Pharmacology of Haemostatis and Thrombosis Flashcards
1
Q
Platelet Activation and Adhesion
A
- endothelial injury exposes sub-endothelial
collagen - Von Willebrand factor binds to the exposed
collagen - other side of Von Willebrand Factor has
binding sites for platelets via GP IB-IX-V
complex (glycoprotein) - tethers platelets to Von Willebrand factor
which is tethered to exposed sub-
endothelial collagen - platelets stick to other platelets and big
platelet plug is formed - platelets become activated upon binding to
Von Willebrand’s Factor - activated platelets can now bind to
fibrinogen - via specific binding glycoproteins: GPIIbIIIa
(GP2b3a) - facilitates further platelet aggregation
(clustering) - Tx receptor on platelet membrane binds
thromboxin - P2Y12 receptor on platelet membrane
binds ADP - GPIIbIIIa crosslinks with fibrinogen to
crosslink with further platelets (fibrinogen
between two platelets) - activated platelets generate thromboxane
A2 from arachidonic acid using enzyme
cyclooxygenase (platelet agonists) - binds to Tx receptor on other platelets
promoting more aggregation, adhesion
and activation - thrombin and ADP are also platelet
agonists - cyclooxygenase results in the release of
prostacyclin from the endothelium, which
inhibits platelet aggregation (acts as a
negative feedback loop) and causes
vasodilation
2
Q
Bernard souilier disease
A
- deficiency of GP Ib-IX-V complex
- hard to form platelet plug
platelets not tethered to Von Willebrand’s
Factor - platelet disorder leads to increased bleeding
3
Q
Glanzmann’s thrombasthenia
A
- bleeding disorder
- deficiency of GPIIbIIIa
- can’t recruit and aggregate platelets
4
Q
Core Drug: Aspirin:
- chemical name
- common uses (2)
A
- acetylsalicylic acid
- has anti-inflammatory effects so often
used for fever/pain - disrupts platelet function
5
Q
Core Drug: Aspirin: side effects:
A
- peptic ulceration
- rash
- hearing loss/tinnitus (high doses)
- Reye’s Syndrome:
- brain and liver damage in children
given aspirin for viral illnesses - *** DO NOT GIVE CHILDREN
6
Q
Core drug: Aspirin: Mechanism of Action:
A
- blocks production of prostaglandins and
thromboxanes - aspirin is an IRREVERSIBLE inhibitor of
cyclooxygenase 1 (COX 1 ) - cyclooxygenase 1 converts arachidonic acid
into thromboxane A2 into useable form - hence no further aggregation, adhesion
and activation of platelets as without
thromboxane less cross-linking between
platelets - WILL ALSO INHIBIT RELEASE OF
PROSTACYCLIN AT HIGH DOSES (COUNTER-
INTUITIVE) 5grams a day is high - Gastric lining resistance to acid is
prostaglandin dependent and hence side
effects of gastric and peptic ulceration
7
Q
Cyclooxygenase 1 causes release of —– from injured endothelium resulting in —————- and ———-
A
- prostacyclin
- inhibits platelet aggregation
- causes vasodilation
8
Q
Thromboxane A2 vs Prostacyclin
A
9
Q
At low doses of aspirin,
A
- selectively inhibits platelets
- platelets can not synthesise new COX
- endothelial can synthesise new COX
- hence thromboxane A2 not released so
less platelet aggregation and
vasoconstriction - but prostacyclin released so inhibition of
platelet aggregation and vasodilation
10
Q
Aspirin low doses
A
11
Q
Core Drug: Aspirin: Clinical Use: Arterial Disease:
A
- in all patients with established vascular
disease:
- IHD (MI, angina)
- Cerebrovascular Disease
- Peripheral Vascular Disease
12
Q
Advantages of core drug aspirin use for arterial disease:
A
- improves prognosis, less mortality, less
adverse events (MI, stroke) - mainstay drug - cheap ++++
13
Q
Low dose of aspirin is
A
75-325 mg/day
300mg during MI
daily normal dose is 75mg
14
Q
Core Drug: Clopidogrel: Mechanism of action:
A
- binds to P2Y12 receptor on platelet
- inhibitor of P2Y12 receptor
- combats acute coronary stent thrombosis
15
Q
Clopidogrel vs aspirin
A
- more effective than aspirin
- similar safety profile
16
Q
Clopidogrel vs aspirin
A
- more effective than aspirin
- similar safety profile
17
Q
Core Drug: Clopidogrel: Clinical Use:
A
- part of “dual anti-platelet therapy” DAPT
- post MI and elective coronary stenting
- recurrent stroke despite aspirin
- first line for peripheral arterial disease
18
Q
Core Drug: Clopidogrel: side effects:
A
- bleeding; affects timing of major surgery
(have to stop few days before) - rash
- increased bleeding DAPT because two anti-
platelets
21
Q
Summary of anti-platelet drugs:
A
