NTA Level 5 • Semester 1 • PST05104

Pharmacodynamics of Antiplatelet Drugs

Pharmacology and Therapeutics • Source Session/Topic 36

Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability.

Session 36: Pharmacodynamics of Antiplatelet Drugs

Total Session Time: 120 minutes

Prerequisites

None

Learning Tasks

By the end of this session students are expected to be able to:

Describe mechanism of action of Antiplatelet Drugs

Describe drug interactions associated with Antiplatelet Drugs

Describe side effects of Antiplatelet Drugs

Describe contraindications of Antiplatelet Drugs

Resources Needed:

Flip charts, marker pens, and masking tape

Black/white board and chalk/whiteboard markers

Computer and LCD projector

SESSION OVERVIEW

Step

Time

Activity/

Content

Step

Time

Activity/

Content

Step

Time

Method

Content

Method

05 minutes

Presentation

Introduction, Learning tasks

45 minutes

Presentation/

Mechanism of Action of Antiplatelet Drugs

45 minutes

Buzzing

Mechanism of Action of Antiplatelet Drugs

Buzzing

20 minutes

Presentation/

Drug Interactions Associated with Antiplatelet

20 minutes

brainstorming

Drugs

brainstorming

Drugs

20 minutes

Presentation

Side Effects of Antiplatelet Drugs

20 minutes

Presentation/

Contraindications of Antiplatelet Drugs

20 minutes

Brainstorming

Contraindications of Antiplatelet Drugs

Brainstorming

05 minutes

Presentation

Key Points

PST 05104 Pharmacology & Therapeutics

286

NTA Level 5 Semester 1 Facilitator Guide

05 minutes

Presentation

Evaluation

PST 05104 Pharmacology & Therapeutics 287 NTA Level 5 Semester 1 Facilitator Guide

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing.

STEP 2: Mechanism of Action of Antiplatelet Drugs (45 minutes)

Activity: Buzzing (5 minutes)

ASK students to pair up and buzz on the following question for 2 minutes

How do Antiplatelet Drugs produce their pharmacological effects?

ALLOW few pairs to respond and let other pairs add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below

Salicylates: acetylsalicylic acid (ASA)

o ASA works by irreversibly inhibiting COX-1, an enzyme that catalyses the formation of cyclic endoperoxide, which in turn is then converted to Thromboxane A2 (TXA2) in platelets. TXA2 is a potent inducer of platelet aggregation and release.

o Inhibition of TXA2 leads to the antiplatelet effects of ASA.

Adenosine Diphosphate (ADP) Blockers

o Platelets are activated by adhering to damaged endothelium by linking of glycoprotein Ia (GPIa) receptors with collagen and GPIb receptors with von Willebrand factor (vWF). The activation of platelets leads to aggregation and clot formation.

o Platelet activation leads to synthesis and release of mediators involved in platelet aggregation: TXA2, Serotonin (5-HT) and ADP.

o Mediators such as ADP promote platelet aggregation by increasing GP receptor expression and promoting binding of fibrinogen to GPIIIa/IIb receptors.

o Ticlopidine, prasugrel, and clopidogrel inhibit the ADP-dependent pathway of platelet activation and subsequent aggregation.

Antiplatelet IIb/IIIa Inhibitors

o IIb/IIIa receptors are located on the outside of platelets, in very high numbers (50,000 to 80,000 per cell); in the resting platelet they are inactive.

o Fibrinogen and vWF bind to IIb/IIIa receptors; once bound, they bind to foreign surfaces and also bridge other platelets to induce platelet aggregation.

PST 05104 Pharmacology & Therapeutics 288 NTA Level 5 Semester 1 Facilitator Guide

These drugs bind to the IIb/IIIa receptor complex on the platelet and prevent binding of endogenous ligands including fibrinogen and vWF, thus inhibiting aggregation of the platelet

Dipyridamole

Dipyridamole was introduced as a vasodilator, but provokes rather than prevents angina (via a steal mechanism).

It is used acutely as in stress tests for ischaemic heart disease (e.g. combined with nuclear medicine myocardial perfusion scanning).

It is also used chronically, combined with aspirin, for its antiplatelet effect in patients with cerebrovascular disease.

Dipyridamole inhibits phosphodiesterase which leads to reduced breakdown of cAMP, and inhibits adenosine uptake with consequent enhancement of the actions of this mediator on platelets and vascular smooth muscle..

STEP 3: Drug Interactions Associated with Antiplatelet Drugs (20 minutes)

Activity: Brainstorming (5 minutes)

Ask students to brainstorm on the following question:

What are drug interactions associated with antiplatelet drugs?

