BOD L8 Regression, Treatment & Prevention of CVD Flashcards
Appreciate the evidence for regression of atherosclerosis. Be aware of a variety of treatments for cardiovascular disease. Be familiar with guidelines for the prevention fo cardiovascular disease.
There is evidence that regression of atherosclerosis can occur. How can this be done?
Reduction of plasma LDL/cholesterol.
Improved diet.
How can coronary heart disease be treated?
Usually angioplasty followed by drugs (lipid lowering, prevents reformation).
Gene therapy unsuccessful but conceptually should work so being developed.
Also thrombolytic therapy.
What is thrombolytic therapy?
Treatment with drugs which break down blood clots, reopening arteries.
What are three natural anticoagulants?
Tissue factor pathway inhibitor (TFP-1)
Thrombomodulin - prevents thrombus formation. Activates protein C, which activates both arms of coagulation cascade.
Antithrombin III - serpins (serine protease inhibitors)
What 3 anticoagulants can be given which act through plasminogen?
Urokinase - naturally occuring in kidneys. Activates plasminogen to become plasmin, which cleaves fibrin in thrombi.
Streptokinase - produced by streptococci, acts upon plasminogen also, forms complex (non-cleavage activation).
Tissue plasminogen activator (tPa) - product of endothelial cells, activates plasminogen.
What is reteplase?
Recombinant tPa, increases half-life from 3mins to 18 mins.
Used as thrombolytic agent administered when heart attack is diagnosed.
What 3 anticoagulents are used originally isolated from leeches?
Hirudin, hirulogs and bivaliridin.
Irreversibly bind thrombin.
What two anticoagulents are given that do not act on plasminogen?
Herapin
Warfarin - Prevents clotting very well.
What is role that platelets play in thrombus formation?
What does this mean for treatment?
Platelet aggregation occurs as part of thrombus formation. Substances which inhibit platelet aggregation can inhibit thrombus formation.
These can be used as larger anticoagulent strategy in treating myocardial ischaemia.
Give two eamples of antiplatelet agents
Aspirin - inhibits COX, reducing producion of thromboxane (which aggregates platelets)
Abciximab - mAb which binds to glycoprotein receptor on platelets thereby preventing aggreation.
Give some general interventions used in lipid lowering systems
Dietary modification - linoleic and linolenic acid, fish oils
Drug treatment, target LDL, HDL and cholesterol.
LDL apheresis (excorporal removal of LDL, similar to dialysis).
Gene therapy for lipid lowering.
What three drugs can be given to lower patients lipids, how do they act?
Fibrates - Decrease VLDL production, increase HDL concentration (by stimulating ApoA1)
Statins - Decrease cholesterol biosynthesis, increase LDL receptor activity, lowering blood LDL. Activate endothelial NO synthase.
Combation drug treatment - used to inhibit cholesterol uptake from small intestine.
How do statins prevent cholesterol biosynthesis?
Inhibiton of HMG CoA reductase
How are angiotensin converting enzyme (ACE) inhibitors used as thrombolytic agents?
Angiotensin prmotes formation of MCP-1 and VCAM-1, which drives: smooth muscle cell proliferation, increases superoxide anions in ECM, drives oxidation of LDL by macrophages and expression of LOX-1 on endothelial cells and macrophages (responsible for internalisation of ox-LDL).
What are coronary angioplasties?
Physical stents inserted into coronary artery which expand lumen of artery and allow higher blood flow.
Usually supported by follow up drugs to prevent closing up.
