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Antiplatelet agents: Nursing Pharmacology

Notes

Notes

ANTIPLATELET AGENTS, PART 1
DRUG NAME
aspirin
clopidogrel (Plavix), prasugrel (Effient), ticagrelor (Brilinta), cangrelor (Kengreal)
CLASS
NSAID
ADP receptor inhibitors
MECHANISM OF ACTION
  • Irreversibly inhibits cyclooxygenase enzymes (COX-1, COX-2)
  • Reduces thromboxane A2 synthesis by platelets
  • Reduces platelet activation and aggregation
  • Inhibit the ADP receptor P2Y12 on platelets (all irreversibly, except for  ticagrelor)
  • Prevent ADP binding to platelets and glycoprotein IIb/IIIa activation
INDICATIONS
  • Myocardial infarction
  • Ischemic stroke
  • Transient ischemic attack
  • Cardiac valve replacement
  • Coronary angioplasty
  • Peripheral artery disease
ROUTE(S) OF ADMINISTRATION
  • PO
  • All: PO
  • Cangrelor: IV
SIDE EFFECTS
Common side effects
  • Undue bleeding: bruising, bleeding gums, hematuria, epistaxis, and gastrointestinal bleeding
  • Headache, fatigue, nausea, and vomiting
  • Boxed warning: gastritis, gastric ulcers, and bleeding
  • Hypersensitivity reactions: anaphylaxis, bronchoconstriction, dyspnea, and wheezing
  • Chronic use: renal insufficiency; ototoxicity
  • Ticagrelor: dyspnea, cough, and back pain
  • Boxed warning (prasugrel and ticagrelor): serious and fatal bleeding
  • Boxed warning (clopidogrel): poor metabolizer
CONTRAINDICATIONS AND CAUTIONS
Contraindications
  • Active internal bleeding, suspected aortic dissection, recent trauma in the past three months, history of intracranial hemorrhage or ischemic stroke in the past three months, coagulopathies or bleeding disorders, before major surgeries, pregnancy and breastfeeding
  • Aspirin: third trimester pregnancy, asthma, children

Use with caution
  • Active peptic ulcer, renal or hepatic impairment

Drug interaction
  • Anticoagulants like heparin and warfarin; thrombolytic medications like alteplase, reteplase, and tenecteplase
  • Clopidogrel with caution with the proton pump inhibitor omeprazole
ANTIPLATELET AGENTS, PART 2
DRUG NAME
cilostazol (Pletal), dipyridamole (Persantine)
abciximab (ReoPro), eptifibatide (Integrilin), tirofiban (Aggrastat)
CLASS
Phosphodiesterase inhibitors
Glycoprotein IIb/IIIa inhibitors
MECHANISM OF ACTION
  • Reversibly inhibit platelet phosphodiesterase III, which increases cAMP levels
  • Inhibit uptake of adenosine molecules, which signal the increase of cAMP within platelets
  • Reduce ADP-induced platelet aggregation
  • Inhibit vascular smooth muscle phosphodiesterase III, which increases cGMP, causing vasodilation
  • Reversibly inhibit the glycoprotein IIb/IIIa receptors on platelets
  • Prevent platelets from binding to fibrinogen and forming a platelet plug
INDICATIONS
  • Myocardial infarction
  • Ischemic stroke
  • Transient ischemic attack
  • Cardiac valve replacement
  • Coronary angioplasty
  • Peripheral artery disease
ROUTE(S) OF ADMINISTRATION
  • PO
  • IV
SIDE EFFECTS
Common side effects
  • Undue bleeding: bruising, bleeding gums, hematuria, epistaxis, and gastrointestinal bleeding
  • Headache, fatigue, nausea, and vomiting
  • Skin rash, Stevens-Johnson syndrome
  • Tachycardia and palpitations
  • Orthostatic hypotension
  • Boxed warning (cilostazol): heart failure
  • Thrombocytopenia, serious bleeding
  • Anaphylaxis
CONTRAINDICATIONS AND CAUTIONS
Contraindications
  • Active internal bleeding, suspected aortic dissection, recent trauma in the past three months, history of intracranial hemorrhage or ischemic stroke in the past three months, coagulopathies or bleeding disorders, before major surgeries, pregnancy and breastfeeding
  • Cilostazol: heart failure

