Pharmacology of stable coronary artery Flashcards
drugs can help by
reducing heart rate, reducing myocardial contractility, afterload
purpose of drug treatment
relieve symptoms, halt the disease process, regression of disease process, prevent myocardial infarction, prevent death
vasodilators
calcium channel blockers, nitrates- oral and sublingual
rate limiting drugs
beta adrenoceptor antagonists, calcium channel blockers, ivabradine
common beta blockers used
bisoprolol, atenolol
beta blockers
reversible antagonists of the B1 and B2 receptors, newer drugs are cardioselective acting primarily on the B1 receptors, block the sympathetic system
beta blockers decrease what three determinants of myocardial oxygen demand
heart rate, contractility, systolic wall tension and also allow improved perfusion of the subendocardium by increasing diastolic perfusion time. this increases the exercise threshold at which angina occurs
contraindications of beta blockers
asthma, peripheral vascular disease (relative contraindication), raynauds syndrome, heart failure (those patients who are dependent on sympathetic drive), existing bradycardia/ heart block
adverse drug reactions of beta blockers
tiredness/ fatigue, lethargy, impotence, bradychardia, bronchospasm, rebound- sudden cessation of beta blocker therapy may precipitate myocardial infarction
drug- drug interactions
primarily pharmacodynamic
what happens when beta blockers with verapamil or diltiazem
bradycardia or cardiac failure
what happens when beta blockers with insulin or oral hypoglycaemics
exaggerate and mask hypoglycaemic actions
what happens when beta blockers with other hypotensive drugs
hypotension
examples of calcium channel blockers
diltiazem, verapamil, amlodipine
calcium channel blockers
prevent calcium influx into myocytes and smooth muscle lining arteries and arterioles by blocking the L type calcium channel
rate limiting calcium channel blockers
CCBs like diltiazem and verapamil reduce heart rate and force of contraction
vasodilators calcium channel blockers
CCBs like amlodipine reduce BP and after load
why never use nifedipine immediate release
may precipitate acute MI or stroke
post MI CCB use
may increase morbidity and mortality in patients with impaired LV function
unstable angina CCB use
evidence that dihydropyridines may increase infarction rate and death in the unstable patient
adverse drug reactions CCBs
ankle oedema, headache, flushing, palpitation
nitrovasodilators examples
glyceryl trinitrate GTN, isosorbide mononitrate, isosorbide dinitrate
how do nitrovasodilators work
relax almost all smooth muscle by releasing NO which then stimulates the production of cGMP which produces smooth muscle relaxation. reduce preload and after load so reduce myocardial oxygen consumption
how do nitrovasodilators relieve angina
arteriolar dilatation and so reducing cardiac after load and thus myocardial work and oxygen demand. peripheral venodilatation and so reducing venous return, cardiac preload and thus myocardial workload
tolerance of nitrate therapy is overcome by
giving asymmetric doses of nitrate 8am and 2pm which incorporates a nitrate free period
adverse reactions to nitrates
headache- increase dose slowly, hypotension- GTN syncope
second line therapy for angina
nicorandil, ivabradine, ranolazine
nicorandil
significant effect. activates ATP sensitive potassium channels allowing entry of potassium into cardiac myocytes and inhibiting calcium influx and so has a negative isotropic action. induces relaxation of vascular smooth muscle and has coronary vasodilator properties
ivabradine
selective sinus node If channel inhibitor, inhibits the If pacemaker current in the sinoatrial node and reduces heart rate. decreases heart rate means decreases myocardial oxygen demand . used for the symptomatic treatment of chronic stable angina in adults with normal sinus rhythm and heart rate greater than 70bpm. reduces myocardial infarction
ranolazine
inhibits persistent or late inward sodium current in heart muscle, this leads to reduction in intracellular calcium levels this results in reduced heart wall tension and reduced oxygen requirements
do not use ranolazine with
clarithromycin, erythromycin or ketoconazole because these antibiotics and antifungal significantly inhibit CYP3A4
antiplatelet therapy
combined with aspirin or P2Y12 inhibitors results in a significant reduction in serious vascular events, non fatal myocardial infarction, non fatal stroke and vascular mortality
anti platelet agents eg aspirin
prevent the formation of platelet aggregates which are important in the pathogenesis of angina, unstable angina and acute MI. aspirin is a potent inhibitor of platelet thromboxane production which stimulates platelet aggregation
P2Y12 inhibitors block what
platelet P2Y receptor which plays a key role in platelet activation and the amplification of arterial thrombus formation
cholesterol lowering agents examples
HMG CoA reductase inhibitors -atorvastatin, simvastatin