Drugs Used in the Treatment of Ichaemic Heart Disease Flashcards
What two things can ischaemic heart disease lead to
Angina and myocardial infarction
In what circumstances does angina arise from ischaemic heart disease
When there is a stable plaque that causes narrowing of the coronary arteries.
In what circumstances does myocardial infarction arise from ischaemic heart disease
When there is an unstable plaque and thrombus formation.
What does vascular endothelium regulate
Smooth muscle tone, permeability and leukocyte adhesion, platelet aggregation and tendency for thrombus formation.
What are four causes of endothelial dysfunction
- elevated and modified LDL, e.g. in hypercholesterolaemia
- Oxygen free radicals caused by smoking, hypertension and activated inflammatory cells
- infectious micro-organisms
- physical damage by turbulent flow.
What are foam cells
Macrophages that take up low density lipoprotiein oxidised by the interaction with oxygen free radicals. They are a component of fatty streaks.
What are the three methods of management of coronary artery disease
- Reduce risk factors for development
- Pharmacological measures
- Surgical intervention.
What risk factors for the development of coronary artery disease can be reduced
Diet, smoking, blood pressure, diabetes
Why are women more protected from endothelial dysfunction until menopause
Due to the presence of oestrogen.
What pharmalogical measures can be used to prevent the development of coronary artery disease
The use of lipid lowering drugs such as statins and fibrates
What are two examples of lipid lowering drugs
Statins and fibrates
What pharmacological measures can be used to treat the angina symptoms of coronary artery disease
Use of nitrates which are cleaved to produce nitric oxide - a potent vasodilator.
What pharmacological measures can be used to prevent thrombosis and myocardial infarction in coronary artery disease
Anti-platelet and anti-coagulant drugs.
What surgical measures can be used in the management of coronary artery disease
- Balloon angioplasty for plaque removal
- Stenting
- Coronary artery bypass grafting.
What are the risk factors for coronary artery disease
- Genetic
- Smoking
- Diet
- Hyperlipidaemia
- Hypertension
- Diabetes
- Age
- Male sex.
What is an example of a fibrate
Benzafibrate
What do fibrates do
They are lipid lowering drugs. They decrease circulating VLDL and triglyceride and increase HDL.
What do statins do
They are lipid lowering drugs which lower LDL levels. They are HMG-CoA reductase inhibitors. This is the rate determining step of cholesterol formation.
What is an example of a statin
Simvastatin
What is the mechanism of action of statins as HMG-CoA reductase inhibitors
LDL is formed by cholesterol which is synthesised in the liver. HMG-CoA reductase is important in the rate limiting step of this process. Statins block the formation of LDL by inhibiting the HMG-CoA reductase enzyme.
What is mevalonate
A precursor for cholesterol
As well as inhibiting the formation of LDL, what else do statins do
They increase the expression of LDL receptors to increase the uptake of LDL.
What is angina
Intermittent chest pain caused by mismatch between demand of oxygen by the heart and supply of oxygen to the heart.
How is angina managed
By reducing the demand on the heart or increasing the oxygen supply to the heart to reduce the imbalance between supply and demand.
What is used to treat angina during an acute attack
- Rest
- Nitrates
What is an example of a nitrate used for treatment of an acute angina attack
Glyceryl trinitrate
What types of drugs are used for prophylaxis of angina to reduce the likelihood of an attack
- Beta adrenoceptor antagonists
- Calcium antagonists
- KATP channel opener
- Longer lasting nitrate
What is an example of a beta adrenocepttor antagonist used for prophylaxis of angina
Atenolol
What is an example of a calcium antagonist used for prophylaxis of angina
Nifedipine
What are two examples of a KATP channel openers used for prophylaxis of angina
Nicorandil and ivabradine
What is an example of a longer lasting nitrate used in prophylaxis of angina
Isosorbide dinitrate
What is the mechanism of action of nitrates
Nitric oxide is released which acts to bring about the conversion of GTP to cGMP at guanylate cyclase. This reduces the availability of calcium ions and causes relaxation of smooth muscle.
What route is used to take nitrates
The parenteral route for rapid absorption.
Why are nitrates effective
They dilate veins, decrease venous return, decreasing the volume of blood returned to the heart and decreasing the strain on the heart. They also decrease peripheral resistance, reducing demand.
