4 Antiplatelets, Anticoagulants and Thrombolytics Flashcards
When are antiplatelets used?
Prophylaxis only for arterial thrombosis to prevent platlet aggregation
Anticoagulants is both arterial and venous thrombosis
When are anticoagulants used?
For arterial and venous thrombosis
To prevent formation of thrombus
Name 4 classes of antiplatelet drugs + examples
- Non-steroidal anti-inflammatory drugs (NSAIDs):
Aspirin - platelet GP IIb/IIIa receptor blockers:
Abciximab, Eptifibatide, Tirofiban - ADP receptor blockers:
Ticlopidine, Clopidogrel - PDE inhibitor:
Dipyridamole
What is the MoA of Aspirin?
Aspirin is an irreversible COX inhibitor
inhibits the synthesis of Thromboxane A2 from arachidonic acid
Recall Thromboxane A2 promotes platelet aggregation
Overall effect: prevents platelet aggregation
see diagram on pg 6 (& pg 23 in nsaids)
efficacy of aspirin
inhibitory effect is rapid and lasts the lifespan of the platelet (~7-10 days)
Name 3 clinical uses for aspirin
- Prophylactic treatment of transient cerebral ischemia
- Reduce the incidence of recurrent myocardial infarction
- Decrease mortality in postmyocardial infarction patients
Name 2 adverse effects of aspirin
Bleeding (Prostacyclin, PGI2)
Gastric upset and ulcers (Prostaglandin, PGE2)
*GI bleeding
Recall Prostaglandin protects walls of stomach
Name 3 platelet GP IIb/IIIa receptor blockers
Abciximab
Eptifibatide
Tirofiban
2 clinical uses for platelet GP IIb/IIIa receptor blockers
- Prevent restenosis after coronary angioplasty
combination therapy: aspirin + heparin + abciximab - Used in acute coronary syndromes
Acute coronary syndrome is a term used to describe a range of conditions associated with sudden, reduced blood flow to the heart. One such condition is a heart attack (myocardial infarction) — when cell death results in damaged or destroyed heart tissue.
MoA of abciximab
a humanized monoclonal Ab directed against the IIb/IIIa complex
reversibly inhibits the binding of fibrinogen and other ligands to GP IIb/IIIa
MoA of eptifibatide
an analog of the sequence at the extreme carboxyl terminal of the delta chain of fibrinogen, which mediates the binding of fibrinogen to the receptor
pretends to be fibrinogen
acts as competitive inhibitor
MoA of tirofiban
a small molecule blocker of the GP IIb/IIIa receptor
Name 2 ADP receptor blockers
Clopidogrel
Ticlopidine
MoA of clopidogrel and ticlopidine
blocks ADP receptors on platelets
→ inhibits ADP induced platelet aggregation
class: ADP receptor blockers
Name a PDE inhibitor
PDE: phosphodiesterase
Dipyridamole
MoA of dipyridamole
inhibits PDE
→ prevents conversion of cAMP to 5’-AMP
→ high cAMP inhibits release of platelet granules )(containing serotonin and ADP)
Recall PDE converts cAMP to 5’ AMP
class: PDE inhibitor
Name 3 anticoagulants
- antithrombin III (ATIII)
- heparin
- warfarin
MoA of Antithrombin III
irreversibly inactivates thrombin (IIa), IXa, Xa by forming stable complexes with them
2a, 9a, 10a
MoA of Heparin
binds to AT III and cause a conformational change, which exposes the active site of AT III for more rapid interaction with the proteases (IIa, IXa, Xa)
To inhibit thrombin (IIa), heparin must bind to AT III and thrombin (IIa)
To inhibit factor Xa, heparin only need to bind to AT III
LMWH has longer duration of action than heparin but doesn’t work on thrombin (IIa)
Name 3 clinical uses for heparin
- treatment of DVT, pulmonary embolism (PE), AMI
- use in combination with thrombolytics for revascularization
Thrombolytics: t-PA, urokinase, streptokinase, anistreplase
use in combination with GP IIb/IIIa inhibitors during angioplasty and placement of coronary stents
GP IIb/IIIa inhibitors: Abciximab, Eptifibatide, Tirofiban
- preferred anticoagulant to use in pregnancy
What is the route of administration for Heparin?
