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Pharmacology - Year 2 AC > Week 3 - Stroke > Flashcards

Week 3 - Stroke Flashcards

1
Q

What is the clinical definition of a stroke?

A

A syndrome of rapid onset or cerebral deficit (usually focal) lasting more than 24 hours or leading to death, with no apparent cause other than a vascular one

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2
Q

What does an interruption of blood supply cause?

A
  • interruption of blood supply
  • cascade of neuronal events
  • neurotoxicity –> irreversible necrosis, cerebral oedema and inflammation
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3
Q

What is an occlusion when referring to a stroke?

A

A lesion with ‘central core’ and ‘ischaemic penumbra’

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4
Q

What is the body’s own clot buster?

A

Plasmin

  • degrades fibrin
  • formed locally from plasminogen - trypsin like substance (protease)
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5
Q

What is fibrin?

A

an insoluble protein formed from fibrinogen during the clotting of blood. It forms a fibrous mesh that impedes the flow of blood.

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6
Q

How is plasmin formed?

A

Plasminogen is activated by plasminogen activators which diffuse in to thrombus and convert plasminogen to plasmin

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7
Q

Plasmin is localised to the clot… What happens to plasmin that escapes in to the circulation?

A

Inactivated by plasmin inhibitors

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8
Q

Name some antiplatelet drugs

A

Aspirin, abciximab, clopidogrel, dipyridamole

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9
Q

What type of stroke is treated with anti-platelet drugs?

A

Ischaemic stroke

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10
Q

What are the 2 mechanisms of action for anti-platelet drugs?

A
  • inhibit platelet aggregation and thrombus formation by preventing GPIIa/IIIb receptor expression
  • preventing GPIIa/IIIb receptor interaction
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11
Q

Even though aspirin is an NSAID, why is it used as an anti-platelet as well?

A
  • inhibits cyclo-oxygenase (COX-1)
  • prevents thromboxane formative

-works acutely so given early in first 24hrs and then typically given for 2 weeks

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12
Q

What does dipyridamole do?

A

-anti-platelet

  • inhibits thromboxane synthase
  • prevents thromboxane formation
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13
Q

What is dipyridamole often used in conjunction with?

A

Aspirin

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14
Q

What does clopidogrel do?

A
  • anti-platelet

- antagonise actions of ADP at purinergic (ADP) receptors

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15
Q

What does abciximab do?

A
  • Ab to GPIIb/IIIa receptors

- prevents linking of platelets to fibres

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16
Q

Name some anticoagulant drugs

A

Antithrombin, heparin, warfarin

17
Q

Name the different types of strokes

A

Haemorrhagic - bleed

Ischaemic - blockage - embolism/thrombosis

Transient ischaemic attack - short lived - few mins to 24hrs - complete recovery

18
Q

Explain what happens in the clotting cascade

A

Clotting factors - proteins - circulate in the blood

  • when blood contacts damaged tissue or exposed collagen - clotting cascade = triggered
  • initiated by the activation of factors VIII or XII
  • these then activate another clotting factor and so on –> cascade of chemical reactions
  • activation of prothrombin (factor II) is a critical step: thrombin converts fibrinogen into fibri
  • fibrin = insoluble, stable, traps platelets –> clot formation
19
Q

What are the various mechanisms of action of anticoagulant drugs?

A
  • activation of antithrombin
  • inhibition of vitamin K reductase
  • direct (selective)inhibition of steps of clotting cascade (eg direct inhibitors of thrombin)
20
Q

How is heparin administered?

A

IV administration as it’s poorly absorbed orally

-works immediately

21
Q

What is heparin’s mechanism of action?

A

Activates antithrombin III (present in liver, lungs and mast cells)

-forms complexes with activated clotting factors - thrombin, factors Xa (FIXa and XIa to a lesser extent) - inactivating them

22
Q

What varies with heparin?

A

The molecular weight

23
Q

What are the 2 forms of heparin?

A

-original unfractionated heparin

-low molecular weight heparin’s
I.e. Heparin fragments - enoxoparin, dalteparin, tinzaparin

24
Q

What is the mechanism of action of warfarin?

A
  • acts on liver to inhibit enzyme Vitamin K reductase
  • enzyme uses vit K to ‘final assemble’ clotting factors II (prothrombin), VII, IX and X
  • gradually diminishes concs. of clotting factors
25
Q

What does warfarin have a similar structure to?

A

Vitamin k

26
Q

What must be done when a patient is on warfarin?

A

-v. complex metabolism in the body so:

Monitoring via INR (international normalised ratio - how much slower is clotting time compared to normal)

-changes because of lots of reasons (e.g diet, drinking, acute illness)

27
Q

State what a consequence might be of taking warfarin

A

-interacts with other drugs - drug related adverse effects

28
Q

Name some thrombin inhibitors

A

Bivalirudin, lepirudin

29
Q

What is the mechanism of action of thrombin inhibitors?

A
  • anticoagulants that bind to and inhibit the activity of thrombin and therefore prevent blood clot formation
  • inactivate free thrombin and also thrombin that is bound to fibrin
  • used to prevent arterial and venous thrombosis
30
Q

What does bivalirudin do?

A
  • thrombin inhibitor
  • helps to prevent platelets in your blood from sticking together and forming a blood clot
  • used to prevent blood clots in people with severe chest pain or other conditions who are having an angioplasty done

Given IV

31
Q

Name some anticoagulant therapy drugs

A

Protamine sulphate, vitamin k

32
Q

What does protamine sulphate do?

A

-combines with heparin to form a stable salt complex which has no anticoagulant activity

33
Q

What is vitamin K used for?

A

Treats vitamin K deficiency and to treat certain bleeding/blood clotting problems

34
Q

Name some thrombotic agents

A

Alteplase (rTPA), streptokinase, urokinase

35
Q

What does rTPA mean?

A

Recombinant tissue plasminogen activators

-recombinant human proteins so non-antigenic

36
Q

Which drunk is currently licenced for the used in acute ischaemic stroke?

A

Alteplase

  • mist confirm ischaemic event before giving rTPA
  • effective only if given within the first 3 hours
37
Q

Name a systematic haemostatic agent

A

Aprotinin

38
Q

What does aprotinin do?

A
  • protease inhibitor - reducing the inflammatory response associated with cardiopulmonary bypass surgery
  • reducing blood loss and the need for blood transfusions in patients undergoing certain types of heart/major surgery

Pharmacology - Year 2 AC (14 decks)

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