1. Anti-arrhythmic drugs
Cardiac arrhythmias are commonly seen during myocardial ischemia, digoxin treatment and anesthesia.
Anti-arrhythmic drugs are used to prevent and treat cardiac arrhythmias.
Cardiac arrhythmias are a frequent problem in clinical practice. Not all arrhythmias require treatment with potentially toxic antiarrhythmic drugs. Arrhythmias that typically require treatment fall into 3 basic categories:
arrhythmias that decrease cardiac output (e.g. severe bradycardia, ventricular tachycardia or fibrillation)
arrhythmias that are likely to precipitate more serious arrhythmias (e.g. atrial flutter may lead to sustained ventricular tachycardia)
arrhythmias that are likely to precipitate an embolism due to creation of vascular stasis (e.g. chronic atrial fibrillation)
Isoproterenol hydrochloride injection is indicated:
For mild or transient episodes of heart block that do not require electric shock or pacemaker therapy.
For serious episodes of heart block and Adams-Stokes attacks (except when caused by ventricular tachycardia or fibrillation).
For use in cardiac arrest until electric shock or pacemaker therapy, the treatments of choice, is available. (For bronchospasm occurring during anesthesia.
As an adjunct to fluid and electrolyte replacement therapy and the use of other drugs and procedures in the treatment of hypovolemic and septic shock, low cardiac output (hypoperfusion) states, congestive heart failure, and cardiogenic shock. (
Seventy times a minute, 100,000 times each day, it beats effortlessly, indefatigability. Your heart is an organ like none other, charged with moving 4,300 gallons of blood each day through the intricate vascular network of our body...
Although displacement of blood is its primary function, each and every beat of this unique muscular pump is initiated and finely regulated by electrical impulses that originate in the heart itself. Electrical currents, not in the form of electrons like those that course through the wires of our house, but in the form of ions, flow across the membrane of each cell causing voltage surges that set the heart in motion. Sodium ions rush into the cells, to be followed by potassium and chloride ions making a quick exit. The resulting voltage spike or action potential regulates the influx of calcium ions that mediate the sliding motion of filaments within each cell causing their shortening or contraction.
This process, repeated in each adjoining cell of the heart, causes the orderly spread of electrical activity and the synchronous contraction of the myocardium (heart muscle). Like other "excitable" tissues, the cells of the heart are electrically connected through low resistance pathways. These pathways facilitate the spread of the electrical impulse, ensuring efficient activation and pumping motion. Without electrical activity, the heart lies motionless and serves no useful purpose. Disorderly electrical activity also known as arrhythmias may also render the heart inefficient or totally useless as a pump. Extreme disorganization of the electrical activity within the heart can lead to sudden death, the single most prevalent mechanism of death in the United States, taking the lives of over 350,000 Americans each year. Nearly every minute of every day someone in this country dies of sudden cardiac death, very often the result of an arrhythmia known as ventricular fibrillation.
Arrhythmias are not always life-threatening. Some, including extrasystoles or "extra beats" may be quite innocuous. Others. like AV nodal tachycardia, although not lethal, may be incapacitating. Still others. like atrial fibrillation may be less crippling, but a nuisance nevertheless.
In recent years, Implantable Cardioverter Defibrillators (ICDs) have become common in the prevention and immediate treatment of ventricular fibrillation. These devices are implanted inside the chest. They monitor the heart rhythm, and in the event of ventricular fibrillation, they administer an electric shock to jolt the heart back into a normal rhythm. The device is similar to the defibrillators carried by emergency paramedic crews. ICDs and antiarrhythmic medications are often used in the same patient. ICDs are also frequently implanted in patients who are at risk of ventricle tachycardia.
To treat bradyarrhythmias
Atropine and Isoproterenol (pacemaker)
To treat tachyarrhythmias
Antiarrhythmic drugs

