Lecture: Antiarrhythmics

Antiarrhythmics are used to treat heart rhythm disorders, called arrhythmias, and to
lessen the symptoms associated with them. Some of the common symptoms of arrhythmias
include heart palpitations, irregular heartbeats, fast heartbeats, lightheadedness, fainting, chest
pain, and shortness of breath.
Arrhythmias may be caused by myocardial infarction, cardiosclerosis, valvularopathy,
some infections, endocrine dysfunctions, acute intoxications, ionic deregulations, overdosage of
glycosides; in children- by hypoxia, hypo and hyperpotasemia, hypoglycemia
Arrhythmias can be divided in:
tachyarrhythmia,
Sinus tachycardia (resting rate >100 beats/min). b-Blockers eliminate
sympathoexcitation and decrease cardiac rate.
Atrial flutter or fibrillation. An excessive ventricular rate can be decreased by
verapamil or cardiacglycosides. These drugs inhibit impulse propagation through the AV node,
so that fewer impulses reach the ventricles.
Ventricular fibrillation. This occurs when the ventricles beat in a very chaotic and
loosely organized fashion. Ventricular fibrillation is a serious, life-threatening condition that
must be corrected immediately or death will likely result. Antiarrhythmic medications are
sometimes prescribed to prevent ventricular fibrillation. 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.
ventricular tachycardia This is a rapid heart rhythm that occurs in the lower chambers of the
heart (ventricles). Ventricular tachycardia can be very dangerous if it progresses to ventricular
fibrillation .
bradyarrhythmia
Sinus bradycardia. An abnormally low sinoatrial impulse rate (<60/min) can be raised
by parasympatholytics. The quaternary ipratropium is preferable to atropine, because it lacks
CNS penetrability . Sympathomimetics also exert a positive chronotropic action; they have the
disadvantage of increasing myocardial excitability (and automaticity) and, thus, promoting
ectopic impulse generation (tendency to extrasystolic beats). In cardiac arrest epinephrine can
be used to reinitiate heart beat. and ectopic pacemaker activity.
The electrical impulse for contraction (propagated action potential;) originates in
pacemaker cells of the sinoatrial node and spreads through the atria, atrioventricular (AV) node,
and adjoining parts of the His-Purkinje fiber system to the ventricles. Irregularities of heart
rhythm can interfere dangerously with cardiac pumping function.
Action potential and ionic currents. The transmembrane electrical potential of cardiomyocytes
can be recorded through an intracellular microelectrode. Upon electrical excitation, a
characteristic change occurs in membrane potentialthe action potential (AP). Its underlying
cause is a sequence of transient ionic currents.
During rapid depolarization (Phase 0), there is a short-lived influx of Na+ through the
membrane. A subsequent transient influx of Ca2+ (as well as of Na+) maintains the
depolarization (Phase 2, plateau of AP). A delayed efflux of K+ returns the membrane potential
(Phase 3, repolarization) to its resting value (Phase 4).

The velocity of depolarization determines the speed at which the AP propagates through the
myocardial syncytium. Transmembrane ionic currents involve proteinaceous membrane pores:
Na+, Ca2+, and K+ channels.

Antiarrhythmic medicines are split into four categories:

