Anticoagulants & Antiplatelets Flashcards
What are the 4 main types of anti platelets
Aspirin (COX inhibitor)
Clopidogrel, Ticagrelor, Prasugrel, Ticlopidine (ADP receptor antagonist)
Abciximab, Tirofiban, Eptifibatide (Glycoprotein 2b/3a inhibitor)
Dipyridamole, Cilostazol (PDE & Adenosine uptake inhibitor)
Aspirin MOA
Irreversibly inhibits COX1 and COX2.
COX1 is responsible for converting arachidonic acid to prostaglandin H2 Which is converted to TXA2
Aspirin SIDE EFFECTS
Gastrointestinal toxicity, nephrotoxicity, hyperventilation, hypothermia, coma in over dose
Aspirin C/Is
Hypertension, kidney dysfunction, Stomach ulcers, Asthma. known hypersensitivity to NSAIDs Rhinitis
Aspirin USE
Antiplatet effect
Analgesic
Antiinflammatory
Aspirin SIDE EFFECTS
Fatal hepatotoxicity with overdose
treat w/active charcoal
Glycoprotein 2b/3a Inhibitor EXAMPLES
Abciximab
Tirofiban
Eptifibatide
GLYCOPROTEIN IIb/IIIa INHIBITOR: MOA
Abciximab Tirofiban Eptifibatide
● These agents prevent platelet aggregation by binding to the glycoprotein 2b/3a and hence prevent cross link between platelet Glycoprotein 2b/3a and fibrinogen
● Hence prevents platelet aggregation
● They are reversible Inhibitors of fibrin
● They are administered only intravenously.
● Clinical application: Acute coronary syndrome
● Prevents restenosis after coronary angioplasty
GP 2a/3b Inhibition means no fibrin links which means no clots
ADP RECEPTOR ANTAGONIST
EXAMPLES
Clopidogrel
Ticagrelor
Prasugrel
Ticlopidine
Clopidogrel
Ticagrelor
Prasugrel
Ticlopidine
MOA
They block the ADP receptor (specifically P2Y12)
● Activated platelet release another chemical mediator called ADP
● ADP binds to P2Y12 and that leads to the activation of Glycoprotein IIb/IIIa which are
required for fibrin mediated crosslink.
● Thus by blocking P2Y12 ADP receptors, these drugs effectively block the formation of
platelet aggregation
● Clinical application: Acute coronary syndrome, prevention and treatment for arterial
thrombosis
● Prevents transient ischemic attacks and strokes, Clopidogrel is used to prevent
thrombosis in patients who have received coronary artery Stent, and in patients who can’t tolerate aspirin.
In summary P2Y12 receptor inhibitor means ADP can’t bind which means no clot
Clopidogrel
Ticagrelor
Prasugrel
Ticlopidine
ADVERSE EFFECT
bleeding,
gastrointestinal disturbances
Clopidogrel
Ticagrelor
Prasugrel
Ticlopidine
CONTRAINDICATIONS
Anaplastic anemia
TTP ( Thrombotic thrombocytopenic purpura )
PDE AND ADENOSINE UPTAKE INHIBITOR/PHOSPHODIESTERASE INHIBITOR:
EXAMPLES
Dipyridamole
Cilostazol
PDE AND ADENOSINE UPTAKE INHIBITOR/PHOSPHODIESTERASE INHIBITOR:
MOA
Inhibit enzyme called phosphodiesterase
● Phosphodiesterase is responsible for breaking down of cAMP to AMP
● By blocking phosphodiesterase, there is
, which
inturn leads to
● This automatically leads to inhibition of platelet activation.
● These agents also inhibit phosphodiesterase in the vascular wall as well as uptake of
adenosine which promotes vasodilation
● Cilostazol and Dipyridamole gives headache (adverse effect)
● Clinical application: prevention of thromboembolic complications of cardiac valve
replacement
IN SUMMARY inhibits cAMP–>AMP conversion by enzyme phosphodiesterase meaning increased cAMP—> Leading to increased Calcium intracellularly so less is to be used in plt activation
Dipyridamole
Cilostazol
ADVERSE EFFECTS
Headache,
Palpitation
PDE AND ADENOSINE UPTAKE INHIBITOR/PHOSPHODIESTERASE INHIBITOR:
Contraindications
heart failure
ADVERSE EFFECTS OF ANTIPLATELET DRUGS:
● Bleeding
● Headache (Cilostazol and Dipyridamole)
Heparin USE
Acute treatment of DVTs,
pulmonary embolism,
Acute myocardial infarction
Heparin MOA
Binds to antithrombin 3 which is responsible for degrading several activated clotting factors like thrombin and factor 10a.
HEPARIN S/E
Bleeding
HIT
Allergic reactions Can treat excessive bleeding caused by heparin with protamine sulfate!
