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C. Cardiovascular Drugs > Anti-platelets & anti-thrombotics > Flashcards

Anti-platelets & anti-thrombotics Flashcards

1
Q

Examples of anti-platelet drugs

A
  1. NSAIDs
  2. Platelet GPIIb/IIIa receptor blockers
  3. ADP receptor blockers
  4. Phosphodiesterase inhibitor
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2
Q

Example of NSAID

A

aspirin

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3
Q

MOA of aspirin

A

Irreversible COX-1 inhibition → inhibition of thromboxane (TXA2) synthesis in platelets → inhibition of platelet aggregation (antithrombotic effect)
- Irreversible in aspirin (so the entire life of platelet – 7-10 days)

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4
Q

PK of aspirin

A

inhibitory effect is rapid and last for the life of the platelet approx. 7 to 10 days

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5
Q

Clinical uses of aspirin

A
  1. prophylactic treatment of transient cerebral ischemia
  2. to reduce the incidence of recurrent myocardial infarction
  3. to decrease mortality in post-myocardial infarction patients
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6
Q

Adverse effects of aspirin

A

Gastric upset and ulcers

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7
Q

Examples of GPIIb/IIIa receptor blockers

A
  1. Abciximab
  2. Eptifibatide
  3. Tirofiban
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8
Q

MOA of Abciximab

A

humanised monoclonal antibody directed against the IIb/IIIa complex > reversibly inhibits the binding of fibrinogen and other ligands to GPIIb/IIIa

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9
Q

MOA of Eptifibatide

A

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

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10
Q

MOA of tirofiban

A

a small molecule blocker of the GPIIb/IIIa receptor

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11
Q

Clinical uses of GPIIb/IIIa receptor blockers

A

prevent restenosis after coronary angioplasty and are used in acute coronary syndromes

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12
Q

MOA of clopidogrel and ticlopidine

A

prevents ADP from binding to the ADP receptor hence preventing platelet aggregation

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13
Q

MOA if dipyridamole

A

Inhibits the breakdown of cAMP to 5’-AMP hence preventing platelet aggregation

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14
Q

Examples of anticoagulants

A
  1. Heparin derivatives
  2. Coumarin derivatives (Warfarin)
  3. Lepirudin, hirudin
  4. Antithrombin III
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15
Q

MOA of heparin

A
  1. The active heparin molecules bind tightly to ATIII and cause a conformational change, which exposes its active site for more rapid interaction with the proteases
  2. to inhibit thrombin, it is necessary for heparin to bind to the enzyme as well as ATIII; to inhibit factor X it is only necessary for heparin to bind to ATIII

LMWHs increase the action of ATIII on factor Xa but not its action on thrombin

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16
Q

Clinical uses for heparin

A
  1. treatment for DVT, pulmonary embolism and AMI
  2. be used in combination with thrombolytics for revascularisation and in combination with GPIIb/IIIa inhibitors during angioplasty and placement of coronary stents
  3. be used when an anticoagulant must be used in pregnancy
17
Q

PK of heparin

A

given IV or SC

NOT GIVEN IN IM AS IT CAN LEAD TO HEMATOMAS

18
Q

Adverse effects of heparin

A
  1. Haemorrhage: stop heparin therapy + protamin sulfate

2. Thrombosis and thrombocytopenia

19
Q

MOA of Warfarin

A

Inhibit hepatic vitamin K epoxide reductase → ↓ hepatic synthesis (recycling) of the active, reduced form of vitamin K → ↓ γ-carboxylation of glutamate residues on coagulation factors II, VII, IX, and X as well as protein C and protein S

20
Q

Clinical uses of warfarin

A

same as heparin except in pregnant woman

21
Q

PK of warfarin

A
  1. warfarin is small and lipid-soluble molecule which is given orally and absorbed quickly and totally
  2. it has a small volume of distribution volume, being strongly bound to plasma albumin (>99%)
  3. its elimination depends on metabolism by hepatic cytochrome P450
22
Q

Adverse effects of warfarin

A
  1. bleeding
  2. 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-carboxyglutamte residues found in bone and blood may be affected by warfarin
23
Q

MOA of vitamin K

A

reduced vitamin K is an essential cofactor in the carboxylation of glutamate residues

24
Q

Clinical uses of vitamin K

A
  1. treatment and/or prevention of bleeding
    - resulting from use of oral anticoagulant drugs (eg warfarin)
    - babies: to prevent hemorrhagic disease of the newborn
  2. for vitamin K deficiencies in adults
25
Q

Examples of thrombolytic agents

A
  1. t-PA (alteplase)
  2. urokinase
  3. streptokinase
  4. anistreplase
26
Q

MOA of thrombolytic agents

A
  1. Fibrinolytics promote the degradation of thrombi by activating plasminogen to plasmin
  2. Plasmin breaks down and deactivates fibrin and fibrinogen → release of fibrin degradation products (e.g, D-dimers)
27
Q

Clinical uses of thrombolytic agents

A
  1. emergency treatment of coronary artery thrombosis

2. peripheral arterial thrombosis and emboli

28
Q

PK of thrombolytic agents

A

intracoronary injection, intravenous injection

29
Q

Adverse effects of thrombolytic agents

A

bleeding

30
Q

Contraindication of thrombolytic agents

A
  1. healing wounds

2. pregnancy

C. Cardiovascular Drugs (6 decks)

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