2. Anti-arrhythmic drugs
At the end of repolarization, when the membrane potential is very negative (about -60 mV), ion channels open that conduct slow, inward (depolarizing) Na+ currents. These currents are called "funny" currents and abbreviated as "If".
Atrial myocytes, ventricular myocytes and Purkinje cells are examples of non-pacemaker action potentials in the heart. Because these action potentials undergo very rapid depolarization, they are sometimes referred to as "fast response" action potentials. .
Transformation of non-pacemaker into pacemaker cells
It is important to note that non-pacemaker action potentials can change into pacemaker cells under certain conditions. For example, if a cell becomes hypoxic, the membrane depolarizes, which closes fast Na+ channels. At a membrane potential of about –50 mV, all the fast Na+ channels are inactivated. When this occurs, action potentials can still be elicited; however, the inward current are carried by Ca++ (slow inward channels) exclusively. These action potentials resemble those found in pacemaker cells located in the SA node, and can sometimes display spontaneous depolarization and automaticity. This mechanism may serve as the electrophysiological mechanism behind certain types of ectopic beats and arrhythmias, particularly in ischemic heart disease and following myocardial infarction.

3. The blockade is state-dependent
Antiarrhythmic drugs (not beta blockers) are thought to bind to receptors located near the intracellular end of voltage-gated ion channels. The binding results in blockade of the ion current.
The blockade is state-dependent
high affinity for activated or inactivated channels
preferentially block channels of depolarized cells
The recovery of channels from drug-induced block is times slower than the recovery of channels from normal inactivation.

4. Anti-arrhythmic drugs
The electrical impulse that triggers cardiac contraction originates in SA node and travels through atria and AV node and then propagates over purkinje system and invades all parts of ventricles.
Arrhythmias are caused by
Abnormalities in the generation or
Abnormalities in the conduction of the electrical impulses or
Both.

5. Normal
Atrial fibrillation

6. Anti-arrhythmic drugs
The following are the causes of arrhythmia
Abnormal generation of impulse
Enhanced / ectopic pacemaker activity
After-depolarization
Abnormal impulse conduction
Re-entry
Conduction block

7. Anti-arrhythmic drugs
Abnormal generation of impulse :
Enhanced automaticity : beta receptor stimulation
Atrial and ventricular cells may have pacemaker activity in hypokalemic conditions.
After-depolarization is of two types Early After Depolarization that occur during late phase 2 or phase 3 as in bradycardia or Delayed After Depolarization that occur during phase 4 when intracellular load is high (digoxin toxicity).
DAD are responsible for arrhythmia due to digitalis excess and ischemia.

9. Anti-arrhythmic drugs
Abnormal conduction of impulse : Re-entry
There has to be an obstacle to homogenous conduction (anatomic or physiological).
Normally electrical excitation becomes extinguished at the end of the circuit due to collision of impulse.
An unidirectional block prevents anterograde impulse but retrograde impulse is propagated.

10. imagine a room full of people all given these instructions: "If you see anyone starting to stand up, then stand up for three seconds and sit back down." If the people are quick enough to respond, the first person to stand will trigger a single wave which will then die out; but if there are stragglers on one side of the room, people who have already sat down will see them and start a second wave, and so on.

12. Anti-arrhythmic drugs
Class I
Mechanism of action
Examples
Comments Ia
Na channel blockers that ↑ APD
Quinidine Procainamide
Large block OPEN Na & K Channels, hence both QRS & QT affected. Ib
Na channel blockers that may slightly ↓ APD
Lidocaine Mexiletine Phenytoin
High affinity for INACTIVATED than open Na channels with rapid unbinding during diastole, hence little effect on QRS; also blocks the small Na plateau current which may slightly shortens the APD. Ic
Na channel blockers that do not change APD
Propafenone Flecainide
Large block of OPEN Na channels & very slow unbinding during diastole markedly prolong QRS.
the current standard of care is that Class I drugs have no role in the prevention of cardiac arrhythmias (and sudden cardiac death) in post-MI patients, and are not recommended in the primary prevention of sudden cardiac death
1b (lidocaine, mexiletine, tocainide and phenytoin). These drugs  work with rapid ventricular rhythms, including ventricular tachycardia and ventricular fibrillation. They have no effect on atrial arrhythmias.
Are weak bases (pKa > 7.0) and block the Na+ channel in the ionized form.
Acidosis will increase and alkalosis will diminish Na + channel blockade.

