L41,42 Background/Pathology IHD

Ischaemic heart disease (IHD) is the same thing as coronary artery disease (CAD) and coronary heart disease (CHD).

Atherosclerosis, a [blank_start]lipid[blank_end] deposition in the subendothelial space, causes IHD. There is endothelial dysfunction with [blank_start]decreased[blank_end] production of NO, less [blank_start]vasodilation[blank_end], increased risk of platelet [blank_start]adhesion[blank_end]. An influx of lipid scavenger cells ([blank_start]macrophages[blank_end]) cause inflammation, calcification and [blank_start]narrowing[blank_end] of the blood vessel by increasing plaque formation.

Atherosclerotic plaque rupture causes a release of [blank_start]tissue[blank_end] factor (TF) and von Willebrand factor (vWF) vWF. More [blank_start]platelets[blank_end] adhere, activate, and aggregate. The coagulation cascade activates resulting in [blank_start]fibrinogen[blank_end] binding platelets to one another causing clot ([blank_start]thrombus[blank_end]) formation.

Which of these is not a risk factor for IHD?

Choose the incorrect statement.

Chronic stable angina is the initial manifestation of IHD in about 50% of patients. It is often caused by obstructive [blank_start]atherosclerotic[blank_end] lesions in the coronary arteries. Vasospasm at the site of an atherosclerotic plaque may further [blank_start]constrict[blank_end] blood flow and contribute to angina. Stable angina is characterised by a plaque with a thick fibrous cap and relatively [blank_start]small[blank_end] lipid core. Patients are generally in no acute distress and describe stable angina pain as a sensation of pressure, heaviness, tightness, or squeezing in the anterior [blank_start]chest[blank_end] area. Pain may radiate to the neck, jaw, shoulder, back, or arm and may be accompanied by dyspnoea, nausea, vomiting, or diaphoresis. Pain lasts a few [blank_start]minutes[blank_end] and is often provoked by [blank_start]exertion[blank_end] (e.g. walking, climbing stairs, gardening) or emotional stress; and relieved within minutes by [blank_start]rest[blank_end] or with sublingual nitroglycerin.

Acute coronary syndrome is the first sign of IHD in about 50% of patients.

Principles of treatment: 1. Angina: Increase myocardial O2 supply (by [blank_start]dilating[blank_end] the cardiac vasculature) and decrease O2 demand (by decreasing heart [blank_start]rate[blank_end], myocardial [blank_start]contractility[blank_end], and afterload) 2. ACS: Re-vascularisation/re-perfusion with mechanical or chemical Tx. - Mechanical: Percutaneous coronary intervention ([blank_start]PCI[blank_end]) = Angiography or [blank_start]angioplasty[blank_end] (using a balloon or a stent), or Coronary artery bypass graft (CABG) - Chemical: Anti-platelets or Anti-coagulants or Fibrinolytics

Match the drug treatment to the purpose for IHD. - Dilate blood vessels and reduce cardiac load: [blank_start]nitrates, CCBs, ACEIs/ARBs, B-blockers[blank_end] - Stabilise atherosclerotic plaques: [blank_start]statins and other lipid-lowering meds[blank_end] - Prevent platelet aggregation: [blank_start]anti-platelets[blank_end] - Prevent propagation of thrombus: [blank_start]anti-coagulants[blank_end] - Break down thrombus: [blank_start]fibrinolytics[blank_end] - Pain relief: [blank_start]morphine[blank_end]

Nitrates are [blank_start]prodrugs[blank_end] that donate nitric oxide, NO. NO increases intracellular [blank_start]cGMP[blank_end], which relaxes [blank_start]smooth[blank_end] muscle cells and causes vasodilation. Frequent or high doses are associated with [blank_start]tolerance[blank_end].

Which of these is not a side effect of nitrates?

Common DHP CCBs are [blank_start]amlodipine and felodipine[blank_end]. Non-DHP CCBS are [blank_start]verapamil and diltiazem[blank_end]. [blank_start]CCBs[blank_end] can cause headache, flushing, dizziness/postural hypotension, peripheral oedema, and constipation. [blank_start]Non-DHP CCBs[blank_end] can cause bradycardia (caution if patient is on a beta blocker).

ACE inhibitors can cause cough due to the build up of bradykinin (which is broken down by ACE).

If we give a β-blocker then we anticipate an increase in HR, and bronchial relaxation.

Anti-platelets: 1. Aspirin: Inhibits [blank_start]COX-1[blank_end] which decreases [blank_start]TxA2[blank_end] meaning less activation and aggregation. 2. Thienopyridines (e.g. [blank_start]clopidogrel, ticagrelor[blank_end]): Inhibits [blank_start]ADP[blank_end] receptor P2Y12 to decrease [blank_start]activation[blank_end] 3. GPIIb/IIIa inhibitors (e.g. [blank_start]abciximab, tirofiban[blank_end]): Inhibit [blank_start]GPIIb/IIIa[blank_end] receptor to decrease [blank_start]aggregation[blank_end]

Anti-coagulants inhibit formation and propagation of thrombi in arteries and veins. In ACS mainly the heparins are used. 1. Unfractionated heparin (UFH) increases the [blank_start]inhibitory[blank_end] action of anti-thrombin (AT) on factors [blank_start]Xa and IIa[blank_end] (and to some extent XIIa, XIa, and IXa). 2. Low molecular weight heparins (LMWHs) increase the inhibitor action of AT on factor [blank_start]Xa >> IIa[blank_end]. LMWH (e.g. enoxaparin) have a [blank_start]smaller[blank_end] molecular weight than UFH, a longer [blank_start]half-life[blank_end], and can be administered [blank_start]subcutaneously[blank_end] (self-administered).

Fibrinolytics break down fibrin stabilised clots. They are used more in pulmonary [blank_start]embolism[blank_end] or stroke than in IHD. Examples are [blank_start]alteplase and reteplase[blank_end], synthetic tissue plasminogen activators ([blank_start]tPAs[blank_end]).