IV or SC
Never give IM → will result in haematomas!
Name 2 adverse effects of Heparin
- Haemorrhage
stop heparin therapy + give protamine sulfate - Thrombosis and thrombocytopenia (platelet count too low)
When do you give protamine sulfate for heparin?
Before surgery
After renal dialysis, open heart surgery
If excessive bleeding occurs
When overdose on heparin
Vitamin K is ___ soluble.
Vitamin K is essential for the formation of clotting factors ___.
fat
II, VII, IX and X
Reduced vitamin K is an essential cofactor in the carboxylation of glutamate residues found in factors 2, 7, 9, 10
Name 2 clinical uses for Vitamin K
- Treatment and/or prevention of bleeding
- resulting from use of oral anticoagulant drugs e.g. warfarin
- babies: to prevent haemorrhagic disease of the newborn - For vitamin K deficiencies in adults
Note that vitamin K takes time to reverse the effects of anticoagulants. If urgent, use fresh frozen plasma
MoA of Warfarin
Inhibits vitamin K reductase
→ depletes active vitamin K
→ inhibits synthesis of clotting factors II, VII, IX and X
Name 2 clinical uses for Warfarin
Same as heparin:
- treatment of DVT, pulmonary embolism (PE), AMI
- use in combination with thrombolytics for revascularization
Thrombolytics: t-PA, urokinase, streptokinase, anistreplase
use in combination with GP IIb/IIIa inhibitors during angioplasty and placement of coronary stents
GP IIb/IIIa inhibitors: Abciximab, Eptifibatide, Tirofiban
but CANNOT USE IN PREGNANCY
Pharmacokinetics of Warfarin
a. Route of administration
b. Elimination
a. Route of administration: Oral
Rapid absorption
Small Vd because strongly bound to plasma albumin
b. Elimination depends on metabolism by hepatic cytochrome P450
Lipid-soluble so strongly bound to plasma albumin
Albumin has hydrophobic binding domains in which drugs such as warfarin and diazepam can bind.
Name 2 adverse effects of Warfarin
- Haemorrhage (bleeding)
- Warfarin should NEVER be administered during pregnancy.
- Warfarin crosses the placenta readily and can cause a hemorrhagic disorder in the fetus.
- Fetal proteins with gamma-carboxyglutamate residues found in bone and blood may be affected by warfarin
if pregnant woman need anticoagulant, use heparin
Warfarin - DDI
Think Cytochrome P450 (Warfarin is metabolised by CYP450)
CYP P450 inducers
- Barbiturates
- Carbamazepine
- Phenytoin
CYP P450 inhibitors (bad, accumulate Warfarin)
- Amiodarone (antiarrhythmic)
- Cimetidine
- Disulfiram
- Imipramine (antidepressant - TCAs)
Name 4 Thrombolytic agents
- t-PA (alteplase)
- urokinase
- streptokinase
- anistreplase
t-PA: tissue plasminogen activator
MoA of thrombolytics
activates conversion of plasminogen to plasmin → plasmin breaks down fibrin into fibrin degradation products
final effect: lysis of current clot
Name 3 clinical uses for thrombolytics
- EMERGENCY treatment of coronary artery thrombosis
- Peripheral arterial thrombosis and emboli
- Ischaemic stroke (< 4.5 h window)
Route of administration of thrombolytics
Intracoronary injection, IV injection
not oral bruh, it’s for emergency!
State 1 adverse effect and 2 contraindications of thrombolytics
Adverse effect: Haemorrhage (Bleeding)
Contraindication: Healing wound, Pregnancy
