Angina treatment Flashcards
Characteristic distribution of angina pain
chest, arm, jaw
brought on by exertion, cold or excitement
chemical factors that cause pain in skeletal muscle may be responsible (K, H, adenosine)
Two types of treatment for angina (general)
reduce chest pain symptoms
prolong survival
What is the coronary window?
during diastole, where the coronary arteries are filing.
The aortic pressure > ventricular pressure.
3 things that shrink the coronary window
- shortening diastole (increased HR)
- increased ventricular end diastolic pressure (eg. progressive decline in ventricular emptying, aortic stenosis)
If cannot eject properly, will have residual blood in ventricles: higher blue line. - reduced diastolic arterial pressure (eg. mitral or aortic valve incompentence, heart failure) ie. if backflow of blood into ventricles due to valve rather than into resistant small artery system.
How do we match tissue demand (exercise) to blood flow
by altering flow at arteriolar level
This is achieved by metabolic control: muscle cell produces byproducts (eg. adenosine) which triggers relaxation of vascular smooth muscle cells
- Neural vasoconstrictors
- Hormonal vasoconstrictors (3)
- Local vasoconstrictors
- sympathetic nerves
- adrenaline, angiotensin 2, vasopressin
- myogenic response, endothelin 1
- 2 hormonal vasodilators
- Local vasodilators
- acetylcholine, atrial-natriuretic peptide (ANP)
- K, CO2, H+, decreased O2, adenosine, NO, bradykinin
Coronary ischaemia is usually the result of which process?
atherosclerosis (which then causes angina)
Sudden ischaemia is usually caused by which process?
Thrombosis (which then may result in cardiac infarction)
Aside from coronary ischaemia, what can also cause angina?
What is this called?
coronary spasms
variant angina
Following ischaemia, what happens in terms of calcium levels?
get cellular calcium overload.
may cause cell death and dysrhythmias
3 Classes of angina
- Variant Angina (vasospasm - is a supply ischaemia)
- Chronic stable angina (fixed stenosis - is a demand ischaemia)
- Unstable angina (thrombus - is a supply ischaemia)
How do antianginal drugs work?
2 broad types
to decrease the metabolic demand of the heart
Organic nitrates, nicorandil and Ca antagonists are vasodilators (decrease preload or afterload)
Beta-blockers and ivabradine slow down the heart (decrease metabolic demand of muscle)
Preload determined by
the venous pressure
venous return to the heart (end-diastolic pressure/volume)
Afterload determined by
aortic or pulmonary artery pressures
Action of beta-blockers
2 examples
- decrease cardiac oxygen consumption by SLOWING THE HEART
[They are blocking ability of sympathetic NS via B1 adrenogenergic recetors to modulate activity of F-type Na channels] - also have antidysrhythmic action
Eg. bisoprolol, atenolol
Action of calcium antagonists
- prevent opening of voltage-gated L-type calcium channel
- therefore block Ca entry
- (inhibits Ca entry upon muscle cell depolarisation) - vasodilator effect mainly on resistance vessels (reduces afterload)
2 Types of calcium antagonists
- Dihydropyridine derivatives eg. amplodipine and lercanidipine
- Rate-limiting eg. verapamil, diltiazem.
These allow less Ca to come in each time a muscle contracts, reducing workload.
Why are calcium antagonists important in treatment of variant angina?
as they dilate the coronary vessels
Which calcium antagonists can reduce and impair AV conduction and myocardial contractility
rate-limiting: verapamil/diltiazem
Main drivers at different stages of myocardial depolarisation
(pi like)
upshoot driven by Na
plateau phase driven by calcium
repolarisation driven by K
Describe SA node depolarisation (neuronal).
Phase 1: gradual drift increase in RMP due to increase Na as funny-type Na channels open (and decrease in K as K channels slowly close). This oscillating flux of Na into cell provides pacemaker potential.
Transient Ca channels help with the final push
Phase 2: moderately rapid depolarisation due to Ca entry via slow L channels
Phase 3: rapid repolarisation as elevated internal Ca stimulates opening of K channels, and get increase in K
What keeps the SA node rate down?
parasympathetic NS
through AV node
What calcium antagonist would you use in a patient with heart failure?
Dihydropyridine derivatives eg. amplodipine and lercanidipine
If using a beta-blocker, which calcium antagonist type would you avoid using?
Rate-limiting: diltiazem or verapamil
also contraindicated in HF, bradycardia, AV block
Side effects of calcium antagonists
headache, constipation, ankle oedema
Antidysrhythmic using calcium antagonist
Verapamil
- slows ventricular rate in rapid AF
- prevents recurrence of supraventricular tachycardia
- no effect on ventricular arrhythmias
How does GTN spray work?
Glyceryl trinitrate is a vasodilator.
IS metabolised to NO and relaxes smooth muscle
- Acts on veins to decrease preload
- In higher concentrations, can affect arteries and decrease afterload
- dilates collateral coronary vessels decreasing cardiac workload. This is particularly useful in variant angina
Organic nitrate not GTN
Isosorbide mononitrate
How do endothelial cells regulate vascular tone?
if shearing stress to endothelial cell - causes NO production, which acts on soluble gyanylate cyclase enzyme in smooth muscle, which acts to convert GTP -> GMP to cause relaxation
K Channel Activator
Nicorandil
- combines activation of KATP channels with nitrovasodilator actions
- arterial and venous dilator
Give 4 conditions where you might use organic nitrates
- stable angina (prevention with GTN, or isosorbide mononitrate long before exercise)
- unstable angina (IV GTN)
- acute heart failure (IV GTN)
- chronic heart failure (isosorbide mononitrate with HYDRALAZINE in patients of African American origin)
Action of Ivabradine
inhibits f-type channels in the heart
reduces cardiac pacemaker activity (inhibits heart rate)
Action of Ranolazine
unique anti-anginal used as last resort
