Antiplatelet agents: Nursing pharmacology

Antiplatelet agents are medications that are mainly used to treat and prevent thromboembolic events like ischemic stroke, transient ischemic attack, and coronary artery disease or myocardial infarction, as well as in clients who underwent cardiac valve replacement or coronary angioplasty, or with those with peripheral artery disease.

Now, antiplatelet medications act by preventing the activation of platelets to form a blood clot. When platelets are activated, they start binding to each other.

In addition, they release various activating substances, such as thromboxene E2 and adenosine diphosphate or ADP to activate other platelets and make them express a new surface receptor called glycoprotein, or GP2B3A.

These receptors help platelets bind to circulating proteins called fibrinogen, which helps link various platelets together.

When platelets attach to the same fibrinogen protein, they're linked together. This allows platelets to rapidly aggregate at the site of injury and form a platelet plug, which is a primary clot that can help stop the bleeding.

Based on their mechanism of action, antiplatelet medications can be divided into four groups. These include NSAIDs like acetylsalicylic acid, often referred to as aspirin, ADP receptor antagonists like clopidogrel, Prosugrel, and ticagrelor, phosphodiesterase inhibitors like dipyridamole and silostazole, and glycoprotein 2B3A inhibitors like siximab, tyrofiban, and eptofibatide.

Aspirin is given orally and works by irreversibly inhibiting the enzymes found within the platelets called cyclooxygenase, or COX1 and COX2.

These enzymes are involved in the production of molecules like thromboxene2 as well as prostaglandins. So in the presence of aspirin, platelets don't produce thromboxene2, resulting in impaired platelet plug formation.

Moreover, since aspirin binds to the COX enzymes irreversibly, its actions last for the entire lifespan of the platelets, which is typically about 7 to 10 days.

Next, ADP receptor antagonists include clopidogrel, Prosigrel, and Tyagrelor, which are taken orally, as well as Kangrelore, which is administered intravenously.

These medications work by binding to a specific ADP receptor on the platelets called P2Y12, and prevent EDP from binding to it.

Without EDP, the platelets can't express GP2B3A on their surface and thus can't bind to fibrinogen and aggregate. All ADP receptor antagonists, except for Tyagrelor act irreversibly.

Moving on, phosphodiesterase inhibitors include dipyridamole, which is given orally and intravenously, and silostazole, which is given orally.

Once administered, these medications act by reversibly inhibiting an enzyme within platelets called phosphodiesterase 3, which normally breaks down a molecule called cyclic adenosine monophosphate or CAMP.

As a result, CAMP increases inside a platelet, leading to a reduced sensitivity of the platelet to ADP so it doesn't activate.

These medications also inhibit the endothelial cells and red blood cells from taking up adenosine molecules circulating in the blood.

This leaves more adenosine molecules floating around the platelets, which bind to the A2 receptors on the platelets surface and signal to increase the platelet CAMP levels.

Additionally, phosphodiesterase inhibitors, especially silostazole, also inhibit phosphodiesterase 3 inside of vascular smooth muscle cells and inhibit the breakdown of cyclic guanosine monophosphate or CGMP.

As a result, the increased levels of CGMP result in vasodilation. This makes ellostazole particularly useful in treatment of coronary artery disease and peripheral artery disease.

Finally, glycoprotein 2B3A inhibitors include abciximab, which is a monoclonal antibody, as well as pyrophyban and eptofibatide, which are synthetic molecules.

These medications are given intravenously and work by reversibly inhibiting the glycoprotein 2B3A receptors on platelets.

As a result, the platelets can bind to fibrinogen and form a platelet plug. Now, the major side effect of antiplatelet medications is undue bleeding, which can manifest as bruising, epistaxis, bleeding gums, gastrointestinal bleeding, and hematuria.

Other common side effects include headaches, fatigue, nausea, and vomiting. Regarding specific side effects, aspirin may lead to gastritis, gastric ulcers, and bleeding, which occur due to a decrease of protective prostaglandins in the gastric mucosa.

Aspirin can also cause hypersensitivity reactions at low doses, which can cause anaphylaxis, bronchoconstriction, dyspnea, and wheezing.

In addition, since it contains salicylate, it is associated with oottoxicity, which may result in tinnitus and hearing loss.

Chronic use of aspirin can damage the kidneys and result in renal insufficiency, due to a decreased blood flow to the kidneys.

On the other hand, side effects associated with ADP receptor antagonists include dyspnea, cough, and back pain. In addition, Prosagrel and Tyagrelor have a boxed warning for serious and fatal bleeding.

Next, clients taking phosphodiesterase inhibitors can develop a skin rash or hypersensitivity reactions like Stevens-Johnson syndrome.

Additionally, these medications can cause tachycardia and palpitations, as well as orthostatic hypotension, and cilostazol has a boxed warning for heart failure.

Finally, glycoprotein 2B3A inhibitors can cause side effects like thrombocytopenia and serious bleeding, as well as anaphylaxis.

Now, due to the risk of bleeding, all antiplatelet medications are contraindicated in clients with active internal bleeding, suspected aortic dissection, or recent trauma in the past 3 months, as well as those with a history of intracranial hemorrhage or ischemic stroke in the past 3 months, and coagulopathies or bleeding disorders.

