Aspirin

From Anvita Health Wiki

Contents 1 Introduction 2 Indications 3 Contraindications 4 Dosage 5 Pharmacokinetics 6 Adverse-effects 7 Drug-interactions 8 Mechanism-of-action 9 More General Terms 10 Additional Terms 11 Internet Database 12 References

Introduction

• Acetylsalicylic acid ( ASA). Enteric-coated acetylsalicylic acid (ECASA). Tradenames: Ecotrin, Empirin, Bayer.

Indications

• treatment of pain, inflammation & fever

• 325 to 650 mg PO every 4-6 hours, max 4 g/day

• prophylaxis for myocardial infarction, stroke, TIA

• 81 to 325 mg PO QD
• may only be effective in patients with systolic blood pressure < 130 mm Hg [6]
• 75-150 mg QD as effective as higher doses [9] 75-162 mg recommended by [16]
• no benefit of added dipyridamole [9]
• 10% less effective than clopidogrel or ticlopidine [9]
• USPSTF recommends aspirin prophylaxis (primary prevention) for: [27,33,35]

• men age 45-79 years when the potential benefit due to a reduction in myocardial infarctions outweighs the potential harm ( GI bleed)
• women age 55-79 years when the potential benefit due to a reduction in strokes outweighs the potential harm ( GI bleed)
• insufficient evidence to recommend aspirin for patients > 79 years of age or in men < 45 or women < 55 years of age [27,33]
• risk for nontrivial bleeding roughly equals benefit in primary prevention of nonfatal myocardial infarction [41]
• no benefit in primary prevention of fatal myocardial infarction [41]

• also see sex differences for aspirin therapy
• stopping aspirin may result in increased risk of heart attack & stroke (increased platelet production) [19]
• 81 mg QD may not reduce atherosclerotic events in adults with type 2 diabetes [24]
• no better than placebo in patients with peripheral arterial disease [29,37]

• treatment of acute MI

• 160-325 mg PO (chewed, not EC), then 325 mg PO QD

• management of rheumatoid arthritis, rheumatic fever, osteoarthritis

• 325 to 650 mg PO every 4-6 hours, max 4 g/day

• Kawasaki disease:

• 100 mg/kg/day PO divided every 6 hours until fever resolves, then 8-10 mg/kg PO QD
• monitor serum concentration

• secondary stroke prevention ( relative risk reduction of 13%)
• combined with warfarin ( INR of 3) for high-risk patients with artificial heart valves (however; increased risk of bleeding
• may diminish risks of cancer, death from cancer, & cancer metastasis [42]

• may diminish risk of colon cancer [9]

• see aspirin & colorectal polyps & Nurses Health Study
• does not reduce mortality from colon cancer [28]
• dose-independent reduction in mortality due to proximal colon cancer & rectal cancer
• no reduction in mortality due to distal colon cancer [38]

• may reduce risk of prostate cancer [9]
• may reduce risk of ovarian cancer [9]
• may reduce risk of breast cancer [12]
• may reduce mortality in patients with breast cancer [36]
• may reduce mortality from several adenocarcinomas [39]

Contraindications

• does NOT block restenosis after coronary angioplasty or carotid endarterectomy
• of NO benefit in primary stroke prevention for men (see sex differences for aspirin therapy)
• old-age alone not indication for low-dose aspirin [17]
• no benefit for low-dose (81 mg) ASA in preventing cancer or cardiovascular disease in women [18]
• no benefit for low-dose (81 mg) ASA in preventing cognitive impairment in middle-age & elderly subjects at moderate cardiovascular risk [23]
• routine use of low-dose aspirin for primary prevention of cardiovascular disease in apparently healthy individuals, including those with elevated blood pressure, diabetes or low ankle-brachial index (< 0.95) [33,36]

• Caution:

• aspirin may cause severe asthma
• a triad of asthma, nasal polyposis & aspirin sensitivity
• control hypertension before starting aspirin [21]
• uncertain net value; reduction in cardiovascular events needs to be weighed against risk of major bleed [30]
  

• pregnancy category = d
• safety in lactation = ?

