Haematological Drugs Flashcards
Give 2 examples of anti-platelet drugs.
Aspirin
Clopidogrel
Describe the mechanism of action of aspirin (acetylsalicylic acid). (4)
- Irreversible inactivation of the COX enzyme
- This decreases platelet thromboxane (TXA2) and endotthelial prostaglandin (PGI2) production
- Decreased platelet thromboxane synthesis causes:
a. Decreased platelet aggregation
b. Decreased thrombus formation - Decreased prostaglandin synthesis causes:
a. Decreased nociceptive sensitisation
b. Decreased inflammation
List 5 side effects of aspirin (acetylsalicylic acid).
Bleeding (<1%) Peptic ulceration Reye's syndrome Angio-oedema Bronchospasm
What are the indications for aspirin? (2)
Discuss important pharmacokinetics/ dynamics of aspirin. (2)
What would you tell the patient when prescribing aspirin? (2)
INDICATIONS:
Secondary prevention of thrombotic events
Pain relief
PHARMACOKINETICS/ DYNAMICS:
Half-life is longer in higher doses
Non-linear pharmacokinetics in overdose
PATIENT INFO:
Avoid over the counter meds containing aspirin
ALWAYS prescribe a PPI with long-term aspirin
Describe the mechanism of action of clopidogrel. (3)
- Irreversibly blocks ADP-receptor on platelet membranes
- This inhibits formation of GPIIb/IIIa complex (which causes platelet aggregation)
- Therefore there is decreased platelet aggregation
a. Therefore there is decreased thrombus formation
List 3 side effects of clopidogrel.
Bleeding (1-10%)
Abdominal pain
Diarrhoea (1-10%)
List 1 indication for clopidogrel.
Discuss the important pharmacokinetics/ dynamics of clopidogrel. (1)
What would you tell the patient when prescribing clopidogrel? (2)
INDICATIONS:
Secondary prevention of thrombotic events
IMPORTANT PHARMACOKINETICS/ DYNAMICS:
Avoid in liver failure
PATIENT INFO:
Never stop clopidogrel without consulting a doctor if you have an arterial stent in place
Stop clopidogrel before surgery
Give 1 example of a thrombolytic drug.
List 2 examples of drug names in this class.
Recombinant tissue plasminogen activator (rtPA)
E.g.
Tenecteplase
Alteplase
Describe the mechanism of action of rtPA. (3)
- Recombinant form of tissue plasminogen activator (t-PA)
- This converts plasminogen into plasmin
- Plasmin breaks down fibrin into fibrin degradation products
a. This causes thrombolysis
List 4 side effects of rtPA drugs (e.g. tenecteplase).
Intracranial haemorrhage
Retroperitoneal bleeding
GI blood loss
Allergy/angio-oedema
What are the indications for rtPA? (3)
NOTE: where relevant, state time limits.
Discuss important pharmacokinetics/ dynamics of rtPA. (3)
What would you tell the patient when prescribing any rtPA drug? (3)
INDICATIONS:
Ischaemic stroke (within 4.5 hours)
Myocardial infarction (within 12 hours)
Massive pulmonary embolism
IMPORTANT PHARMACOKINETICS/ DYNAMICS:
Alteplase - bolus infusion
Tenecteplase - single bolus
Drug interactions with other blood-thinning drugs
PATIENT INFO:
Educate about risk to benefit ratio:
NNT: 3
BUT 1 in 20 will come to harm from bleeding (i.e. fairly common)
Describe the mechanism of action of unfractionated heparin. (2)
- Stimulates antithrombin III
a. This inhibits thrombin
b. Therefore, no thrombus formation - Inhibits multiple clotting factors
a. Therefore, no coagulation cascade
List 3 side effects of unfractionated heparin.
What is the risk of major bleeding?