13. Anti-arrhythmic drugs
Class I : Sodium channel blockers:
State dependent blocking action (high affinity for open/inactivated channel) causes
effective refractory period (ERP).
Rate dependent blocking action (greatest at fast heart rates)
Class Ia: recovery time 1-10 sec (Moderate)
Class Ib: recovery time < 1 sec (Weak)
Class Ic: recovery time > 10 sec (Strong)
1b (lidocaine, mexiletine, tocainide and phenytoin). These drugs  work with rapid ventricular rhythms, including ventricular tachycardia and ventricular fibrillation. They have no effect on atrial arrhythmias.

14. Anti-arrhythmic drugs
1b (lidocaine, mexiletine, tocainide and phenytoin). These drugs  work with rapid ventricular rhythms, including ventricular tachycardia and ventricular fibrillation. They have no effect on atrial arrhythmias.

15. Anti-arrhythmic drugs
Effect of Class I antiarrhythmic agents on reentrant excitation. Left: Reentrant excitation in the absence of drug. A region of subendocardial ischemia causes membrane depolarization and inactivation of Na channels. Consequently normal excitation delivered the Purkinje fibers is not strong enough to penetrate into healthy myocardium below. Conduction progressively slows (as indicated by the wavy line) and eventually is blocked, producing a block in one direction (unidirectional block) as indicated by the red line. Meanwhile the stimulus conducted by other normal pathways succeeds in depolarizing a large mass of ventricular tissue that can add together to produce a large retrograde stimulus that can conduct slowly through the ischemic zone into the normal Purkinje tissue above, and establish a reentrant circuit. This can produce a stable arrhythmia such as a ventricular tachycardia (VTach). Right: Class I drugs will selectively increase ERP and depress conduction, an effect that is more marked in depolarized tissue (Figures 5&6). Class I drugs can also affect action potential duration to a variable extent (as indicated by the orange arrow at top, right). Class Ia drugs block IKr to prolong the APD, an effect that also contributes to prolonging the ERP.
1b (lidocaine, mexiletine, tocainide and phenytoin). These drugs  work with rapid ventricular rhythms, including ventricular tachycardia and ventricular fibrillation. They have no effect on atrial arrhythmias.

16. Anti-arrhythmic drugs
CLASS IA : Quinidine
Cinchona bark, dextro isomer of quinine.
It blocks the sodium channel and also potassium channel.
It has anti-muscarinic (decrease the AV node refractory period, which can result in a rapid acceleration of ventricular rate) and alpha blocking action.
Quinidine is used primarily for malaria, but not for arrhythmias due to its side effects, proarrhythmia & better drug options being available.
Class Ia drugs produce anticholinergic effects on the heart due to their ability to block m2 receptors (quinidine) or block autonomic ganglia (procainamide). Anticholinergic side effects include urinary retention in male patients with prostate hypertrophy, dry mouth, blurred vision, constipation and worsening of pre-existing glaucoma. An additional, potentially life-threatening situation of dangerous acceleration of ventricular rate can also occur when attempting to treat atrial flutter or fibrillation with a Class Ia drug alone (see Figure 13). Why does this occur? Why is this potentially harmful? What would you do differently to prevent it from occurring?

17. Anti-arrhythmic drugs
CLASS IA : Quinidine
It is bitter and irritant.
Quinidine is also an inhibitor of the cytochrome P450 type 2D6.
It ↑↑ plasma digoxin by displacing it from tissue binding sites and decreasing its excretion.
Used (rarely because of proarrhythmic effects) in the treatment of supraventricular tachycardia (after AV block) and ventricular tachycardia
It is an inhibitor of CYT P450 system.

18. Anti-arrhythmic drugs
CLASS IA : Quinidine : Adverse effects :
GIT : Diarrhea, nausea, vomiting and cinchonism – ringing in ears.
Precipitate torsades de pointes by prolonging QT interval
Sodium lactate: to treat quinidine overdose, increases Na current, reduces drug-receptor binding, alkalininizing tissue!!)

