SIHD and Angina- Therapy Flashcards
What is included under the umbrella ischaemic heart disease?
- ACS
- Chronic or stable ischaemia
What is included in chronic or stable ischaemia?
- Angina pectoris
- Silent ischaemia
What are the risk factors for ischaemic heart disease?
- Hypertension
- Smoking
- Hyperlipidaemia
- Hyperglycaemia
- Male
- Post-menopausal females
What is the purpose of drug treatment for ischaemic heart disease?
- Relieve symptoms
- Halt the disease process
- Regression of the disease process
- Prevent MI
- Prevent death
What marks the start of hyperlipidaemia?
Atherosclerosis
What is hyperlipidaemia?
- Disease of the muscular arteries
- Progressive deposition of cholesterol esters
What vessels are affected by hyperlipidaemia?
- Coronary arteries
- Cerebral arteries
How do atherosclerotic lesions start?
- As fatty streaks
- Subendothelial accumulation of large foam cells (derived from macrophages plus SM cells) filled with lipid
What are fibrous plaques?
- More advanced than fatty streaks and the cause of disease
- Develop from fatty streaks
- Projects into arterial lumen
- Reduce blood flow
Where do most atherosclerotic changes occur?
- In the intimal layer
- Accumulation of monocytes. lymphocytes, foam cells and connective tissue
What is the origin of most foam cells?
Smooth muscle
What is the main structure of an atheroma?
- Necrotic core
- Fibrous cap
What does stable IHD arise as a result of?
Mismatch between myocardial blood/oxygen supply and demand
What may precipitate an angina attack?
- Any stress which increases cardiac work and myocardial oxygen demand
- Anything which increases heart rate, stroke volume or blood pressure
What is demand ischemia?
Ischaemia during stress (physical/emotional)
What are the determinants of demand ischaemia?
- Heart rate
- Systolic blood pressure
- Myocardial wall stress
- Myocardial contractility
What is supply ischaemia?
Ischaemia at rest
What are the determinants of supply ischaemia?
- Coronary artery diameter and tone
- Collateral blood flow
- Perfusion pressure
- Heart rate (duration of diastole)
What is the common pathology of ischaemic heart disease?
-Atherosclerosis
Type III atherosclerotic lesion
Preatheroma
Type IV atherosclerotic lesion
Atheroma
Type V atherosclerotic lesion
Fibroatheroma
Type VI atherosclerotic lesion
Complicated lesion
How can drugs help in IHD?
- Decreasing myocardial oxygen demand by reducing cardiac workload
- Increasing the supply of oxygen to ischaemic myocardium
How can cardiac workload be reduced?
- Reduce heart rate
- Reduce myocardial contractility
- Reduce afterload
What is the drug therapy for IHD?
- B-blockers
- Ivabridine
- Calcium channel blockers
- Nitrates
- Potassium channel openers
- Aspirin/clopidogrel/ticagrelor
- Cholesterol lowering agents
What drugs are rate limiting?
- B-blockers
- Ivabridine
- Calcium channel blockers
What drugs are vasodilators?
- Calcium channel blockers
- Nitrates
What drugs are cholesterol lowering agents?
- HMG CoA reductase inhibitors
- Fibrates
Give 2 examples of B blockers.
- Bisoprolol
- Atenolol
What are B blockers?
- Reversible antagonists of the B1 and B2 receptors
- Newer drugs are cardioselective acting primarily on the B1 receptors
- These agents block the physiological responses to adrenaline and noradrenaline
What are the 3 major determinant of myocardial oxygen demand that B blockers decrease?
- Heart rate
- Contractility
- Systolic wall tension
What do B blockers allow?
Improved perfusion of the subendocardium by increasing diastolic perfusion time
What affect for B blockers have on the heart?
- Decrease heart rate
- Decrease the force of myocardial contraction
- Decrease cardiac output
- Decrease the velocity of contraction
- Decrease blood pressure
- Protect cardiomyocytes from oxygen free radicals formed during ischaemic episodes
What do B blockers do by reducing HR, force of contraction and BP?
Increase the exercise threshold at which angina occurs and so move the balance point at which the demand for oxygen outstrips the supply of oxygenated blood
What is rebound phenomena?
Sudden cessation of B blocker therapy may precipitate MI
Who is at risk of rebound phenomena?
Patients with angina and men over 50 receiving B blockers for other reasons
What are the contraindications for B blockers?
- Asthma
- Peripheral vascular disease
- Raynauds syndrome
- Heart failure
- Bradycardia/ heart block
What adverse drug reactions can occur with B blockers?
- Tiredness/fatigue
- Lethargy
- Impotence
- Bradycardia
- Bronchospasm
- Rebound
What drug-drug interactions can occur with B blockers?
- Primary pharmacodynamics
- Hypotension: hypotensive agents
- Bradycardia: verapamil, diltiazem
- Cardiac failure: negatively inotropic agents
- Exaggerate and mask hypoglycaemic actions of insulin
Give 3 examples of calcium channel blockers.