Dosage

• prevention of stroke, heart attack: 75-81 mg PO QD

• lifetime therapy for secondary prevention [40]

• headache, myalgia, arthralgia: 325-650 mg every 4 hours or 325-975 mg every 6 hours

• Tabs: 81, 325, 500, 650, 975 mg.
• Suppository: 120, 200, 300, 600 mg.
  
• Enteric-coated as effective as plain aspirin in prevention of cardiovascular disease [11]
  
• Quick-release form: 325 mg, 500 mg ( Bayer)
  

• proton pump inhibitors should be considered for patients on long-term antiplatelet therapy if: [3]

• history of peptic ulcer or gastrointestinal bleeding
• dual antiplatelet therapy or concomitant anticoagulation
• additional risk factors (age >= 60, steroid use, dyspepsia, or gastroesophageal reflux).

• in patients with a history of ulcer histories who are starting chronic antiplatelet therapy, test for & eradicate H pylori [3]
  
• famotidine 20 mg BID prevents peptic ulcers & erosive esophagitis in patients taking low-dose aspirin [32]

Pharmacokinetics

• hydrolyzes to salicylate by esterases in the GI mucosa, erythrocytes, synovial fluid & blood
• salicylate is metabolized by the liver
• 1/2 life of parent compound is 15-20 minutes
• 1/2 life of salicylate is 3-10 hours
• onset of analgesia is 30 minutes
• duration of action is 3-4 hours
  

• elimination via kidney
• 1/2life = 0.25-0.33 hours

Adverse-effects

• nausea/vomiting
• dyspepsia/ heartburn
• gastrointestinal ulceration (0.06%/year 75-500 mg daily)

• low dose in combination with proton pump inhibitor minimizes risk of GI bleed [15,20,25]
• risk of cardiovascular complications after stopping low dose aspirin outweighs risk of GI bleed in patients who take aspirin for secondary prophylaxis [34]
• clopidogrel alone is more likely to cause recurrent GI bleeding than aspirin combined with a PPI [34]

• anemia
• rash
• dyspnea
• bronchospasm
• renal impairment
• exacerbation of gout, low-dose aspirin interferes with uric acid secretion [5]
• tinnitus
• allergic reactions ( anaphylactoid reactions)

• urticaria
• angioedema
• results from inhibition of cyclooxygenase
• no skin testing is available
• antigen desensitization if NSAIDs are imperitive
• leukotriene & 5- lipoxygenase inhibitors attenuate allergic reaction to aspirin

• may be associated with nasal polyps & rhinosinusitis
• increases risk of hemorrhagic stroke [7,8] (0.02%/year), especially with hypertension [21]
• doses > 200 mg/day double the risk of bleeding [12]
• does NOT increase risk of intracranial hemorrhage with head trauma in the elderly [13]

• Toxicity: (management)

• overdose

• induce emesis with ipecac
• gastric lavage with saline
• follow with activated charcoal

• dehydration

• IV fluids (normal or 1/2 normal saline) with KCl
• do NOT use D5W

• metabolic acidosis - sodium bicarbonate
• hyperthermia - spone baths, fan, cooling blanket
• coagulopathy/hemorrhage - IV vitamin K
• hypoglycemia (with coma, seizures, or mental status change)

• dextrose 25 g IV

• seizures: diazepam 5-10 mg IV
  
• drug adverse effects of NSAIDs
• drug adverse effects of antiplatelet agents

Drug-interactions

• corticosteroids increases risk of GI & renal-related toxicity
• aspirin may antagonize uricosuric effect of probenecid
• aspirin increases methotrexate levels by binding site displacement & inhibiting renal excretion
• increased risk of bleeding when coadministered with warfarin
• may displace valproic acid from binding sites & increase toxicity
• ibuprofen may inhibit antiplatelet activity of aspirin [10]
  