19. Anti-arrhythmic drugs
Class IA : Procainamide
Used for the treatment of ventricular tachycardia (second/third choice after amiodarone & lidocaine).
Chronic use result in a positive anti-nuclear antibody (ANA) titer and SLE like syndrome (arthralgia and arthritis) especially in slow acetylators.
It is less anticholinergic in nature
Because of the proarrhythmic effects of procainamide, its use with lesser arrhythmias is generally not recommended.
Chronic use of Class I Antiarrhythmics should be avoided in patients with a history of coronary artery disease (e.g. angina, prior MI) due to increased proarrhythmia in these patients, based upon the results of the Cardiac Arrhythmia Suppression Trials (CAST 1 & 2).
Lupoid syndrome: high incidence, after several months of treatment. More frequent in slow acetylator phenotypes. Syndrome dissappears after drug discontinuation
A lupus-like syndrome occurs in 20-25% of patients on procainamde for more than one year.
Patients taking procainamide commonly develop a positive anti-nuclear antibody (ANA) titer, with or without lupus symptoms

20. Anti-arrhythmic drugs
Class IA : Procainamide
Procainamide is converted to N-acetylprocainamide (NAPA), which blocks potassium channels (prolongs APD, but does not block Na channels).
NAPA accumulation has been implicated in producing torsade de pointes in patients with renal failure.
Because of the proarrhythmic effects of procainamide, its use with lesser arrhythmias is generally not recommended.
Chronic use of Class I Antiarrhythmics should be avoided in patients with a history of coronary artery disease (e.g. angina, prior MI) due to increased proarrhythmia in these patients, based upon the results of the Cardiac Arrhythmia Suppression Trials (CAST 1 & 2).
Lupoid syndrome: high incidence, after several months of treatment. More frequent in slow acetylator phenotypes. Syndrome dissappears after drug discontinuation
A lupus-like syndrome occurs in 20-25% of patients on procainamde for more than one year.
Patients taking procainamide commonly develop a positive anti-nuclear antibody (ANA) titer, with or without lupus symptoms

21. Anti-arrhythmic drugs
CLASS IB : Lidocaine: Least cardiotoxic :
Block Na channels: preference for INACTIVATED channels in partially depolarized cells of ischemic area.
High first pass metabolism – not given orally
Used in treatment of ventricular arrhythmia and also in digoxin induced arrhythmias.
Main toxicity is neurological – drowsiness, confusion and nystagmus.
The class IB drugs, which include lidocaine, tocainide, and mexiletine, are "pure" Na+ channel blockers which do not block K+ channels (2), and tend to decrease APD in the His-Purkinje system and in ventricular muscle. This decrease in APD is more significant in portions of the His-Purkinje system where the APD is normally longer (5). The class IB drugs, however, bind to the Na+ channel largely in the inactivated (i.e., depolarized) state (4), and as a result, Vmax is selectively decreased in automatic ventricular tissue or in diseased tissues where the equilibrium potential is less negative (e.g., after myocardial infarction).
Drug of 2nd choice (vs amiodarone) to terminate VTach and prevent VFib after DC cardioversion
Used only in a hospital setting (not effective orally)
Ineffective against atrial arrhythmias
It is a Na + channel blocker and does not delay the channel recovery time (< 1 s). Decrease APD due to block of slow Na current.
Class Ib antiarrhythmic agents are sodium channel blockers. Class Ib agents have fast onset and offset kinetics, meaning that they have little or no effect at slower heart rates, and more effects at faster heart rates. Class Ib agents shorten the action potential duration and reduce refractoriness. These agents will decrease Vmax in partially depolarized cells with fast response action potentials. They either do not change the action potential duration, or they may decrease the action potential duration.
Class Ib agents are indicated for the treatment of ventricular tachycardia and symptomatic premature ventricular beats, and prevention of ventricular fibrillation.
Class Ib agents include lidocaine, mexiletine, tocainide, and phenytoin.
LIDOCAINE : High concentrations (> 9 μg/ml) may cause convulsions & respiratory depression/arrest; inhibitory centers in the CNS are typically inhibited first, resulting in seizure activity; respiratory depression occurs at higher doses.

