Haematological Drugs Flashcards
What is an example of an anti-platelet drug?
- Acetylsalicylic Acid (Aspirin)
* Clopidogrel
What is the mechanism of action for aspirin?
- 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.
What is the main indication (use) of aspirin?
- secondary prevention of thrombotic events
* pain relief
List some side effects of aspirin
- bleeding
- peptic ulceration
- angioedema
- bronchospasm
- Reye’s syndrome (rare)
What information should you tell the patient before starting Aspirin?
- avoid over the counter preparations that contain aspirin
* some patients advised to take a PPI alongside long-term aspirin
What drug class is clopidogrel?
an anti-platelet drug
What is the mechanism of action for Clopidogrel?
- irreversibly blocks the ADP-receptor on platelet cell membranes
- consequently inhibits formation of GPIIb/IIIa complex, required for platelet aggregation
- decreased thrombus formation
What is the main indication of clopidogrel?
secondary prevention of thrombotic events
What are the side effects of clopidogrel?
- bleeding
* abdominal pain/diarrhoea
What is important clinically regarding Pharmacokinetics/dynamics for clopidogrel?
Avoid in liver failure
What information should you tell the patient before starting Clopidogrel?
- advise to stop before surgical procedures
* patients shouldn’t stop it without consulting doctor if they have an arterial stent in-situ
What class of drugs are Tenecteplase and Alteplase?
Recombinant Tissue Plasminogen Activator (rtPA)
What is the mechanism of action of rtPAs?
- recombinant form of tissue plasminogen activator
- catalyses conversion of plasminogen to plasmin
- promotes fibrin clot lysis
What are the indications of Recombinant Tissue Plasminogen Activators?
- acute ischaemic stroke within 4.5hrs of onset
- MI within 12hrs of onset
- massive PE
List the side effects of Tenecteplase and Alteplase
- bleeding
* allergic reaction/angioedema
What are important pharmacokinetic/dynamic features to note clinically regarding rtPAs?
- bolus-infusion regimen is used for Alteplase
- Tenecteplase is given as a single bolus
- PD interactions with other blood thinners
What info should you tell the patient before starting Tenecteplase or Alteplase?
When using thrombolytic drugs, patients should be aware of risk:benefit ratio, which should include reference to rate of bleeding complications
What is are examples of a Heparin drug?
Unfractionated Heparin;
LMW Heparin
What is the mechanism of action of heparins?
- enhances activity of antithrombin III
- antithrombin III inhibits thrombin
- heparins also inhibits multiple other factors of the coagulation cascade
- this produces its anticoagulant effect
What are the indications of heparins?
- treatment and prophylaxis of thromboembolic diseases, including induction of vitamin K antagonists.
- renal dialysis
- acute coronary syndrome treatment
what are the side effects of heparin?
- bleeding (major haemorrhage risk can be as 3.5%
- heparin-induced thrombocytopenia
- osteoporosis
(LMW heparins have less risk)
what are important pharmacokinetic/dynamic features to note clinically regarding unfractionated heparins?
- administered by continuous IV infusion or subcut injection
- complex kinetics - non-linear relationship between dose/ 1/2 life and effect - needs TDM
- effect monitored using activated PTT
- anticoagulant effect reversed by protamine
- unfractionated heparin has a shorter duration than LMW Heparin
- used in preference to LMW heparin, in selected patients, due to the shorter duration of action and reversability with protamine
What information should be given to patients before starting heparin?
- risk of bleeding
- regular blood monitoring required
- (for LMW heparin) - will need blood testing prolonged therapy
what are important pharmacokinetic/dynamic features to note clinically regarding LMW heparins?
- subcut injection
- more predictable dose-response relationship than unfractionated
- 2-4 times longer plasma half-life than unfractionated
- clearance is mostly renal, therefore longer 1/2 life if have renal failure
- less readily reversed with protamine than unfractionated heparin
What type of drug is warfarin?
a vitamin K antagonist
what is the mechanism of action of warfarin?
- 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
What are the indications of warfarin?
- treatment of venous thromboembolism
* thromboprophylaxis in: AF / metallic heart valves / cardiomyopathy
List the side effects of warfarin
- bleeding
- warfarin necrosis
- osteoporosis
What are important pharmacokinetic/dynamic features to note clinically regarding warfarin?
- numerous drug interactions / food interactions
- reversal by giving vitamin K
- polymorphisms in key metabolising enzymes
- needs therapeutic drug monitoring and monitored loading regimen
- monitored with INR and dose adjusted according to indication
What information should be given to patients before starting warfarin?
- need for compliance / attendance at visits for monitoring
- are needed with alcohol
- must inform doctor before starting new drugs - avoid over counter aspiring preparations
What is an example of a direct thrombin inhibitor?
Dabigatran (a DOAC/NOAC)
What is the mechanism of action for dabigatran?
- direct thrombin inhibitor, prevents conversion of fibrinogen to fibrin
- this prevents thrombus formation
What are the indications for dabigatran?
- prophylaxis of venous thromboembolism
* thromboprophylaxis in non-valvular AF
List some side effects of direct thrombin inhibitors
- bleeding
* dyspepsia
What are important pharmacokinetic/dynamic features to note clinically regarding direct thrombin inhibitors?
- rapid onset of action
- no available antidote currently
- no food/few drug interactions
What info should be given to a patient before starting a direct thrombin inhibitor?
• risk of bleeding
Give some examples of Factor Xa Antagonists
rivaroxaban,
apixaban (a DOAC)
what is the mechanism of action for Factor Xa Antagonists?
- inhibits conversion of prothrombin → thrombin, reducing conc. of thrombin in blood
- this inhibits formation of fibrin clots
What are the indications of Factor Xa Antagonists?
- prophylaxis of venous thromboembolism
- thromboprophylaxis in non-valvular AF
- Tx of venous thromboembolism
What are some side effects of Factor Xa Antagonists?
bleeding and nausea
What are important pharmacokinetics/dynamics features to note regarding Factor Xa Antagonists?
- predictable drug interactions
- no need for therapeutic monitoring
- currently no antidote
- for Apixaban - 75% metabolised by liver, rest is renally excreted
What info should be given to a patient before starting a Factor Xa Antagonist?
risk of bleeding