Classification of antiarrhyphmics
1. Remedies that act cardiac conductibility
2. blockers of Ca channels:
Group IA: Quinidine.
Verapamil
Procainamide
Diltiazem
Disopyramide
Galapamil
Ajmaline
3. Potassium channel blockers.
Group IB:
Amiodarone
Lidocaine
Bretylium tosilate
Mexiletine
4. Chloride channel blockers:
Phenytoine
Alinidine
Tricainide
Various groups: A. Potassium drugs
Group IC
Potassium chloride
Flecainide
Asparcam
Encainide
Panangine
Propafenone
B. Digitals:
Digoxin
Moracizine
Digitoxin
Celanide
C. Adenosine
Remedies with the influence on the efferent cardiac innervations
1) Remedies that decrease the adrenergic influence:
- Propranolol
- Atenolol
- Metoprolol
- Oxprenolol
2) Remedies that stimulate the adrenergic influence
- adrenomimetics- izoprenaline
- Sympathomimetics- ephedrine
3) Remedies with cholinergic influence:
- Anticholinesterases- Edrophonium
- adrenomimetics: phenylephrine
4) Remedies that decrease cholinergic action:
-Atropine
Effects of antiarrhythmics. Antiarrhythmics of the Na+-channel blocking type reduce the
probability that Na+channels will open upon membrane depolarization (membrane
stabilization). The potential consequences are 1) a reduction in the velocity of depolarization
and a decrease in the speed of impulse propagation; aberrant impulse propagation is impeded. 2)
Depolarization is entirely absent; pathological impulse generation, e.g., in the marginal zone of
an infarction, is suppressed. 3) The time required until a new depolarization can be elicited, i.e.,
the refractory period, is increased; prolongation of the AP (see below) contributes to the increase
in refractory period. Consequently, premature excitation with risk of fibrillation is prevented.
Mechanism of action. Na+-channel blocking antiarrhythmics resemble most local anesthetics in
being cationic amphiphilic molecules ( exception: phenytoin). Their low structural specificity is
reflected by a low selectivity towards different cation channels. Besides the Na+ channel, Ca2+
and K+ channels are also likely to be blocked. Accordingly, cationic amphiphilic
antiarrhythmics affect both the depolarization and repolarization phases. Depending on the
substance, AP duration can be increased (Class IA), decreased (Class IB), or remain the same
(Class IC).
Antiarrhythmics representative of these categories include: Class IAquinidine,
procainamide, ajmaline, disopyramide, propafenone; Class IBlidocaine, mexiletine, tocainide,

as well as phenytoin; Class ICflecainide. Note: With respect to classification, !-blockers have
been assigned to Class II, and the Ca2+-channel blockers verapamil and diltiazem to Class IV.
Commonly listed under a separate rubric (Class III) are amiodarone and the b-blocking agent
sotalol, which both inhibit K+-channels and which both cause marked prolongation of the AP
with a lesser effect on Phase 0 rate of rise. Therapeutic uses. Because of their narrow
therapeutic margin, these Antiarrhythmics are only employed when rhythm disturbances are of
such severity as to impair the pumping action of the heart, or when there is a threat of other
complications. The choice of drug is empirical. If the desired effect is not achieved, another drug
is tried. Combinations of antiarrhythmics are not customary. Amiodarone is reserved for special
cases.

Class IA antiarrhythmics have been used for many years, typically for supraventricular
tachycardia (SVT), abnormal heart rhythms that arise in parts of the heart above the ventricles
(lower chambers) or less often in the ventricles themselves. These are called supraventricular
arrhythmias. These drugs have only a moderate effect on sodium channels and usually prolong
the duration of repolarization - the time it takes to "recharge" the heart after every beat. Some of
these drugs, such as quinidine, also reduce the force of heart muscle contractions. They may not
be suitable for patients with heart failure and other conditions that weaken the pumping ability of
the heart
Class I - membrane stabilizers
- depress depolarization of cardiac cell membrane by restricting entry of fast sodium current resulting in
reduction in the maximum rate of rise of phase 0 of the action potential. This leads to slower rate of
conduction, increased threshold for excitation and prolongation of the effective refractory period.
- also reduce rate of phase 4 diastolic depolarization, at doses which have no other effects, causing a
reduction in spontaneous automaticity.
- class I drugs further subdivided by their effect on the duration of the action potential:
Ia
- lengthen action potential
- slow rate of rise of phase 0
- prolong repolarization
- prolong refractoriness by blocking several types of potassium channel
- prolong PR, QRS, QT
- moderate-marked sodium channel blockade
- eg quinidine, procainamide, disopyramide
Ib
- shorten action potential
- limited effect on rate of rise of phase 0
- shorten repolarization
- shorten QT
- raise fibrillation threshold
- mild-moderate sodium channel blockade

- little effect on refractoriness since there is essentially no blockade of potassium channels

- eg lignocaine, mexilitine, phenytoin, propafenone
Ic
- no effect on length of action potential
- markedly reduces rate of rise of phase 0
- little effect on repolarization
- markedly prolongs PR and QRS
- marked Na channel blockade
- prolong refractoriness by blocking outward-rectifying potassium channels
- eg flecainide

