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Compare to skeletal muscle which needs a stimulus to contract, the heart is a more specialized organ and contains cells that display automaticity (Harvey and Champe, 1997). In the heart conduction of impulses begins at the sinoatrial node across to the atria, from the atria it travels to the atrioventricular node down to the bundle of His to the Purkinje fibres and finally to the ventricles (Walker and Whittlesea, 2006). This sequence of events is called the sinus rhythm.
Sinus rhythm may become impaired by many factors. The two most common impairments occur as a result of blockage of a blood vessel or the failure of a blood vessel to dilate or contract properly (Gard, 2001). Failure of the heart to contract rhythmically is generally referred to as an arrhythmia. To be precise an arrhythmia is defined as "an abnormal cardiac rhythm usually involving a change in rate or regularity" (Walker and Whittlesea, 2006).
Arrhythmias may arise for a range of reasons. Any interruption in the conduction of action potentials carried out by specialised tissues around the heart will influence cardiac rhythm (Gard, 2001). A delay in electrical conductivity may also cause arrhythmia to occur. The reason for this is that delay causes re-depolarisation of some cells which have already passed through the refractory period hence you get a disruption to normal rhythm of the heart (Gard, 2001). Other types of arrhythmia such as ectopic beats and fibrillation develop when non pacemaker cells depolarises spontaneously (Gard, 2001). A perfect example of this is the opening of voltage gated sodium channels which occur prematurely (Gard, 2001). In order to have a successfully and rational treatment plan it is important to understand the mechanism of the disease.
Mechanism of Arrhythmia
Many arrhythmias arise due abnormal impulse generation. This may occur due to an abnormal automaticity or an enhanced normal automatic rhythm (Gladson, 2006). The shortening of diastolic depolarization through the stimulation of catecholamine may result in alteration of the pacemaker (SA) rate (Gladson, 2006). The highest rate of spontaneous discharge occurs in the siano-atrial node, which controls the heart rate. Should the siano-atrial node fail to generate an electrical impulse, then the tissue with the next fastest rate takes over (Gladson, 2006). This is often the atrioventricular node (AV), which is capable of generating impulses 45 times/minute.
Following the AV node is the His-Purkinje system which can initiate impulses at 25 discharges per minute (Gladson, 2006). Abnormal automaticity takes place due to the development of an ectopic focus that usually occurs at a much faster rate than the siano-atrial node or other potential pacemaker (Gladson, 2006). This event generally occurs in the Purkinje fibres and is referred to as ectopic pacemaker activity.
Ectopic pacemaker activity may also lead to another event underlying many arrhythmias termed delayed after depolarisation (Gladson, 2006). This event occurs in phase 4 and happens as a result of excessive calcium which is release from the sacroplasmic reticulum (Gladson, 2006). Excessive calcium is thought to activate the sodium-calcium exchange and as a result one calcium ion is brought out of the cell in exchange for three sodium ions into the cell. This exchange mechanism produces depolarization (Gladson, 2006).
Another phenomenon known as early after-depolarization may also give rise to abnormal automaticity. This event occurs in phase two or three and results from a slow heart rate (bradycardia) or as a result of drugs that lengthens the action potential (Gladson, 2006).
A variety of arrhythmias are also caused by re-entry rhythm. Reentrant rhythm can affect the ventricles, atria and nodal tissues depending on the location of the reentry circuit (gladsome, 2006). Essentially, the reentry circuit depicts a condition in which conduction is partially blocked.
Generally conduction occurs in both directions when an impulse travels around a ring of tissue. Upon meeting the two impulses will cancel out each other when they meet. On the other hand, if the tissue has ischemic damage to the extent that it causes a blockade of one impulse but the second can get through an incessant sequence of activity can occur. This event is known as circus movement and takes place with a unidirectional block.
Management of Cardiac Arrhythmias
Once cardiac arrhythmia has been detected and characterized and the underlying cardiac disease defined, then a decision must be made as to whether to treat the arrhythmia (Winkle et al., 2007). If a decision is made to treat the arrhythmia, then the aim of the anti-arrhythmic therapy should be defined in advance for each patient (Winkle et al., 2007).
Drugs used to treat arrhythmias are called anti-arrhythmic agents. Clinically they can be classified according to the type of arrhythmias they act on (BNF, 2010). For example, those that acts on supraventricular arrthymias (e.g. verapramil), those that act on ventricular arrhythmias (e.g. Lidocaine (lignocaine)) and those that act on both supraventricular and ventricular arrhythmias (e.g. amiodarone).
Anti-arrhythmias drugs can also be classified base on the effects they have on the electrical behaviour of myocardial cells during activity (BNF, 2010). There are four classes.
Class I: Sodium- channel blockers (e.g.Lidocaine)
Class II: Î²-Adrenoreceptor blocker
Class III: K+ Channel blocker (e.g. amiodarone)
Class IV: Calcium-Channel blockers
There are many drugs that are used to treat arrhythmias however for the purpose of this essay I will focus on the anti-arrhythmic drugs amiodrone and lignocaine (lidocaine).
Amiodarone is a derivative of benzofuran and has two atoms of iodine attached to it. It is structurally similar to triiodothyronine (T3) and Thyroxine (T4) (khan, 2008). Amiodarone is classified as a class III drug but has more than one class of antidysrhythmic action (Rang et al., 2009). Amiodarone substantially prolong the cardiac action potentially and it is categorized as a class III drug based on this special feature (Rang et al., 2009).
Amiodarone is extremely effective at suppressing arrhythmias particularly supraventricular and ventricular arrhythmias. However its use is limited due to the severity of its adverse effects during chronic administration (Ritter et al., 2007).