• drug interaction(s) of anti-platelet agents with SSRIs
• drug interaction(s) of aspirin with proton pump inhibitors
• drug interaction(s) of antiplatelet agents with proton pump inhibitors
• drug interaction(s) of lithium carbonate with NSAIDs
• drug interaction(s) of beta-adrenergic receptor antagonists with salicylate
• drug interaction(s) of salicylates with sulfonylureas
• drug interaction(s) of NSAIDs with SSRIs
• drug interaction(s) of aspirin with NSAIDs
• drug interaction(s) of warfarin with antiplatelet agents
• drug interaction(s) of NSAIDs with beta blockers
• drug interaction(s) of NSAIDs with ARBs
• drug interaction(s) of NSAIDs with ACE inhibitors
• drug interaction(s) of NSAIDs, diuretics & angiotensin II receptor antagonists
• drug interaction(s) of NSAIDs, diuretics & ACE inhibitors
• drug interaction(s) of NSAIDs & loop diuretics
• drug interaction(s) of NSAIDs & aspirin

Mechanism-of-action

• inhibits prostaglandin synthesis

• cyclo-oxygenase 1

• GI effects
• renal effects
• inhibition of platelet aggregation

• cyclo-oxygenase 2

• anti-inflammatory properties

• acts on temperature regulation center in the hypothalamus
• inhibits formation of thromboxane A2

