 mL/minute).
According to the Beers Criteria, aspirin is considered a potentially inappropriate medication (PIM) in geriatric adults. Aspirin may cause new or worsening gastric or duodenal ulcers, and there is an increased risk of GI bleeding and peptic ulcer disease in high-risk groups including those above 75 years of age, or those taking oral or parenteral corticosteroids, anticoagulants, or antiplatelet medications. The risk of ulcers, gross bleeding, or perforation is cumulative with continued use. The Beers panel recommends avoiding chronic use of aspirin doses more than 325 mg/day in high-risk patients, including those with a history of gastric or duodenal ulcers, unless other alternatives are not effective and the patient can take a gastroprotective agent. The use of a gastroprotective agent, like a proton-pump inhibitor or misoprostol, reduces but does not eliminate, GI risks. Use caution when aspirin is used for the primary prevention of cardiac disease and colorectal cancer in adults 70 years of age and older. Several studies suggest a lack of net benefit when used for primary prevention in older adults with cardiac risk factors, but the evidence is not conclusive. Aspirin is generally indicated for secondary prevention in older adults with established cardiac disease.
Avoid aspirin use during the third trimester of pregnancy (starting at 30 weeks of gestation) due to the risk of premature closure of the fetal ductus arteriosus and persistent pulmonary hypertension in the neonate. If NSAID treatment is deemed necessary between 20 to 30 weeks of pregnancy, limit use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours. Discontinue the NSAID if oligohydramnios occurs and follow up according to clinical practice. These recommendations do not apply to low-dose 81 mg aspirin prescribed for certain conditions in pregnancy. Use of NSAIDs around 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required. Salicylates have also been associated with alterations in maternal and neonatal hemostasis mechanisms, decreased birth weight, and perinatal mortality. Avoid aspirin 1 week prior to and during labor and obstetric delivery because it can result in excessive blood loss at delivery. Prolonged gestation and labor due to prostaglandin inhibition have been reported.
Daily low-dose (e.g., 75 to 162 mg/day) aspirin therapy may be considered as an antiplatelet drug for use during breast-feeding if medically needed and as recommended by guidelines.  If it is used during lactation, monitor the nursing infant for bruising and bleeding. After daily low-dose aspirin (e.g., 81 mg/day), no aspirin is excreted into breast milk and salicylate levels are low. Higher doses and other chronic use are not recommended as salicylates are excreted into breast milk, with higher doses resulting in disproportionately higher milk levels which could cause adverse effects in infants. Mean peak breast milk concentrations of salicylate in 6 nursing mothers after aspirin doses of 500, 1,000, and 1,500 mg were 5.8, 15.8, and 38.8 mg/L, respectively. Salicylate concentrations were detectable in breast milk within 1 hour of dosing and reached maximum concentration within 2 to 6 hours. Alternative analgesics and antipyretics considered to be usually compatible with breast-feeding for the treatment of mild pain, headache, or fever include acetaminophen and ibuprofen.
The activity of aspirin is due to its ability to inhibit cyclooxygenase (COX). Cyclooxygenase is responsible for the conversion of arachidonic acid to prostaglandin G2 (PGG-2), the first step in prostaglandin synthesis and precursor to prostaglandins of the E and F series. Cyclooxygenase exists in 2 isozymes: cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). In vivo, aspirin is hydrolyzed to salicylic acid and acetate. However, hydrolysis is not required for aspirin activity. Aspirin irreversibly inhibits COX by acetylation of a specific serine moiety (serine 530 of COX-1 and serine 516 of COX-2). Aspirin is about 170-times more potent in inhibiting COX-1 than COX-2. In comparison, salicylic acid has little or no ability to inhibit COX in vitro despite inhibiting prostaglandin synthesis at the site of inflammation in vivo. The exact mechanism of prostaglandin inhibition by salicylic acid is unclear; however, salicylates produce the majority of classic NSAID effects. Theories regarding the potential mechanism for salicylic acid include inactivation of transcriptional regulatory proteins (e.g., NF-kappaB), which regulate expression of inflammatory proteins. Aspirin appears to inhibit COX through two pathways and seems to have a different mechanism of action than other salicylates. Aspirin does not inhibit the peroxidase activity of COX and does not suppress leukotriene synthesis by lipoxygenase pathways. 