ALLOW few students to respond

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

Salicylates: acetylsalicylic acid (ASA)

o Aspirin not only influences haemostasis when co-administered with warfarin by its effect on platelet function, but also increases the likelihood of peptic ulceration, displaces warfarin from plasma albumin, and in high doses decreases prothrombin synthesis. When low doses of aspirin are taken regularly with warfarin may be more than offset by clinical benefits to patients at high risk of thromboembolism following cardiac valve replacement.

o For details refer session on Pharmacodynamics of Antinflammatory drugs

Dipyridamole

Dipyridamole increases the potency and duration of action of adenosine.

This may be clinically important in patients receiving dipyridamole in whom adenosine is considered for treatment of dysrhythmia.

PST 05104 Pharmacology & Therapeutics 289 NTA Level 5 Semester 1 Facilitator Guide

STEP 4: Adverse Effects of Antiplatelet Drugs (20 minutes)

Antiplatelet Drugs

Salicylates: acetylsalicylic acid (ASA)

o GI: GI effects are caused by reduced levels of a PG (produced by COX-1) that protects the lining of the stomach. They can range in severity from upset stomach to GI bleeds and ulcers.

o Bleeding is caused by the antiplatelet effect.

o Tinnitus: Ringing of the ears is typically only seen at higher doses. o For details refer Pharmacodynamics of Antinflammatory drugs

Adenosine Diphosphate (ADP) Blockers o Bleeding

o Rash, diarrhea: mechanism not known

o Severe neutropenia is a rare side effect associated with ticlopidine but not with clopidogrel.

o It necessitates discontinuation of the drug.

o Thrombotic thrombocytopenic purpura (TTP): has been associated with ticlopidine and less commonly with clopidogrel.

Antiplatelet IIb/IIIa Inhibitors o Bleeding

o Thrombocytopenia is the most serious complication. Thrombocytopenia is immune-mediated and occurs in 5% of patients but is severe in 1%.

STEP 5: Contraindications of Antiplatelet Drugs (20 minutes)

Activity: Brainstorming (5 minutes)

Ask students to brainstorm on the following question:

What are the contraindications of antiplatelet drugs? ALLOW few students to respond?

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below Antiplatelet Drugs

Salicylates: acetylsalicylic acid (ASA)

o Hypersensitivity (allergy) to ASA. Can be fatal.

o Not for use in children. Causes Reye‘s syndrome, an often fatal encephalopathy in children that has been associated with the use of ASA during viral infection.

Adenosine Diphosphate (ADP) Blockers

o Active bleeding: These agents impair clotting and prolong bleeding.

PST 05104 Pharmacology & Therapeutics 290 NTA Level 5 Semester 1 Facilitator Guide

Significant hepatic impairment: Clopidogrel and ticlopidine agents need a functioning liver in order to be converted to their active metabolites. Hepatic complications have also been reported with both agents but are extremely rare.

Antiplatelet IIb/IIIa Inhibitors

High risk of bleeding, including but not limited to the following: Recent surgery, recent stroke, thrombocytopenia (low platelet count) and recent GI bleed.

STEP 6: Key Points (5 minutes)

Hemorrhage is a particular problem with agents displaying less specificity for newly formed thrombi (streptokinase and urokinase).

STEP 7: Evaluation (5 minutes)

What are the adverse effects of ASA?

What is the mechanism of action of clopidogrel?

What are contraindications of antiplatelet drugs?

PST 05104 Pharmacology & Therapeutics 291 NTA Level 5 Semester 1 Facilitator Guide

References

Katzung, B. G. (2018). Basic and clinical pharmacology. New York: Mcgraw Hill Education.

Santos, R. R., Rang, H. P., Dale, M. M., Ritter, J. M., & Flower, R. J. (2007). Rang & Dale Farmacologia. Rio de Janeiro: Elsevier.

Tripathi, K. (2018). Essentials of Medical Pharmacology. Place of publication not identified:

Jaypee Brothers Medical P.

Ministry of Health and Social Welfare. (2013). Standard Treatment Guidelines & National Essential Medicines List Tanzania Mainland (4th ed.). Dar es salaam, Tanzania government printers.

Robert L. Talbert, Gary C. Yee, Gary R. Matzke, Barbara G. Wells, L. Michael. (2014). Pharmacotherapy: A Pathophysiologic Approach (9th ed.). New York, McGraw-Hill Education.

Sally S.R, Jeanne C.S. (2000). Introductory Clinical Pharmacology (6th ed) New York, Lippincott Williams and Wilkins.

School of Pharmaceutical sciences. (2011).Tanzania Pharmaceutical Handbook (2nd ed.).

Dar es Salaam, ARDHI University press.

The Royal Pharmaceutical Society of Great Britain. (2007). Martindale, the Extra Pharmacopoeia (5TH ed). London, pharmaceutical press.

The Royal Pharmaceutical Society of Great Britain. 2009. British National Formulary (59th ed). London, BMJ Group and RPS Publishing.

PST 05104 Pharmacology & Therapeutics 292 NTA Level 5 Semester 1 Facilitator Guide

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