drug interactions of aspirin (antiplatelet)
TRANSCRIPT
DRUG INTERACTIONS OF ANTIPLATELETS (PART 1)(DRUG INTERACTIONS OF ASPIRIN)
Dr P.NAINA MOHAMED PhD
Pharmacologist
INTRODUCTION
• ANTIPLATELETS ARE THE DRUGS WHICH DECREASE THE AGGREGATION OF PLATELETS
AND INHIBIT THE THROMBUS FORMATION.
• ASPIRIN IS AN ANTIPLATELET DRUG AND IT PRODUCES ANTIPLATELET ACTIVITY IN
LOWER DOSES (75-100 MG DAILY), WHILE HIGHER DOSE OF ASPIRIN (UP TO 3600 MG
DAILY IN DIVIDED DOSES) IS REQUIRED FOR IT’S ANALGESIC EFFECTS.
• ASPIRIN HAS BEEN PRESCRIBED FOR THE PRIMARY PREVENTION OF
CARDIOVASCULAR EVENTS IN LOW RISK PATIENTS, IN RECENT YEARS.
INTERACTION BETWEEN ONE OR MORE COADMINISTERED MEDICATIONS LEADING TO CHANGE IN THEIR EFFECTIVENESS OR TOXICITY, IS TERMED AS “ADVERSE DRUG INTERACTION”.
ANTIPLATELETS CAN INTERACT WITH PRESCRIPTION DRUGS, OVER-THE-COUNTER
(OTC) MEDICATIONS, HERBAL PRODUCTS, DIETARY SUPPLEMENTS, VITAMINS,
FOODS, DISEASES, AND GENETICS (FAMILY HISTORY).
MECHANISM OF PLATELET AGGREGATION
HTTPS://WWW.NCBI.NLM.NIH.GOV/BOOKS/NBK53449/
Vascular injury Capture of plateletsAdhesion of Platelets to
the subendothelium
Activation of platelets by ADP and collagen
present at the sites of vascular injury
Increased intracellular concentration of calcium
ions
Stimulation of membrane
phospholipase A2 activity
Liberation of arachidonic acid from
membrane phospholipids
Formation of prostaglandin H2 (PGH2) from Arachidonic acid by
the enzyme Cyclooxygenase 1 (COX-1)
PGH2 is further metabolized to
Thromboxane A2 (TXA2) by thromboxane
synthase
TXA2 is a potent activator of platelets
Platelet aggregation
ANTIPLATELETS• IRREVERSIBLE CYCLOOXYGENASE (COX) INHIBITORS
ASPIRIN
• ADP RECEPTOR INHIBITORS (THIENOPYRIDINES)
CLOPIDOGREL
PRASUGREL
TICLOPIDINE
• ADP RECEPTOR INHIBITORS (NON-THIENOPYRIDINES)
TICAGRELOR
CANGRELOR
ELINOGREL
• ADENOSINE REUPTAKE INHIBITORS
DIPYRIDAMOLE
• GLYCOPROTEIN IIB/IIIA INHIBITORS (IV USE ONLY)
ABCIXIMAB
EPTIFIBATIDE
TIROFIBAN
• PHOSPHODIESTERASE INHIBITORS
CILOSTAZOL
• PROTEASE-ACTIVATED RECEPTOR-1 (PAR-1) ANTAGONISTS
VORAPAXAR
MECHANISM OF ANTIPLATELET ACTIVITY OF ASPIRIN
• 75-100 MG DAILY DOSE OF ASPIRIN IS CAPABLE OF PROVIDING CARDIOPROTECTION THROUGH ITS ANTIPLATELET ACTIVITY.
HTTPS://WWW.NCBI.NLM.NIH.GOV/PMC/ARTICLES/PMC3195738/
AspirinIrreversible inhibition of
Cyclooxygenase 1 (COX-1)
Prevention of formation of prostaglandin H2 (PGH2) from Arachidonic acid
Decreased formation of Thromboxane A2 (TXA2)
Inhibition of Platelet activation & aggregation
ASPIRIN & LIVE INFLUENZA VIRUS VACCINE
• SYMPTOMS OF REYE'S SYNDROME INCLUDE DROWSINESS, CONFUSION, SEIZURES, COMA AND IN SEVERE CASES, REYE'S SYNDROME CAN RESULT IN DEATH.
