W3 Coronary Heart Disease and Thromboembolic CV pathologies (SM) Flashcards
Coronary Circulation (for info)
What occurs from thickening of internal surface of arteries?
- Two tiny arteries leaving out the aorta
- Profuse blood to the myocardium
- Handles high pressure (irrespective of heart contraction or relaxation)
Inflammation and build-up of fatty deposits along the innermost layer of the coronary arteries. This thickening, called atherosclerosis, narrows the arteries and can decrease or block the flow of blood to the heart
Thickening of the internal surface of arteries or progression of atherosclerotic lesions, occlude and affect oxygen supply to heart muscles (ISCHEMIA)- a major cardiac problem- progress to angina, coronary artery disease.
Coronary thrombosis- Myocardial Infarction (MI)
Coronary artery flow- Angina (obstruction)- Ischemia (lack of oxygen supply)
What is angina?
Describe the cause and effect of stable angina.
=Severe Chest pain
Cause:
Atherosclerotic lesions
(atheroma/fibrous plaque) narrow coronary arteries and reduce their ability to dilate
Effect:
Stable (typical) angina = Reduced capacity of the artery. Chest pain due to exertion or stress (recovery by rest).
No change in troponin & ECG
Describe the cause and effect of unstable angina:
Cause:
Lesions rupture and stimulate platelet aggregation/thrombus formation. Thrombus occludes the artery and prevents blood flow/supply
Effect:
Unstable angina:
Rapid reduction of blood flow due to rupture and thrombus- Severe chest pain requires urgent treatment
No change in troponin, but some ST depression in ECG
What are some examples of Antianginal drugs? (6)
- Nitrates (for acute attacks or preventive measures) sublingual glyceryl trinitrate (short treatment) (GTN spray)
- Beta-blockers
- CCB’s
- l(f) current blockers (new class)
- Late inward sodium channel blocker
- Potassium channel activator
Nitric acid-cytoplasmic-guanylyl cyclase receptors – vasodilation
What is the function of NO?
How does NO dilatate blood vessels?
(Role of GTN)
NO= Endothelium-derived vasodilator factor- gasotransmitters
- NO stimulates cytoplasmic guanylyl cyclase
- Elevation of intracellular [cGMP]
- Activation of protein kinase G
- Smooth muscle relaxation (Vasodilation)
- PDE isoform breaks down cGMP
Antianginal drugs:
Nitrates (for acute attacks or preventive measures)
Names of 2 types?
Effect on
Systemic vasculature?
Cardiac?
Coronary?
Two types: Direct & Organic (require enzymatic process)
Systemic vasculature:
*vasodilation
(venous dilation > arterial dilation)
*decreased venous pressure
*decreased arterial pressure (small effect)
Cardiac:
*reduced preload and afterload (decreased wall stress)
*decreased oxygen demand
Coronary:
*prevents/reverses vasospasm
*vasodilation (primarily epicardial vessels)
*improves subendocardial perfusion
*increased oxygen delivery
What are examples of nitrates?
*isosorbide dinitrate (organic)
*isosorbide mononitrate (organic)
*nitroglycerin
*erythrityl tetranitrate
*pentaerythritol tetranitrate
*sodium nitroprusside (direct)
What type of angina is contraindicated with beta-blockers?
What is prescribed as an alt?
Prinzmetal angina= inc vascular spasms
Dihydropyridine derivative calcium-channel blockers (such as amlodipine) may be effective in patients with Prinzmetal’s angina (a rare condition or type of angina, intense vasospasm
What are the effects of beta-blockers in treating angina?(3)
Examples?
- Cardio specific depression of sympathetic activity
- Reduce heart rate- lengthened diastole
- Increase oxygen supply to the myocardium
(patients with variant angina or HF are contra-indicated for B-blockers)
Atenolol, bisoprolol fumarate, metoprolol tartrate, propranolol hydrochloride
Antianginal drugs:
An example is
I(F) CURRENT INHIBITORS (second line option)
How do they work?