Use with caution
  • Active peptic ulcer, renal or hepatic impairment

Drug interaction
  • Anticoagulants like heparin and warfarin; thrombolytic medications like alteplase, reteplase, and tenecteplase
NURSING CONSIDERATIONS: ANTIPLATELET AGENTS
ASSESSMENT AND MONITORING
Assess
  • Vital signs
  • Laboratory test results; e.g., CBC, PT, aPTT, lipid profile, liver and renal function tests
  • Client history; e.g., clopidogrel: poor metabolizer allele; cilostazol: heart failure

Monitor
  • Laboratory test results; side effects
  • Desired therapeutic effects; e.g., absence of thrombotic events, decreased claudication
CLIENT EDUCATION
Lifestyle modifications
  • E.g., low sodium, low refined sugar, low fat, high fiber diet; physical activity as tolerated; weight reduction as indicated; smoking cessation, alcohol in moderation

Clopidogrel
  • Purpose of medication: inhibit platelet activity, formation of clots; decrease risk of thrombotic events
  • Take once each day with or without food at the same time each day
  • Avoid grapefruit / grapefruit juice: will decrease effectiveness of medication
  • Common side effects: bleeding
    • Report unusual bruising, signs of bleeding
    • Seek medical attention for signs / symptoms of significant bleeding; e.g., dark urine or stools, coughing up blood, or sudden headache or back pain
  • Seek immediate emergency care for sudden onset of confusion, vision changes, trouble speaking, one-sided weakness
  • Review bleeding precautions; e.g., use a soft bristled toothbrush, electric razor; avoid other medications that affect platelets; avoid activities that can cause injuries such as contact sports
  • Report use of antiplatelet medication to all healthcare providers; consult with primary healthcare provider before invasive procedures

Cilostazol
  • Purpose of medication: reduce the symptoms of intermittent claudication
  • Takes a few weeks to notice improvement; continue medication as prescribed
  • Take medication on an empty stomach either 30 minutes before or 2 hours after a meal
  • Avoid grapefruit / grapefruit juice: will increase risk of the toxic effects of cilostazol
  • Side effects; e.g.,  tachycardia, palpitations, headache, dizziness, diarrhea
  • Report signs / symptoms of Stevens-Johnson syndrome; e.g., rash, blistering, fever
  • Interacts with many other prescription / non-prescription medications, vitamins, and herbal products
    • Talk with healthcare provider before taking medication or supplement
Transcript

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 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 thromboxane A2 and adenosine diphosphate or ADP, to activate other platelets and make them express a new surface receptor called glycoprotein IIb/IIIa or GPIIb/IIIa.

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 are 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, prasugrel, and ticagrelor; phosphodiesterase inhibitors like dipyridamole and cilostazol; and glycoprotein IIb/IIIa inhibitors like abciximab, tirofiban, and eptifibatide.

Aspirin is given orally and works by irreversibly inhibiting the enzymes found within the platelets called cyclooxygenase or COX-1 and COX-2. These enzymes are involved in the production of molecules like thromboxane A2, as well as prostaglandins.

So, in the presence of aspirin, platelets don’t produce thromboxane A2, 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, prasugrel, and ticagrelor, which are taken orally, as well as cangrelor, which is administered intravenously.

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

Without ADP, the platelets can’t express GPIIb/IIIa on their surface and thus, can’t bind to fibrinogen and aggregate. All ADP receptor antagonists, except for ticagrelor, act irreversibly.

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

Once administered, these medications act by reversibly inhibiting an enzyme within platelets called phosphodiesterase III, 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 platelet surface and signal to increase the platelet cAMP levels.

Additionally, phosphodiesterase inhibitors, especially cilostazol, also inhibit phosphodiesterase III 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 cilostazol particularly useful in the treatment of coronary artery disease and peripheral artery disease.

Finally, glycoprotein IIb/IIIa inhibitors include abciximab, which is a monoclonal antibody; as well as tirofiban and eptifibatide, which are synthetic molecules.

These medications are given intravenously and work by reversibly inhibiting the glycoprotein IIb/IIIa receptors on platelets. As a result, the platelets can’t 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 ototoxicity, 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, prasugrel and ticagrelor 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 IIb/IIIa 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 three months, as well as those with a history of intracranial hemorrhage or ischemic stroke in the past three months, and coagulopathies or bleeding disorders.

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