Haematological drugs Flashcards
Antiplatelet drugs: Acetylsalicylic acid (Aspirin):MOA
- Irreversible inactivation of cyclooxygenase (COX) enzyme.
- This reduces platelet thromboxane (TXA2) production and endothelial prostaglandin (PGI2) production.
- Reduced platelet thromboxane production reduces platelet aggregation and thrombus formation
- Reduced prostaglandin synthesis decreases nociceptive sensitisation and inflammation.
Indications for aspirin use (Acetylsalicylic acid)
- Secondary prevention of thrombotic events
* Pain relief
Acetylsalicylic acid (Aspirin): SE
- Bleeding (<1% Patients)
- Peptic ulceration
- Angiooedema
- Bronchospasm
- Reye’s syndrome (very rare)
Important pharmakokinetics and Pt infor for Acetylsaliclic acid (aspirin)
Important pharmacokinetics / pharmacodynamics:
• Half-life becomes longer with very large doses (pharmacokinetics may be non-linear in overdose)
Patient information:
• Avoid over the counter preparations that contain aspirin.
• Some patients may be advised to take a Proton Pump Inhibitor alongside long-term aspirin.
Antiplatelet drug: Clopidogrel: MOA
Mechanism of action:
• Irreversibly blocks the ADP-receptor on platelet cell membranes.
• Consequently inhibits formation of GPIIb/IIIa complex, required for platelet aggregation.
• Decreased thrombus formation.
Indications for Clopidogrel and SE
Indication(s):
• Secondary prevention of thrombotic events
Side effects:
• Bleeding (1-10% of Patients)
• Abdominal pain / diarrhoea (1-10% of Patients)
Pharmakokinetics and Pt info for CLopidegrel
Important pharmacokinetics / pharmacodynamics:
• Avoid in liver failure
Patient information:
• Patients may be advised to stop clopidogrel before surgical procedures.
• Patients should not stop clopidogrel without consulting their doctor if they have an arterial
Recombinant Tissue Plasminogen Activator (rTPA) Example(s) of drugs: • Tenecteplase • Alteplase MOA?
Mechanism of action:
• Recombinant form of tissue plasminogen activator
• Catalyses conversion of plasminogen to plasmin
• Promotes fibrin clot lysis
Indications and SE for Recombinant Tissue Plasminogen Activator (rTPA)
Indication(s):
• Acute ischaemic stroke within 4.5 hours of onset
• Myocardial infarction within 12 hours of onset
• Massive pulmonary embolism
N.B Not all thrombolytic drugs are licenced for all of these indications.
Side effects:
• Bleeding
• Allergic reaction / angiooedema (1%)
Recombinant Tissue Plasminogen Activator: Pharmacokinetics and Pt info.
Important pharmacokinetics / pharmacodynamics:
• Bolus-infusion regimen is used for alteplase
• Tenecteplase is given as a single bolus
• Pharmacodynamic interactions with other blood thinners (antiplatelets / anticoagulants)
Patient information:
• When using thrombolytic drugs, patients should be made aware of the risk-benefit ratio, which should include reference to the rate of bleeding complications.
Heparins: unfractionated heparin
MOA
Mechanism of action:
• Enhances activity of antithrombin III.
• Antithrombin III inhibits thrombin.
• Heparins also inhibit multiple other factors of the coagulation cascade.
• This produces its anticoagulant effect.
Indications and SE for unfractionate heparin
Indication(s): • Treatment and prophylaxis of thromboembolic diseases, including induction of vitamin K antagonists. • Renal dialysis (haemodialysis) • Acute Coronary Syndrome treatment Side effects: • Bleeding (Major haemorrhage risk can be as high as 3.5%) • Heparin-induced thrombocytopenia • Osteoporosis
Important pharmacokinetics and Pt info
Important pharmacokinetics / pharmacodynamics:
• Administered by continuous intravenous infusion or subcutaneous injection
• Complex kinetics - non-linear relationship between dose / half-life and effect – needs TDM
• Effect monitored using activated partial thromboplastin time (aPTT)
• Anticoagulant effect can be reversed with protamine.
• Unfractionated heparin has a shorter duration of action than LMW Heparin.
• Used in preference to LMW Heparin, in selected patients, due to the shorter duration of action and reversability with protamine (for example, Peri-operatively.)
Patient information:
• Risk of bleeding
• Regular blood monitoring required
Heparins: Low molecular weight heparin
MOA
Mechanism of action:
• Enhances activity of antithrombin III.
• Antithrombin III inhibits thrombin.
• Heparins also inhibit multiple other factors of the coagulation cascade.
• This produces its anticoagulant effect.
