Pharmacology of CVS - Angina Flashcards
What is angina?
→ Angina is chest pain or pressure when there is a build up of lactic acid during anaerobic respiration
→ due to not enough blood flow to the heart muscle.
Signal via cardiac nerves and upper posterior nerve roots
What are the symptoms of angina pectoris?
→crushing chest pain, also in the jaw, shoulders, arms, etc.
→shortness of breath
→sweating
→ nausea
How many people suffer from angina pectoris in the UK and what is the prevelance?
→2 million sufferers in the UK
2-4% of Western countries
What are the symptoms of typical angina?
→ typical angina
→ substernal chest discomfort of characteristic quality + duration
→provoked by exertion or emotional stress
→symptoms attributed to myocardial ischemia
→short duration radiation to left arm, neck, jaw. Lasts 2-5 minutes
How can typical angina be relieved?
→ rest + medications
Why is stable angina classified as predictable?
→ recurrent episodes have a similar onset pattern, duration + intensity
What does a coronary spasm lead to? (Prinzmetal angina)
Caused by drugs like cocaine.
→ Critical reduction in blood flow so oxygen supply is inadequate
What is supply ischaemia?
→ When there is decreased coronary blood flow due to vasospasm or a thrombus / blockage
What is demand ischaemia?
→Increased demand for oxygen in the heart muscle
→ Due to fixed stenosis
What are precipitating factors for angina?
→ Increased sympathetic activity
→ Increased contractility - exercise, emotion or stress
→ Increased vasoconstriction
What are the three ways to treat angina?
→ Improving perfusion
→ Reducing metabolic demand
→ Prevention
How do you improve perfusion with angina?
→ Increase oxygen delivery by improving coronary blood flow
→ coronary vasodilators
How do you reduce metabolic demand with angina?
→ Decrease cardiac work
→ Using vasodilators ( reduce afterload + preload)
→ Using cardiac depressants ( reduce HR + contractility)
How do you prevent angina?
→ Prophylactic to reduce risk of episodes → lipid lowering → anti-coagulants → Fibrinolytic →anti-platelet
What does clot formation lead to? (unstable angina)
→ Occludes the artery
→ There is a critical reduction in blood flow so oxygen supply is inadequate even at rest
What does a narrowed coronary artery lumen lead to? (stable angina)
→ Restricted blood flow to area of the myocardium it supplies
→ Oxygen is receives is insufficient when the heart has to work harder
→ Anaerobic respiration
→Pain
How is preload reduced by giving nitrates?
→ Peripheral venodilation
→ Decreases intraventricular pressure
→ Cardiac preload decreases
→reduced oxygen demand by decreasing the work of the heart
How is afterload reduced by giving nitrates?
→ Arterial dilation
→ Decreases total TPR
→ Reduces afterload
→reduced oxygen demand
What are adverse effects of nitrates and why?
→ Headache, flushing, syncope ( arterial dilation)
→ Postural hypotension ( venodilation)
→ Reflex tachycardia ( sympathetic outflow)
How does nitric oxide work?
→NO synthase makes NO from L-arginine
→ NO activates guanylyl cyclase
→ It activates cGMP
→ Activates protein kinase G
→cGMP converted to GMP by phosphodiesterase type 5
How does PKG reduce smooth muscle tone?
→ Increase uptake of Ca2+
→ Myosin light chain dephosphorylation
→ Activates K+ channels causing hyperpolarization + closing VGCC
What do organic nitrates mimic?
→ Mimic the effects of endogenous nitric oxide
How do beta blockers reduce CO and lower blood pressure?
→ Inhibit funny current in the SA node
→ Reduce the force of cardiac contractions- improves exercise tolerance
act on beta 1 receptors in SA node and ventricular myocytes
How do beta blockers slow heart rate?
→ Lengthens diastole and gives more time for coronary perfusion
→ Improves myocardial oxygen supply
What are the contraindications and adverse side effects of beta blockers?
ASTHMA
→ Blocking beta two can cause constriction + bronchospasm
HEART BLOCK
→ AV conduction is poor can block AV node
→side effects: fatigue, bronchospasm, postural hypotension
How do calcium blockers reduce contractility?
