Drugs Acting on the CVS Flashcards
What are cardiovascular drugs used to treat?
Arrythmias Heart failure Angina Hypertension Risk of thrombus formation
What can cardiovascular drugs alter?
The rate and rhythm of the heart
The force of myocardial contraction
Peripheral resistance and blood flow
Blood volume
What can cause arrhythmias?
Ectopic pacemaker activity
After-depolarisations
Re-entry loop
How can ectopic pacemaker activity lead to arrhythmias?
Damaged area of myocardium becomes depolarised and spontaneously active. The latent pacemaker region is activated due to ischaemia, and dominates over the SA node
What are after-depolarisations?
Abnormal depolarisations following the action potential
What are after-depolarisations thought to be caused by?
High intracellular Ca
What does a longer action potential in after-depolarisation lead to?
A longer QT interval
What causes a re-entry loop?
Conduction delay, whereby normal spread of excitation is disrupted due to damaged area .
When will a re-entry loop occur?
When there is incomplete conduction damage leading to uni-directional block
What happens if you get several small re-entry loops in the atria?
Atrial fibrillation
What can cause several small reentry loop in the atria?
Being stretched over time
What are the basic classes of anti-arrythmic drugs?
I. Drugs that block voltage gated Na channels
II. Antagonists of ß-adrenoreceptors
III. Drugs that block K channels
IV. Drugs that block Ca channels
What is a typical example of a class I anti-arrythmic drug?
Lidocaine
What channels does lidocaine block?
Voltage gated Na channels
Only those that are in an open or inactive state
How quickly does lidocaine dissociate?
Quickly- in time for next AP
What is the advantage of lidocaine?
Normal firing of APs is not stopped, but it prevents the firing of APs too close to one anoterh
Why can lidocaine be used as an anti-arrythmic?
Because Na channels are blocked, after-depolarisations cannot trigger another AP
Give two examples of class II anti-arrythmic drugs
Propanolol
Atenolol
How do class II anti-arrythmic drugs work?
They block sympathetic action by acting on ß1 receptors in the heart, decreasing the slope of the pacemaker potential in the SAN
Inhibits adenylyl cyclase, decreasing intropy
What are class II anti-arrythmic drugs also known as?
Beta-blockers
When are beta-blockers used?
After a MI
What are beta-blockers used after an MI?
To combat increases in sympathetic activity
To reduce oxygen demand of myocardium
How do class III anti-arrythmic drugs work?
Prolong the action potential, by blocking K channels (which are responsible for repolarisation). The absolute refractory period is lengthened, preventing another AP from occurring too soon
Why are class III drugs not generally used?
Because they can also be pro-arrythmic
Give an example of a class IV anti-arrythmic drug?
Verapamil
How do class IV drugs work?
Decreases slope of pacemaker potential at SA node
Decreases AV node condutction
Decreases force of contraction
Some coronary and peripheral vasodilation
Where is adenosine produced?
Endogenously
What does adenosine act on?
A1 receptors at AV node
What kind of receptor are A1 receptors?
GPCR
What happens on stimulation of A1 receptors?
Inhibits adenylyl cyclase
How does adenosine work as an anti-arrythmic?
It enhances K conductance and hyperpolarises cells of conduction tissue
Essentially, what does adenosine do?
‘Resets’ the heart
What drugs have an important role in in the treatment of chronic heart failure?
ACE-inhibitors
Diuretics
How to ACE-inhibitors treat chronic heart failure?
They prevent the formation of the vasoconstrictor angiotesin II, thus promoting vasodilation of arterioles and venus dilation. This decreases both afterload and preload on the heart
Why do ACE-inhibitors have a diuretic action?
Because angiotensin II promote aldosterone release from the adrenal cortex (zona glomerulosa)
Why does the inhibition of aldosterone act as a diueretic?
Aldosterone causes Na and water retention, increasing blood volume- so reducing it decreases blood volume and decreases pre-load to the heart
What is the principle of angina treatment?
Reducing the work load of the heart
What drugs are used to treat angina?
ß-blockers
Organic nitrates
What drugs improve blood supply to the heart?
Organic nitrates
Ca channel blockers
How do organic nitrates treat angina?
The reaction of organic nitrates with thiols (-SH groups) in vascular smooth muscle causes NO2- to be released. NO2- is reduced to NO, which is a powerful vasodilator. NO activates guanylate cyclase, increasing cGMP and lowering intracellular Ca2+ to cause relaxation of vascular smooth muscle.
What is the primary action or organic nitrates?
Acts on the venous system as a venodilator, lowering central venous pressure and preload. The heart fills less; therefore force of contraction is reduced (Starlings Law).
What is the secondary action of organic nitrates?
Acts on the coronary arteries, improving O2 delivery to the ischaemic myocardium.
What do some heart conditions carry?
An increased risk of thrombus formation
Give 2 examples of heart conditions that carry an increased risk of thrombus formation
Atrial fibrillation
Valve disease
What may be used when a heart condition carries an increased risk of thrombus formation?
Anti-thrombotic drugs
Give an example of an anti-thrombotic drug?
Warfarin
Give an example of an anti-platelet drug?
Aspirin
When may aspirin be used?
After a MI or in coronary artery disease, when there is a risk of MI
Why may aspirin be used when there is a risk of MI?
To reduce the risk of platelet rich arterial clots forming
Why is hypertension an important cardiovascular condition?
Since it carries the rest of developing cardiovascular disease of stroke
What do drugs used in the treatment of hypertension act to do?
Reduce cardiac output and/or peripheral resistance
What drugs are used in the treatment of hypertension?
ACE-inhibitors
Diuretics
Adrenoceptor blocks
Ca channel blockers
