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.

1. DRUG INTERACTIONS OF
ANTIPLATELETS (PART 1)
(DRUG INTERACTIONS OF ASPIRIN)
Dr P.NAINA MOHAMED PhD
Pharmacologist

2. 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).

3. MECHANISM OF PLATELET AGGREGATION
HTTPS://WWW.NCBI.NLM.NIH.GOV/BOOKS/NBK53449/
Vascular injury Capture of platelets
Adhesion 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

4. 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

5. 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/
Aspirin
Irreversible 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

6. 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

7. 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

8. 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

9. 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

10. 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/

11. ASPIRIN & METHOTREXATE
• IF CONCOMITANT ADMINISTRATION OF ASPIRIN AND METHOTREXATE IS NECESSARY, MONITOR
CLOSELY FOR METHOTREXATE TOXICITY.
HTTPS://WWW.NCBI.NLM.NIH.GOV/PUBMEDHEALTH/PMH0016427/

12. 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

13. 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 irritation
Increased risk of serious GI
adverse effects (Ulceration,
Bleeding, Perforation)

14. 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 hypoprothrombinemic
effect of aspirin
- Gastric erosion
Increased risk of bleeding

15. 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

16. ASPIRIN & FIBRINOLYTICS
• CLOSE MONITORING FOR BLEEDING IS RECOMMENDED, IF CONCOMITANT USE IS REQUIRED.
HTTPS://WWW.NCBI.NLM.NIH.GOV/PUBMED/1834805

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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.

25. 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

26. 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
• HTTPS://WWW.ACADEMIC.OUP.COM/EURHEARTJ/ARTICLE/24/19/1707/495173/DRUG-DRUG-INTERACTIONS-
INVOLVING-ANTIPLATELET
• HTTP://WWW.NATURE.COM/NRCARDIO/JOURNAL/V8/N10/FULL/NRCARDIO.2011.128.HTML
• HTTP://WWW.SCIENCEDIRECT.COM/SCIENCE/ARTICLE/PII/S2211594312000974
• HTTPS://WWW.RESEARCHGATE.NET/PUBLICATION/47788995_ANTIPLATELET_DRUG_INTERACTIONS
• HTTP://REFERENCE.MEDSCAPE.COM/DRUG-INTERACTIONCHECKER
• HTTPS://WWW.DRUGS.COM/DRUG_INTERACTIONS.HTML
• HTTP://WWW.WEBMD.COM/INTERACTION-CHECKER/
• HTTP://WWW.RXLIST.COM/DRUG-INTERACTION-CHECKER.HTM
• HTTPS://WWW.NPS.ORG.AU/AUSTRALIAN-PRESCRIBER/ARTICLES/WARFARIN-ANTIPLATELET-DRUGS-AND-THEIR-
INTERACTIONS