• AVOID ADMINISTRATION OF ASPIRIN OR ASPIRIN-CONTAINING THERAPY FOR AT LEAST 4 WEEKS FOLLOWING VACCINATION WITH INFLUENZA LIVE VIRUS.
HTTP://WWW.WEBMD.COM/DRUGS/2/DRUG-1082-3/ASPIRIN-TABLET/DETAILS/LIST-INTERACTION-DETAILS/DMID-1297/DMTITLE-SALICYLATES-INFLUENZA-VIRUS-VACCINE-LIVE/INTRTYPE-DRUG
ASPIRIN & KETOROLAC
• CONCOMITANT USE OF ASPIRIN AND KETOROLAC IS CONTRAINDICATED DUE TO CUMULATIVE RISKS OF SERIOUS GI ADVERSE EVENTS (PEPTIC ULCERS, GASTROINTESTINAL BLEEDING AND GI PERFORATION).
HTTPS://LINK.SPRINGER.COM/ARTICLE/10.2165%2F00003088-198917050-00003
Additive Gastrointestinal
Irritation
• Enhanced gastrointestinal adverse effects (Peptic ulcers, GI bleeding and GI Perforation)
Aspirin + Ketorolac
• Increased serum ketorolac levels
Reduced Plasma protein binding of
Ketorolac
Contraindicated
ASPIRIN & CHICKEN POX (VARICELLA) VACCINE
• PEOPLE SHOULD AVOID USING SALICYLATES FOR 6 WEEKS AFTER GETTING VARICELLA VACCINE.
HTTPS://WWW.CDC.GOV/VACCINES/VPD/VARICELLA/HCP/RECOMMENDATIONS.HTML
ASPIRIN & DICHLORPHENAMIDE
• SERUM BICARBONATE CONCENTRATIONS SHOULD BE ESTIMATED REGULARLY.
HTTPS://WWW.NCBI.NLM.NIH.GOV/PMC/ARTICLES/PMC1442363/
Aspirin + Dichlorphenamide
Aspirin induce hypocapnea
(Reduced CO2 in blood)
Decreased availability of CO2 for the production
of bicarbonate
Prevention of excretion of
hydrogen ions
Elevated risk of fatal metabolic acidosis
ASPIRIN & ANTIDIABETICS
• MONITOR THE PATIENT'S BLOOD GLUCOSE AND MONITOR THE PATIENT FOR CLINICAL SIGNS OF
HYPOGLYCEMIA.
HTTPS://WWW.NCBI.NLM.NIH.GOV/PMC/ARTICLES/PMC4175901/
ASPIRIN & METHOTREXATE
• IF CONCOMITANT ADMINISTRATION OF ASPIRIN AND METHOTREXATE IS NECESSARY, MONITOR
CLOSELY FOR METHOTREXATE TOXICITY.
HTTPS://WWW.NCBI.NLM.NIH.GOV/PUBMEDHEALTH/PMH0016427/
ASPIRIN & IBUPROFEN
• DAILY ASPIRIN USERS SHOULD BE ADVISED TO INGEST ASPIRIN AT LEAST 2 HOURS PRIOR TO
IBUPROFEN.
HTTPS://WWW.RESEARCHGATE.NET/PUBLICATION/47788995_ANTIPLATELET_DRUG_INTERACTIONS
Aspirin + Ibuprofen
Ibuprofen Competes with
Aspirin for COX-1 binding site
Decreased antiplatelet effect
of Aspirin
ASPIRIN & NSAIDS
• CLOSELY MONITOR THE PATIENTS FOR GI BLEEDING AND INGEST ASPIRIN AT LEAST 2 HOURS
PRIOR TO AN INTERACTING NSAID.
