Arrhythmias And Drugs Flashcards
What are some tachycardic causes of arrhythmias?
- Ectopic pacemaker activity
- Damaged area of myocardium becomes depolarised and spontaneously active
- Latent pacemaker region activated due to ischaemia (dominate over SA node)
- Afterdepolarisations
- Abnormal depolarisations following the action potential (triggered activity)
- Atrial flutter / atrial fibrillation
- Re-entry loop
- Conduction delay
- Accessory pathway
What are some bradycardia causes of arrhythmia?
- Sinus bradycardia
- Sick sinus syndrome (intrinsic SA node dysfunction)
- Extrinsic factors such as drugs (beta blockers, some Ca channel blockers)
- Conduction block
- Problems at AV node o bundle of His
- Slow conduction at AV node due to extrinsic factors (beta blockers, some Ca2+ channel blockers)
When are delayed after-depolarisations most likely to occur?
Delayed after-depolarisations
Most likely to happen if intracellular Ca2+ high
Ca2+ causes depolarisations when shouldn’t and could cause tachycardia
When are early after-depolarisations most likely to occur?
- Early after-depolarisations are more likely to happen if AP prolonged
- Occur before repolarisation
- Can lead to oscillations - Can lead to pronounced ventricular tachycardia
- Longer AP and longer QT interval
- Long QT syndrome or Drug induced (pro arrhythmic effects) as interfere with K channels in the heart.
Re-entrant mechanisms for generating arrhythmias
Problem occurs if there is incomplete conduction damage (unidirectional block)
Excitation can take a long route (as long, allow normal side to depolarise) to spread the wrong way through the damage area, setting up a circus of excitations.
When do multiple re-entrant circuits occur?
If they occur in the atria, it can lead to atrial fibrillation.
It is possible to get several small re-entry loops in the atria, leading to atrial fibrillation.
When can a re-entry loop be created?
AV-node Re-entry:
Fast and slow pathways in the AV node create a re-entry loop.
Ventricular pre-excitation:
An accessory pathways between atria and ventricles creates a re-entry loop such as in Wolff-Parkinson-White syndrome.
What are the 4 basic classes of anti-arrhythmic drugs?
- Drugs that block voltage-sensitve sodium channels
- Antagonists of B-adrenoreceptors
- Drugs that block potassium channels
- Drugs that block calcium channels.
How does Lidocaine work?
This is class Ib.
It is a drug that blocks the voltage gated Na+ channels.
Use-dependant block. Only blocks voltage gated Na+ channels in open or inactive state - therefore preferentally blocks damaged depolarised tissue.
Little effect 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 IV
Damaged areas of myocardium may be depolarised and fire automatically
More Na+ channels are open in depolarised tissue
- Lidocaine blocks these Na+ channels (use dependant)
- Prevents automatic firing of depolarised ventricular tissue
NOT used prophylactically following an MI
- Even if the patient is in VT, generally use other drugs.
How to B-adrenoreceptor antagonists work?
- Class II
- E.g. Propanalol, Atenolol (betablockers)
- Block sympathetic action
- act at B1 adrenoreceptor in the heart
- Decrease slope of pacemaker potential in SA node and slow conduction at AV node.
What are B blockers use for?
- Can prevent supraventricular tachycardia
- B-blockers slow conduction in AV node
- Slow ventricular rate in patients with AF
-
Used following MI
- MI often caused increased sympathetic activity
- Arrhythmias may be partly due to increased sympathetic activity
- B-blockers prevent ventricular arrhythmias.
- Also reduce oxygen demand
- Reduced myocardial ischaemia
- Beneficial following MI
How do class III anti-arrhythmic drugs work?
- Drugs that block K+ channels
- Prolong the action potential - mainly by blocking the K+ channels
- This lengthends the absolute refractory period
- In theory, would prevent another AP occuring too soon - BUT in reality it can be pro-arrhythmic.
- They are not generally used because of this property.
Amiodarone?
- This is included as a type III anti-arrhythmic but has other actions in addition to blocking K+ channels.
- It is used to treat tachycardia associated with Wolff-Parkinson-White syndrome (re-entry loop due to an extra conduction pathway)
- Effective for suppressing ventricular arrhythmias post MI.
What is verapamil?
- A Drug that block Ca2+ channels
- Decrease slope of AP at SA node.
- Decreases AV nodal conduction
- Decreases force of contraction (negative intropy)
- Also some coronary and peripheral vasodilation.
- (Dihydropyridine Ca2+ channel blockers are not effective in preventing arrhythmias but do act on vascular smooth muscle. - e.g Amlodipine, felopidine, nicardipine ect)
How does Adenosine work?
- Produced endogenously at physiological levels
- BUT, can also be administered IV
- Acts on A1 receptors at AV node but has a very short half-life (seconds).
- Enhances K+ conductance
- Hyperpolarises cells of conducting tissue.
- Anti-arrhythmic
- Doesn’t below in any classes mentioned
- Useful for terminating re-entrant SVT.
What are ACE inhibitors?
- EG perindopril
- They inhibit 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
What is the effect of ACE inhibitors?
They decrease the vasomotor tone (decrease BP)
Reduce afterload of the heart
ALSO decrease fluid retention - decrease blood volume
Reduce preload of the heart
BOTH effects reduce the work load of the heart
What are ARBs?
- Angiotensin II receptor blockers
- Inpatients that can’t tolerate ACEi
- There are used in treatment of heart failure and hypertension.
- E.g. Losartan
Diuretics
- Used in treatment of heart failure and hypertension
- Loop diuretics useful in congestive failure.
- e.g. ferusemide
- Reduces pulmonary and peripheral oedema
- Other diuretics such as thiazide diuretics useful in more mild cases of congestion.
Ca2+ channel blockers
- Dihydropyridine Ca2+ channel blockers are not effective in preventing arrhythmias but act on vascular mouth muscle.
- E.g. Amlodipine, Nicardipine
- Decrease peripheral resistance
- Decrease arterial BP
- Reduce workload of the heart by reducing afterload.
- Other types of Ca2+ blockers eg verapamil and dilitiazem act on heart
- Reduce workload of heart by reducing force of contraction.
- Ca2+ channel blockers useful in hypertension, angina, coronary artery spasm and SVTs.
What are positive inotropes?
- Positive inotropes increase contractility and thus cardiac output.
- Cardiac glycosides - Dioxin
- B-adrenergic agonists - Dobutamine.
How do cardiac glycosides work?
Primary mode of action is to block Na+/K+ ATPase
- Ca2+ is extruded via the Na+-Ca+ exchanger
- Driven by Na+ moving down concentration gradient
- Cardiac glycosides block Na+/K+ ATPase
- Leads to a rise in the intracellular Na+
- Ths results in a decrease in activity of Na+-Ca2+ exchanger
- It causes an increase an increase in intracellular Ca2+so more Ca2+ is stored in the SR
- Increased force of contraction.
Work but make heart work harder so no long term benefits - need to reduce workload of heart.
What effect do cardiac glycosides have on heart rate?
Cardiac glycosides also caused increased vagal activity.
- Action via central nervous system to increase vagal activty
- Slows AV conduction
- Slows heart rate
Cardiac glycosides may be used in heart failure where there is an arrhythmia such as AF