22. Anti-arrhythmic drugs
CLASS IC : Flecainide
This is a class of potent Na channel blocker
Drugs of this class have negative inotropic effect and highly pro-arrhythmogenic especially in setting of myocardial infarction.
Flecainide is indicated for life threatening ventricular fibrillation and refractory or symptomatic supraventricular arrhythmia.
Ic anti-arrhythmic drugs block Na channels in the purkinje HiS system. Class Ic antiarrhythmic agents markedly depress the phase 0 depolarization (decreasing Vmax). They decrease conductivity, but have a minimal effect on the action potential duration. Of the sodium channel blocking antiarrhythmic agents (the class I antiarrhythmic agents), the class Ic agents have the most potent sodium channel blocking effects.
Class Ic agents are indicated for life-threatening ventricular tachycardia or ventricular fibrillation, and for the treatment of refractory atrial fibrillation. These agents are potentially pro-arrhythmic, especially in settings of structural heart disease (e.g. post-myocardial infarction), and are contraindicated in such settings.
Class Ic agents include encainide, flecainide, moricizine, and propafenone.

23. Anti-arrhythmic drugs
CLASS II : Beta blockers :
Propranolol, Metoprolol, Carvedilol
CLASS III : Agents widening APD : K channel blockers :
Amiodarone, Sotalol, Ibutilide
CLASS IV : CCB :
Verapamil, Diltiazem

24. Anti-arrhythmic drugs
CLASS II : BETA BLOCKERS :
Propranolol, Metoprolol, Esmolol, Carvedilol
These diminish phase 4 depolarization – decreasing automaticity
Prolong AV conduction
Prevent re-infarction & sudden death in patients with a history of CHF or MI
Used for the control of ventricular rate in patients with atrial fibrillation
Propranolol
Propranolol is a non-selective β1/β2 blocker, and was the first beta blocker developed. Most beta blockers (selective or non-selective) share similar clinical efficacy against cardiac arrhythmias.
Metoprolol
Metoprolol is a commonly used β1-selective beta blocker.
Carvedilol
Carvedilol is a nonselective β1/β2 blocker that also blocks α-receptors, IKr, and at higher doses blocks L-type Ca channels, the transient outward current (Ito) and IKs. In addition it has antioxidant effects and inhibits endothelin
Beta blockers prevent or terminate tachyarrhythmias caused by increased sympathetic tone, excessively high levels of circulating plasma catecholamines, or tissue supersensitivity to catecholamines. (The latter may develop following a myocardial infarction that damages sympathetic nerves within the wall of the heart, resulting in a “denervation supersensitivity” in regions distal to the lesion.)
Acebutolol is a cardioselective beta blocker with ISA (Intrinsic Sympathomimetic Activity, like Pindolol). It is therefore more suitable than non cardioselective beta blockers, if a patient with Asthma bronchiale or chronic obstructive pulmonary disease (COPD) needs treatment with a beta blocker.

25. Anti-arrhythmic drugs
BETA BLOCKERS

26. Anti-arrhythmic drugs
CLASS III : POTASSIUM CHANNEL
BLOCKERS : Amiodarone
It is an iodine containing highly lipophilic anti-arrhythmic with multiple actions
Block K channels
Block inactivated Na + channels
Inhibit Ca channels
Amiodarone & Dronedarone
The most commonly used Class III drug is amiodarone. It is effective against both ventricular and atrial arrhythmias. Amiodarone has some unusual characteristics including a very long half life of several weeks, a relative lack of selectivity – it blocks Na, K, and Ca channels, as well as α− and β-adrenergic receptors. It is in essence a nonselective “antiarrhythmic shotgun”. While several of its multiple effects likely contribute to its clinical efficacy as an antiarrhythmic, its ability to prolong the APD is considered to be “most important” by many, hence its classification as Class III drug.

