Pharmacology of the CVS

Question 1

Define angina pectoris

Answer 1

To choke the chest

Question 2

Symptoms of angina pectoris

Answer 2

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

Question 3

Describe angina pectoris symptoms develop

Answer 3

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

Question 4

Describe the traditional classification of types of angina based on chest pain symptoms

Answer 4

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

Question 5

Describe the new classification of types of angina

Answer 5

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

Question 6

Describe the aetiology (causes) of stable angina

Answer 6

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

Question 7

Describe the characteristics of stable angina

Answer 7

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

Question 8

Describe the aetiology of unstable angina

Answer 8

Clot formation occludes artery -> Critical reduction in blood flow so that oxygen supply is inadequate even at rest -> Pain

Question 9

Describe characteristics of unstable angina

Answer 9

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

Question 10

Describe the aetiology of prinzmetal angina

Answer 10

Coronary spasm (e.g. by cocaine) -> Critical reduction in blood flow so that oxygen supply is inadequate -> Pain

Question 11

Describe characteristics of prinzmetal angina

Answer 11

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

Question 12

Describe aetiology of microvascular angina

Answer 12

Impaired coronary circulation -> Reduced coronary perfusion -> Pain

Question 13

Describe characteristics of microvascular angina

Answer 13

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

Question 14

Describe the strategies for treating angina

Answer 14

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

Question 15

Describe effects of nitrate on patients with angina

Answer 15

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)

Question 16

Describe mechanism of nitrate

Answer 16

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

Question 17

Describe beta-blockers as angina treatment

Answer 17

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

Question 18

Describe mechanism of action for beta blockers

Answer 18

Reduces sympathetic activity of noradrenaline and adrenaline on beta1 adrenoceptors in heart

Question 19

Describe Ca2+ channel blockers as angina treatment

Answer 19

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

Question 20

Describe Ca2+ channel blocker mechanism of action

Answer 20

Reduce Ca2+ influx through voltage-gated L-type Ca2+ channels in smooth and cardiac muscle

Question 21

State and describe the effects of the prophylactic drugs for angina

Answer 21

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

Question 22

Describe nicorandil

Answer 22

Potassium channel activator, causes hyperpolarisation so decrease of VGCCs and Ca2+ entry, coronary vasodilatation.

Question 23

Describe ivabradine

Answer 23

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

Question 24

Describe ranolazine

Answer 24

Late sodium current inhibitor -> Reduces Ca2+ in ischaemic myocardial cells -> Reduce oxygen demand, reduce compression of small intramyocardial coronary vessels -> improves myocardial perfusino