HTTP://WWW.TANDFONLINE.COM/DOI/ABS/10.1517/14740338.2014.924924?JOURNALCODE=IED
S20
Aspirin + NSAIDs (Ketoprofen, Naproxen, Meloxicam, Piroxicam)
Additive GI irritationIncreased risk of serious GI adverse effects (Ulceration,
Bleeding, Perforation)
ASPIRIN & WARFARIN
• MONITOR THE PROTHROMBIN TIME (PT) OR INTERNATIONAL NORMALIZED RATIO (INR) AND WATCH
THE PATIENT FOR SIGNS OF BLEEDING IF ASPIRIN AND WARFARIN MUST BE USED TOGETHER.
HTTPS://LINK.SPRINGER.COM/ARTICLE/10.1007%2FS11239-009-0413-4
Aspirin + Warfarin
- Displacement of warfarin from plasma albumin
- Inhibition of metabolism of warfarin
- Direct hypoprothrombinemiceffect of aspirin
- Gastric erosion
Increased risk of bleeding
ASPIRIN & COUMARINS
• FREQUENT MONITORING OF THE PROTHROMBIN TIME (PT) IS INDICATED, IF CONCURRENT USE
OF ASPIRIN AND COUMARINS CANNOT BE AVOIDED.
HTTPS://WWW.NCBI.NLM.NIH.GOV/PMC/ARTICLES/PMC1499595/PDF/BMJCRED00617-0036.PDF
Aspirin + Coumarins and other anticoagulants
(Acenocoumarol, Dicumarol, Phenprocoumon,
Anisindione, Phenindione)
- Hypoprothrombinemia
- Inhibition of platelet aggregation
- Displacement of Coumarins and other anticoagulants from protein binding sites
Increased risk of bleeding
ASPIRIN & FIBRINOLYTICS
• CLOSE MONITORING FOR BLEEDING IS RECOMMENDED, IF CONCOMITANT USE IS REQUIRED.
HTTPS://WWW.NCBI.NLM.NIH.GOV/PUBMED/1834805
ASPIRIN & ANTIPLATELETS
• MONITOR THE SIGNS AND SYMPTOMS OF ACTIVE BLEEDING, IF COADMINISTRATION CANNOT
BE AVOIDED.
HTTP://ONLINELIBRARY.WILEY.COM/DOI/10.1111/J.1365-
2796.2010.02299.X/ABSTRACT;JSESSIONID=3DFE9823DD3790D3C64469AEC534BB43.F04T04
Aspirin + Antiplatelets (Clopidogrel, Prasugrel, Ticagrelor, Ticlopidine,
Dipyridamole, Abciximab, Eptifibatide, Tirofiban)
Additive inhibition of platelet aggregation
Increased risk of bleeding
ASPIRIN & TREPROSTINIL
• MONITOR FOR SIGNS AND SYMPTOMS OF BLEEDING.
HTTPS://WWW.NCBI.NLM.NIH.GOV/PMC/ARTICLES/PMC3555423/
Aspirin + Treprostinil
Additive antiplatelet
effects
Increased risk of bleeding
ASPIRIN & ANAGRELIDE
• CLOSE MONITORING OF SIGNS AND SYMPTOMS OF BLEEDING MAY BE WARRANTED.
HTTPS://WWW.NCBI.NLM.NIH.GOV/PUBMED/16398570
Aspirin + Anagrelide
Anagrelide inhibits maturation of
magakaryocytes in to platelets
Additive antiplatelet activity
Increased risk of bleeding
ASPIRIN & CILOSTAZOL
• IF CONCURRENT USE IS REQUIRED, ADMINISTER ASPIRIN AND CILOSTAZOL WITH CARE AND
MONITOR FOR SIGNS AND SYMPTOMS OF BLOOD LOSS.
HTTP://WWW.SCIENCEDIRECT.COM/SCIENCE/ARTICLE/PII/S1078588409000446
Aspirin + Cilostazol
Cilostazol also inhibits platelet
aggregation
Additive Antiplatelet
activity
Increased risk of bleeding
ASPIRIN & ACE INHIBITORS
• THE CLINICIAN SHOULD WEIGH THE BENEFITS AGAINST THE RISKS OF COMBINING THESE TWO
AGENTS.