.Quinidine Like all other class I antiarrhythmic agents, quinidine primarily works by blocking
the fast inward sodium current (INa). Quinidine's effect on INa is known as a use dependent block.
This means that at higher heart rates, the block increases, while at lower heart rates the block
decreases. The effect of blocking the fast inward sodium current causes the phase 0
depolarization of the cardiac action potential to decrease (decreased Vmax).
- decrease maximum rate of rise of phase 0
- depresses spontaneous phase 4 depolarization in automatic cells (results in prolonged QT)
- in general slows conduction through atrial, ventricular and Purkinje fibres causing QRS
prolongation but usually has no effect on sinus rate or R interval
- antivagal action may accelerate AVN conduction
Effects:

- decreasing of depolarization
- parasympapholitic properties
- adrenolitic properties: (it decreases arterial pressure)
- decreasing of automatism
- decreasing of excitability
- decreasing of conductibility
- decreasing of contractility
- increasing the cardiac rate
- increasing of the effective refractory period
Indications: tachyarrhythmias
Flutter and fibrillation
Supraventricular tachycardia
Re entry arrhythmias
Atrial tachycardia and atrial fibrillation.
Side effects: moderate toxicity, ,
- high plasma levels cause myocardial depression, vasodilatation and hypotension
- sinus arrest
- liver toxicity.
- AV dissociation
- QT prolongation and hence torsades de pointes. All type 1a drugs associated with risk of
torsades but quinidine appears to be the worst offender
- nausea, vomiting and diarrhoea are common
- cinchonism: headaches, tinnitus, partial deafness, disturbed vision and nausea
- hypersensitivity reactions: fever, purpura, thrombocytopaenia, hepatic dysfunction
- may ppt haemolytic anaemia in patients with glucose-6-phosphate dehydrogenase deficiency
Contraindications: arrhythmias caused by digitalis, , atrioventricular block, hyperpotassiemia,
hypocalcaemia . in children.
Pharmacokinetics:
Admin: PO - absorption rapid and almost complete. SR preparations available bu their
bioavailability may be lower than that of the standard formulation Never given IV as may cause
severe hypotension and myocardial depression
Distrib: peak plasma concentrations at 2-3 hrs. 80% bound to albumin. Volume of distribution

reduced in cardiac failure resulting in higher plasma levels which may lead to toxicity
Elim: 85-90% hydroxylated in liver to metabolites with less anti-arrhythmic activity. t1/2 5-7
hours. Only 10-15% excreted unchanged in the urine but renal excretion can be usefully
increased if urine is acidified. Conversely heart failure or the administration of antacids or
thiazides may lead to metabolic alkalosis and cause toxicity
Drug interactions
- diuretic induce hypokalaemia can produce life-threatening arrhythmias in patients on drugs
which prolong QT interval. Characteristic arrhythmia is VT
- may increase serum digoxin levels
- cimetidine and some beta blockers reduce hepatic blood flow and may cause toxic
concentrations
- concentrations decreased by hepatic enzyme inducers (eg phenytoin , phenobarbitone)
Procainamide: It has the same action as quinidine, but parasimpaphilitic action is less active.
Half life-2-3 hours.
Indications: - atrial, junctional and ventricular arrhythmias - may be more effective than
lignocaine in the treatment of VT
- use limited by short half-life
Adverse effects
Cardiac
- rapid IV injection may decrease CO and cause vasodilatation resulting in hypotension
- increases PR interval +/- increase degrees of heart block. compared with disopyramide and
procainamide exerts least vagolytic effect
- may result in QRS and QT prolongation especially in slow acetylators
Others
- long term oral use associated with drug-induced SLE
- GI disturbance (less common than with quinidine)
Drug interactions
- diuretic induced hypokalaemia can cause life threatening arrhythmias in patients on drugs
which prolong the QT interval. Characteristic arrhythmia is VT.
Pharmacokinetics
Admin: IV/PO. 85% bioavailable with rapid absorption - peak levels occur 1 hr after
administration
Distrib: 15% plasma protein bound. Concentration in heart and most other tissue > plasma
Metab: 30% metabolized to active metabolite N-acetyl procainamide. Slow acetylators require
smaller maintenance doses
Elim: 90% in urine unchanged or acetylated. Excretion decreased in renal failure, alkaline urine
and CCF. t1/2 2-3.5 hrs - slow release preparation available
Disopyramide:
Mode of action
- similar to quinidine
- increases atrial } abolishes ectopic &
refractory period } re-entrant atrial
- decreases sinus node }arrhythmias
refractory period
- anti-cholinergic effect (> quinidine/procainamide): antagonizes vagal actions and may be useful
in suppressing supra-ventricular arrhythmias
- slows conduction in accessory pathway and sometimes prolongs His-Purkinje refractory period,
although it has little effect on PR, QT, or QRS duration
- some Ca blocking effects
half life: 6 hours.
Pharmacokinetics

