| What are some causes of arrythmias | Ectopic pacemaker activity --> damaged area of myocardium becomes depolarised and spontaneously active
Afterdepolarisations --> Abnormal depolarisations following the action potential
Re-entry loops --> Conduction delay and Accessory pathway |
| What are afterdepolarisations | Anything which prolongs the duration of the action potential can allow afterdepolarizations to occur
On a ECG it comes at as a longer QT interval due to longer AP
More likely with high [Ca2+]
Can cause premature AP to fire leading to arrythmias |
| What is the re-entrant mechanism for generating arrythmias | Incomplete conduction damage (unidirectional block)
Excitation can then take a longer route to spread the wrong way through a damaged area , setting up a circus of excitation
And these can give rise to arrhythmias |
| What is Wolff Parkinson White syndrome | Example of a Paroxysmal supraventricular tachycardia
In this condition there are additional points of conductivity between the atria and ventricles
Additional accessory pathway
This is called the Bundle of Kent
This basically acts as a second AV node but less regulated and can lead to arrhythmic activation of the heart |
| What are the 5 classes of drugs used to treat arrhythmias | Drugs that block voltage sensitive Na+ channels
Antagonists of beta-adrenoreceptors
Drugs that block K+ channels
Drugs that block Ca2+ channels
Others e.g. Adenosine, Magnesium etc. |
| What is the mode of action of Lidocaine | Sometimes used following MI if patient shows signs of ventricular tachycardia → given IV
Damaged areas of myocardium may be depolarised and fire automatically
More Na+ channels are open in depolarised tissues and Lidocaine can block these channels and prevent automatic firing |
| What is the mode of action of beta blockers and/or beta-adrenoreceptors antagonists | Blocks sympathetic action
Act at Beta-1 adrenoreceptors in the heart
Decreases the slope of pacemaker potential in the SA node
Can prevent supraventricular tachycardias and arrythmias
Also reduces Oxygen demand so it reduces myocardial ischaemia which is beneficial post MI |
| Mode of action of drugs that block K+ channels | Prolongs the AP
Mainly by blocking K+ channels
This lengthens the absolute refractory period
Prevents another APP from occurring too soon
Not generally used tho
Used to treat tachycardia associated with Wolff Parkinson-White syndrome (re-entry loop due to an extra conduction pathway) |
| Mode of action of Ca2+ channel blockers | Example is Verapamil
Decreases the slope of pacemaker potential at SA node
Decreases AV nodal conduction
Decreases force of contraction
Also cause some coronary and peripheral vasodilation
The dihydropyridine Ca 2+ channel blockers are not effective in preventing arrhythmias, but do act on vascular smooth muscle |
| Mode of action of adenosine | Produced endogenously
Acts on A1 receptors at AV node
Enhances K+ conductance
Hyperpolarized cells of conducting tissue
Stops heart momentarily and resets the rhythm
Administered IV |
| What are some features of heart failure | Chronic heart failure is the failure of the heart to provide sufficient output to meet the body’s requirement
Reduced force of contraction
Reduced cardiac output
Reduced tissue perfusion
Oedema → due to back pressure |
| How do ACE inhibitors work | Drugs which inhibit the action of angiotensin converting enzyme are important in the treatment of heart failure
Prevent the conversion of angiotensin I to angiotensin II
Decrease vasomotor tone ( blood pressure is reduced )
Reduced afterload of the heart
Decrease fluid retention so there is decrease in blood volume
Reduce preload of the heart
Reduce work load of the heart
Angiotensin II receptor blockers (ARBs) have similar effects e.g. losartan |
| What are some factors that induce positive lusitropy | Lusitropy --> refers to the ability of the myocardium to relax following excitation contraction coupling
Beta adrenergic agonists → Phospholamban is an antagonist of SERCA in the non phosphorylated state |
| What are some factors that induce negative lusitropy | High cytoplasmic calcium
SERCA not working properly
Alkalosis
Increased affinity of troponin C
Cardiac glycosides --> cardiac glycosides inhibit the Na+‐K+‐ATPase on cardiac and other tissues, causing intracellular retention of Na+, followed by increased intracellular Ca2+ concentrations |
| What are the action of cardiac glycosides | Ca2+ is extruded via the Na +-Ca 2+ exchanger
Driven by Na+ moving down its concentration gradient
Cardiac glycosides block the Na+/K+ ATPase
Hence leads to rise in Na+ conc intracellularly
Rise in intracellular Na + leads to decrease in activity of Na + -Ca 2+ exchanger and this causes increase in [Ca2]
Hence more is stored in the sarcoplasmic reticulum
Increased force of contraction → Positive inotropic effect
Cardiac glycosides also increase vagus nerve activity → parasympathetic NS so slows down HR and AV conduction |
| What is the action of organic nitrates | Action on the venous system, venodilation leads to lower preload
Reduces workload of the heart
Heart fills less therefore force of contraction is reduced
This lowers oxygen demand
Venodilation reduces venous pressure and the return of blood to the heart
Action on coronary arteries improves O2 delivery to the ischaemic myocardium and acts on collateral arteries rather than arterioles so dilation increases amount of blood flow |