HTTP://ONLINELIBRARY.WILEY.COM/DOI/10.1111/J.1527-5299.2000.80174.X/FULL
Aspirin + ACE Inhibitors (Captopril, Enalapril,
Imidapril, Temocapril, Delapril, Ramipril,
Perindopril, Cilazapril)
Aspirin blocks cycloxygenase and
decreases the production of vasodilator and
natriuretic Prostaglandins
Decreased effects of ACE Inhibitors
ASPIRIN & CORTICOSTEROIDS
• MONITOR PATIENTS FOR DECREASED EFFECTIVENESS OF ASPIRIN.
HTTPS://LINK.SPRINGER.COM/ARTICLE/10.2165%2F00003088-198917050-00003
Aspirin + Corticosteroids (Prednisolone, Prednisone,
Dexamethasone, etc.)
Corticosteroids increase the elimination of Aspirin
Sub therapeutic Aspirin serum concentrations
ASPIRIN & GTN (NITROGLYCERIN)
• MONITOR FOR AN EXAGGERATED RESPONSE TO NITROGLYCERIN, AS EVIDENCED BY HEADACHE
AND SYNCOPE.
HTTPS://WWW.NCBI.NLM.NIH.GOV/PUBMED/6420164
Aspirin + GTN (Nitroglycerin)
Decreased clearance of Nitroglycerin
Elevated Nitroglycerin
concentrations
CONCLUSION
• DRUG INTERACTIONS CAN RESULT IN SIGNIFICANT MORBIDITY AND MORTALITY AND THUS
MINIMIZING THE RISK FOR DRUG INTERACTIONS SHOULD BE A GOAL IN DRUG THERAPY.
• THE PATIENTS ON ANTIPLATELET THERAPY SHOULD BRING A LIST OF ALL OF THE DRUGS THEY
ARE TAKING INCLUDING PRESCRIPTION DRUGS, OVER-THE-COUNTER DRUGS, AND ANY
SUPPLEMENTS, HERBAL OR OTHERWISE, DURING THEIR VISIT TO THE DOCTOR OR
PHARMACIST.
• THE RISK OF ADVERSE EFFECTS COULD BE REDUCED BY HEALTHCARE PROFESSIONALS
THROUGH THE SCREENING, EDUCATION, AND FOLLOW UP ON SUSPECTED DRUG
INTERACTIONS.
• IF POSSIBLE, THE PATIENTS ARE RECOMMENDED TO FILL ALL THEIR PRESCRIPTIONS AT ONE
PHARMACY.
• PHARMACISTS CAN PLAY A CRUCIAL ROLE IN IDENTIFYING POSSIBLE DRUG INTERACTIONS BY
ASKING PATIENTS ABOUT THEIR HERBAL AND OTHER ALTERNATIVE MEDICINE PRODUCT USE.
REFERENCES
o STOCKLEY’S DRUG INTERACTIONS, 9E
KAREN BAXTER
o GOODMAN & GILMAN'S: THE PHARMACOLOGICAL BASIS OF THERAPEUTICS, 12E
LAURENCE L. BRUNTON, BRUCE A. CHABNER, BJÖRN C. KNOLLMANN
o BASIC & CLINICAL PHARMACOLOGY, 12E
BERTRAM G. KATZUNG, SUSAN B. MASTERS, ANTHONY J. TREVOR
o A MANUAL OF ADVERSE DRUG INTERACTIONS
J.P. GRIFFIN, P.F. D'ARCY
o CLINICAL MANUAL OF DRUG INTERACTION PRINCIPLES FOR MEDICAL PRACTICE
GARY H. WYNN, JESSICA R. OESTERHELD, KELLY L. COZZA, SCOTT C. ARMSTRONG
o HANDBOOK OF DRUG INTERACTIONS: A CLINICAL AND FORENSIC GUIDE
ASHRAF MOZAYANI, LIONEL RAYMON
REFERENCES• HTTP://WWW.MICROMEDEXSOLUTIONS.COM
• HTTPS://LINK.SPRINGER.COM/ARTICLE/10.2165%2F00003088-198917050-00003
• HTTP://ONLINELIBRARY.WILEY.COM/DOI/10.1111/J.1365-2796.2010.02299.X/FULL
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• HTTP://WWW.WEBMD.COM/INTERACTION-CHECKER/
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