CVS session 9: drugs and the CVS Flashcards
How might ectopic pacemaker activity disturb cardiac rhythm?
Damaged area of myocardium becomes depolarised as it is spontaneously active. Latent pacemaker region is activated due to ischaemia, and this dominates over the SA node
E.g. atrial fibrillation and atrial flutter
What are after-depolarisations?
Abnormal depolarisations following the action potential
- Delayed after-depolarisations: this is a risk after a prolonged action potential, more likely to happen where there is a high [Ca2+]
- Early after-depolarisations: more likely if there is a prolonged action potential and therefore a longer QT interval. Can lead to oscillations ( a ripple effect)
What is a re-entry loop?
A conduction delay and use of an accessory pathway. Incomplete conduction (unidirectional block) so excitation can take a long time to spread the wrong way through the damaged area. Can’t get past the block unless travel in the opposite direction.
It is possible to get several small re-entry loops leading to atrial fibrillation (due to the multiple ectopic foci)
What causes disturbances to cardiac rhythm?
I.e. arrhythmias/dysrhythmias (same thing). Bradycardia, atrial flutter, atrial fibrillation, ventricular fibrillation, ventricular tachycardia, supra ventricular tachycardia
Due to:
- Ectopic pacemaker activity
- After-depolarisations
- Re-entry loops
What drugs can affect the rate and rhythm of the heart?
Class I: Na+ channel blockers Class II: beta adrenoceptor antagonists Class III: K+ channel blockers Class IV: Ca2+ channel blockers Adenosine
Describe the action of class I anti-arrhythmics
Block voltage-sensitive Na+ channels e.g. the local anaesthetic lidocaine
Only block channels in an open or inactive state, so the drugs are use-dependent as channels have to be open then begin to inactivate in order to be blocked. Dissociate rapidly in time for the next AP by leaving the channel
Effect:
- little effect in normal cardiac tissue
- not used prophylactically or following MI
- SOMETIMES used following an MI if the patient has ventricular tachycardia. In VT damaged areas of myocardium may be depolarised and fire automatically, so Na+ channels are open, so lidocaine can prevent automatic firing of depolarised ventricular tissue and leave the other channels unaffected
Describe the action of class II drugs
Antagonise beta adrenoceptors so called beta blockers, e.g. propranolol, atenolol
Block beta 1 adrenoceptors in heart so block sympathetic activity, so decrease the slope of the pacemaker potential thus reducing heart rate.
Used following MI:
-MI increases sympathetic activity so can cause arrhythmias
-beta blockers prevent arrhythmias, reduce O2 demand (so reduce ischaemia) and slow conduction in AV node (help prevent supra ventricular tachycardia)
Describe the action of class III drugs
K+ channel blockers so lengthen the absolute refractory period, thus prolonging the action potential. In theory this prevents another AP occurring too soon but in reality this can be pro-arrhythmic, so such drugs are not commonly used
Exception is amiodarone
Why is amiodarone the only class III anti-arrhythmic used?
Has other actions in addition to blockage of K+ channels so this action does not predominate. Used to treat tachycardia associated with Wolff-Parkinson-White syndrome (re-entry loop due to an extra conduction pathway)
Describe the action of class IV anti-arrhythmics
Ca2+ channel blockers such as verapamil. Actions: decrease the slope of the action potential at the SA node, decrease AV node conduction and decrease the force of contraction (negative inotrope)
What is the action of dihydropyridine Ca2+ channel blockers?
Not effective in preventing arrhythmias as don’t affect the type of L-type calcium channels that are present in the heart
Act on vascularr smooth muscle
E.g. amlopidine, felopidine, nicardipine
Describe the action of adenosine as an antiarrhythmic
Produced endogenously and administered intravenously. Acts on A1 receptors (adenosine 1 receptors not adreno!) at the AV node, to enhance K+ conductance which hyper polarises the cells of conducting tissue
What is heart failure?
A chronic failure of the heart to provide sufficient output to meet the body’s requirements. Features:
- reduced force of contraction
- decreased cardiac output
- decreased tissue perfusion
- peripheral and pulmonary oedema
Drugs used for treatment principally decrease the workload of the heart, by reducing after load (resistance to pump out) and preload (return of blood to the heart)
How can cardiac glycosides be used to treat heart failure?
Prototype: digoxin. Compounds derived from foxgloves. Improve symptoms by increasing myocardial contractility, but are not a long-term solution as they increase workload!
Action 1: blocks Na+/K+ ATPase
- more Na+ is retained inside the cell
- this reduces the activity of NCX as it offsets the gradient, so more Ca2+ is retained inside the cell
- more Ca2+ causes more Ca2+ release from ER (CICR), so more available to bind to troponin-C so increases contractility (positive inotropy)
- inhibition of pump in vascular smooth muscle also causes depolarisation so vasoconstriction also occurs (but when given in heart failure the improved cardiac output reduces resistance so stops vasoconstriction)
Action 2: increases parasympathetic vagal activity
- decreases SA node firing rate (negative chronotropy)
- reduces conduction velocity through AV node (negative dromotropy)
Main clinical effects in heart failure: increased inotropy and ejection fraction, decreased preload and pulmonary congestion/oedema; very little impact on heart rate
How might beta adrenoceptor agonists be used in short-term management of heart failure?
Not used in long term as increase workload of heart! E.g. dobutamine
Mimic actions of sympathetically-released NA and circulating adrenaline, acting on mainly beta 1 adrenoceptors in the heart. They increase heart rate, contractility and conduction velocity, via their coupling to Gs proteins
Uses: cardiogenic shock (need to increase BP) and acute reversible heart failure (e.g. following cardiac surgery)
Major side effect=arrhythmia
