Dipyridamole is used as an Antiplatelet drug by inhibiting the reuptake of adenosine. Dipyridamole can interact with many drugs including ADP blockers (Clopidogrel, Prasugrel, Ticlopidine, Ticagrelor, etc), Glycoprotein IIB/IIIA inhibitors (Abciximab, Tirofiban, etc.), Fibrinolytics (Reteplase, Tenecteplase, Streptokinase, etc.), Adenosine, Treprostinil, Sulfinpyrazone, Regadenoson, Distigmine and Ginkgo.

1. DRUG INTERACTIONS OF
ANTIPLATELETS (PART 3)
(DRUG INTERACTIONS OF DIPYRIDAMOLE)
Dr P.NAINA MOHAMED PhD
Pharmacologist

2. INTRODUCTION
• DIPYRIDAMOLE IS AN ADENOSINE REUPTAKE INHIBITOR.
• DIPYRIDAMOLE IS USED TO PREVENT BLOOD CLOTS AFTER HEART VALVE
REPLACEMENT IN COMBINATION WITH ANTICOAGULANTS.
• INTERACTION BETWEEN ONE OR MORE CO-ADMINISTERED 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. ANTIPLATELETS
• IRREVERSIBLE CYCLOOXYGENASE (COX) INHIBITORS
 ASPIRIN
• ADP RECEPTOR BLOCKERS (THIENOPYRIDINES)
 CLOPIDOGREL
 PRASUGREL
 TICLOPIDINE
• ADP RECEPTOR BLOCKERS (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

4. MECHANISM OF ACTION OF
DIPYRIDAMOLE
HTTP://STROKE.AHAJOURNALS.ORG/CONTENT/36/10/2170.SHORT
HTTP://WWW.SCIENCEDIRECT.COM/SCIENCE/ARTICLE/PII/0049384883903560
Dipyridamole
- Inhibition of platelet cAMP-
phosphodiesterase
– Inhibition of adenosine
reuptake by vascular and blood
cells
- Enhancement of Prostacyclin
biosynthesis
- Reduction of enzymatic
cAMP-degradation
– Adenosine and possibly
Prostacyclin stimulate the
cAMP formation through the
activation of adenylcyclase
Increased platelet cAMPInhibition of platelet function

5. RIOCIGUAT & PDE
INHIBITORS
• HTTPS://WWW.NCBI.NLM.NIH.GOV/PMC/ARTICLES/PMC4218670/#B32-PTJ3911749
Riociguat + Nonspecific
PDE inhibitors
(Dipyridamole or
Theophylline) or Specific
phosphodiesterase (PDE) 5
inhibitors (Sildenafil,
Tadalafil, or vardenafil)
- Riociguat stimulates
soluble GC and increase
cGMP levels
– PDE inhibitors prevent
degradation of cGMP and
increase cGMP levels
Additive
Hypotensive
effects
Contraindicated

6. DIPYRIDAMOLE & ADP
BLOCKERS
 MONITOR THE SIGNS AND SYMPTOMS OF BLEEDING, IF DIPYRIDAMOLE AND ADP
BLOCKERS (CLOPIDOGREL, PRASUGREL, TICLOPIDINE, TICAGRELOR, ETC) ARE USED
CONCURRENTLY.
HTTPS://WWW.NCBI.NLM.NIH.GOV/PMC/ARTICLES/PMC3187865/
Dipyridamole + ADP
blockers (Clopidogrel,
Prasugrel, Ticlopidine,
Ticagrelor, etc)
Additive antiplatelet
activity
Increased risk of
bleeding

7. DIPYRIDAMOLE &
GLYCOPROTEIN IIB/IIIA
INHIBITORS
 THE SIGNS AND SYMPTOMS OF BLEEDING SHOULD BE MONITORED, IF DIPYRIDAMOLE
AND GLYCOPROTEIN IIB/IIIA INHIBITORS (ABCIXIMAB, TIROFIBAN, ETC.) ARE USED
CONCURRENTLY.
HTTP://ONLINELIBRARY.WILEY.COM/DOI/10.1002/AJH.10451/PDF
Dipyridamole+
Glycoprotein IIB/IIIA
inhibitors
(Abciximab, Tirofiban,
etc.)
Additive antiplatelet
activity
Enhanced risk of
bleeding