27. Class III agents predominantly block the potassium channels, thereby prolonging repolarization. Since these agents do not affect the sodium channel, conduction velocity is not decreased. The prolongation of the action potential duration and refractory period, combined with the maintenance of normal conduction velocity, prevent re-entrant arrhythmias. (The re-entrant rhythm is more like to interact with tissue that has become refractory).
Class III antiarrhythmic agents exhibit reverse use dependent prolongation of the action potential duration (Reverse use-dependence). This means that the refractoriness of the ventricular myocyte increases at lower heart rates. This increases the susceptibility of the myocardium to early after-depolarizations (EADs) at low heart rates. Antiarrhythmic agents that exhibit reverse use-dependence are more efficacious at preventing a tachyarrhythmia than converting someone into normal sinus rhythm. Because of the reverse use-dependence of class III agents, at low heart rates class III antiarrhythmic agents may paradoxically be more arrhythmogenic.
Amiodarone is indicated for the treatment of refractory VT or VF, particularly in the setting of acute ischemia. Amiodarone is also safe to use in individuals with cardiomyopathy and atrial fibrillation, to maintain normal sinus rhythm.
Sotalol is indicated for the treatment of atrial or ventricular tachyarrhythmias, and AV re-entrant arrhythmias. Ibutilide is the only antiarrhythmic agent currently approved by the Food and Drug Administration for acute conversion of atrial fibrillation to sinus rhythm.
Class III agents include amiodarone, azimilide, bretylium, clofilium, dofetilide, tedisamil, ibutilide, sematilide, and sotalol.

28. Anti-arrhythmic drugs
Class III : Amiodarone :
Used in wide range of ventricular and atrial arrhythmia.
Adverse effects :
Pulmonary fibrosis, Hepatotoxicity
Skin pigmentation, Corneal deposits
Thyroid abnormalities – hypothyroidism (common)
Amiodarone inhibits CYP 450 & can cause drug interactions.
Amiodarone has multiple effects on thyroid function that can cause either hypothyroidism (most commonly), or hyperthyroidism. The structure of amiodarone contains two iodine molecules, and when taken at therapeutic doses results in a large intake of inorganic iodine. The normal daily iodine intake is ~0.3 mg, whereas a normal 200 mg maintenance dose releases 6 mg of iodine following hepatic metabolism. In normal patients, high levels of iodine typically contribute to a transient inhibition of thyroid hormone synthesis due to an auto-regulatory mechanism within the thyroid (the Wolff-Chaikoff effect). Amiodarone also blocks the conversion of T4 to T3 and one of its active metabolites blocks T3-receptor binding to nuclear receptors (Ross, 2012). These mechanisms are responsible for amiodarone's hypothyroid side effects.
In contrast, in iodine-deficient patients, or patients with latent Graves' disease the excess iodine from amiodarone provides increased substrate, resulting in enhanced thyroid hormone production and hyperthyroidism (Ross, 2012).
Skin deposits of the drug can result in a photodermatitis that causes a gray-blue tint of the skin when exposed to sunlight.
Corneal microdeposits are present in most patients, but are considered a benign side effect.
Pulmonary fibrosis is another (potentially lethal) side effect associated with amiodarone, and is seen primarily in patients taking very high doses of the drug; it is rarely seen with commonly used doses.
Dronedarone is a newer analog of amiodarone that lacks iodine atoms, and has a similar lack of selectivity for blocking different ion channels and adrenergic receptors. It has a half life of 24 hours, and lacks the thyroid and pulmonary toxicity. It has been approved by the FDA for the treatment of atrial fibrillation. The drug also carries a “black box” warning against its use in acute decompensated or advanced (class IV) heart failure because of an increased risk of mortality observed in clinical trials (Hume & Grant, 2012).
Stimulation of collagen production (mainly in lung)
Risk of rhabdomyolysis, which can lead to kidney failure or death, when simvastatin is used with amiodarone.
In USA, the license for amiodarone is only for recurrent ventricular fibrillation and hemodynamically unstable ventricular tachycardia after other anti-arrhythmic drugs are not tolerated.
Due to the iodine content of the agent (37.3% by weight), abnormalities in thyroid function are common. Hypothyroidism is 6% and Hyperthyroidism is 2%. They are due to Wolff-Chaikoff effect and Jodbasedow effect respectively.

