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PHAR222 > l8 > Flashcards

l8 Flashcards

1
Q

Clot Formation

A
  1. Damaged endothelium reveals underlying collagen & other proteins
  2. Platelets aggregate and adhere to surface to form a temporary seal
  3. Blood clotting factors form strong, durable thrombin‐fibrin clot
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2
Q

Why interfere with blood clotting?

A
  • Venous thrombosis
  • Myocardial infarction (heart attack)
  • Cerebral artery occlusion (stroke)
  • Peripheral artery thrombosis,
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3
Q

Venous thrombosis

A

blood clot forms in a vein

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4
Q

Myocardial infarction

A

(heart attack)

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5
Q

Cerebral artery occlusion

A

(stroke)

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6
Q

Peripheral artery thrombosis

A

blood clot forms in peripheral arteries
Can prevent clood from travelling through to lung to the heart.

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7
Q

Explain how clotting factors work

A
  • Clotting factor = serine protease - enzyme that speeds up the breakdown of another protein.
  • The clotting factors are initially inactive and called zymogens.
  • When placed with its glycoprotein co-factor, the clotting factor is activated and is then able to catalyze the next reaction
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8
Q

Explain the cascade and CF for an intrinsic damage

Abnormal blood vessel

A
  1. XII
  2. XI
  3. IX
  4. X
  5. prothrombin –(Xa)–> thrombin + fibrinogen
  6. Thrombin fibrin clot
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9
Q

Explain the cascade and CF for an extrinsic damage

Damage tissue

A
  1. VII
  2. x –(VIIa)–> Xa
    3.5. prothrombin –(Xa)–> thrombin + fibrinogen
  3. Thrombin fibrin clot
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10
Q

What inhibits thrombin

A

Antithrombin III

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11
Q

Agents that deplete functional clotting factors

A

– Warfarin
– Heparin
– Direct enzyme inhibitors: dabigatrin and rivaroxaban

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12
Q
  • Agents that accelerate clot lysis
A

– Tissue plasminogen activator

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13
Q
  • Antiplatelet drugs
A

– Aspirin
– Clopidogrel

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14
Q

Preventing clotting factor synthesis with

A

Warfarin

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15
Q

Vitamin K

A

cofactor for post‐ translational carboxylation of glutamic acid groups on Factors II, VII, IX & X

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16
Q

What does warfarin do to vitamin k

A

Warfarin inhibits Vitamin K recycling from KO (inactive) to KH2 (active

17
Q

VKORC1

A

Vitamin K Epoxide Reductase Complex 1

18
Q

Heparin will inhibit:

A

Inactivation of Xa and Thrombin

19
Q

Heparin is

A
  • Mixture of glycosaminoglycans
  • Molecular weight ranges 3000 to 58000
  • Strong acid, so strong electronegative charge
20
Q

Heparin: mechanism of action

A
  • Binds to Lysine on Antithrombin III (ATIII)
  • Conformational change to ATIII.
  • increase affinity for activated factors of intrinsic arm, esp. Xa & thrombin
  • Accelerated inactivation of these
  • Prevents conversion of fibrinogen to fibrin
  • Stops clot propagation.
21
Q

Direct enzyme inhibitors

Dabigatran inhibits what

A

IIa (2a) or thrombin

22
Q

Direct enzyme inhibitors

Rivaroxaban inhibits what

A

Xa/10a

23
Q

(tissue plasminogen activator) t‐PA

A
  • Recombinant human protein
  • IV Administration Immediate onset of action
  • Relieves blockage of critical
  • vessels, e.g. coronary artery occlusion (heart attack)
24
Q

Clot lysis with t-PA

A
  1. Plasminogen is cleaved by t-PA
  2. Releases plasmin
  3. Plasmin facilitates lysis as it digests fibrin, fibrinogen and factor 2, 5, 7

Main point is that plasmin facilitates lysis for 3

25
Q

Antiplatelet Drugs: Aspirin & Clopidogrel

A
  • irreversible acetylation and inhibition of cyclooxygenase (COX) enzyme so no TxA2
  • Clopidogrel’s active metabolite blocks platelet ADP receptors irreversibly
26
Q

Aspirin (acetyl salicylic acid) in cox

A
  1. Acetylation of NH2‐terminal serine of cyclooxygenase (irreversible)
  2. Permanent loss of TxA2 production
  3. Defective platelet clot formation
  4. Protection from thrombotic disorders
27
Q

Synthesis of ThromboxaneA2 (TxA2) in Platelets

A
  1. Arachidonic acid
    cyclooxygenase
  2. Prostaglandin G2
  3. Prostaglandin H2
  4. TxA2
28
Q

TxA2 and ADP do what?

A

enhance platelet aggregation & adhesion

29
Q

How is warfarin taken

A

– Oral; Vit K has to deplete before it works; – Needs regular monitoring of coagulation

30
Q

How is heparin taken

A

IV

31
Q

How is Factor IIa and Factor Xa inhibitors taken

A

– Oral,monitoring not needed in most patients

Dabigatrin and rivaroxaban

32
Q

Why is aspirin and clopidogrel taken

A

Mostly for arterial disease ;Lower bleeding risk than anticoagulant drugs

33
Q

How is Thrombolytic drugs taken

tissue plasminogen activator

A

– Treatment of established, life threatening thrombosis

IV

34
Q

Warfarin is a teratogen
t/f

A

true

35
Q

Tissue plasminogen activator (tPA) is particularly effective against platelet clots
t/f

A

false

36
Q

Tissue plasminogen activator (tPA) can lyse thrombi in the coronary circulation, preventing myocardial damage from developing
t/f

A

true

37
Q
A

PHAR222 (25 decks)

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