angina Flashcards
angina pectoris: symptoms
Crushing or squeezing sensation in chest with pain radiating into the neck, jaw, & arms (esp. left side)
Shortness of breath; dizziness
Not a disease itself, but a symptom of myocardial ischaemia
Build-up of metabolites (adenosine, CO2, lactate, K+ ions) activates sensory nerves
stable angina
One or more coronary artery has significant structural stenosis (>70%) due to atherosclerosis
Blood flow is sufficient at rest, but O2 demand not met upon exertion
Attacks are predictable (e.g. in response to exercise, stress, cold) and resolve within 5-10 min
Myocardial high-energy phosphates (ATP, PCr) are depleted, which may cause impaired contraction and relaxation
Treat underlying atherosclerosis, e.g. use of statins to lower cholesterol
unstable angina
Attacks are unpredictable, occur at rest, are more intensely painful, and often last >30 min
Caused by coronary artery occlusion due to platelet adhesion to ruptured atherosclerotic plaque
Use of anti-platelet drugs is important
Exacerbated by release of vasoconstricting factors from platelet aggregation and by endothelial damage
An acute coronary syndrome (ACS): part of a spectrum of conditions that result from myocardial ischaemia (e.g. MI)
variant angina
Attacks unpredictable, intensely painful and occur at rest or while sleeping, particularly early in the morning
Caused by transient coronary artery occlusion due to vasospasm
Vasospasm often occurs in vicinity of plaques, but ~30% have no evidence of atherosclerotic lesions
Exacerbated by smoking and cocaine use
Likely caused by endothelial dysfunction / hypersensitivity as a consequence of oxidative stress
dilation of coronary arteries
stable angina: Dilating upstream vessels cannot increase downstream supply (static stenosis)
variant angina: Relieving spasm will increase supply downstream
Can be dangerous in stable and unstable angina due to coronary steal, i.e. where dilatation of vessels diverts more blood to already well perfused areas
In vessel where dilatation cannot occur, less blood is delivered because of the fall in input pressure
myocardial O2 demand
Contraction: 75% mostly on cross-bridge cycling and some on Ca2+ sequestration for relaxation
> 95% of ATP comes from oxidative phosphorylation
⸫ energy use is directly proportional to O2 consumption (myocardial volume oxygen, MVO2)
Do less work (unload the heart)
↓ heart rate
↓ contractility
↓ afterload
↓ preload
=> less O2 demand
dilatation of arteries: vasodilators effectively reduced myocardial 02 demand
decrease in after-load (force against which left ventricle contracts) DECREASE IN:
total peripheral resistance
myocardial work
myocardial O2 demand
dilation of veins: vasodilators effectively reduce myocardial o2 demands
decrease pre-load (diastolic pressure that distends LV)
DECREASE IN:
venous return
stretch of myocardium
sarcomere length = less cross-bridge formation
force of contraction ( Frank-Starling mechanism)
myocardial work
myocardial O2 demand
nitrovasodilators
Most commonly used anti-anginals
Glyceryl trinitrate (GTN): nitroglycerine
Not orally active (destroyed by first-pass metabolism)
Taken as sub-lingual tablet or spray
Rapid onset, but action short-lived (20-30 min)
Uses:
Rapid relief of ongoing anginal attack (all forms)
Prophylaxis in stable angina (i.e. taken before exercise)
Transdermal formulation for sustained prophylaxis
I.V. injection for unstable injection (if sublingual ineffective)
long acting nitrovasodilators
Isosorbide dinitrate (ISDN)
Isosorbide mononitrate (ISMN)
Taken orally (effective by mouth)
Slower in onset, but prolonged duration up to 12 hours
Used for sustained prophylaxis in all forms of angina
nitric oxide
activates soluble guanylate cyclase (sGC)
Cytoplasmic (soluble) enzyme
Receptor on soluble guanylate cyclase contains a ferrous (Fe2+) haem moiety (like O2 binding site of haemoglobin)
NO binds to haem receptor —> enzyme activation
—> converts GTP to cGMP
—>↑ cGMP –> vasodilatation
effect of nitrate at dose used
- primary ventilation
ventilation —-> decrease in central venous pressure—-> decrease in pre-load—-> decreases in cardiac output —–> 1. decrease in cardiac work and therefore—-> relief or angina
or
- reflex tachycardia—-> maintenance of arterial blood pressure
nitrovasodilators side effects
Headache (due to dilatation of cerebral arteries)
Flushing & postural hypotension
Tolerance occurs with continuous use: -
Results in gradual loss of efficacy
Multiple mechanisms: e.g. impaired conversion to NO; increased ROS, which can inactivate NO; over-compensation by RAAS
Long-acting formulations require drug free “washout” periods to restore / maintain efficacy
E.g. stop dosing overnight
other drugs for angina
Ivabradine: blocks pacemaker current in SA node to decrease in HR
Nicorandil: vasodilatation via nitrate-like action + opening of K+ channels
Ranolazine: mechanisms? Efficacy? No effect on haemodynamics