What is nicorandil
A potassium channel opener (KATP opener)
What is the mechanism of action of nicorandil
It increases the action of ATP sensitive channels in smooth muscle cells which prevents contraction and relaxes the muscle. This reduces the load on the heart.
Where do beta adrenoceptor blockers act
Beta adrenoceptor blockers block beta-1 receptors in the heart and also in the kidney.
What is the mechanism of action of beta-adrenoceptor blockers
On cardiac beta 1 adrenoceptors, beta blockers reduce heart rate and therefor oxygen demand. On renal beta 1 adrenoceptors, beta blockers reduce blood volume by reducing renin release and the activation of RAAS. Resistance in the arterioles and therefore preload is reduced so oxygen demand is reduced.
What is ivabradine
It is an ATP sensitive potassium channel opener
What is the mechanism of action of ivabradine
It opens ATP sensitive calcium channels, allowing an inflex of potassium ions and reducing the rate of spontaneous depolarisation during action potential generation in SA node cells. This reduced heart rate and O2 demand.
What are nifedipine and dilthiazem
Calcium antagonists
What is the action of calcium antagonists
Calcium antagonists prevent the opening of voltage dependent calcium ion channels. This prevents the re-entry of calcium into the cardiac muscle so this reduces the availability of calcium ions for contractility. This reduces the force of contraction and oxygen demand.
What are anti-thrombotic drugs used for
To reduce the risk of thrombus formation if an atherosclerotic plaque ruptures.
What two drugs are usually used in anti-thrombotic therapy
Anti-coagulants and anti-platelets.
What happens if there is damage to the endothelium
There is collagen in the sub-endothelial layer which is exposed and triggers the aggregation of platelets to the area of damage.
What stabilises the thrombus
Fibrin strands.
What happens to platelets when they are activated
They change shape and degranulate to release ADP and ATP.
What are two types of anti-platelet drugs
Cyclooxygenase inhibitors, P2Y12 inhibitors and thrombin receptor antagonists.
What is an example of a cyclooxygenase
Aspirin
What does aspirin do
It irreversibly inhibits COX, and prevents the formation of TxA2 and platelet activation.
What are the roles of cyclooxygenase in thrombosis
- To convert arachidonic acid into prostaglandin precursors
- To produce prostacyclin which is responsible for producing mucus in the stomach
Why should aspirin not be used in people with decreased mucus in their stomach
Because aspirin is a cyclooxygenase inhibitor and cyclooxygenase is responsible for the production of prostacyclins which produce mucus in the stomach.
What are two examples of P2Y12 inhibiors
Clopidogrel and ticagrelor
What do P2Y12 inhibitors do
Blocks the effect of ADP and prevents platelet activation.
What is the role of P2Y12 in the normal production of a thrombus
P2Y12 receptors are present on the surface of platelets and ATP acts on these to increase the activity of calcium and activate the platelets.
What happens if P2Y12 receptors are inhibited
The platelets are not activated so there is less platelet activity and thrombus formation decreases.
What is an example of a thrombin receptor antagonist
Voripaxar
What do thrombin receptor antagonists do
Prevent the activation of PAR-1 receptors on platelets.
What is the risk associated with anti-thrombotic drugs
Bleeding.
What is ATIII
Antithrombin III
What is the role of ATIII
The body’s own anti-thrombotic mechanism. It prevents the formation of fibrin which binds to receptors on platelets and stabilises thrombi.
What is the role of heparin
To bind to antithrombin III and promote its anti-thrombotic action
What is the role of anti-coagulant drugs
To prevent the formation of fibrin which stabilises the platelet plug
What are three examples of anti-coagulant drugs
Heparin, warfarin and rivaroxaban
Which anti-coagulant drug can be given intravenously
Heparin
Which anti-coagulant drugs can be given orally
Warfarin and rivaroxaban.
What is the mechanism of action of rivaroxaban
It is a factor 10a inhibitor which inhibits the formation of thrombi as it stops the conversion of prothrombin to thrombin and therefore fibrinogen to fibrin.
What is the mechanism of action of warfarin
Warfarin is a vitamin K inhibitor. Some of the products of oxidised vitamin K are used in the clotting cascade - factors 2,7,9 and 10 so warfarin inhibits the formation of these factors and stops the progression of the clotting cascade.
What are the negative aspects of the use of warfarin
- It has a narrow therapeutic index
- There is a high risk of bleeding
- Blood levels must be checked regularly
What are the consequences of MI
- Ischaemia
- Cell death
- Heart failure.