In addition, antiplatelet medications should be avoided before major surgeries, as well as during pregnancy and breastfeeding.

Aspirin should especially not be used during the 3rd trimester of pregnancy. Additionally, aspirin is also contraindicated in clients with asthma due to the risk of bronchoconstriction, as well as in children recovering from viral infections, as it is associated with Ray syndrome.

On the other hand, silostazol is contraindicated in clients with heart failure. Meanwhile, clopidogrel has a boxed warning for use in clients who are poor metabolizers.

Meaning they have two non-functional copies of the CYP2C19 enzyme that's needed to metabolize and activate the medication.

As a result, clopidogrel is not effective in these clients. Regarding precautions, antiplatelet medications should be used with caution in clients with an active peptic ulcer, as well as in those with renal or hepatic disease, as they're metabolized in the liver and excreted by the kidneys.

In addition, they should be used with caution in clients taking anticoagulants like heparin and warfarin, or thrombolytic medications like Altaplace, Retaplace, and tinectoplace, which can increase the risk of bleeding.

Clopidogrel should be used with caution with the proton pump inhibitor, omeprazole, since it can reduce the activation of clopidogrel.

All right, if your client is prescribed an antiplatelet medication, first assess your client's vital signs and review their most recent laboratory test results, including CBC, PT, APTT, and lipid profile, as well as liver and renal function tests.

If they are prescribed clopidogrel, check their medical records to confirm they have not been identified as a poor metabolizer of the medication.

On the other hand, if they're prescribed silostazole, confirm the client does not have a history of heart failure. Next, if your client is prescribed clopidogrel to prevent stroke, explain how the medication helps to reduce the risk by inhibiting platelet activity and the formation of clots.

Instruct them to take their medication once each day with or without food, at the same time each day. And that they should avoid consuming grapefruit or drinking grapefruit juice, since this will decrease the effectiveness of their medication.

Let them know that the most common side effect is bleeding, and that even minor cuts may take longer to stop bleeding. Also, prompt them to report if they notice any unusual bruising or signs of minor bleeding.

And stress the importance of seeking medical attention right away if they notice signs or symptoms of significant bleeding, such as dark urine or stools, bleeding that does not stop, coughing up blood, and if they experience a sudden headache or back pain.

Now, if the medication is not working effectively, your client can still be at risk for clot formation. So remind them to also self-monitor for sudden onset of confusion, vision changes, trouble speaking, or one-sided weakness.

Should any of these signs or symptoms occur, instruct your client to seek emergency medical care immediately. Then, review routine bleeding precautions they should take while taking this medication, such as using a soft bristle toothbrush or electric razor, avoiding other medications like aspirin that affect platelets, and avoiding activities that can cause injuries such as contact sports.

Remind your client to report their use of antip-platelet medication to all of their healthcare providers, including dentists, and to consult with their primary healthcare provider before undergoing an invasive procedure.

Now, if your client with peripheral arterial disease is prescribed Cilostazol, explain how the medication helps to reduce the symptoms of leg pain during walking.

Let them know that it may take a few weeks for them to notice improvement. Despite that, remind them to continue taking Cilostazol as prescribed, and to not stop taking it without talking to their healthcare provider first.

Next, instruct them to take their medication on an empty stomach either 30 minutes before or 2 hours after a meal. And caution them to avoid consuming grapefruit or drinking grapefruit juice, since it will increase the risk of the toxic effects of Cilostazole.

Then, let them know that they may experience side effects like a fast heartbeat and palpitations, as well as headache, dizziness, and diarrhea.

Prompt your client to contact their healthcare provider if these persist, as well as to report if they develop signs and symptoms of Stevens-Johnson syndrome.

Such as rash, blistering, and fever. Lastly, because Cilostazole interacts with many other prescription and non-prescription medications, as well as vitamins and herbal supplements, caution your client to talk with their healthcare provider before taking any other medication or supplement.

Finally, when caring for clients receiving antiplatelet therapy, review with your client lifestyle modifications they should incorporate to reduce the risk of atherosclerosis and vaso-occlusive or thromboembolic events.

These include following a diet that's low sodium, low refined sugar, low fat, and high fiber, as well as physical activity as tolerated, weight reduction as indicated, smoking cessation, and alcohol in moderation.

During therapy, continue to monitor your client's laboratory test results and for side effects. Lastly, evaluate for the desired therapeutic effects, such as an absence of thrombotic events and decreased claudication.

All right, as a quick recap, antiplatelet agents are given to treat or prevent thromboembolic events and include aspirin, ADP receptor antagonists, phosphodiesterase inhibitors, and glycoprotein 2B3A inhibitors.

These medications interfere with the ability of platelets to aggregate and form a clot. When caring for a client taking antiplatelet therapy, nursing considerations include client assessment and monitoring for side effects and the therapeutic response to the medication.

Client teaching is focused on safe self-administration, lifestyle modifications to reduce the risk of thromboembolic events, and potential side effects to recognize and report.