Antiplatelet Drugs

• Low dose aspirin (81-325 mg/day), P.o.; irreversible (acetylation) COX-1 inhibition; contraindicated in pts hypersensitive to ASA or other NSAIDs (Ecotrin; Bayer; generics)

• Ticlopidine (management of pts at risk of thrombotic stroke); blocks ADP induced aggregation, platelet release reactions; irreversible effect for life of platelet; P.O.; risk of agranulocytosis (0.8%) (Ticlid)

• Clopidogrel (chemically related to ticlopidine), inhibits binding of ADP to platelet membrane receptor; irreversible effect; P.O.; used in preventing stroke, M.I., peripheral vascular thrombosis; lower risk of agranulocytosis. (Plavix)

• Dipyridamole- platelet phosphodiesterase inhibitor, increases intracellular cAMP. Now approved in combination with low dose Aspirin (Aggrenox)

• Tirofiban - (non-peptide antagonist of glycoprotein Iib/IIIa platelet receptor involved in binding of fibrinogen causing aggregation of platelets); platelet aggregation inhibition reversible upon stopping drug; indicated in unstable angina and acute coronary syndromes; I.V. only- indicated only in hospital settings. (Aggrastat)

Endothelium produces nitric oxide, which has significant inhibitory effects. We can see that Ticlopidine and Clopidogrel block the low-affinity purinergic receptor (type II). PGI2 (prostacycline) also prevents platelet clumping.

ASA is a COX-1 inhibitor, which blocks synthesis of thromboxane. Low dose aspirin can reduce a second M.I. by up to 50%!!! If a pt is on Vioxx or Celebrex they are taking COX-2 inhibitors, which have NO EFFECTS on platelets. Ibuprofen and other NSAIDs have very, very weak effects on platelets, if not negligible.

Aspirin does not block the thromboxane receptor. The only way to block the thromboxane cascade is to block its synthesis indirectly (ASA does this by blocking COX-1).

A pt’s bleeding time is the most efficacious way to measure their platelet functions. A normal bleeding time is about 5 minutes (for a pt with normal platelet counts). This is only an average value though, there is wide variation in bleeding times as seen on the graph.
Low dose ASA increases bleeding time an average of 11 minutes, but there is some variability – some pts will bleed much longer. Acetaminophen (Tylenol) does NOT have antiplatelet effects; pts taking Tylenol will show no changes in bleeding time!!!

DO NOT have a pt stop their ASA dose for your convenience; i.e. for reduced bleeding time in perio or other surgery. Pts took 2 ASA tabs (600mg) and thromboxane was reduced to zero. Over 12 days the pts were monitered; it takes about 7-10 days to get back to normal thromboxane levels. Although ASA’s acetyl group permanently and irreversibly binds to COX-1, a low maintenance dose is continued every day because new platelets are made each day.

Prostacyclin levels are also diminished when a pt takes ASA, but it does recover as opposed to thromboxane, which remains low when the pt is on a low-dose aspirin regimen. This prostacyclin effect does not happen with Ticlid or Plavix, which is an advantage of these drugs over aspirin.

Chewed aspirin has quicker effects than if its dissolved in solution, which has quicker effects than if its swallowed. However, we don’t want people to chew it or take it in solution because it is acidic and can injure the gingival and mucosa of the oropharynx.

Halfprin 162mg aspirin has been approved for suspected acute M.I. (other aspirins are not indicated for suspected acute M.I.). This is a marketing strategy, studies don’t show any difference between the 162 mg dose and the baby-aspirin dose of 81mg.

The definite reductions in vascular events observed with 160mg/day in ISIS-2 resemble those observed with higher doses (300-1500 daily) in the long-term trials. Higher doses of aspirin are several times more gastrotoxic than lower doses but don’t seem to be any more effective. At present therefore, when long term antiplatelet therapy is to be used after MI, unstable angina, transient cerebral ischmia, or stroke, a dose of about 160mg/day may be preferred.

The old forms for perio surgery authorization used to indicate that the pt should not take ASA for 1 week prior to surgery. This criterion is VERY INAPPROPRIATE for any perio or oral surgery.

So, DO NOT stop antiplatelet or anticoagulant medications before surgeries, if the bleeding bothers you use hemostasis methods.

A study showed that preoperative bleeding time was 1.8 minutes for pts who stopped their aspirin (100 mg/day) 7 days before surgery compared to 3.1 minutes for pts continuing aspirin therapy. While bleeding time differences were statistically significant, bleeding times for both groups were within normal limits. There was no problem with uncontrolled bleeding before or after oral surgery. Normal hemostasis procedures were sufficient in both groups.

If a pt is taking antiplatelet low dose aspirin (81mg-325mg/day), instruct them to avoid ibuprofen (Advil, Motrin). Taking ibuprofen in a single dose, as well as multiple daily dosing, results in blocking aspirin’s antiplatelet action by competing for the platelet COX-1 enzyme (which mediates the aspirin effect). Acetaminophen, COX-2 inhibitors, and the NSAID diclofenac DO NOT have this inhibitory effect on aspirin.

When the acetyl group of the aspirin encounters and binds the serine residue in the COX-1 domain of the platelet membrane, aspirin has its anti-platelet effects (inhibition of COX-1). However, when ibuprofem enters the site, it does not inhibit COX-1. Instead it blocks ASA’s anti-platelet effects by competing for the same site.

Plavix is not a salicylate compound! It blocks the ADP receptor on the platelet’s membrane and significantly increases bleeding time. There are no significant efficacy differences between fatal and non-fatal vascular effects in pts taking Plavix versus those takine Aspirin. Pts are prescribed Plavix if they cant handle aspirin (due to allergy or GI problems induced by aspirin).
With Plavix we see a slight increase in incidence of platelet, bleeding and clotting disorders as compared to aspirin.

Ticlid can cause life-threatening hematological adverse reactions, including neutropenia/ agranulocytosis and thrombotic thrombocytopenic purpura (TTP). This was found in 2.4% of the population. So the pt on Ticlid must be monitored for agranulocytosis! This drug is decreasing in popularity because of this. So if a pt is on Ticlid, make sure to ask if they’ve had recent blood tests.


Aggrenox is a combination of low dose ASA 925 mg) and dipyridamole, and is efficacious for the prevention of strokes due to a synergistic reaction between the two drugs.

Category: Pharmacology Notes