Indications and SE of low molecular weight heaprin
Indication(s):
• Treatment and prophylaxis of thromboembolic diseases, including induction of vitamin K antagonists.
• Renal dialysis (haemodialysis)
• Acute Coronary Syndrome treatment
Side effects:
• Bleeding (Major haemorrhage risk can be as high as 3.5%)
• Heparin-induced thrombocytopenia (Less risk than unfractionated heparin)
• Osteoporosis (Less risk than unfractionated heparin)
Pharmacokinetics and Pt info for low molecular weight heparin
Important pharmacokinetics / pharmacodynamics:
• Subcutaneous injection
• More predictable dose-response relationship than Unfractionated Heparin.
• 2-4 times longer plasma half-life than Unfractionated Heparin
• Clearance is mostly via a renal pathway, thus the half-life can be prolonged in patients with renal failure, so dose adjustment may be needed.
• Regular coagulation monitoring is not required.
• Less readily reversed with protamine, than Unfractionated Heparin.
Patient information:
• Risk of bleeding
• Requires injection
• Will need blood testing in prolonged therapy (Full Blood Count, to monitor for thrombocytopenia).
Vitamin K antagonists: warfarin. MOA
Mechanism of action:
• Inhibits vitamin K epoxide reductase.
• Prevents recycling of vitamin K to reduced form after carboxylation of coagulation factors II, VII, IX and X.
• Prevents thrombus formation.
Indications and SE of vitamin K antagonist (warfarin)
Indication(s):
• Treatment of venous thromboembolism
• Thromboprophylaxis in: AF / metallic heart valves / cardiomyopathy
Side effects:
• Bleeding (risk increases with increasing INR)
• Warfarin necrosis
• Osteoporosis
Pharmacokinetic and pharcodynamics of Vit K antagonist.
Important pharmacokinetics / pharmacodynamics:
• Numerous drug interactions / food interactions
• Reversal by giving vitamin K
• Polymorphisms in key metabolising enzymes (VKORC1 and CYP2C9)
• Needs therapeutic drug monitoring and monitored loading regimen
• Monitored with INR and dose adjusted according to indication
Patient info to be given to patients: Vit K antagonists.
Patient information:
• Need for compliance / attendance at visits for monitoring
• Care needed with alcohol
• Must inform doctor before starting new drugs – avoid over the counter aspirin preparations
MOA of Direct Thrombin Inhibitors (Dabigatran)
Mechanism of action:
• Direct thrombin inhibitor; prevents conversion of fibrinogen to fibrin.
• This prevents thrombus formation.
Indications and SE for Dabigatran (direct thrombin inhibitors)
Indication(s): • Prophylaxis of venous thromboembolism (especially post-operative) • Thromboprophylaxis in non-valvular AF Side effects: • Bleeding • Dyspepsia
Pharmacokinetics and Pt info
Important pharmacokinetics / pharmacodynamics:
• Rapid onset of action
• No food / few drug interactions (not metabolised via CYP 450)
• No need for therapeutic monitoring
• Currently no available antidote
Patient information:
• Risk of bleeding
Factor Xa Antagonists: Rivoroxaban
Mechanism of action:
• Inhibits conversion of prothrombin to thrombin, reducing concentrations of thrombin in the blood.
• This inhibits the formation of fibrin clots.
Factor Xa Antagonist: Rivaroxaban- indicationand SE
Indication(s): • Prophylaxis of venous thromboembolism (especially post-operative) • Thromboprophylaxis in non-valvular AF • Treatment of venous thromboembolism Side effects: • Bleeding • Nausea
Pharmacokinetics and Pt info: Rivaroxaban
Important pharmacokinetics / pharmacodynamics:
• Predictable drug interactions (metabolised via CYP 450, inc CYP3A4)
• No need for therapeutic monitoring
• Currently no available antidote
Patient information:
• Risk of bleeding
Factor Xa Antagonist: Apixaban. MOA
Mechanism of action:
• Inhibits conversion of prothrombin to thrombin; reducing concentrations of thrombin in the blood.
• This inhibits the formation of fibrin clots.
Apixaban indications and SE
Indication(s): • Prophylaxis of venous thromboembolism following hip or knee replacement surgery. • Thromboprophylaxis in non-valvular AF. Side effects: • Bleeding • Nausea
Apixaban Pharmacokinetics and Pt info
Important pharmacokinetics / pharmacodynamics:
• Predictable drug interactions (metabolised via CYP 450 and substrate for p glycoprotein)
• 75% is metabolised by the liver, the rest being renally excreted.
• No need for therapeutic monitoring
• Currently no available antidote.
Patient information:
• Risk of bleeding