Bleeding
Thrombocytopenia
Osteoporosis
Major haemorrhage risk: 3.5%
What are the indications for unfractionated heparin? (4)
Discuss important pharmacokinetics/ dynamics of unfractionated heparin. (5)
What would you tell the patient when prescribing unfractionated heparin? (2)
INDICATIONS: Treatment/prophylaxis of thromboembolic diseases Induction of vitamin K antagonists Renal dialysis Acute coronary syndrome
IMPORTANT PHARMACOKINETICS/ DYNAMICS:
- Administration: IV or subcut
- Non-linear pharmacokinetics
- Monitoring needed (aPTT)
- Reversible with protamine
- Duration of action: shorter than LMWH
PATIENT INFO:
Risk of bleeding
Regular blood monitoring required
Discuss the differences in pharmacokinetics/ dynamics of low molecular weight heparin, compared to UFH. (6)
Administration: subcut injection
Pharmacokinetics:
- More predictable dose-response relationship
- 2-3x longer half-life
Pharmacodynamics:
-Renal clearance (needs dose adjustment in renal impairment)
Other info:
- Does NOT need regular monitoring
- Less easily reversible with protamine
What type of drug is fondaparinux?
Synthetic heparin
Describe the mechanism of action of fondaparinux. (1)
List 2 indications of fondaparinux.
What is the main side effect?
MECHANISM:
- Enhances activity of antithrombin
a. Therefore prevents thrombus formation
INDICATIONS:
VTE prevention after surgery
Acute coronary syndrome
SIDE EFFECTS:
Bleeding
Discuss important aspects of pharmacokinetics/ dynamics of fondaparinux. (5)
What would you tell the patient about fondaparinux? (2)
PHARMACOKINETICS/ DYNAMICS:
- Administration: injection only
- Once a day regimen (long half-life)
- Renal clearance
- Does NOT need monitoring
- Less easily reversed
PATIENT INFO:
Risk of bleeding
Needs injection
Give 2 examples of factor Xa inhibitors.
Rivaroxaban
Apixaban
Describe the mechanism of action of rivaroxaban. (2)
List 2 side effects of rivaroxaban.
- Inhibits conversion of prothrombin to thrombin
- This reduces concentration of thrombin in blood
a. This inhibits thrombus formation
SIDE EFFECTS:
Bleeding
Nausea
What are the indications for rivaroxaban? (3)
Discuss important pharmacokinetics/ dynamics of rivaroxaban. (3)
What would you tell the patient when prescribing rivaroxaban? (1)
INDICATIONS:
VTE prophylaxis
VTE treatment
Thromboprophylaxis in non-valvular AF
IMPORTANT PHARMACOKINETICS/ DYNAMICS:
- Metabolised by CYP450 (therefore drug interactions with inducers/inhibitors)
- No need for monitoring
- No antidote for reversal
PATIENT INFO:
Risk of bleeding
Give 1 example of a direct thrombin inhibitor.
Dabigatran
Describe the mechanism of action of dabigatran. (1)
List 2 side effects.
- Direct thrombin inhibitor: prevents conversion of fibrinogen to fibrin
a. This prevents thrombus formation
SIDE EFFECTS:
Bleeding
Dyspepsia
What are the indications for dabigatran? (2)
Discuss important pharmacokinetics/ dynamics of dabigatran. (4)
What would you tell the patient when prescribing aspirin? (1)
INDICATIONS:
VTE prophylaxis
Thromboprophylaxis in non-valvular AF
IMPORTANT PHARMACOKINETICS/ DYNAMICS:
- Rapid onset of action
- No food interactions; few drug interactions
- No need for monitoring
- No antidote
PATIENT INFORMATION:
Risk of bleeding
Describe the mechanism of action of warfarin. (2)
- Inhibits vitamin K epoxide reductase
- This prevents recycling of vitamin K to its reduced form after carboxylation of factors 2, 7, 9 and 10
a. This prevents vitamin K from activating the clotting factors a second time
b. Therefore there is no thrombus formation
List 3 side effects of warfarin.
Bleeding
Warfarin necrosis
Osteoporosis
What are the indications for warfarin? (4)
Discuss important pharmacokinetics/ dynamics of warfarin. (5)
What would you tell the patient when prescribing warfarin? (4)
INDICATIONS: VTE treatment Thromboprophylaxis in: -AF -Metallic heart valves -Cardiomyopathy
IMPORTANT PHARMACOKINETICS/ DYNAMICS:
- Many food/drug interactions
- Reversible by giving vitamin K
- Rate of metabolism varies between patients due to polymorphisms in key metabolising enzymes
- Requires monitored loading dose
- Requires monitoring with INR
PATIENT INFO:
- Compliance is crucial
- Careful with alcohol
- Always inform doctor before starting new drugs
- Avoid over the counter aspirin