• irreversibile platelet effects last 10 days

• inhibits NF-kappa B in macrophages

More General Terms

• salicylate
• antiplatelet agent

Additional Terms

• sex differences for aspirin therapy

Internet Database

PubChem: 2244
PubChem: 71089

References

1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 14
3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
5. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, American College of Physicians, Philadelphia 1998, 2006
6. Prescriber's Letter 7(8):47 2000
7. Prescriber's Letter 9(2):7 2002
8. Journal Watch 22(4):33, 2002 USPTF 3 2002 guidelines
9. Prescriber's Letter 9(5):29 2002 Journal Watch 23(8):62, 2003
10. Prescriber's Letter 10(3):15 2003
11. Prescriber's Letter 10(4):21 2003
12. Prescriber's Letter 10(11):63 2003
13. Journal Watch 23(23):183-84, 2003 Spektor S et al, J Neurosurg 99:661, 2003 PMID: [1]
14. Journal Watch 24(13):101, 2004 Terry MB, Gammon MD, Zhang FF, Tawfik H, Teitelbaum SL, Britton JA, Subbaramaiah K, Dannenberg AJ, Neugut AI. Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. JAMA. 2004 May 26;291(20):2433-40. PMID: [2]
15. Prescriber's Letter 12(3): 2005 Safety of Clopidogrel (Plavix) in Patients at Risk for Ulcers Detail-Document#: [3] (subscription needed) [4]
    - Journal Watch 25(4):29, 2005 Chan FK, Ching JY, Hung LC, Wong VW, Leung VK, Kung NN, Hui AJ, Wu JC, Leung WK, Lee VW, Lee KK, Lee YT, Lau JY, To KF, Chan HL, Chung SC, Sung JJ. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med. 2005 Jan 20;352(3):238-44. PMID: [5]
    - Cryer B. Reducing the risks of gastrointestinal bleeding with antiplatelet therapies. N Engl J Med. 2005 Jan 20;352(3):287-9. No abstract available. PMID: [6]
16. Prescriber's Letter 12(4): 2005 Primary Prevention of Cardiovascular Disease in Women Detail-Document#: [7] (subscription needed) [8]
17. Journal Watch 25(15):118, 2005 Nelson MR, Liew D, Bertram M, Vos T. Epidemiological modelling of routine use of low dose aspirin for the primary prevention of coronary heart disease and stroke in those aged > or =70. BMJ. 2005 Jun 4;330(7503):1306. Epub 2005 May 20. <PubMed> PMID: [9] <Internet> [10]
18. Cook NR, Lee IM, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE. Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial. JAMA. 2005 Jul 6;294(1):47-55. PMID: [11]
19. Prescriber's Letter 12(9): 2005 The Risks of Stopping Low-Dose Aspirin Detail-Document#: [12] (subscription needed) [13]
20. Targownik LE & Al-Mamfud A The prevalence of risk factors for gastrointestinal complications and use of gastroprotection among persons hospitalized for cardiovascular disease. Aliment Pharmacol Ther 2006; 23:743 Using Aspirin in Hypertensive Patients PMID: [14]
21. Prescriber's Letter 14(10): 2007 Using Aspirin in Hypertensive Patients Detail-Document#: [15] (subscription needed) [16]
22. Prescriber's Letter 15(8): 2008 Can Aspirin 162 mg a Day Keep The Doctor Away? Detail-Document#: [17] (subscription needed) [18]
23. Price JF et al. Low dose aspirin and cognitive function in middle aged to elderly adults: Randomised controlled trial. BMJ 2008 Sep 1; 337:a1198. <PubMed> PMID: &dopt=Abstract (<Internet> [19]
24. Ogawa H et al, Low-Dose Aspirin for Primary Prevention of Atherosclerotic Events in Patients With Type 2 Diabetes JAMA. 2008;300(18) <PubMed> PMID: [20] <Internet> [21]
25. Prescriber's Letter 15(21): 2008 Reducing the Risk for GI Bleeding with Antiplatelet Drugs Detail-Document#: [22] (subscription needed) [23]
26. Bhatt DL et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. Am J Gastroenterol 2008 Nov; 103:2890.
    - Bhatt DL et al, ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2008 Oct 28;52(18):1502-17. PMID: &dopt=Abstract
    - Bhatt DL et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation 2008 Oct 28; 118:1894. PMID: [24]
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28. Cole BF et al Aspirin for the chemoprevention of colorectal adenomas: Meta-analysis of the randomized trials. J Natl Cancer Inst 2009 Feb 18; 101:256. PMID: &dopt=Abstract
    - Grau MV et al. Nonsteroidal anti-inflammatory drug use after 3 years of aspirin use and colorectal adenoma risk: Observational follow-up of a randomized study. J Natl Cancer Inst 2009 Feb 18; 101:267. PMID: [26]
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31. Prescriber's Letter 16(6): 2009 Detail-Document#: [30] (subscription needed) [31]
32. Taha AS Famotidine for the prevention of peptic ulcers and oesophagitis in patients taking low-dose aspirin (FAMOUS): a phase III, randomised, double-blind, placebo-controlled trial. Lancet, Volume 374, Issue 9684, Pages 119-125, 11 July 2009 PMID: [32]
33. U.S. Preventive Services Task Force recommendation statement. Aspirin for the Prevention of Cardiovascular Disease [33]
34. Sung JJY et al Continuation of low-dose aspirin in peptic ulcer bleeding: A randomized trial. Ann Intern Med. 2010 Jan 5;152(1):1-9. Epub 2009 Nov 30. <PubMed> PMID: [34] <Internet> [35]
    - Prescriber's Letter 17(3): 2010 COMMENTARY: Using Low-Dose Aspirin After a GI Bleed PATIENT HANDOUT: Aspirin and Your Heart PATIENT HANDOUT SPANISH VERSION: La Aspirina y el Corazon GUIDELINES: Recommendations on the Management of Patients with Nonvariceal Upper Gastrointestinal Bleeding Detail-Document#: [36] (subscription needed) [37]
35. Prescriber's Letter 17(2): 2010 Aspirin for Primary Prevention Detail-Document#: [38] (subscription needed) [39]
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    - Berger JS. Aspirin as preventive therapy in patients with asymptomatic vascular disease. JAMA 2010 Mar 3; 303:880. PMID: [43]
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39. Rothwell PM et al Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials Lancet. 2011 Jan 1;377(9759):31-41. Epub 2010 Dec 6. <PubMed> PMID: [45] <Internet> [46]
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42. Rothwell PM et al Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. The Lancet, Early Online Publication, 21 March 2012 <PubMed> PMID: [50] <Internet> [51]
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43. National Guideline Clearinghouse Aspirin for the prevention of cardiovascular disease: U.S. Preventive Services Task Force recommendation statement. ngc-guideline: [58]

aspirin (Ecotrin, Empirin, Bayer aspirin, ASA)