29. Clinical indications of Amiodarone:
Pigmentation Related to Amiodarone
Clinical indications of Amiodarone:
Acute suppression of post-MI ventricular arrhythmias in the Coronary Care Unit
Preferred drug to maintain normal sinus rhythm in patients with atrial fibrillation (rhythm control)
Risk of rhabdomyolysis, which can lead to kidney failure or death, when simvastatin is used with amiodarone.
In USA, the license for amiodarone is only for recurrent ventricular fibrillation and hemodynamically unstable ventricular tachycardia after other anti-arrhythmic drugs are not tolerated.
Due to the iodine content of the agent (37.3% by weight), abnormalities in thyroid function are common. Hypothyroidism is 6% and Hyperthyroidism is 2%. They are due to Wolff-Chaikoff effect and Jodbasedow effect respectively.

30. Anti-arrhythmic drugs
Other Class III : K channel blockers
Sotalol : Treatment of ventricular and atrial arrhythmia but needs monitoring.
Dofetilide and Ibutilide : Treatment of atrial flutter and fibrillation
Torsades de pointes is the most serious side effect of this K channel blockers.
Sotalol
Sotalol is Class III antiarrhythmic that consists of a mixture of stereoisomers, one of which (d-Sotalol) selectively blocks IKr, and the other (l-sotalol) is a non-selective beta blocker. The clinical use of sotalol has been limited by both its antiarrhythmic efficacy (a common issue for most antiarrhythmics), and its Class III-related associated side effect of Torsade de pointes (1.5-2% incidence). There is a “Black Box Warning” that when patients are to be initiated on sotalol therapy, they should be monitored for at least 3 days in a facility that can provide cardiac resuscitation and continuous electrocardiographic monitoring. It is indicated for both life-threatening ventricular arrhythmias and maintenance of normal sinus rhythm in patients with atrial fibrillation/flutter.
Sotalol:
Adjuvant drug to reduce ICD (implantable cardioverter-defibrillator) shocks in patients with an ICD
Drug of 2nd choice to prevent the re-occurrence of atrial fibrillation (rhythm control)
Ibutilide
Ibutilide shares a similar ~2% incidence of producing Torsades de pointes. It is indicated as an i.v. injection for the rapid conversion of atrial fibrillation or atrial flutter of recent onset to sinus rhythm. Patients with atrial arrhythmias of longer duration are less likely to respond.
Ibutilide increases the action potential duration by increasing the slow sodium current.
Torsades de pointes is the most serious side effect of dofetilide, ibutilide and sotalol therapy.
Pronunciation: \tȯr-ˌsäd(z)-də-ˈpwant\
Bretylium : Treatment of ventricular arrhythmia after lidocaine has failed.

31. Anti-arrhythmic drugs
Class IV : Calcium channel blockers: Verapamil and Diltiazem
These are used in the treatment of PSVT (supraventricular tachycardia) next to adenosine.
These are used to control the ventricular rate in chronic atrial fibrillation.
Used in angina and prophylaxis of migraine.
They reduce the contractility of the heart, so not appropriate to use in heart failure.
Ca channels behave much like Na channels: their behavior is voltage-dependent and is governed by movement of activation and inactivation gates. However, Ca channels have a more positive “threshold” for activation, and slower kinetics of opening and inactivating. In normal atrial and ventricular cells, their primary function is to produce the action potential plateau and modulate the strength of muscle contraction. However, in the more depolarized regions of the SAN and AVN, they are also responsible for conduction and refractoriness.
The primary cellular mechanism of action of Ca channel blockers is to slow AVN conduction and increase the AVN ERP.
They reduce the contractility of the heart, so not appropriate to use in heart failure.

34. Anti-arrhythmic drugs
Adenosine : Drug of choice for PSVT
It activates the K channels in the AV node. – hyper polarization;
AV conduction is slowed.
Short half life ~ 10 s
Terminates the paroxysmal supraventricular tachycardia (PSVT)
Bronchospasm is the major adverse effect
Adenosine is not dangerous when VT is masquerading SVT, as adenosine is not dangerous as its transient effects leaves VT unchanged whereas verapamil could be fatal in VT because of myocardial depression or vasodilation.
SA Node and AV node are slowed down.
No hemodynamic deterioration
Adenosine has an indirect effect on atrial tissue causing a shortening of the refractory period. When administered via a central lumen catheter, adenosine has been shown to initiate atrial fibrillation because of its effect on atrial tissue. In individuals with accessory pathways, the onset of atrial fibrillation can lead to a life threatening ventricular fibrillation.