→ Reduce Ca2+ entry into the myocytes
How do calcium blockers cause more coronary blood flow?
→ Direct coronary vasodilatation
What is the effect of reducing TPR/ BP/ Afterload due to calcium channel blockers?
→ Heart works less hard to eject blood
How do Ca2+ blockers cause less O2 consumption?
→ Reducing the force of contraction
What are adverse effects of Ca2+ blockers?
→ Lower limb oedema- increased capillary pressure in lower limbs
→ Flushing + headache- excess vasodilation
→ Reflex tachycardia
What is a risk of using Ca2+ blockers?
→ Blocking Ca2+ channels in the heart can change electrical conduction + contractility
What is the mechanism of action of Ca2+ blockers in ventricular myocytes and vascular smooth muscle?
→ Reduce Ca2+ influx through voltage gated L-type channels in smooth + cardiac muscle
→In ventricular myocytes, they block the beta 1 receptors- reduced PKA, reduced CICR, reduced contractility
→In vascular smooth muscle, they block alpha 1 receptors, PLC, PKC, Na channels, reduced vasoconstriction
What are three drugs given when Ca2+ blockers don’t work?
→ Nicorandil, ivabradine and ranolazine
What are three prophylactic drugs for angina?
→ aspirin - reduces platelet aggregation
→ clopidogrel - reduces platelet aggregation
→ Statins - reduces cholesterol
What are the characteristics of unstable angina?
→unpredictable
→pain symptoms more severe, and lasts longer
→happens at rest with little exertion or trigger
→not relieved by rest and medications
→serious, emergency
Which type of angina is common young people?
Prinzmetal angina
→cocaine
What are the symptoms and how can atypical angina be relieved?
→heart burn, Raynaud’s phenomenon, sweating, dizziness
→medication
How does microvascular angina arise?
→impaired vasodilation in coronary circulation/ increased constriction
→reduced coronary perfusion
→pain
→patients do not have obstructive coronary artery disease
Why is microvascular angina hard to diagnose and how is it done?
→because coronary microvasculature cannot be directly imaged in vivo
→positron emission tomography or cardiac magnetic resonance are used to assess coronary microvasculature blood flow
What are some prophylactic drugs for angina?
→Aspirin- inhibits COX which reduced thromboxane A2, and platelet aggregation(GPIIb/IIa expression)- reduces thrombosis
→Clopidogrel- inhibits ADP receptor on platelets reduces aggregation, reduces thrombosis
→ Statins- HMG Co-a reductase inhibitor- reduced cholesterol levels
How does nicorandil work?
→K+ channel, hyperpolarisation- VGCC reduced and Ca2+ entry reduced so coronary vasodilation.
Has a nitrate moiety so there’s venodilation via NO generation
How does ivabradine work?
specific inhibitor of funny cuurent in SA nose- slows heart rate
→decrease pacemaker potential frequency- decreases heart rate to reduce myocardial O2 demand
How does ranolazine work?
→late Na+ inhibitor- reduces Ca2+ in ischaemic myocardial cells which reduces oxygen demand
→reduce compression of small intramyocardial coronary vessels- improves myocardial perfusion
Examples of beta blockers, nitrates and Ca2+ channel blockers
BETA BLOCKERS:
→atenolol
→bisoprolol
NITRATES:
→glyceryl trinitrate, isosorbide mononitrate
Ca2+ CHANNEL BLOCKERS:
→dihydropyridines(vascular)- amplodipine, nifedipine
→benzothiazepines(cardiac) - verapamil
→diphenylalkyamines(both)- diltiazem
What is the first line of action in symptom control?
→ GTN +
→beta blocker or Ca2+ channel blocker
What is the second line of treatment in symptom control?
→dihydropyridine calcium channel blocker to beta-blocker
→nicorandil, ivabradine, ranolazine
What are the primary prevention methods?
→lifestyle advice →aspirin daily →lipid lowering therapy →ACE inhibitor →angiotensin II receptor agonist