Antithrombotic Actions: Aspirin-induced inhibition of thromboxane A2 (TXA2) and prostacyclin (PGI-2) has opposing effects on hemostasis. TXA2 is a potent vasoconstrictor and platelet agonist, while PGI-2 inhibits platelet aggregation and vascular smooth muscle contraction. However, data suggest that the effects of aspirin-induced TXA2 inhibition predominate clinically. This may be due to the ability of vascular endothelial cells to regenerate new COX and recover normal function, while COX inhibition in platelets is irreversible due to the limited amount of mRNA and protein synthesis in these cells. This distinction also allows for the use of very low doses of aspirin to retard platelet aggregation. The antithrombotic actions of aspirin are primarily mediated by COX-1 inhibition; COX-1 produces TXA2. Aspirin may also inhibit platelet activation by neutrophils. The antiplatelet effects of aspirin result in a prolonged bleeding time, which returns to normal roughly 36 hours after the last dose of the drug. Antiplatelet effects occur before acetylsalicylic acid is detectable in the peripheral blood due to exposure of platelets in the portal circulation.  In very high and toxic doses, aspirin also exerts a direct inhibitory effect on vitamin K-dependent hemostasis by inhibiting the synthesis of vitamin K-dependent clotting factors. Prothrombin synthesis is impaired, resulting in hypoprothrombinemia.
Anti-inflammatory Actions: The antiinflammatory action of aspirin is believed to be a result of peripheral inhibition of COX-1 and COX-2, but aspirin may also inhibit the action and synthesis of other mediators of inflammation. It is thought that COX-2 is the more important pathway for the inflammatory response since COX-2 is inducible in settings of inflammation by cytokines. Inhibition of COX-2 by aspirin suppresses the production of prostaglandins of the E and F series. These prostaglandins induce vasodilation and increase tissue permeability, which, in turn, promotes the influx of fluids and leukocytes. Ultimately, the classic symptoms of inflammation result: swelling, redness, warmth, and pain. Aspirin does not only decrease capillary permeability (which reduces swelling and the influx of inflammatory mediators), but it can also reduce the release of destructive enzymes from lysozymes. 
Analgesic Actions: Salicylates are effective in cases where inflammation has caused sensitivity of pain receptors (hyperalgesia). It appears prostaglandins, specifically prostaglandins E and F, are responsible for sensitizing the pain receptors; therefore, salicylates have an indirect analgesic effect by inhibiting the production of further prostaglandins and do not directly affect hyperalgesia or the pain threshold. Salicylates may also interfere with pain perception centrally by activity within the hypothalamus. The total serum salicylate concentrations associated with analgesic activity are 30 to 100 mcg/mL. 
Antipyretic Actions: Salicylates promote a return to a normal body temperature set point in the hypothalamus by suppressing the synthesis of prostaglandins, specifically PGE-2, in circumventricular organs in and near the hypothalamus. Salicylates rarely decrease body temperature in afebrile patients. Paradoxically, toxic doses of salicylates may increase body temperature by increasing oxygen consumption and metabolic rate. The total serum salicylate concentrations associated with antipyretic activity are 30 to 100 mcg/mL. 
Gastrointestinal Effects: Adverse gastrointestinal effects from salicylates may be mediated through decreased prostaglandin synthesis due to inhibition of COX-1. A direct irritant effect on gastric mucosa may also be involved. Salicylates increase the permeability of the gastric mucosa to cations, thus increasing the entry of acid into the mucosa. Salicylates are also known to stimulate the chemoreceptor trigger zone, resulting in nausea and vomiting. 