Admin: PO/IV. Following MI patients achieve lower plasma levels after oral dose.
Distrib: peak levels within 2 hrs. 25% plasma protein bound but binding saturable and depends
both on disopyramide and metabolite concentrations - contributes to its unusual pharmacokinetic
property of higher renal clearance at higher plasma levels. Volume of distribution decreases
following MI
Metab: liver - 40% metabolized to a metabolite which is only slightly less active against atrial
arrhythmias but is inactive against ventricular arrhythmias
Elim: drug and metabolite excreted in urine - decrease dose in severe renal failure. t1/2 4-6 hrs,
increased following MI
Clinical uses
- AV nodal, AV re-entry and ventricular arrhythmias. Should not be used to treat AF or atrial
flutter without prior control of ventricular rate with beta blockers or verapamil
- useful in preventing paroxysms of AF
Adverse effects
Cardiac
- myocardial depression; may be clinically important. Related both to plasma levels and rate of
administration. Contra-indicated in heart failure, severe LV dysfunction
- prolongs QT -predisposes to re-entrant VT and especially torsades de pointes
- sinus node depression
Other
- anticholinergic activity may lead to urinary retention, dry mouth, blurred vision etc
- may precipitate glaucoma
Side effects: Atropine like effects Contraindication : cardiac failure
Ajmaline is alkaloid of Rawolphii. It has short duration of action. Half-life- 5-8 minutes.
I B. Class IB antiarrhythmics are the least effective at blocking sodium channels. They work by
slowing nerve impulses in the heart, but they can make abnormal heart tissue less sensitive.
Usually, they shorten the time required for the heart to electrically reset or repolarize for a new
heartbeat. They are used primarily to treat ventricular arrhythmias.
Lidocaine is an antiarrhythmic and local anesthetic. Lidocaine selectively affects ischemic or
depolarized Purkinje and ventricular tissue and has little effect on atrial tissue: the drug reduces
action potential duration, but because it slows recovery of sodium channels from inactivation, it
does not shorten the effective refractory period. It inhibits Ca and Na influx in phase IV.
Effects: decreasing of automatism
Increasing of cardiac rate
local anesthesia
Indications: first line drug for VT after acute MI and cardiac surgery
-it is used in intensive therapy
- ventricular arrhythmias
- myocardial infarction (as antiarrhythmias and as anesthetic)
- intoxication with digitals
- ventricular tachycardia
- Ventricular fibrillation.
The way of administration is intravenous.
Half-life is 1,8-2 hours, and binding with plasmatic proteins in 70 %.
Adverse effects
- high concentrations may cause bradycardia, hypotension and even asystole
- -ve inotrope
- in 10% of patients may induce ventricular arrhythmias
- GI upset with nausea and vomiting
- CNS: parasthesiae, twitching and generalized tonic-clonic seizures
Injection rate may be important in precipitating toxic reactions, which are also related to free
drug concentration, which is particularly determined by the concentration of acute phase protein

