Understanding Arrhythmias Flashcards
Causes of arrhythmia
Tachycardia - Ectopic pacemaker activity
Damaged area of myocardium becomes depolarised and spontaneously active
Latent pacemaker region activated due to ischaemia, which dominates over SA node
Afterdepolarisations
– abnormal depolarisations following the action potential (triggered activity)
Can progress to Atrial flutter / atrial fibrillation
-Bradycardia
Sinus bradycardia
can be caused by Sick sinus syndrome (an intrinsic SA node dysfunction)
Could be due to Extrinsic factors such as drugs (beta blockers, some Ca2+ channel blockers)
Could be due to Conduction block - Problems at AV node or bundle of His
Slow conduction at AV node due to extrinsic factors ((beta blockers, some Ca2+ channel blockers)
Delayed and early after-depolarisations
Delayed - Could be due to a high IC Ca2+ content (if it reaches potential, then it can trigger an AP before it should, if this happens too frequently then it can lead to ventricular tachycarida)
Early after-depolarisations (triggered activity)
Can lead to oscillations
More likely to happen if AP prolonged
Longer AP – longer QT
Re-entrant mechanism for generating arrhymias
Incomplete conduction damage (unidirectional block) - excitation can take a long route to spread the wrong way through the damaged area, setting up a circus of excitation
Usually when 2 impulses meet they cancel each other out - however with this block, one pulse can keep going - if its a unidirectional block then pulse can then go round and round in a circuit setting up a tachycardia
If there are Multiple re-entrant circuits in the atria
It can lead to atrial fibrillation
Don’t see any p waves on the ECG
AV nodal re-entry:
Fast and slow pathways in the AV node create a re-entry loop
Which leads to Ventricular Pre-excitation
An accessory pathway between atria and ventricles creates a re-entry loop such as in Wolff-Parkinson-White syndrome
Drugs affecting the rate and rhythm of the heart
There are 4 basic classes of anti-arrhythmic drugs.
I. Drugs that block voltage-sensitive sodium channels
II. Antagonists of
Dugs which block voltage dependent Na+ channels (class 1)
E.g. lidocaine
Typical example is the local anaesthetic lidocaine (class Ib) Use-dependent block.
Only blocks voltage gated Na+ channels in open or inactive state – therefore preferentially blocks damaged depolarised tissue
No effect on AP generation in normal cardiac tissue because it dissociates rapidly
Blocks during depolarisation but dissociates in time for next AP
Lidocaine
Sometimes used following MI
– only if patient shows signs of ventricular tachycardia
– given intravenously
Damaged areas of myocardium may be depolarised and fire automatically - therefore lidocaine prevents this
More Na+ channels are open in depolarised tissue
– lidocaine blocks these Na+ channels (use-dependent)
– prevents automatic firing of depolarised ventricular tissue
Not used prophylactically following MI
– Even in patients showing VT generally use other drugs
ß-adrenoreceptor antagonists (class 2)
Examples: propranolol, atenolol (Beta blockers)
Block sympathetic action
– act at ß
Drugs that block K+ channels (class 3)
Class III anti-arrhythmics
Prolong the action potential – mainly by blocking K+ channels
This lengthens the absolute refractory period
In theory would prevent another AP occurring too soon - BUT
– In reality this is true but can also be pro-arrhythmic – Prolong QT interval
Drugs that block K+ channels
Prolong the action potential
Not generally used because they can be also be pro-arrhythmic
One exception – amiodarone
Included as a type III anti-arrhythmic, but has other actions in addition to blocking K+ channels
Used to treat tachycardia associated with Wolff-Parkinson-White syndrome (re-entry loop due to an extra conduction pathway)
Effective for supressing ventricular arrhythmias post MI
Drugs that block Ca2+ channels (class 4)
Examples: verapamil, diltiazem (non-dihydropyridine types)
Decreases slope of action potential at SA node
Decreases AV nodal conduction
Decreases force of contraction (negative inotropy)
Also some coronary and peripheral vasodilation
Dihydropyridine Ca2+ channel blockers are NOT effective in preventing arrhythmias, but do act on vascular smooth muscle
Examples: Amlodipine, nifedipine, nicardipine act on vasculature
Other drugs acting on CVS