Respiratory Effects: The respiratory effects of salicylates lead to acid/base changes and alterations in electrolyte and water balance. Salicylates stimulate respiration directly and indirectly resulting in respiratory alkalosis. This is caused by a salicylate-induced increase in oxygen consumption, primarily in skeletal muscle, leading to increased carbon dioxide production and respiratory stimulation. Increased alveolar ventilation balances the increased carbon dioxide production; therefore, plasma carbon dioxide (PaCO2) does not change. Salicylate-induced respiratory alkalosis is compensated for by increasing renal excretion of bicarbonate, which is accompanied by increased sodium and potassium excretion. The serum bicarbonate concentration is then lowered and the serum pH returns to normal (i.e., compensated respiratory alkalosis). However, if the respiratory response to hypercapnia has been depressed (e.g., administration of a barbiturate or opiate agonist), salicylates will cause a significant increase in PaCO2 and respiratory acidosis. Hyperventilation also occurs due to direct stimulation of the respiratory center in the medulla. At high salicylate plasma concentrations (350 mcg/mL or more), marked hyperventilation will occur, and at serum concentrations of about 500 mcg/mL, hyperpnea will be seen. Finally, at high-therapeutic and at toxic doses, aspirin can affect oxidative phosphorylation, however, this action is insignificant at lower doses. Other changes in acid-base status (e.g., metabolic and respiratory acidosis) and electrolyte and water balance (hypokalemia, hypernatremia, dehydration) may be seen during salicylate intoxication. 
Renal Effects: In addition to changes in sodium and fluid status secondary to acid/base changes, salicylates may decrease renal blood flow and glomerular filtration rate, which may be accompanied by water and potassium retention, in sodium-restricted patients and patients with impaired renal function or hypovolemic states. Changes in renal function are due to inhibition of renal prostaglandin synthesis, which increase renal blood flow and maintain normal renal function. Salicylate-induced renal effects are uncommon in patients with normal renal function.
Uricosuric Effects: Salicylates act on the renal tubules to affect uric acid excretion. Lower doses (e.g., 1 to 2 g/day) of salicylates inhibit the active secretion of uric acid into the urine via the proximal tubules. However, high doses (more than 3 g/day) of salicylates inhibit the tubular reabsorption of uric acid, resulting in a uricosuric effect. Uric acid secretion is not changed at intermediate dosages. While once used for their uricosuric properties, other agents have replaced salicylates for this purpose.
Aspirin is administered orally or rectally. Salicylic acid is widely distributed with high concentrations in the liver and kidney. During chronic administration, salicylate concentrations in the fetus may be higher than those in the mother. Aspirin is poorly protein-bound as compared to salicylic acid. However, aspirin may acetylate albumin, resulting in changes the ability of albumin to bind other drugs. Protein binding of salicylic acid to albumin varies with serum salicylate and albumin concentrations. At salicylate concentrations of 100 mcg/mL or less, salicylic acid is 90% to 95% protein-bound; approximately 70% to 85% protein-bound at 100 to 400 mcg/mL; and only 20% to 60% protein-bound at serum concentrations of more than 400 mcg/mL. Patients with low serum albumin have higher free salicylate concentrations.
