Lecture 12 Ischaemic Heart Disease II Flashcards Preview

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Flashcards in Lecture 12 Ischaemic Heart Disease II Deck (54)
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What are the main aims of angina therapy

To keep the coronary plaques as stable as possible to avoid acute clot blockage and to reduce pain for the patient


What are the two types of approach in treating angina and how do they differ

Symptomatic – Reduce the symptoms by reducing strain on the heart by increasing the vasodilation of the arteries and veins. Prognostic – to improve the outcome for the patient


Give some examples of symptomatic approaches to treating IHD

Nitrates (such as glyceryl trinitrate and isosorbide mononitrate to increase vasodilation. Aspirin and antiplatelet drugs to decrease the chance of thrombotic event. Ca2+ channel blockers and/or K+ channel activators. Morphine to reduce the pain


Which kinds of drugs are used as a prognostic approach in treating IHD

Aspirin statins β blockers and ACE inhibitors


Nitrates are the first line drugs used in angina how are they administered and how do they work

Nitrates are usually administered as a spray sublingually and work on the larger arteries to promote coronary vasodilation


What are the two mechanisms of nitrates

The primary mechanism is to relax vascular smooth muscle but the secondary mechanism acts to reduce cardiac work by a redirection of flow towards the ischaemic areas of heart muscle


Outline the mechanism of action of nitric oxide

NO activates soluble guanylyl cyclase and increases cGMP which activates PKG. PKG then phosphorylates MLCP which dephosphorylates myosin leading to relaxation of smooth muscle.


Outline some of the adverse effects of nitrates

Marked hypotension headaches and tolerance


What causes tolerance in nitrate use

Nitrate tolerance is associated with a depletion of thiol groups (-SH) that are involved in the initial step of de-nitration of nitro-glycerine


Give an example of a short acting nitrate and how it is delivered

Glycerine trinitrate (GTN) is a short acting nitrate that is administered sublingually and is effective within 1-2 minutes. Its duration of effects last around 30mins


Give an example of a longer acting nitrate and how it is delivered

Isosorbide mononitrate is a longer acting nitrate that is orally administered 2x daily


What are Ca2+ channel blockers used in treating IHD

They non-selectively blocks the contraction of vascular smooth muscle by inhibiting L type Ca2+ channels


What are the three classes of Ca2+ channel blocker

Dihydropyridines (amlodipine) phenylalkylamines (verapamil) and benzothiazepines (diltiazem)


Which CCB is cardiac selective



What are the broad side effects of CCB use in IHD

Flushing and headache due to vasodilator action


What usual side effect is seen with verapamil

Verapamil can cause constipation due to effects on gastrointestinal nerves or smooth muscle


What are the main benefits of using aspirin to treat IHD

Aspirin reduces mortality and also the risk of a future heart attack


What class of drugs does aspirin belong to



What is the mechanism of action of aspirin

Aspirin irreversibly acetylates COX enzymes preventing the conversion of arachidonic acid to prostaglandin H2. This in turn prevents the production of thromboxane A2 which stimulates platelet aggregation


How does aspirin mediate its anti-inflammatory effects

Through an inhibition of NFκ-B


Why does the action of aspirin last for a long period of time

Aspirin is known as a suicide inhibitor. Because it forms a covalent bond with COX aspirin binds permanently to the enzyme. Hence the duration of aspirin’s effects depends on ability of the body to synthesise new COX enzymes. Aspirins effects of platelets last even longer as they are enucleate and so can't make any more COX enzyme hence its acts for the lifetime of the platelet which is around 10 days


How is aspirin absorbed and removed from the body

Aspirin is a weak acid and so is protonated in the stomach making it able to cross the mucosa. The majority however is absorbed in the ileum due to the high surface area created by the villi. The majority of the aspirin is hydrolysed in 30mins by esterase’s in the liver (75% metabolised in the liver) but also plasma


What are the side effects of aspirin use

GI bleeding deafness and tinnitus


Give an example of a drug which aspirin can interact with

Aspirin can lead to a massive increase in warfarin levels


Aspirin is an antiplatelet drug what other class of drugs is it often used in combination with in IHD

Anti-coagulant drugs such as heparin


Enoxaparin is another heparin like drug used as an anticoagulant. How does it act

Enoxaparin binds to and potentiates the anticoagulant antithrombin to form a complex that irreversibly inactivates clotting factor Xa.


What is the mechanism of action of K+ channel activators in the treatment of IHD

K+ channel activation leads to K+ efflux and a hyperpolarisation of the membrane potential which in turn acts to decrease Ca2+ levels. This leads to decreased vasoconstriction


Give an example of a K+ channel activator used in IHD and explain how it acts

Nicorandil both acts as an NO donor causing relaxation of the smooth muscle but also activates K+ channels to cause dilation.


What are the main side effects of K+ channel activators

Headaches GI ulceration


What is the main contraindication of K+ channel activators

Phosphodiesterase inhibitors like sildenafil. This is contraindicated as using both can lead to marked hypotension