Clinical Pharmacology of Stable Coronary Artery Disease Flashcards
What is the most common cause of death in pre-retirement males ?
Acute coronary syndrome:
- MI- STEMI or NSTEMI
- Unstable angina
Stable coronary artery disease
- Angina
- Silent ischaemiaWhat is the epidemiology of angina ?
ISD data suggests 34.3/1000 for men ages 65-74 and 59.7/1000 for men 7yrs and over live with angina
For women in the same age groups: 23.3 and 38.5/1000
What are the risk factors for angina ?
Hypertension Smoking Hyperlipidaemia Hyperglycaemia Previous CAD Existing PVD Male Post-menopausal females
How does stable coronary artery disease arise ?
As a result of a mismatch between myocardial blood/oxygen supply and demand
What is demand ischaemia ?
Ischaemia during stress (emotional or physical)
What is supply ischaemia ?
Ischaemia at rest
What are the determinants of demand ?
HR
Systolic BP
Myocardial wall stress
Myocardial contractility
What are the determinants of supply ?
Coronary artery diameter and tone
Collateral blood flow
Perfusion pressure
HR (duration of diastole)
How do drugs help correct the imbalance ?
Decreasing myocardial oxygen demand by reducing cardiac workload
Reduce HR
Reduces myocardial contractility
Reduce afterload
Increasing the supply of O2 to iscahemic myocardium
What is the purpose of drug treatment ?
Relieve symptoms Halt the disease process Regression of the disease process Prevent myocardial infarction Prevent death
What rate limiting drugs can be used for SCAD ?
B-blockers
Ca channel blockers
Ivabradine
What are the vasodilating drugs used for SCAD ?
Ca channel blockers
Sodium current inhibitor
What other drugs are used ?
Potassium channel activators - nicorandil Sodium current inhibitor - ranolazine Aspirin/clopidogrel/ticagrelor Cholesterol lowering agents: - HMG CoA reductase inhibitors - Fibrates
What are B-blockers ?
Beta blockers are reversible antagonists of the B1 and B2 receptors
Block the sympathetic system
What 3 determinants of myocardial O2 demand does B-blockers decrease ?
HR
Contractility
Systolic wall tension
What does B-blockers reduce ?
HR
Force of contraction
BP
What will B-blockers increase ?
Beta blockers 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 are the contraindications of B-blockers ?
Asthma Peripheral Vascular Disease - Relative contraindication Raynaud's Syndrome Heart failure Those patients who are dependent on sympathetic drive Existing Bradycardia / Heart block
What are the adverse drug reactions to B-blockers ?
Tiredness Fatigue Lethargy Impotence Bradycardia Bronchospasm Rebound- sudden cessation of beta blocker therapy may precipitate MI
What are the drug-drug interactions of B-blockers ?
Primarily Pharmacodynamic
Hypotension when used with other hypotensive agents
Bradycardia when used with other rate limiting drugs such as verapamil or diltiazem
Cardiac failure when used with negatively inotropic agents such as verapamil, diltiazem
Exaggerate and mask hypoglycaemic actions of insulin or oral hypoglycaemics
What are examples of B-blockers ?
Bisoprolol
Atenolol
What do calcium channel blockers do ?
Prevent calcium influx into myocytes and smooth muscle lining arteries and arterioles by blocking the L-Type calcium channel
What do the rate limiting CCBs do ?
Reduce heart rate and force of contraction
What are some examples of rate limiting CCBs ?
Diltiazem
Verapamil
What do the vasodilating CCBs do ?
Reduce BP and afterload
What is an example of vasodilating CCBs ?
Amlodipine
What are the contraindications of CCBs ?
NEVER USE NIFEDIPINE IMMEDIATE RELEASE may precipitate acute MI or stroke
Post- MI- may increase morbidity and mortality in patients with impaired LV function
Unstable angina- Evidence that dihydropyridines may increase infarction rate and death in the unstable pateint
What are the adverse drug reactions to CCBs ?
Ankle oedema
Headache
Flushing
Palpitations
What nitro-vasodilators can be used for angina ?
Glyceryl trinitrate (GTN)
- Sublingual, buccal, transdermal
Isosorbide mononitrate
- Sustained release formulation, tablets
Isosorbide dinitrate
- Sustained release formulation, tablets
What is the pharmacology of nitro-vasodilators ?
Relax almost all smooth muscle by releasing NO which stimulates the production of cGMP which produces smooth muscle relaxation
Reduce preload and afterload
How can nitrates relieve angina ?
Arteriolar dilatation and so reducing cardiac afterload and thus myocardial work and oxygen demand
Peripheral venodilatation and so reducing venous return, cardiac preload and thus myocardial workload
Relieving coronary vasospasm
How fast can a tolerance to nitrates develop ?
Rapidly
Overcome this by gibing asymmetric doses of nitrates 8am and 2pm
What are the adverse drug reactions to nitrates ?
Headache- increase dose slowly
Hypotension- GTN syncope
What is an example of a potassium channel activator ?
Nicorandil
What is the mechanism of K channel activators ?
Activates ATP sensitive potassium channels allowing entry of potassium into cardiac myocytes and inhibiting calcium influx and so has a negative inotropic action
Induce relaxation of vascular smooth muscle and has coronary vasodilator properties
What is an example of a selective sinus node If inhibitor ?
Ivabradine
What is the mechanism of Ivabradine ?
Inhibits the If pacemaker current in the SAN and reduces HR
Reduced HR = reduced myocardial O2 demand
Used for the symptomatic treatment of chronic stable angina in adults with normal sinus rhythm and heart rate ≥ 70 bpm
What are the indications for ivabradine ?
Adults unable to tolerate or with a contra-indication to the use of beta-blockers
in combination with beta-blockers in patients inadequately controlled with an optimal beta-blocker dose
What does ivabradine reduce ?
Fatal and nonfatal MIs
What is an example of late Na+ current inhibitor ?
Ranolazine
What is the mechanism of Ranolazine ?
Inhibits persistent or late inward sodium current (INa) in heart muscle.
This leads to reduction in intracellular calcium levels
This results in reduced heart wall tension and reduced oxygen requirements
What are the drug interactions of Ranolazine ?
Ranolazine is metabolised CYP3A4
It also inhibits CYP2D6
Do not use with clarithromycin, ketoconazole
What antiplatelet therapy can be used ?
Aspirin
Clopidogrel
Ticagrelor
Prasugrel
What do antiplatelets agents do ?
Prevent the formation of platelet aggregates which are important in the pathogenesis of angina, unstable angina and acute MI
What does aspirin inhibit ?
Potent inhibitor of platelet thromboxane production which stimulates platelet aggregation
What drugs belong to the P2Y12 inhibitors ?
Clopidogrel
Ticagrelor
Prasugrel
What do the P2Y12 inhibitors block ?
Block the platelet P2Y12 receptor, which plays a key role in platelet activation and the amplification of arterial thrombus formation
What should be used in pateints with a high or moderate risk of ischaemic events who do not have a high risk of bleeding ?
Dual antiplatelet therapy
What is the most commonest cause of admission with GI bleed ?
Aspirin
What are examples of cholesterol lowering agents- statins ?
Atorvastatin
Simvastatin