Ivabradine selectively blocks the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels present within the SA nodes and lowers the heart rate without affecting the contractility of the cardiac muscle
Antianginal drugs:
An example is
Class ID sodium-channel blocker (second line options
How do they work?
Ranolazine blocks late inward
sodium currents occurring during
phase 2 of ventricular action
potentials
Antianginal drugs:
An example is Nicorandil- A Potassium channel activator (second-line option)
How do they work?
Nicorandil activates the ATP-sensitive K+
channels to enhance K+ efflux and
hyperpolarisation of vascular smooth muscle cells.
Consequently, reduce Ca2+ entry and reduce cardiac contraction.
What types of calcium channel blockers are involved in treating angina?
Cardiac-specific CCBS like verapamil hydrochloride or diltiazem hydrochloride
Dihydropyridine derivative calcium-channel blockers (such as amlodipine) may be effective in patients with Prinzmetal’s angina (a rare condition or type of angina, intense vasospasm)
Antianginal drugs
Second-line options? (3)
- I(F) CURRENT INHIBITORS
Ivabradine selectively block the Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels present within the SA nodes and lowers the heart rate without affecting the contractility of the cardiac muscle - Potassium channel activator
Nicorandil activates the ATP-sensitive K+
channels to enhance K+ efflux and
hyperpolarisation of vascular smooth muscle cells.
Consequently reduce Ca2+ entry and reduce cardiac contraction.
- Class ID sodium-channel blocker
Ranolazine blocks late inward sodium currents occurring during phase 2 of ventricular action potentials
Myocardial Infarction
Non-ST segment Elevation MI
(NSTEMI):
Cause?
Non-ST segment Elevation MI
(NSTEMI):
- Myocardial ischaemia and necrosis
(but still functional due to some
blood flow)
- Changes in troponin & no change in
ECG
Severe coronary artery narrowing, transient occlusion,or microembolization of thrombus and/or atheromatous
material
Myocardial infarction-severe
ST segment elevation MI
(STEMI)
Cause?
-Dysfunction and death (necrosis) of cardiac myocytes in the ventricular wall
-Troponin level rise, elevation of ST segment in ECG
Caused by:
complete and prolonged occlusion of an epicardial coronary blood vessel
Thrombus Vs Embolus/Embolism
Thrombus- Blood clot still attached to/ in artery structure
(Vein or capillaries: Recollect Deep vein
thrombosis, Varicose vein)
Embolus- Blood clot broken off from thrombus and flowing freely in the bloodstream and vessel which could lead to artery blockage
What are the roles of Protein C and S?
Natural anticoagulant
regulate anticoagulation
- hypercoagulation is caused by protein C and S deficiency
What is Polycythemia?
Too many cells in the blood
Blood viscosity inc
Blood flow dec
poor oxygen supply and ischemia
complete blockage of blood vessel
What are the steps in Haemostasis?
- Vascular Spasm: pain reflux, constriction of vascular smooth muscle, trigger clotting chemicals/factors needed & directed to site of injury
- Platelet Activation- Plug
Endothelial Damage
Exposed Collagen - Platelets stick to exposed collagen
(swell like star shaped cells)
Platelets stimulate ADP,
Thromboxane A2 and Serotonin
-staying still
Platelet-Endothelial Interaction (ADP-mediated process- Healthy)
Activated platelets stimulate the release
ADP which acts on P2Y receptors in
platelets to activate positive feedback
(more platelet plug formation)
In healthy, ADP binds to P2Y receptor and
stimulate the release of prostacyclin & NO
from endothelial cells to prevent plug
formation
In atherosclerosis, the ADP-mediated
platelet plug formation becomes abrupt
and accelerated due to the endothelial
dysfunction/damage.
What is fibrinolysis?
Plasminogen, plasma protein trapped in clot-converted Plasmin-digest Fibrin
Clot retraction concurrent with vessel repair
The actin and myosin in platelets contract and pull on fibrin strands
* Platelet-derived growth factor (PDGF)
* Stimulate smooth muscle and fibroblast division
* Vascular endothelial growth factor (VEGF)
* Rebuild endothelial lining by multiplying endothelial cell