alpha-1 acid glycoprotein. Latter increases after MI so that although long-term infusions may
lead to increasing total lignocaine concentrations the free drug level may remain fairly constant.
- crosses placenta rapidly but information on its use in pregnancy is limited. No reports of
teratogenicity
Drug interactions
- hepatic clearance reduced in patients receiving cimetidine, propranolol or halothane
Contraindications: Cardiac block, liver failure, convulsions in the anamnesis.
Pharmacokinetics
Admin: IV
Distrib: volume of distribution 1.5 l/kg in normals, 0.5 l/kg in heart failure
Elim: 70-80% metabolized by liver. However hepatic clearance decreases when blood flow to
the liver decreases as it does after MI. Metabolites have less anti-arrhythmic effect but may have
greater CNS excitatory properties and may be responsible for some of the undesirable effects
Mexiletine has the similar mechanism of action. It can be administrated orally.
Phenytoin: has also antiepileptic property. It can be used in digitalis-inclused arrhythmias.
IC- antiarrhythmics are strong sodium channel blockers. They also slow nerve impulses in the
heart, but have little effect on repolarization. They may be used for supraventricular and some
ventricular arrhythmias. Class Ic antiarrhythmics cannot be used in patients who have had a prior
heart attack or a weakened heart muscle due to heart failure (CHF).
Flecainide is the prototype drug with class IC. It is powerful depressants of sodium current.
This drug has no effect on ventricular action potential duration or the QT interval. It increases the
QRS duration of the ECG.
Mode of action
- depresses phase 0 and slows conduction throughout the heart
- delays repolarization in (canine) vnetricular muscle with significant prolongation of
intracardiac monophasic action potential
- causes concentration related increase in PR, QRS and intra-atrial conduction intervals and
prolongs effective ventricular refractory period
- sinus node function may also be affected particularly in patients with intrinsic sinus node
disease
Effects: - decreasing of the depolarization
- bradycardia
Indications: refractory ventricular arrhythmias
- supraventricular arrhythmias
- extrasistoly
- arrhythmias through re entry mechanism
- life-threatening tachyarrhythmias: supra-ventricular or ventricular
- most effective drug at blocking conduction by anomalous pathways
Adverse effects
- up to 30% of patients
- -ve inotrope: exacerbation of CCF
- proarrhythmic effects: more common in patients with severe underlying cardiac dysfunction
and more malignant arrhythmias. Torsades may occur even in patients without structural heart
disease
- dizziness
- visual disturbance eg blurring
- headache
- nausea
- tremor
- diarrhoea
- conduction blocks including bundle branch block, complete heart block

- sinus arrest
- increase in pacing thresholds
- increased difficulty in cardioversion of tachyarrhythmias
Contraindication: atrioventricular block, myocardial infarction
Pharmacokinetics
- admin: PO/IV; well absorbed with peak plasma concentrations after 3 hrs
- elim: 70% metabolised in liver to 2 major metabolites, one of which is active (1/5 of potency of
parent). Remainder excreted directly in urine
t1/2: 12-27 hrs
Use in pregnancy
- have been a few reports of safe and effective use in pregnancy. Crosses placenta readily
- lack of toxic fetal effects possibly due to a lower sensitivity of immature cardiac tissue to its
electrophysiological effects
Drug interactions
- results in minimal increase in digoxin levels
- both flecainide and propranolol levels are increased by co-administration of these drugs
Calcium channel blockers: These drugs inhibit the influx of Ca in phase II and IV
Effects:
- batmotropic negative effects
- decreasing of the excitability
- dromotropic negative effect
- inotropic negative effect
- chronotopic negative effect
- increase of the effective refractory period
Indications; flutter, atial fibrillation, supraventricular tachicardia, angina, hypertensions,
These drugs help to slow abnormally rapid heartbeats. They also widen the blood vessels and
may decrease the heart's pumping strength. They are often used to treat high blood pressure, but
usually are not prescribed for people with heart failure or other structural damage to the heart.
(They may be used to treat heart faliure caused by a thickened heart muscle, hypertrophic
obstructive cardiomyopathy. They also may be useful in treating coronary artery disease, or CAD
(clogged blood vessels to the heart).
Some arrhythmias are treated with Type IV antiarrhythmics such as:
Diltiazim (Cardizem, Tiazac)
Verapamil (Dovera, Isoptin, Calan)
Potassium channel blockers: Mechanism of action: They decrease Ca influx and K reflux in II
and III phase. They slow nerve impulses by acting directly on the heart tissues. Type III
medications lengthen the duration of repolarization without affecting the heart's normal electrical
conduction. Efforts to develop new antiarrhythmic drugs have focused on Type III medications
because they are less likely to adversely affect the heart's pumping ability and they act on tissues
in both the upper and lower chambers of the heart.
At present, Type III antiarrhythmics are generally the most successful drugs for treating
both supraventricular (SVT) and ventricular arrhythmias. They often are prescribed in addition to
an ICD in patients at high risk for sudden cardiac arrest (SCA). Medications help to reduce the
frequency and severity of abnormal rhythms so that patients receive fewer shocks from the ICD.
Amiodarone and sotalol are the most frequenty used drugs of this class. Patients taking these and
other antiarrhythmic drugs often must be monitored closely by a heart rhythm specialist.
Effects: - batmotropic negative effects
- decrease of the excitability
- dromotropic negative effect
- chronotopic negative effect
- increasing of the effective refractory period
Indications: - ventricular and supraventricular arrhythmias
- WPW syndrome