- Diltiazem
- Verapamil
- Amlodipine
What do calcium channel blockers do?
Prevent calcium influx into myocytes and smooth muscle lining arteries and arterioles by blocking the L-type calcium channels
What CCBs are rate limiting?
Diltiazem and verapamil reduce heart rate and force of contraction
What CCBs are vasodilating?
Nifedipine or amlodipine may produce a reflex tachycardia
How do CCBs reduce myocardial work load?
Reduce vascular tone and so produce vasodilation and reduce afterload
How do CCBs reduce myocardial oxygen requirements?
Rate limiting CCBs reduce the heart rate and force of myocardial contraction
What affect can CCBs have on coronary vessels?
May produce coronary vasodilation
What should you never use CCB wise?
NEVER USE NIFEDIPINE IMMEDIATE RELEASE
What are the contraindications for CCBs?
- Post MI
- Unstable angina
What may rapidly acting vasodilating CCBs do?
Precipitate acute MI or stroke
Why should CCBs not be given post MI?
May increase the morbidity and mortality in patients with impaired LV function
Why should CCBs not be given to those with unstable angina?
Evidence that dihydropyridines may increase infarction rate and death in the unstable patient
What adverse drug reactions can occur with CCBs?
- Ankle oedema
- Headache
- Flushing
- Palpitation
Give 3 examples of nitrovasodilators.
- Glyceryl trinitrate
- Isosorbide mononitrate
- Isosorbide dinitrate
How can glyceryl trinitrate (GTN) be administered?
- Sublingual
- Buccal
- Transdermal
How can Isosorbide mononitrate be administered?
- Sustained release formulation
- Tablets
How can isosorbide dinitrate be released?
- Sustained release formulation
- Tablets
What is the pharmacology behind nitrovasodilators?
-They relax almost all smooth muscle by releasing NO which then stimulated the release of cGMP which produces smooth muscle relaxation
How do nitrovasodilators reduce myocardial oxygen consumption?
Reduce preload and afterload
How do nitrates relieve angina?
- Arteriolar dilatation and so reduced cardiac afterload and thus myocardial work and oxygen demand
- Peripheral venodilation and so reduces venous return, cardiac preload and thus myocardial work load
- Relieves coronary vasospasm
- Redistributes myocardial blood flow to ischaemic areas of the myocardium
Why is GTN used?
- Rapid treatment of angina pain
- To avoid first pass metabolism
- May be used frequently and prophylactically
Why are oral nitrates used?
- Can be give as a once a day sustained release formulation
- Prophylaxis
Why are IV nitrates used?
Main stay treatment of unstable angina where they are used combination with heparin
How is tolerance to the effects of nitrate therapy overcome?
- Giving asymmetric doses of nitrate 8am and 2pm
- Using a sustained release preparation which incorporates a nitrate free period
What are the adverse drug reactions with nitrates?
- Headaches (increase dose slowly)
- Hypotension producing GTN syncope
Give an example of a potassium channel opener
Nicorandil
What do potassium channel openers do?
- Active silent potassium channels
- The entry of potassium into cardiac myocytes inhibits the calcium influx and so has a negative inotropic action
Why are potassium channel openers now third line treatment?
Can result in Crohns like bowel ulcerations
What is ivbradine?
A selective sinud node I channel inhibitor
What does ivabridine do?
- Slows the diastolic depolarisation slope of the SA node
- Results in a reduction in heart rate
- Reduces heart rate and myocardial oxygen demand
Give an example of an anti-platelet agent.
Low dose aspirin (75-150mg)
What is aspirin
A potent inhibitor of platelet thromboxane production
What does thromboxane stimulate?
Platelet aggregation and vasoconstriction
What is the most common cause of admission with GI bleed?
Low dose aspirin
What does clopidogrel do?
Inhibits ADP receptor activated platelet aggregation
When is clopidogrel used?
- Prevention of atherosclerotic events in PVD
- ACS
How does clopidogrel differ in its incidenc of bleeding to aspirin?
Same incidence of bleeding but possibly lower GI bleeding
Give 3 examples of cholesterol lowering agents.
- Simvastatin
- Pravastatin
- Atorvastatin
What are simvastatin, pravastatin and atorvastatin examples of?
HMG CoA reductase inhibitors
What is the treatment regime for IHD?
- B blocker
- Rate limiting CCB
- Dihydropirinde CCB
- Ivabridine/ranolazine
- Nicorandil
- Aspirin
- Statin
- Long acting nitrate
- Refer to cardiology for work up and possible stenting
What are the indications for ivabridine?
- In adults unable to tolerate or with contr-indications to B blockers
- In combination with B blockers in patients inadequately controlled with an optimal B blocker dose
What is ivabradine used for?
Symptomatic treatment of chronic stable angina in adults with normal sinus rhythm and heart rate >70bpm
Ivabridine is only effective in reducing the incidence of coronary artery disease in who?
Patients with heart rate of 70 bpm or over
