Pharmacology of the CVS Flashcards
Define angina pectoris
To choke the chest
Symptoms of angina pectoris
Feeling of cramping and severe constriction in the chest, referred pain, jaw, shoulders, neck and arms, may be associated with shortness of breath, sweating, nausea and heart rate
Describe angina pectoris symptoms develop
Myocardial ischaemia causes the release of compounds including potassium, lactate, adenosine, bradykinin and prostaglandins
This activates myocardial pain receptors
This causes sensory neurons to send a signal to the brain, causing pain perception
Describe the traditional classification of types of angina based on chest pain symptoms
Typical angina - Substernal chest discomfort of characteristic quality and duration
Provoked by exertion or emotional stress
Relieved by rest and/or nitrates within minutes
Atypical angina - Presentation of two of the above characteristics
Non-anginal - Presentation of only one or none of the chest pain characteristics
Describe the new classification of types of angina
Stable angina - Myocardial ischemia, coronary artery disease
Unstable angina - DUe to complications from stable angina
Prinzmetal angina - Usually due to a spasm in the coronary arteries, happens in cycles
Microvascular angina - Patients have angina symptoms, no evidence of CAD, normal coronary angiogram
Describe the aetiology (causes) of stable angina
Narrowed coronary artery lumen -> Restricted blood flow to area of myocardium it supplies -> Oxygen received is insufficient, heart has to work harder -> Anaerobic respiration -> Pain
Describe the characteristics of stable angina
Predictable, short duration radiation to left arm, neck, jaw or back, precipitaed by exertion, increased cardiac demand, warning for heart attack/stroke, relived by rest/medication
Describe the aetiology of unstable angina
Clot formation occludes artery -> Critical reduction in blood flow so that oxygen supply is inadequate even at rest -> Pain
Describe characteristics of unstable angina
Unpredictable, pain symptoms more severe and last longer, happens at rest with little exertion, no trigger, not relieved by rest/meds, progression from stable angina, serious emergency
Describe the aetiology of prinzmetal angina
Coronary spasm (e.g. by cocaine) -> Critical reduction in blood flow so that oxygen supply is inadequate -> Pain
Describe characteristics of prinzmetal angina
Occurs while resting and during night/early morning, episodes last 5-15 mins, rare (1 in 100 cases of angina), younger patients, very painful, pain from chest to head/shoulder/arm, heart burn, nausea, sweating, dizziness, palpitation, migraines, Raynaud’s phenomenon, spasm in coronary arteries, take medication
Describe aetiology of microvascular angina
Impaired coronary circulation -> Reduced coronary perfusion -> Pain
Describe characteristics of microvascular angina
Impaired coronary circulation from abnormal vasodilation/increased vasoconstriction, patients have no obstructive coronary artery disease, occurs with exertion and at rest, hard to diagnose due to imaging, PET/CMR used to assess blood flow, treatment vary depending on cause
Describe the strategies for treating angina
To improve perfusion -> Increase oxygen delivery by improving coronary blood flow -> Treat with coronary vasodilators
To reduce metabolic demand -> Reduce oxygen demand by decreasing cardiac work -> Vasodilators and cardiac depressants
Prevention of angina -> Prophylactic to reduce risk of subsequent episodes -> Use lipid lowering drugs, anti-coagulants, fibrinolytic, anti-platelet
Describe effects of nitrate on patients with angina
E.g. GTN, isosorbide mononitrate
Effects: Peripheral venodilation -> Decrease intraventricular pressure -> Decrease cardiac pressure
Arterial dilation -> Decrease TPR -> Reduce afterload
Both actions lower oxygen demand by decreasing the work of the heart.
Adverse effects
Throbbing headache, flushing and syncope (arterial dilation), postural hypotension (venodilation), reflex tachycardia (sympathetic outflow)
Describe mechanism of nitrate
Endogenous NO synthesised through endothelium NO synthase and L-arginine.
NO donors cause dilatation of smooth muscle. NO -> Guanylyl cyclase -> cGMP -> Protein kinase G
PKG reduces smooth muscle tone -> Myosin light chain dephosphorylation -> Increase uptake of Ca2+ by SR, causing a decrease in cytoplasmic levels -> Activate K+ channels causing hyperpolarisation and closing VGCC
Describe beta-blockers as angina treatment
Ex. Atenolol, bisoprolol
Effects:
1. Inhibits If pacemaker current in the sinoatrial node -> Decrease heart rate
2. Reduce the force of cardiac contractions -> Improves exercise tolerance
3. Both of these actions reduce cardiac output and lower blood pressure
Slower heart rate -> Lengthens diastole and gives more time for coronary perfusion, improving myocardial oxygen supply
Adverse effects: Bronchospasm, fatigue, postural hypotension
Contraindication -> Asthma - Block beta2 receptor can cause constriction and bronchospasm, heart block where atrial-ventricle conduction is poor - may block AV node
Describe mechanism of action for beta blockers
Reduces sympathetic activity of noradrenaline and adrenaline on beta1 adrenoceptors in heart
Describe Ca2+ channel blockers as angina treatment
Ex. dihydropyridine (Vascular) - amplodipine, nifedipine, benzothiazepines - Verapamil, diphenylalkyamines - Diltiazem
Effects: Reduce Ca2+ entry into cardiac myocytes -> Reducing contractility
Direct coronary vasodilatation -> More coronary blood flow
Reduced TPR / BP / afterload -> Heart works less hard to eject blood
Reduce force of contraction -> less oxygen consumption
Adverse effects - Lower limb oedema (increased capillary pressure)
Flushing and headache (excess vasodilatation)
Reflex tachycardia: vasodilatation - increased sympathetic activity
Caution
Blocking Ca2+ channels in the heart may alter electrical conduction and contractility
Describe Ca2+ channel blocker mechanism of action
Reduce Ca2+ influx through voltage-gated L-type Ca2+ channels in smooth and cardiac muscle
State and describe the effects of the prophylactic drugs for angina
Aspirin - Inhibits COX, decrease thromboxane A2 and paltelet aggregation (GPIIb/IIIa expression)
Clopidogrel - Inhibits ADP receptor on platelets, reduces aggregation
Statins - HMG Co-A reductase inhibitor, decrease of cholesterol levels
Describe nicorandil
Potassium channel activator, causes hyperpolarisation so decrease of VGCCs and Ca2+ entry, coronary vasodilatation.
Describe ivabradine
Specific inhibitor of the If current in the sino-atrial node, slow sinus heart rate, decreases pacemaker potential frequency, decreases heart rate to reduce myocardial oxygen demand
Describe ranolazine
Late sodium current inhibitor -> Reduces Ca2+ in ischaemic myocardial cells -> Reduce oxygen demand, reduce compression of small intramyocardial coronary vessels -> improves myocardial perfusino