8. DIPYRIDAMOLE &
FIBRINOLYTICS
• CLOSE MONITORING FOR BLEEDING IS RECOMMENDED, IF CONCOMITANT USE OF
DIPYRIDAMOLE AND FIBRINOLYTICS SUCH AS RETEPLASE, TENECTEPLASE,
STREPTOKINASE, ETC. IS REQUIRED.
HTTP://WWW.NEUROLOGY.ORG/CONTENT/79/13_SUPPLEMENT_1/S68.LONG
Dipyridamole +
Fibrinolytics
(Reteplase,
Tenecteplase,
Streptokinase, etc.)
Additive effects
Increased risk of
bleeding

9. DIPYRIDAMOLE &
ADENOSINE
• PATIENTS RECEIVING DIPYRIDAMOLE SHOULD BE GIVEN LOWER DOSES OF
ADENOSINE.
• DIPYRIDAMOLE AND ADENOSINE HAS BEEN USED THERAPEUTICALLY TO
PRODUCE CONTROLLED HYPOTENSION DURING SURGERY.
HTTPS://WWW.NCBI.NLM.NIH.GOV/LABS/ARTICLES/3577821/
DIPYRIDAMOLE +
ADENOSINE
Potentiation of effects
of Adenosine
Adenosine toxicity
(Hypotension,
Dyspnea, Vomiting)

10. DIPYRIDAMOLE &
TREPROSTINIL
MONITORING OF BLEEDING MAY BE WARRANTED , IF COADMINISTRATION IS
REQUIRED.
HTTP://WWW.SCIENCEDIRECT.COM/SCIENCE/ARTICLE/PII/S1094553914000169
Dipyridamole
+ Treprostinil
Additive
antiplatelet
effects
Increased risk
of bleeding

11. DIPYRIDAMOLE &
SULFINPYRAZONE
• MONITOR THE SIGNS AND SYMPTOMS OF BLEEDING, IF USED CONCOMITANTLY.
HTTP://EUROPEPMC.ORG/ABSTRACT/MED/2426024
Dipyridamole +
Sulfinpyrazone
Additive
antiplatelet effects
Increased risk of
bleeding

12. DIPYRIDAMOLE &
REGADENOSON
• IF POSSIBLE, PATIENTS SHOULD BE ADVISED TO DISCONTINUE DIPYRIDAMOLE
AT LEAST 2 DAYS PRIOR TO REGADENOSON ADMINISTRATION.
HTTPS://LINK.SPRINGER.COM/ARTICLE/10.1007/S00259-011-1853-6
Dipyridamole +
Regadenoson
Both agents are
adenosine receptor
agonists
Additive effects
(Hypotension,
bradycardia, heart block,
arrhythmia, and other
cardiovascular effects)

13. DIPYRIDAMOLE & DISTIGMINE
• MONITOR THE PATIENT FOR DISTIGMINE EFFICACY.
• LARGER DOSES OF DISTIGMINE MAY BE NECESSARY.
HTTP://PSYCNET.APA.ORG/RECORD/1987-19596-001
Dipyridamole +
Distigmine
Both are
structurally
similar
Competitive
inhibition
Decreased
distigmine
effectiveness

14. DIPYRIDAMOLE & GINKGO
• MONITOR BLEEDING TIME AND SIGNS AND SYMPTOMS OF EXCESSIVE BLEEDING
OR BRUISING, IF BOTH AGENTS ARE TAKEN SIMULTANEOUSLY.
HTTP://WWW.SCIENCEDIRECT.COM/SCIENCE/ARTICLE/PII/S0167527303006272
Dipyridamole +
Ginkgo
Ginkgolide B inhibit
the platelet
activating factor
(PAF) induced
platelet aggregation
Increased risk of
bleeding

15. 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.

16. 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

17. 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