DRUG INTERACTIONS OF ANTIPLATELETS (PART 3)

(DRUG INTERACTIONS OF DIPYRIDAMOLE)

Dr P.NAINA MOHAMED PhD

Pharmacologist

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).

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

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

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

effectsContraindicated

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

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

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

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)

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

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

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)

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

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

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

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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INTERACTIONS-INVOLVING-ANTIPLATELET

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• HTTPS://WWW.RESEARCHGATE.NET/PUBLICATION/47788995_ANTIPLATELET_DRUG_INTERACTIONS

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• 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