Session 7: Cardiac Arrhythmias and CVS Drugs CHECK CARD 22 AGAIN Flashcards
What are cardiovascular drugs used to do?
To treat arrhythmias, heart failure, angina, hypertension and risk of thrombus formation.
Causes of tachycardia.
Ectopic pacemaker activity Afterdepolarisations Atrial flutter/fibrillation Re-entry loop by conduction delay or accessory pathway
Causes of bradycardia.
Sinus bradycardia like sick sinus syndrome or extrinsic factors such as drugs like beta-blockers and some Ca2+ blockers. Conduction block like problems at AV node or bundle of His.
Common cause of delayed after-depolarisation?
If intracellular Ca2+ high but it happens after repolarisation.
Explain re-entrant mechanism leading to the generation of an arrhythmia.
When there is incomplete conduction damage also called uni-directional block the excitation can take a long route to spread the wrong way through the damaged area setting up a circus of excitation. Multiple small re-entry loops in the atria can lead to atrial fibrillation.
Cause of AV nodal re-entry loop.
Fast and slow pathways in the AV node create a re-entry loop.
Cause of ventricular pre-excitation.
If there is a breach in the fibrous ring leading to an accessory pathway between ventricles and atria. This can cause an re-entry loop called Wolff-Parkinson-White syndrome
There are 4 basic classes of anti-arrhythmic drugs. Which?
I - Drugs that block voltage-sensitive sodium (Na+) channels II - Antagonists of B-adrenoceptors III - Drugs that block potassium (K+) channels IV - Drugs that block calcium (Ca2+) channels
Give an example of Class I which block voltage-dependant Na+ channels.
Local anaesthetic lidocaine
Explain how Class I drugs work.
They only block voltage gated Na+ channels in open or inactive state. This means that they preferentially block damaged depolarised tissue like in an MI.
Does class I drugs work on normal cardiac tissue?
It has little to no effect because it dissociates rapidly.
Explain use of lidocaine.
Can be used sometimes following an MI however only if patient shows signs of ventricular tachycardia. This is given intravenously. Damaged areas of myocardium may be depolarised and fire automatically and randomly independent on any other input. More Na+ channels are open in depolarised tissue so lidocaine works by blocking these Na+ channels and prevents the automatic firing of depolarised ventricular tissue.
Give example of Class II b-adrenoceptor antagonists.
Propanolol and atenolol.
Briefly explain how Class II drugs work.
Block sympathetic action on b1-adrenoreceptors in the heart. They decrease slope of pacemaker potential in SA node and slows conduction at AV node.
What are Class II drugs used for?
It can prevent supraventricular tachycardia to slow down the heart rate. It also slows ventricular rate in patients with atrial fibrillation. Can be used following MI because MIs often causes increased sympathetic activity. They also prevent ventricular arrhythmias. Also reduces O2 demand.
Explain how Class III K+ channel blockers work.
They prolong action potential by blocking K+ channels to lengthen the absolute refractory period.
In theory this should prevent another AP occuring to son but instead in reality it can be pro-arrhythmic instead by prolonging QT interval.
Class III K+ blockers are not used a lot because of the risk of being pro-arrhythmic instead of helping.
However there is an exception of something used. Which drug?
Amiodarone.
Explain why amiodarone is used.
It is called a dirty drug because it doesn’t only have one action.
It has other actions as well as blocking K+ channels.
It can be used to treat tachycardia associated with Wolff-Parkinson-White syndrome (re-entry loop disease).
It is also effective for suppressing ventricular arrhythmias after an MI.
Give examples of Class IV Ca2+ channel blockers.
Verapamil and diltiazem which are non-dihydropyridine types.
Explain how non-dihydropyridine class IV drugs work lie verapamil and diltiazem.
They decrease the slope of action potential at the SA node.
They decrease AV nodal conduction as well (same slope as in SA node)
Decrease force of contraction and also some coronary and peripheral vasodilation.
What is the difference between non-dihydropyridine and dihydropyridine Ca2+ blockers?
Dihydropyridine blockers are not effective in preventing arrhythmias however they act on vascular smooth muscle.
Adenosine is another anti-arrhythmic drug. Explain how it works.
It is produced endogenously but can be administered IV as well.
It acts on A1 (adenosine) receptors at the AV node.
Enhances K+ conductance to hyperpolarise cells of conducting tissue (activates K+ channels). It essentially causes a transient heart block. It is one-off treatment only given once.
This means that it is useful in terminating re-entrant supraventricular tachycardia.
Give other drugs that act on CVS.
ACE inhibits and Angiotensin II receptor blockers
Diuretics
Calcium channel antagonists
Positive inotropes like cardiac glycosides and dobutamine
Alpha adrenoceptor blocker and beta blockers
Anti-thrombotic drugs.
Give an example of an ACE-inhibitor.
Peroindopril
Explain action of ACE-inhibitors.
Explain what it is used for.
