Antianginal pharmacology Flashcards
What is Angina Pectoris?
When oxygen supply to myocardium (muscle of the heart) is insufficient for its needs which results in a tight chest pain.
- Latin for tight chest hence a main symptom/indicator
Leads to a Retrosternal cardiac pain:
- Intense, diffuse, gripping, constricting, suffocating chest pain
- Feels like a “bear hug”
- May radiate to arms, neck and jaw
- Difficult to distinguish from “heart burn”
ANGINA PECTORIS IS A SYMPTOM NOT A DISEASE, the underlying disease is normally Atherosclerosis.
What ultimately happens with Atherosclerosis?
- Ultimately you block one of the blood vessel that supply blood to the heart
- Theres 2 points where blood vessels narrow due to atherosclerosis and this results in less blood getting through and this starts to starve the heart tissue and heart myocytes of blood.
What are the aims of treatment of Atherosclerosis?
- Alleviate/relieve the acute symptoms
- To minimise the frequency of ischaemia (Lack of blood supply and lack of oxygen supply to these cardiomyocytes)
- Reduce progression of atherosclerosis (secondary prevention - using statins, aspirin, ACEI in diabetes etc)
What are the triggers of angina?
Normally the cardiomyocytes in the heart and the coronary blood supply will balance the oxygen needs with the oxygen supply.
- Oxygen needs:
The oxygen needs relate to the increased cardiac workload:
- Exercise
- Emotion
- GI perfusion
- Peripheral vasoconstriction - Oxygen supply
Restricted coronary perfusion:
- Narrowing of the coronary arteries
- Limits to dilation (can’t dilate enough hence limiting blood supply)
- Aortic stenosis (if you block the aorta you limit the blood supply)
Normally the supply and demand is balanced however in angina it’s tipped one way. Increase in demand/needs and reduce in supply which ultimately cause angina.
How can you reduce oxygen demand for angina?
- Reduce cardiac workload
- Reduce perfusion demands
E.g. Rest, stress, smoking, weight
- Reduce pre-load
By using a ventilator e.g. Nitrates
- Reduce after load
By dilating the arteries by using calcium channel blockers and nitrates - Reduce cardiac rate/contractility
- Negative inotrope/chronotrope e.g. B-blockers, CCB to slow the rate and contractility - Improve the efficiency of heart (non-pharmacological)
- Exercise
- Stop smoking
How can you improve oxygen supply?
- Increase Coronary blood flow by:
1. Arterial dilator e.g. CCB, nitrate
2. Surgery e.g. bypass, angioplasty, stent
What are anti-anginal agents?
- They are organic nitrates for acute attacks, they mimic the effects of nitric oxide
- CCBs (dilates the coronary arteries)
- B-adrenoreceptor antagonists (to slow heart rate hence reduce metabolic demand of the heart)
What are the organic nitrates?
Most popular one is Glyceryl trinitrate.
- Very effective in angina
- Quick onset and short duration of action hence really quick but doesn’t work for a long time.
Isosorbide mononitrate
- Longer duration of action
What is the mechanism of action of nitrates?
- Nitric oxide (NO) is released from organic nitrates
- Nitric oxide donors
- Relaxes all smooth muscle
- Mainly effects the CV system
- Endothelial cells normally make NO
Lower doses
- Marked dilatation of large veins
- Reduction in Central venous pressure (reduced pre load)
- Reduction in Cardiac output and oxygen consumption due to vasodilation
- Little effect on arterioles/little change in BP
Higher dose/chronic use
- Arteriolar dilatation, fall in BP, reduced CO resulting in headache
Normally we need lower dose because we don’t need a change in blood pressure but just to relax the coronary arteries.
What is shear stress?
Nitric oxide is normally used in the CV system as a vasodilator. Normally the endothelial cells will send shear stress which will then trigger to make NO. NO will diffuse across the membranes an and get in the smooth muscle cells and cause vascular relaxation.
What effects does nitrates have on the coronary circulation?
- Increase coronary flow in normal subjects
- Reduction of vascular resistance - Dilation of coronary arteries despite a fall in BP
- Diverts blood from normal to ischaemic areas, known as a pharmacological by-pass
What are the pharmacokinetics and stability of nitrates?
- Glycerol trinitrate (Nitroglycerin)
- Absorbed sublingually (under the tongue) - rapid relief
- Rapidly metabolised in liver (30mins)
- Can’t be swallowed - Sprays
- Tablets
- Glass bottles as volatile substances - Patches
How does B-Blockers work for angina?
Reduce oxygen consumption only
1. Slow the heart - hence less oxygen consumption in the heart
- Depress the myocardium
- No effect on coronary arteries
- Provide secondary prevention
- Improve exercise capacity
- Contraindicated in coronary spasm
- Slow withdrawal (up-regulated receptors) - Indications
- Angina prophylaxis
- Unstable angina
How does Calcium channel blockers work for angina?
- Diverse groups of drugs
- Three main classes:
- Phenylalkylamines eg verapamil
- Dihydropyridines eg nifedipine, amlodopine
- Benzothiazepines eg diltiazem - Block calcium ions entering cells in the smooth muscle cells through preventing
opening of voltage-gated L-type calcium channels
- Bind a1 subunit of the cardiac L-type calcium channels but at
different sites hence more vasodilation - Main effects on cardiac and vascular smooth muscle, inhibiting Ca2+
entry caused by depolarisation in these tissues
- verapamil is relatively cardioselective
- nifedipine is relatively smooth muscle selective
- diltiazem is intermediate - Cardiac actions
- Antidysrhythmic effects(mainly atrial tachycardia) because of impaired
atrioventricular conduction
- Reduced contractility
- Negative inotropic and chronotropic effect (but little effect on CO -due to
reduction in peripheral resistance)
- Verapamil – contra-indication in heart failure - Vascular smooth muscle – mainly nifedipine
- arteriolar dilatation – reduce blood pressure (reduce afterload)
- coronary vasodilatation –used in patients with variant angina (spasm)