HEPARIN CONTRAINDICATIONS
Hypersensitivity
History of HIT
Active bleeding
NOACS:
Direct inhibitor thrombin:
DABIGATRAN
NOACS
Direct inhibitor of X
RIVAROXABAN
NOACS USE
Acute and chronic anticoagulation needs
Used instead of Warfarin in certain patients.
Heparin EXAMPLES
Enoxaparin
Dalteparin
Fondaparinux
DIRECT FACTOR X INHIBITORS
EXAMPLES
Apixaban-
Rivaroxaban-
Edoxaban-
Direct thrombin inhibitors: EXAMPLES
Bivalirudin
Argatroban
dabigatran
Heparin MOA
● Binds to natural anticoagulant called antithrombin III.
● Primary function of antithrombin is to inactivate factor Xa and thrombin.
● Drugs bind to antithrombin and accelerate its activity
● Heparin binds to factor Xa and thrombin and rapidly inactivated them
● Low molecular weight heparin finds it hard to inactivate thrombin hence it radipdly
inactivates factor Xa
● Fondaparinux also finds it hard to inactivate thrombin hence it radipdly inactivates factor
Xa
Side effect is bleeding, HIT(heparin induced thrombocytopenia), osteoporesis
● Bleeding is stopped by Protamine Sulfate (only for heparin) (binds with heparin and
forms stable inactive complex) (no antidote for fondaparinux)
● Clinical application: venous thrombosis, myocardial infarction
Direct Factor X Inhibitors MOA
Apixaban
Rivaroxaban
Edoxaban
Apixaban
● NOAC
Rivaroxaban
● NOAC
Edoxaban
● Binds to active site of factor Xa and prevents conversion of prothrombin to thrombin
● Available orally
● Clinical application: venous thrombosis, pulmonary embolism
● Adverse effect - bleeding (no antidote)
DIRECT THROMBIN INHIBITORS:
MOA
Directly inhibit thrombin, thereby interfering w/ intrinsic and extrinsic factors.
Humanized antibody fragment (Fab) designed as a specific reversal agent for the anticoagulant effect of dabigatran.
● Idarucizumab binds free and thrombin-bound dabigatran and neutralizes its activity.
DIRECT THROMBIN INHIBITORS:
Side effects:
● Low blood potassium (hypokalemia) ● Delirium. ● Constipation. ● Fever. ● Pneumonia. ● Headache
Subclasses of direct thrombin inhibitors
a) univalent direct thrombin inhibitors
b) bivalent direct thrombin inhibitors
Univalent Direct Thrombin Inhibitors:
Binds only to the active site
● Drugs:argatroban,dabigatran(NOAC)
(Treatment for overdose of dabigatran - Idarucizumab)
Bivalent Direct Thrombin Inhibitors:
Binds to active site and exosite of thrombin
● Drugs:bivalirudin
● Advantage: Does Not join with factor IV and hence good for treatment of HIT(heparin induced thrombocytopenia)
Clinical application: HIT patients Adverse effect = bleeding
Warfarin is a
Vitamin K antagonist
Warafrin is used in
Chronic anticoagulation in patients at risk for thromboembolic events
Warfarin MOA
Vitamin K is needed for the synthesis of f
● Factors II (thrombin), VII, IX, X are inactive and by vitamin
K(reduced form of vitamin K)
● Vitamin K reduced is converted to Vitamin K epoxide in presence of oxygen and carbon
dioxide
● Hence fully active clotting factors
Vitamin K is needed for the synthesis of f
● Factors II (thrombin), VII, IX, X are inactive and by vitamin
K(reduced form of vitamin K)
● Vitamin K reduced is converted to Vitamin K epoxide in presence of oxygen and carbon
dioxide
● Hence fully active clotting factors
IN SUMMARY, Inhibits the synthesis of Vit. K dependent factors: 2, 7, 9, and 10 thus increasing bleeding
Warfarin SE
Bleeding
Skin changes
Teratogen
Warfarin Contraindication
Open wounds
Uncontrolled HTN
Active ulcer disease
Clopidogrel
Ticagrelor
Prasugrel
Ticlopidine
USE
Treat acute coronary syndrome w/aspirin.
Prevent thrombosis Patients who can’t tolerate aspirin
ABCIXIMAB (IV)
EPTIFIBATIDE
TIBROFIBIAN
USE
Acute coronary syndromes
ABCIXIMAB (IV)
EPTIFIBATIDE
TIBROFIBIAN
MOA
Binds to glycoprotein 2b3a located on the surface of platelets, prevents fibrinogen from binding and crosslinking, thus hindering platelet aggregation
ABCIXIMAB (IV)
EPTIFIBATIDE
TIBROFIBIAN
SE
Bleeding
Thrombocytopenia
Diffuse alveolar hemorrhage
ABCIXIMAB (IV) EPTIFIBATIDE TIBROFIBIAN
Contraindications
Hypersensitivity Internal bleeding past 6 weeks
Phosphodiesterase:
EXAMPLES
DIPYRIDAMOLE
CILOSTAZOL
DIPYRIDAMOLE
CILOSTAZOL
USE
Treat claudication symptoms in patients with peripheral arterial disease.