Aspirin has a half-life of 15 to 20 minutes in adults as it is rapidly hydrolyzed by the liver to salicylic acid. Salicylic acid is primarily metabolized in the liver. Metabolites include salicyluric acid (glycine conjugate), the ether or phenolic glucuronide, and the ester or acyl glucuronide. In addition, a small amount is metabolized to gentisic acid (2,5-dihydroxybenzoic acid) and 2,3-dihydroxybenzoic and 2,3,5-dihydroxybenzoic acids. Salicyluric acid and salicyl phenolic glucuronide are formed via saturable enzyme pathways, and therefore, exhibit non-linear pharmacokinetics. The elimination half-life of salicylic acid varies with dosage. After a single low dose, the serum half-life of salicylic acid is 2 to 3 hours, but can increase to 12 hours with anti-inflammatory doses and up to 15 to 30 hours after overdoses. Because of decreased serum protein binding, the effect of increasing doses is more pronounced on free salicylate concentrations than total salicylate concentrations. Approximately 80% to 100% of the salicylic acid from a single salicylate dose is excreted within 24 to 72 hours in the urine as free salicylic acid (10%), salicyluric acid (75%), salicylic phenolic (10%) and acyl (5%) glucuronides, and gentisic acid (less than 1%). The excretion of free salicylic acid is variable and depends upon the dose and the urinary pH. In alkaline urine, more than 30% of the dose may be eliminated as free salicylic acid, but in acidic urine only about 2% is eliminated as free salicylic acid.
Affected cytochrome P450 isoenzymes and drug transporters: none
Aspirin is absorbed orally via passive diffusion as unchanged drug and as hydrolyzed salicylic acid from the upper intestine and partly from the stomach. Approximately 70% of an aspirin dose reaches the circulation unchanged; the remaining 30% is hydrolyzed to salicylic acid during absorption by esterases in the GI tract, plasma, or liver. The rate of absorption is dependent upon many factors including oral formulation, gastric and intestinal pH, gastric emptying time, and the presence of food. Aspirin is rapidly absorbed after oral administration, and bioavailability of regular aspirin in adults is approximately 40% to 50%. Effervescent and soluble tablets are most rapidly absorbed, followed by uncoated or film-coated tablets, and then enteric-coated tablets and extended-release formulations. The absorption from enteric-coated tablets and sustained-release preparations is delayed and bioavailability is significantly lower compared with regular aspirin.   Peak plasma salicylate concentrations occur in approximately 30 to 60 minutes for effervescent tablets, 45 to 120 minutes for film-coated tablets, 4 to 12 hours for extended-release tablets, and 8 to 14 hours for enteric-coated tablets. Food decreases the rate, but not the extent, of absorption. Salicylic acid is more ionized as the pH increases; however, a rise in pH increases the solubility of ionized salicylic acid and increases the dissolution of aspirin tablets. The overall effect of increased pH is an increase in absorption. Time to peak aspirin concentrations is 15 to 240 minutes depending upon the formulation. Plasma aspirin concentrations decrease as salicylic acid concentrations increase. Steady-state salicylate serum concentrations are similar after administration of plain, uncoated tablets and enteric-coated tablets.
The bioavailability of aspirin after rectal administration in adults has been reported to be 20% to 40%. Peak concentrations are reached approximately 4 hours after rectal administration in adults. Limited pharmacokinetic data in 8 children (5 to 9 years) revealed that the absorption of aspirin was very slow after rectal administration and was highly dependent on retention time. In children that retained the suppository for 5 hours or less, urinary recovery was 54% to 64%. Therefore, aspirin given rectally may not attain effective serum concentrations.
Pharmacokinetic data are unavailable in patients with hepatic impairment; however, aspirin is extensively metabolized in the liver and patients with hepatic impairment may have decreased elimination.
Pharmacokinetic data are unavailable in patients with renal impairment. Aspirin is renally excreted and patients with renal impairment may have decreased elimination. Aspirin is 50% to 100% hemodialyzable.
Neonates would be expected to have a slower clearance of aspirin due to their immature hepatic function. Pharmacokinetic data are very limited in children. Data from 10 children (2 to 7 years) who received aspirin revealed a mean elimination half-life for salicylic acid of 3.4 hours. This is similar to what has been reported in adults.
The pharmacokinetics of aspirin are altered in children with Kawasaki disease. These patients have been shown to achieve lower salicylate concentrations compared with healthy children receiving the same aspirin dose due to a combination of impaired bioavailability and/or increased clearance.
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