Drug Therapies Flashcards
Mechanism of action: antiplatelet agents
-Cyclo-oxygenase inhibition (Aspirin)
-P2Y12 inhibitors (Clopidogrel, Prasugrel, Ticagrelor)
-GPIIb/IIIa inhibitors (Tirofiban, Epifibatide)
Indications for antiplatelet agents
-Acute coronary syndrome (secondary prevention):
=Dual antiplatelet therapy for 6 months: Aspirin (300 mg loading dose, 75mg OD) + P2Y12 inhibitor (ie. Clopidogrel 300mg/600mg loading dose for emergency PCI so STEMI, 75mg OD) , followed by lifelong single antiplatelet therapy. Thrombotic complications PCI= Triofiban etc
-Stable coronary artery disease: single antiplatelet therapy Aspirin or Clopidogrel (75mg OD)
Important contraindications of antiplatelets
-Recent GI/intracranial bleeding
-Bleeding disorders
-Thrombocytopenia
Important side effects/ cautions of antiplatelets
GI bleeding (consider co-prescribing with a proton-pump inhibitor [ie. omeprazole])
Mechanism of action: anticoagulants
-Oral anticoagulants:
=Vitamin K antagonist (Warfarin) *requires close INR monitoring [half-life ~ up to 2-3 days]
=Direct Factor Xa inhibitor (Apixaban, Rivaroxaban, Edoxaban) [half-life ~ 12 hours]
=Direct thrombin inhibitor (Dabigatran) [half-life ~ 12 hours]
-Parenteral anticoagulants:
=Antithrombin III agonist (Unfractionated heparin) [half-life ~ 60 minutes] *APTT/ACT monitoring
=Antithrombin III-mediated selective inhibition of factor Xa (Fondaparinux) [half-life ~ 15 hours]
Indications: anticoagulants
-Acute coronary syndrome: Fondaparinux 2.5mg SC OD (longer half life so one dose) or Unfractionated heparin (frequent bolus/ infusion) if undergoing emergency PCI
-Atrial fibrillation/flutter (prevention of stroke): Warfarin or Direct Factor Xa inhibitor or Direct thrombin inhibitor
-Metallic prosthetic valve (target INR depends on type and location of valve) (only warfarin)
Important contraindications: anticoagulants
recent GI/intracranial bleeding, bleeding disorders, thrombocytopenia,
*end-stage renal failure (warfarin or unfractionated heparin should be used as unpredictable bioavailability)
Important side effects/ cautions of anticoagulants
Bleeding (Direct Factor Xa inhibitors or Direct thrombin inhibitors should be favoured in patients with labile INR on warfarin), Heparin-induced thrombocytopenia (risk of venous and arterial thrombosis, unfractionated)
Reversal agents for anticoagulants
Warfarin (Vitamin K), Unfractionated heparin (protamine), Direct factor Xa inhibitors (adexanet alfa)
Mechanism of action: lipid lowering therapies
-HMG-CoA reductase inhibitors
=(Pravastatin < Simvastatin < Atorvastatin < Rosuvastatin)
-Cholesterol-absorption inhibitors (Ezetimibe)- intolerant/ additional
-PCSK9 inhibitors (Evolocumab, Alirocumab)- inactivated LDL receptors, severe FH
-Fibrates (infrequently used due to limited evidence)
Indications: lipid lowering therapies
-Primary prevention of CVD
=in particular, patients with important risk factors (ie. type 2 diabetes, chronic kidney disease, familial hypercholesterolaemia)
-Secondary prevention of CVD
Important contraindications: lipid lowering therapies
acute liver disease, pregnancy and breastfeeding (delay or advice contraception in women of childbearing age)
Important side effects/ cautions: lipid lowering therapies
GI disturbance (ie diarrhoea), muscle aches, rhabdomyolysis (increased risk with concurrent fibrates and cytochrome P450 inhibitors ie. macrolide antibiotics, antifungals)
Mechanism of action: renin-angiotensin-aldosterone system antagonists
-Angiotensin-converting enzyme inhibitor, ACEi (ie. Ramipril, Enalapril)
-Angiotensin receptor blocker, ARB (ie. Losartan, Candesartan)
-Mineralocorticoid receptor antagonist, MRA (ie. Spironolactone, Eplerenone)
Indications: renin-angiotensin-aldosterone system antagonists
-Chronic Heart failure (ACEi/ARBs + MRA)
-Hypertension (ACEi/ARBs)
-Post-MI secondary prevention (ACEi/ARBs)