Anti- thrombotics Flashcards
Simplified biochemistry of tissue damage
Membrane Phospholipid damage
–> Arachidonic acid ,
- Which releases leukotrienes (5-LO) which causes inflammation.
- COX 1 & 2
-Prostacyclin (anti-coagulant) (stops platelet)
-Thromboxane A2 (Pro-coagulant)
-Prostaglandins
Prostacyclin and Thromboxane is a negative feedback mechanism
Anti-platelet drugs
Aspirin
Abciximab
Clopidogrel
Platelet aggregation
When platelets are released they also trigger the release of other substances such as vWF, Collagen , fibrinogen. These substances then join together from one platelet to another which allow two platelets to aggregate and build up on the site that is damaged.
Platelet receptors are activated by many factors:
Dont have to learn for the exam but just memorise
- 5HT
- Adr
- ADP
- TXA2
- PAF
- Vasopressin
- Thrombin
- Collagen
Aspirin
inhibits COX 1&2 pathway which means that thromboxane, prostacyclin and Prostaglandin not produced
Same as non-steroidal anti-inflammatory drugs
Aspirin adverse effects
- Hypersensitivity
- Potentiates other NSAIDs
- ‘Bleeds’
GI tract
Gums
Urinary tract - Increased bleeding in association with warfarin, heparin, clopidogrel (NOACs)
- Heart burn
- Nausea
- Ototoxic
- Bronchospasm
Aspirin is also found in other medications such as Alka-Seltzer
Aspirin and viral Infections
- Reyes disease
- Multi organ disorder
- Brain and Liver most effected
- Aspirin not given to children
IIb IIIa receptor antagonists
blocks the IIb IIIa receptor to prevent fibronogen bridges from being formed so platelet aggregation does’t occur
Examples of IIb IIIa receptor antagonists
Abciximab (ReoPro) an antibody
* Non-specific tight receptor binding and slow reversibility of platelet inhibition up to 14 days
Eptifibatide (Integrilin)
* Specific inhibitor. It has a short half-life and platelet function recovers 2-4 hours after cessation of the treatment.
Tirofiban (Aggrastat).
* selective inhibitor
* rapid onset of action (5 minutes)
* rapidly reversible (4-6 hours).
Lamifiban
* Selective inhibitor
* half-life of approximately 4 hours.
Clopidogrel
Clopidogrel is a P2Y12 receptor antagonist. The P2Y12 receptor is a subtype of adenosine diphosphate (ADP) receptor found on platelets.
Clopidogrel binds to the P2Y12 receptor on platelets, blocking the action of ADP.
ADP is a key mediator in platelet activation and aggregation. By inhibiting its receptor:
Platelet activation is reduced.
Clopidrogel adverse effects
Bleeding
* bloody or tarry stools,
* blood in urine, visible or on dipstick
* coughing up blood: Upper GI or Resp. Tracts
* vomit that looks like coffee grounds (digested blood).
chest pain /discomfort
CNS related
* sudden numbness or weakness
* sudden headache,
* confusion,
* Visual, speech or balance disturbances
nausea,
Sweating
weakness,
pale skin,
fever
jaundice
Coagulation Instrinsic pathway
This pathway is activated by damage to the blood vessel wall or exposure of blood to negatively charged surfaces like collagen.
Sequence of Events:
Factor XII (Hageman factor) is activated to XIIa.
XIIa activates Factor XI to XIa.
XIa activates Factor IX to IXa (requires calcium).
IXa, along with Factor VIIIa (activated by thrombin), activates Factor X to Xa in the common pathway.
Coagulation Extrinsic pathway
Trigger: Exposure of tissue factor (Factor III) from damaged tissues.
Sequence of Events:
Tissue factor binds to Factor VII, activating it to VIIa.
The TF-VIIa complex activates Factor X to Xa in the common pathway.
C
Coagulation common pathway
The intrinsic and extrinsic pathways converge at the activation of Factor X.
Sequence of Events:
* Factor Xa (activated by either intrinsic or extrinsic pathway) combines with Factor Va to form the prothrombinase complex.
- Prothrombinase converts prothrombin (Factor II) into thrombin (Factor IIa).
- Thrombin converts fibrinogen (Factor I) into fibrin (Factor Ia).
- Fibrin monomers polymerize to form a fibrin mesh that stabilizes the platelet plug.
- Thrombin also activates Factor XIII, which cross-links fibrin strands, stabilizing the clot.
Heparin
Is a polysaccharide, (or complex sugar)
Heparin has no anticoagulant properties of its own it catalytically enhances the binding properties of Antithrombin (ATIII).
ATIII normally binds clotting factors sluggishly, when combined with heparin, it binds clotting factors instantaneously, therefore reducing fibrin formation