ACE inhibitors and AngII receptor blockers
Diuretics
Calcium channel antagonists
Positive inotropes – cardiac glycosides, dobutamine
Alpha adrenoceptor blocker and Beta blockers
Antithrombotic drugs
Adenosine - not really an exogenous drug - more produced endogenously at physiological levels
BUT can also be administered intravenously
Acts on alpha1 receptors at AV node but has a very short half-life
Enhances K+ conductance – hyperpolarises cells of conducting tissue
Anti-arrhythmic – doesn
ACE - inhibitors
Example: Perindopril
Inhibits the action of angiotensin converting enzyme
Important in the treatment of hypertension AND heart failure
Prevents conversion of angiotensin I to angiotensin II
– Angiotensin II acts on the kidneys to increase Na+ and water reabsorption
– Angiotensin II is also a vasoconstrictor
ACEi can cause a dry cough (excess bradykinin)
Very valuable in treatment of heart failure (Chronic failure of the heart to provide sufficient output to meet the body
Diuretics
Used in treatment of heart failure and hypertension due to the production of more urine - removing fluid from the body
Loop diuretics useful in congestive heart failure
– Example furosemide
– Reduces pulmonary and peripheral oedema
Other diuretics such as thiazide diuretics useful in more mild cases of congestion
Calcium channel antagonists
Dihydropyridine Ca2+ channel blockers are not effective in preventing arrhythmias, but act on vascular smooth muscle
Examples: Amlopidine, nicardipine - These:
– Decrease peripheral resistance – Decrease arterial BP – Reduce workload of the heart by reducing afterload
Other types of Ca2+ blockers eg verapamil and diltiazem act on heart
– Reduce workload of heart by reducing force of contraction
Ca2+ channel blockers useful in hypertension, angina, coronary artery spasm, SVT
Positive inotropes
Positive inotropes increase contractility and thus cardiac output
E.g. Cardiac glycosides – Example: digoxin - blocks Na in the Na+/K+ transporter - therefore build up of ca in cell - taken up by SR, more calcium on next force of contraction
ß-adrenergic agonists – Example: dobutamine
Cardiac glycosides
Have been used to treat heart failure for over 200 years
improves symptoms but not long term outcome
Digoxin is the prototype – Extracted from leaves of the foxglove digitalis purpurea
Primary mode of action is to block Na+/K+ ATPase, so Na+ builds up in the cell so Na+-Ca2+ exchanged isn’t as effective so Ca2+ isn’t removed and can build up in the cell to be taken up by SR
Action of cardiac glycosides on heart rate
Cardiac glycosides also cause increased vagal activity
– action via central nervous system to increase vagal activity
– slows AV conduction
– slows the heart rate
Cardiac glycosides may be used in heart failure when there is an arrhythmia such as AF
Cardiac glycosides will relieve symptoms by making heart contract harder
But there is no long-term benefit
Don
ß-adrenoreceptor agonists
Dobutamine
Selective ß1- adrenoreceptor agonist
Stimualtes , ß1receptors present at the SA node and on ventricular myocytes
uses in cardiogenic shock and acute but reversible heart failure
Helps generate more CO
Nitrates in treatment of angina (MI)
Angina occurs when O2 supply to the heart does not meet its need
But of limited duration and does not result in death of myocytes
Ischaemia of heart tissue – Chest pain - Usually pain with exertion
Organic Nitrates - Reaction of organic nitrates with thiols (-SH groups) in vascular smooth muscle causes NO2- to be released
NO2- is reduced to NO (Nitric Oxide)
Nitric oxide is released endogenously from endothelial cells
Examples
– GTN spay (quick, short acting)
– Isosorbide dinitrate (longer acting)
NO is a powerful vasodilator PARTICULARLY EFFECTIVE ON VEINS
Why do organic nitrates preferentially act on veins
Maybe because there is less endogenous nitric oxide in veins
At normal therapeutic doses it is most effective on veins - less of an effect on arteries
Very little effect on arterioles
NO causes vasodilation:
NO activates granulate cyclase -This increases cGMP
This lowers IC Ca2+ conc
This causes reaction of vascular smooth muscle - less contraction
How does this help alleviate symptoms?
PRIMARY ACTION - action on venous system -venodilation lowers preload - reduces work load of the heart
– heart fills less therefore force of contraction reduced (Starling
