Ischaemic Heart Disease Flashcards
What is the definition of IHD
A condition whereby there is an inadequate supply of blood and oxygen to a part of the myocardium.
What are the determinants of myocardial oxygen demand?
Heart rate, myocardial contractility and myocardial wall tension/stress. Adequate oxygen supply needs, adequate coronary artery flow and satisfactory oxygen-carrying capacity.
What are the different classifications of IHD?
Stable IHD-chronic stable exertional angina
STEMI,NSTEMI, Unstable agina
Microvascular angina, Ischaemia due to coronary artery spasm.
What are somes causes of perfusion reduction?
Reduction in the artery lumen, coronary artery spasm, arterial thrombi and emboli and congenital abnormalities.
What are the effects of disturbances in vascular endothelium functioning?
Local loss of vascular tone (contractile ability of smooth muscle is decreased)
Inability to maintain an anti-thrombotic surface.
Control of inflammatory cell adhesion and Diapedesis (the passage of blood cells through capillary walls into tissues)
What are some consequences of atherosclerosis?
Epicardial artery diameter is reduced, plaque is exposed to the blood and platelet aggregation and activation occurs. The coagulation cascade is activated and causes deposits of fibrin strands. This then causes the formation of a thrombus composed of platelet aggregates, fibrin strands and trapped RBCs.
What happens in the absence of oxygen during ischemia?
Fatty acids cannot be metabolised thus glucose is converted to lactate. Intracellular pH decreases and ATP and creatine phosphate decreases. This can lead to impaired cell membrane function.
What is the clinical presentation of stable angina pectoris?
Chest discomfort that may be described as heaviness, pressure, chest thighness, choking, levine’s sign. The pain can also radiate to other areas of the body.
What are the ways we can increase blood supply to the myocardium?
Increasing O2 supply and decrease O2 demand (affected by heart rate and contractility)
What are some indications of nitrates?
Angina (prophylaxis for chronic stable exertional angina, increase in effort tolerance - long-acting nitrates. Relief of acute anginal pain.
ACS, Arterial hypertension and heart failure.
What are some effects of nitric oxide in vascular dysfunction?
L-arginine eNOS-dependant conversion to NO is impaired. This decreases NO synthesis, which decreases NO-mediated vasorelaxtion. Increased NO degradation by scavenging ROS. ROS with NO forms superoxides that can cause atheroscelrosis.
What is the MOA of nitrates?
Nitrates are metabolised by aldehyde dehydrogenase to form nitric oxide. This increases intracellular cGMP levels. cGMP-dependant protein kinase inhibits inositol triphosphate dependant calcium release. This decreased calcium inhibits myosin light chain kinase which detaches MLC from actin filaments. This causes smooth muscles relaxation and causes vasodilation, platelet disintegration and prevents adhesion.
What are the pharmacokinetics of nitrates?
Nitroglycerin: rapid absorption (1 minute). From sublingual route. Extensive first pass metabolism. More sustained action when applied as a ointment.
Isosorbide mononitrate: no first pass metabolism. Half-life 4-6 hours.
Isosorbide dinitrate: good absoprtion, food reduces oral absorption. Extensive first pass hepatic metabolism.
How do we overcome tolerance to nitrates?
Avoid use of high doses, a nitrate free period of 8-12 hours. Continuous IV infusion of nitroglycerin should be avoided.
What are side effects of nitrates?
Tachycardia, postural hypotension, throbbing headaches, dizziness and weakness, nausea and vomiting.