DIPYRIDAMOLE
CILOSTAZOL
MOA
Inhibits the enzyme cyclic AMP phosphodiesterase 3, an enzyme involved in breakdown of cAMP, so ↑cAMP → inhibits TxA2 synthesis and ↑prostacyclin production. Platelet aggregation is thus inhibited.
DIPYRIDAMOLE
CILOSTAZOL
SEs
Headache
Palpitations
Gi upset
DIPYRIDAMOLE
CILOSTAZOL
SE
Headache
Palpitations
Gi upset
DIPYRIDAMOLE
CILOSTAZOL
contraindications
Congestive HF
LMWH heparin:
EXAMPLES
ENOXAPARIN
DALTEPARIN
ENOXAPARIN
DALTEPARIN
use
Acute treatment of DVTs
Pulmonary embolism
MI
ENOXAPARIN
DALTEPARIN
MOA
Inactivates both 10 and 2a. They bind to natural anticoagulants circulating in blood - Antithrombin 3.
By binding they accelerate its activity.
ENOXAPARIN
DALTEPARIN
SEs
Bleeding
HIT
ENOXAPARIN
DALTEPARIN
Active major Gi bleed History of HIT within last 100 days.
ACETAMINOPHEN
PARACETAMOL
USE
Antipyretic
Analgesic
ACETAMINOPHEN
PARACETAMOL
MOA
BlocksCOX1&2 permanently, thus blocking TxA2 → bleeding
ACETAMINOPHEN/ PARACETAMOL
S/Es
Fatal hepatotoxicity with overdose Treat paracetamol overdose with activated charcoal & acetylcysteine.
ACETAMINOPHEN/ PARACETAMOL
Contraindication
Known hypersensitivity to NSAIDs Asthma
Rhinitis
What is the first line treatment of MI in ED?
Aspirin
How do we control warfarin levels
Using INR
What is the normal INR range
2-3
What is the antidote for heparin overdose
Protamine Sulfate
How do we control heparin dose
By checking APTT levels, it should be 1.5-2.5
What kind of block does aspirin have to cox 1
Ireversible
What do medical professionals do in an aspirin overdose ?
Platelet infusion because aspirin effect last 7-12 days so we cannot wait
What is the recommended aspirin level
300mg
What is the MOA of heparin
Heparin catalyses the formation of antithrombin 3 which blocks factor 10 and 2
What are the types of heparin?
Unfractioned (Huge Monoamers) - Used in hospitals.
Fractioned/Standard (Smaller)- Used at home ie LMWH
What is the indication of use of heparin and warfarin
PE,
Pregnancy,
Immobilisation after surgery
Past covid patient (to reduce d-dimer and due to cytokine storm)
What is heparin measured in?
Units are the safest dose
b/c they are many ways used by companies to process and produce heparin
What is the anticoagulant of choice in pregnancy and why?
Heparin because it does not cross the placenta
Four S/Es of Heparin
- Bleeding
- Thrombocytopenia/HIT
- Osteoporosis
- Necrosis at site of injection
Antidote for heparin overdose
Protamine Sulfate
List 2 Vitamin K antagonist
warfarin & Acenocrumorol
List the Vitamin K dependent factors
2, 7, 9, 10
Disadvantage of vitamin K antagonist
Metabolised via Cytochrome 450 therefore there are many interactions with drugs and food, it also stays in the body longer leading to an increased bleeding risk.
What do we do in the case of a warfarin overdose
Give the patient vitamin k or in emergencies give then 2,7,9,10
How long should we wait to se factors after Vit.k Administration
Up to 72 hours
MOA of vitamin k antagonist
warfarin
Blocks enzyme vitamin k epoxide reductase which allows the reduced form of vitamin k to be recycled
What class of drug is dabigatran and rivaroxoban
New oral anticoagulant
MOA of Dabigatran
Inhibits thrombin —> No coagulation
MOA of Rivaroxaban
Inhibits factor X—> No coagulation
Should INR be checked?
In any case of bleeding
Warfarin food and drug interactions
Alcohol
Aspirin
Fluoroquinolones
Grapefruit/ Fruit
What things may affect the treatment of Vitamin K antagonists
Wrong diet Hepatocellular disorder Viral Infection Chronic alcoholism Hepatic congestion Increased catabolism of coagulation/ clotting factors Hepatitis
Describe the effect of cimetidine on Warfarin