35. Anti-arrhythmic drugs
Adenosine :
Magnesium :
Used in torsades de pointes
Used in digoxin induced arrhythmia

36. Anti-arrhythmic drugs
Conclusions :
Atrial flutter and fibrillation can be treated by class III antiarrhythmic agents.
Supraventricular tachycardia is treated by adenosine, CCB and beta blockers.
Ventricular arrhythmias are usually treated by amiodarone / lidocaine.
Vagal maneuver ( valsalva maneuver, massage of carotid sinus , by applying pressure at the criciod cartilage for about five seconds with circular movements)
Valslava maneuver increase the vagal tone and can also be done by applying ice pack to the face ( performed specially in children)
Treatment of AF depends on the cause and on whether the arrhythmia is chronic or of recent onset. There are four distinct issues that are important to consider in patients with AF:
rate control (control of rate of beating of the ventricles);
rhythm control via conversion of the atrial fibrillation to sinus rhythm;
maintenance of sinus rhythm following conversion; and
prevention of embolic stroke from thrombi that form in the fibrillating atria.
Beta blockers are the closest to ideal class of anti-arrhythmic drugs because of broad spectrum of activity and safety record.

37. Anti-arrhythmic drugs
Panel A: Kaplan-Meier Estimates of Death from Cardiovascular Causes (Primary Outcome). Among 1376 patients with atrial fibrillation and congestive heart failure who were followed for a mean of 37 months, 182 patients (27%) in the rhythm-control group died from cardiovascular causes, as compared with 175 patients (25%) in the rate-control group (hazard ratio, 1.06; 95% confidence interval, 0.86 to 1.30). (From Roy et al, 2008). Panel B: Kaplan-Meier Estimates of the Percentage of Patients Remaining Free of Recurrence of Atrial Fibrillation in the two treatment groups (hazard ratio for recurrence among patients in the amiodarone group, 0.43 [95 percent confidence interval, 0.32 to 0.57]). Follow-up began 21 days after randomization (designated day 0). (From: Roy et al, 2000).
There are two approaches to the treatment of AFib: rate control, allowing AFib to persist but controlling the ventricular rate by drugs affecting the AV node ERP, and rhythm control – with cardioversion to normal sinus rhythm & chronic treatment with antiarrhythmic drugs to prevent the reoccurrence of AFib.
Arguments in favor of rate control include: 1) its easily achievable in most patients; 2) avoidance of use of antiarrhythmic agents with less desirable side effects/toxicity; 3) risk of stroke can be reduced by anticoagulant therapy.
Arguments in favor of rhythm control include: 1) rhythm control reduces the odds of thromboembolism; 2) it was thought that patients who remain in AFib have a worse outcome than those treated with drugs that maintain a sinus rhythm. (Of course! Who would argue with that?….but what does the evidence say???)
In 2008, the results of two studies, one in North America, and one in Europe were published in the New England Journal of Medicine. In both studies, rhythm control provided no advantage over ventricular rate control with respect to survival (Fig 15A). On the basis of these results, rate control is currently considered an equally “safe” approach for the treatment of AFib, and rhythm control (if it is used) can be abandoned early if it is not fully satisfactory (e.g. the patient cannot tolerate the side effects of the drugs used to suppress AFib). Surgical procedures (e.g. Mini Maze procedure) involving catheter ablation of ectopic foci around the pulmonary veins may also be successful in patients with otherwise relatively normal hearts.
WARNING: Patients who have had AFib for more than 2-3 days duration must be adequately anticoagulated, generally for 2 weeks prior to attempting cardioversion. If emergency cardioversion is considered, a transesophageal echocardiogram can be used to determine the presence or absence of left atrial thrombi