Mechanism of Action
As mention above amiodarone is a class III agent that is very effective in the prophylaxis and suppression of arrhythmias. One of the main effects of amiodarone is that it extends the duration of the action potential but has no impact on its rate of rise (Ritter et al., 2007). It also prolongs repolarization by causing a reduction of the cell membrane permeability to potassium currents (Ritter et al., 2007). Amiodarone also causes a reduction in the slope of diastolic depolarization and this action decrease the resting heart rate at the sinus node (Ritter et al., 2007). It impedes AV nodal and atrial conduction but has no effect on ventricular conduction.
The effects of amiodarone are complex. Upon oral administration of amiodarone the duration of action potential is lengthen and thus the effective refractory period in all cardiac tissues as well as accessory pathways (Khan, 2009). The effect of amiodarone tends to overlap the other classes of antiarrhythmics. For example during phase two and three of the cardiac action potential amiodarone is known to produce potent sodium channel blockade and effect normally seen by class I drugs (Khan, 2009). Consequently the drug depresses His-Purkinje and myocardial conduction.
Amiodarone also acts by blocking calcium channel, slowing cardiac conduction and as a less potent Î²-Adrenoceptor blocker it may have central antiadrenergic effects (kalant and Roschlou, 2000). As mentioned earlier amiodarone has two atoms of iodine attached to it. This high iodine content exerts an antithyroid action, the effects of which may be antiarrhythmic (kalant and Roschlou,. 2000)
Treatment in Cardiac Arrhythmia (Dosage)
Amiodarone is given intravenously (this is only indicated for patients with recurring ventricular fibrillation and unstable angina) (Khan, 200). A first loading dose of 5mg/Kg in 250 ml of 5% glucose is infused over a period of twenty minutes to two hours ( this is done to prevent hypotension) (Ritter et al.,2000). In the case of life threatening arrhythmias this maybe repeated for two days. In the case of cardiac arrest with frequent or refractory ventricular fibrillation 150-300mg of amiodarone is given by slow injection over one to two minutes (Ritter et al., 2000).
When a response is established, the patient will then begin oral treatment, generally a low dose regimen is used. 200mg three times a day for a period of one week this is reduced to 200mg twice a day for a further week or two until the desired effect is achieved (Khan, 2007). A maintenance dose of 200mg a day or the required minimum dose to control the arrhythmias after a period of four weeks is given (Khan, 2007).
After a period of four weeks, the goal is to attain a serum level of 2µg/ml amiodarone and 2µg/ml of the active metabolite desethyl aminodarone (Khan, 2009). First loading dose of amiodarone (5mg/kg) is given intravenously followed by an oral dosing can reduced the time to optimal arrhythmic control (Khan, 2007).
Lidocaine is one of the most extensively used local anesthetics and is beneficial in treating cardiac arrhythmias particularly ventricular arrhythmias (Cummins, 2007). Immediately after a myocardial infarction lidociane is given by intravenous infusion for the treatment and prophylaxis of ventricular arrhythmias (Rang et al., 2009). Lidocaine is given intravenously because it is extensively metabolized by the liver (first pass) and as such prevents the achievement of an effective plasma concentration by the oral route (Ritter, 2000).
Mechanism of action
Lidocaine is a class I antiarrhythmic agent and is a weak sodium channel blocker (Waller and Waller, 2010). Lidocaine is beneficial in treating ventricular arrhythmias arising during myocardial ischemia. Lidocaine acts by suppressing ventricular arrhythmias primarily by decreasing automaticity by lowering the slope of diastolic depolarization (phase 4) (Lucita and Eapen 2008). By further depressing the conduction in re-entrant pathways, lidocaine may terminate re-entrant ventricular arrhythmias and as such unidirectional block is converted to bidirectional block (Lucita and Eapen 2008). This action averts the influx of wavefronts from zones of ischemic myocardium.
It has also been shown that lidocaine reduces the disparity in the duration of action potentials between normal and ischemic zones (Lucita and Eapen, 2008). Lidocaine also prolongs refractoriness and conduction in ischemic tissue.
Lidocaine exerts its effects by causing a decrease in Vmax (phase 0) of the action potential. Lidocaine reduces the action potential duration and the refractory period of ventricular myocardial cells and normal Purkinje fibers (Kalant and Roschlau, 1998). The effect of this reduction is grater on action potential than that on the effective refractory period. Consequently the effective refractory period is prolonged relative to the duration of the action potential. In atrial tissue, lidocaine has little activity on the duration of action potentials (Kalant and Roschlau, 1998).
There is no effect on sinus-node function in normal subjects but this may be depressed in patients with previous sinus-node dysfunction (Kalant and Roschlau, 1998). Ventricular reentry is eliminated by lidocaine using a similar mechanism to that for quinidine (another class 1 antiarrhythmic drug). Conduction is slowed by lidocaine and this occurs most in diseased (ischemic or hypoxic) tissues and at high rates of stimulation.
Treatment in Cardiac Arrhythmia (Dosage)
Lidocaine is given by i.v. injection as an initial dose of 1.0-1.5 mg/Kg (75-100mg). After five to ten minutes a second bolus of 0.75 -1.0 mg/kg is administered (Khan, 2007). The dose should be halved in patients with severe hepatic disease, or as in the case of severe heart failure, cardiogenic shock, during concurrent administration of cimetidine and in patients over 65 years of age hepatic blood flow should be reduced (Khan, 2000).
The first bolus is given concurrently with the commencement of the intravenous infusion of lidocaine. This is done so as to prevent a lag between the bolus and the infusion (Khan, 2000). Infusion is commenced at 2 mg/ml. A third bolus of 50mg is administered in the case of recurrent arrhythmias and the rate of infusion is increased to 3mg/min (Khan, 2000). Before increasing the rate of infusion to a maximum of 4 mg/min careful reevaluation of the clinical situation should be carried out.