Inhibits the action of angiotensin converting enzyme (ACE) which is supposed to cleave angiotensin I to angiotensin II. Where angiotensin II causes vasoconstriction, stimulates Na+ reabsorption and stimulates production of aldosterone which will also stimulate Na+ reabsorption.
ACE inhibitors decrease vasomotor tone which lowers blood pressure and reduce afterload of the heart. Also decrease fluid retention. Reduces preload of the heart.
It is important in treatment of hypertension and heart failure.
Side-effect of ACE inhibitors.
Can cause dry cough due to excess of bradykinin.
Explain action of Angiotensin II receptor blockers and why they are used.
Same use as ACE inhibitors. They block the action of the active enzyme angiotensin II.
This is used in patients who can’t tolerate ACE inhibitors.
Used to treat heart failure and hypertension
Explain action of diuretics and their use.
Treatment of heart failure and hypertension.
Loop diuretics are very useful in congestive heart failure (biventricular).
An example is furosemide and they work by reducing pulmonary and peripheral oedema by acting on the ascending loop and makes fluid leave body via urine in kidneys.
Give examples of Dihydrioyridine Ca2+ channel blockers.
Amlodipine and nicardipine
Action of dihydropyridine Ca2+ channel blockers and their use.
Decrease TPR
Decrease arterial BP
Reduce workload of the heart by reducing afterload.
They are useful in hypertension, angina, coronary artery spasms and SVTs.
Give action of positive inotropes.
Increase contractility and therefore cardiac output.
Examples of positive inotropes.
Cardiac glycosides and b-adrenergic agonists.
Give example of cardiac glycoside.
Digoxin
Give action of cardiac glycosides and their use.
Blocks Na+/K+ ATPase as a positive inotrope.
This causes Na+ to stay in the cell. This means that NCX won’t work properly as NCX is supposed to make Na+ enter in exchange for Ca2+. This causes both Na+ and Ca2+ to rise in cell.
Ca2+ will then be stored in a larger amount in SR. In successive APs more Ca2+ will be released causing increased force of contraction (+ve inotropy).
Cardiac glycosides also have an effect on heart rate.
Explain it.
They also cause increased vagal activity which slows AV conduction and slows the heart rate.
This means that cardiac glycosides may be used in heart failure when there is an arrhythmia such as AF.
Give example of B-adrenoceptor agonist.
Dobutamine
Explain action of dobutamine and use of it.
Stimulates B1-receptors present at SA node and AV node and on ventricular myocytes.
It is used to treat cardiogenic shock and acute but reversible heart failure.
Why are cardiac glycosides not very good at treating heart failure long term?
They will relieve symptoms by making the heart contract harder but it is a bit like flogging a dying horse. There is no long-term benefit and will only make the heart eventually stop working faster.
Instead of using cardiac glycosides to treat heart failure, what can be used?
Something to reduce workload.
ACE inhibitors, or Angiotensin II receptor blockers and diuretics would be better to use for heart failure.
Beta-blockers can also be used to reduce workload of the heart.
Treatment of angina (myocardial ischaemia)
Angina occurs when O2 supply to the heart does not meet its need.
Nitrates are used
Explain action of organic nitrates and their use.
Reaction of organic nitrates with thiols (-SH groups) in vascular smooth muscle causes NO2- to be released.
NO2- is then reduced to NO.
NO is a powerful vasodilator particularly effective on veins very little effect on arteries and arterioles.
GTN spray and isosorbide dinitrate are examples of organic nitrates.
Explain how nitric oxide causes venodilation.
NO activates guanylate cyclase to cause GTP go to cGMP.
cGMP goes to PKG and lowers the intracellular Ca2+.
This causes relaxation of vascular smooth muscle.
How does NO help to alleviate symptoms of angina?
Action on venous system causing venodilation will lower preload.
Reduces work load of heart and the heart fills less therefore reduced force of contraction needed.
This lowers O2 demand.
Action on coronary collateral arteries improves O2 delivery to the ischaemic myocardium (acts on collateral arteries but not arterioles)
How to treat angina.
Reduce workload of the heart like organic nitrates, b-adrenoreceptor blockers, Ca2+ channel antagonists.
Improve the blood supply to the heart (coronary) via Ca2+ channel antagonists and minor effect of organic nitrates.
Give heart conditions that increase the risk of thrombus formation.
Atrial fibrillation
Acute myocardial infarction.
Mechanical prosthetic heart valves
Give examples of antithrombotic drugs.
(Main groups)
Anticoagulants
Prevention of venous thromboembolism
Antiplatelet drugs
Give specific examples of antithrombotic drugs.
Heparin
Warfarin
Aspirin
Clopidogrel
Mode of action of heparin.
What is its primary use?
Inhibits thrombin which is supposed to cleave fibrinogen into fibrin.
Acutely for short term action.
Mode of action of warfarin.
When is it given?
Antagonises action of vitamin K which is needed in coagulation.
It is used as an antithrombotic drug however it has no acute use because it takes time for it to take effect.
Mode of action of aspirin and clopidogrel.
+ use.
Used following acute MI or high risk of MI.
Antiplatelet drugs.
