Atherosclerosis and Thrombosis

Question 1

What is atherosclerosis?
(precursor to all CV disease)

Answer 1

-Formation of atheroma within walls of blood vessel.
-Reduced arterial lumen.
-Loss of perfusion
-Result of loss of elasticity (increases likelihood of rupture).
-Predisposition to thrombus formation

Question 2

Atheroma

Answer 2

Accumulation of
lipid plaques within the walls of a vessel

Question 3

Lipoproteins

Answer 3

Transport lipids in blood as they are insoluble in water.
5 Classes: chylomicrons, VLDL, IDL, LDL, HDL

Question 4

Apolipoproteins

Answer 4

Cell surface receptors direct lipoproteins to specific tissue receptors and mediate enzymatic reactions

Question 5

Atherosclerosis, pathogenesis

Answer 5

-Lipid deposition in the intima
- smooth muscle and ECM proliferation
- production of protruding fibrous plaque

Question 6

Atherosclerosis Lead to …

Answer 6

Ischaemia - lumen sufficiently narrowed
Myocardial infarction - sudden occlusion by plaque rupture and thrombosis.
Aneurysm - walls are weakened.
Embolism - blood clot breaks lose

Question 7

Thrombosis

Answer 7

Inappropriately activated haemostasis, pathological

Question 8

Haemostasis

Answer 8

The physiological response of blood vessels to injury to prevent blood loss. [Vascular wall, platelets, coagulation cascade]

Question 9

Statins

Answer 9

-HMG-CoA reductase inhibitors, limit the synthesis of Mevalonate.
-Increase cellular LDLR so increase clearance of LDL from the circulation.
-Inhibit synthesis of Apo B-100 n

Question 10

How to lower cholesterol? Drug and example

Answer 10

Statins = atorvastatin
- reduces synthesis of cholesterol in hepatocytes.

Question 11

Antiplatelet drugs?

Answer 11

Aspirin, clopidogrel, anticoagulants (warfarin)

Question 12

Aspirin

Answer 12

-Irreversible inhibition of
COX-1
-Whole new platelets
need to be synthesised
rather than just an
enzyme.
-Reduces platelet plug formation
-Reduces clots
 Less risk of atherosclerosis
 Less risk of thrombosis and embolism

Question 13

How to stop platelets adhering to each other?

Answer 13

Low dose of aspirin stops activation of platelets and them adhering together.

Question 14

Clopidogrel

Answer 14

P2Y12 antagonist, prevents platelet activation, used in conjunction with aspirin.

Question 15

Anticoagulants (function, drug examples)

Answer 15

Inhibit various members of clotting cascades.
Warfarin, direct oral anticoagulants (DOACS).

Question 16

Warfarin

Answer 16

-Vitamin K antagonist
-Inhibits factors 2, 7, 9 and 10

Question 17

DOACS

Answer 17

Factor Xa inhibitors = apixaban, rivaroxaban, edoxaban
Thrombin inhibitors= dabigatran, melagatran

Question 18

How can you prevent blood clotting and get rid of clots?

Answer 18

Anticoagulants

Question 19

Targets for anticoagulants

Answer 19

Better to target factors of coagulation cascade in the common pathway rather than the intrinsic and extrinsic pathway so it works on both e.g Xa edoxaban.

Question 20

How to treat atherosclerosis?

Answer 20

-lifestyle changes (lose weight, less cholesterol in diet, exercise more)
- reduce cholesterol statins
-Stents (surgical) squash plaques
-thin blood aspirin etc
-clot busters

Question 21

Clot busters

Answer 21

Fibrinolytics/thrombolytics
-enzymatic degradation of fibrin
-plasmin digests fibrin breaking down the clot
-used in stroke or myocardial infarction

Streptokinase (Alteplase) activates plasminogen conversion to plasmin.