Drugs and cardiac conduction disorders Flashcards
What is the Vaughan Williams classification of anti-arrhythmics?
- Class I - membrane stabilising drugs (lidocaine, flecainide)
- Class II - beta blockers
- Class III - amiodarone; soltalol (also class II)
- Class IV - calcium channel blockers (verapamil but does not include dihydropyridines)
What are the 2 types of arrhythmias?
- *Abnormal automaticity**
- An area of the heart begins to fire impulses at a rate faster than the SA node
- This causes the ventricles to over-ride the impulses from the SA node and the heart beat is driven by the ventricles instead
- *Abnormal re-entry**
- Often results from scar tissue in a ventricle following an MI
- As scar tissue does not conduct electricity, the impulse circles around the scar tissue with each cycle causing the ventricles to contract
- There might also be an accessory pathway between the atria and ventricles like the bundle of Kent in Wolff-Parkinson-White syndrome where conduction is bi-directional meaning impulses can travel from atria to ventricle and from ventricle to atria through the accessory pathway causing contractions
What is meant by a chronotropic and inotropic agent?
Chronotrope = affects HR Inotrope = affects strength of contraction
Describe how the 3 classes of sodium channel blockers (Class I anti-arrhythmics) work.
Class Ia
Quinidine, procainamide, disopyramide
- Inhibit Na channels and K channels on atrial and ventricular myocytes and cells of the purkinje fibres
- Blocking of Na channels = decreased sodium entering cell = slower depolarisation - lengthens duration of action potential
- Blocking K channels = less K leaving cell so leads to slower rate of repolarisation and longer effective refractory period
Ib
- Lidocaine
- Mexiletine
Commonly used to treat ischaemic arrhythmias following MI
- Inhibit the Na+ channels in purkinje fibre cells, ventricular myocytes but not atrial myocytes.
- Not as potent in blocking Na+ as class Ia
- More likely to bind to depolarised cells damaged by ischaemia as they have trouble maintaining their negative membrane potential
- Cause a slight decrease in refractory period (unknown mechanism)
Ic
Flecainide
Inhibit Na+ channels in atrial, ventricular and purkinje myocyte cells
Strongest potency out of the 3 class I types
Used for ventricular tachycardia which turns into ventricular fibrillation
Used for refractory arrhythmias only when other classes haven’t worked as class Ic are the most likely to cause arrhythmias
Where are B1 and B2 adrenergic receptors found?
B1
- Mainly found in the heart
- Found in both pace-maker and non-pace maker cells
B2
- Mainly found in smooth muscle cells (blood vessels)
How do B-blockers work in pacemaker and non-pacemaker cells?
Selective vs non-selective B blocker examples?
- In pace maker cells, B-Blockers prevent epinephrine and norepinephrine from binding to b-receptors and this indirectly decreases the number of L-type calcium channels that open = slower pacemaker potential.
- Decreases rate of SA node firing = decreases HR.
In non pace-maker cells (cardiac myocytes) beta blockers also indirectly prevent the opening of L-type calcium channels
- This decreases the amount of intracellular calcium available to muscle fibres and therefore, weakens for force of contraction of the muscle
- By reducing both HR and force, beta blockers reduce the cardiac oxygen demand
- Beta blockers can be divided into selective and non-selective
- *Selective B1 blockers**
- Begin with letters from the first half of the alphabet A-M
- Atenolol
- Acebutolol
- Betaxolol
- Bisoprolol
- Metoprolol
- Esmolol
- *Non-selective B1 blockers**
- Target all beta receptors start from second half of alphabet N-Z
- Timolol
- Propanolol
Indications for beta blockers?
As they decrease cardiac oxygen demand they are used in…
- Supraventricular tachycardias such as AF and atrial flutter
- Prophylaxis for arrhythmias in individuals who experienced recent MI
Side effects of beta blockers? (Cardiac and Extracardiac)
- *Cardiac side effects**
- SA node depression = bradycardia, heart block, heart failure
- *Extracardiac side effects**
- Fatigue, sedation, sleep disturbance, sexual dysfunction, dyspnoea & broncho-spasm
- Bronchospasm more common in propanolol due to their effect on B2 receptors in the lungs
- Hypoglycaemia unawareness
Contraindications for beta blockers?
- Not used in asthmatics as can cause broncospasm due to effect on B2 receptors in lungs
- Not used with calcium channel blockers due to additive effect on conduction velocity through AV node - can result in AV block
- In the treatment of pheochromocytoma and in cocaine toxicity - can lead to hypertension and aortic dissection
How do Class III (potassium channel blocker) anti-arrhythmics work?
Work by blocking the potassium channels in myocardiocytes which slows repolarisation and prolongs the action potential and refractory period in all cardiac tissues (longer QT interval)
Class III (potassium channel blocker) drug examples?
- Amiodarone - most common
- Dronedarone
- Sotalol
- Ibutilide
- Dofetilide
How does Amiodarone work?
What are it’s indications?
Side effects of amiodarone?
- Has blocking actions on several channels (K+ and inactivated Na+ channels and beta-adrenoceptors)
- Long half life (10-100 days) due to iodine in structure and therefore, lipophillic and accumulates in tissues
- Useful in most arrhythmias such as AF, atrial flutter, life-threatening ventricular tachycardia
- Used when other drugs have failed to work due to its long half life (as it is lipophilic) & severe side effects.
Side effects
- Thyroid dysfunction - hypo or hyper
- Photosensitivity
- Pulmonary alveolitis and fibrosis
- Neuropathy
- Constipation
- Corneal deposits
- Liver dysfunction
- Cardiovascular issues - bradycardia, heart block and heart failure
How do Class IV (Calcium channel blockers) work?
What are the 2 groups of CCBs?
Examples of drugs in the groups and indications?
Ca channel blockers bind and inhibit voltage-dependent L-type calcium channels
There are 2 groups of calcium channel blockers
DIHYDROPYRIDINES Selective for calcium channels on vascular smooth muscle - not antiarrhythmic - Amlodipine - Nicardipine - Nifedipine - Used to treat HTN
NON-DIHYDROPYRIDINES
Target pace maker and non pace maker cells in the heart
- Pace maker cells = Reduce calcium entering cell causing a slower depolarisation
- Non-pace maker cells = Decrease amount of calcium entering cell causing a weaker force generated during heart contraction
- Class IV antiarrhythmics
- Verapamil (angina and SVT)
- Diltiazem (HTN & SVT)
How does adenosine work as an anti-arrhythmic?
When is it used?
Side effects?
- Stimulates A1-adenosine receptors and opens Ach sensitive K+ channels and inhibits L-type calcium channels
- This hyperpolarises the cell membrane in the AVN and by inhibiting Ca channels, slows conduction in the AVN = lowering HR and decreasing conduction velocity
- *Indications**
- IV used to terminate paroxysmal supraventricular tachycardia including Wolff-Parkinson-White syndrome
- *Side effects**
- Flushing
- Hypotension
- Bronchoconstriction
- Dyspnoea
- Chest pain
- Rapid onset of action (20-30sec) and short duration (10 sec) so side effects are short-lived.
How does digoxin work?
What are it’s indications?
Side effects?
Digoxin is a cardiac glycoside that increases the force of myocardial contraction and reduces conductivity within the atrioventricular (AV) node.
This reduces HR and conduction velocity
- *Indications**
- Oral admin in AF
- IV admin in rapid uncontrolled atrial flutter and fibrillation
- *Side effects**
- Narrow therapeutic window so easy to overdose and cause arrhythmias
- Specific sign of overdose = atrial tachycardia with AV block.