The way of administration- orally

They are accumulated in muscular and adipose tissue
Plasmatic concentration after 5 days
Half life- 13-77 days
Effect exists 7 mouths after the treatment.
Side effects: syndrome similar to lupus erythematosus.
Sinus bradycardia, asthma
Photosensibility
Hypothyroidism
Neurological deregulations
Contraindications: atrioventricular block
pregnancy
bradycardia
endocrine diseases
Amiodarone
Mode of action
class III anti-arrhythmic with weak class I, II (b blocker) and class IV actions
prolongs effective refractory period of myocardial cells, AV node and anomalous
pathways
depresses automaticity of SA and AVN
may also be a non-competitive blocker of a and b receptors
haemodynamic effects: coronary vasodilator (direct effect on smooth muscle, Ca channel
blockade, and a blockade), peripheral vasodilator, negative inotrope
Pharmacokinetics
Administration: IV/PO.
Distribution: enormous apparent volume of distribution (70 l/kg). Stored in fat and other tissues.
T1/2 after multiple dosing of 54 days
Elimination: metabolized in liver and excreted via biliary and intestinal tracts
Clinical uses
effective against most tachyarrhythmias
patients with poor LV function or patients with frequent ventricular ectopics post MI
although did reduce "arrhythmia deaths"
Adverse effects
bradycardia, heart block and proarrhythmic effects. Latter are mild compared to other
anti-arrhythmics
congestive cardiac failure (2-3%)
hypotension (28% following IV administration. Not dose related)
increases defibrillation threshold
corneal microdeposits which cause visual haloes and photophohia. Dose related and
resolve when drug discontinued
hyperthyroidism, hypothyroidism, interference with thyroid function tests
photosensitivity
eosinophilic lung infiltration (early, fever, SOB, cough)
pulmonary fibrosis
hepatitis
tremor, ataxia, peripheral neuropathy, fatigue, weakness. Usually occur during loading.
Dose related
skin discolouration
Drug interactions
displaces digoxin from binding sites and, more importantly, interferes with elimination
inhibits warfarin metabolism
b blockers and Ca antagonists augment the depressant effect of amiodarone on SA and
AVN function as well as negative inotropic effects
raises quinidine and phenytoin concentrations

Bretylium
Class III
Mode of action
- increases action potential duration and refractory period of cardiac cells
- antifibrillatory effect on ventricular muscle - may be more important than class III effects in
emergency treatment of malignant ventricular arrhythmias
- initially causes noradrenaline release and then produces the equivalent of a sympathectomy,
preventing noradrenaline release (class II effect)
Clinical use
- useful adjunct to DC shock in managing life-threatening ventricular arrhythmias, especially
refractory VF
- theoretical advantages of lignocaine but no advantage has been demonstrated clinically
Dose
5mg/kg IV over 15-20 min but in an emergency often given over 1-2 min
Adverse effects
Postural hypotension most significant side effect. Nausea and vomiting possible
Various groups:
Adenosine: is a normal component of the body but when it is given in high doses (6-12 mg) as an
intravenous bolus the drug reduces calcium current. Adenosine is extremely effective in AV
nodal arrhythmias. It has an short duration of action (15 seconds).
Mode of action - stimulates specific A1 receptors on the surface of cardiac cells thus influencing
adenosine sensitive K channel cAMP production
- slows sinus rate
- prolongs AVN conduction, usually causing high degree AV block
Pharmacokinetics
- admin: IV
- elim: taken up by RBCs and deaminated in plasma
t1/2 < 2 secs
Clinical use
- narrow complex tachycardia: drug of choice to terminate AVRT or AVNRT. Will not revert AF
and may transiently increase ventricular rate in AF associated with WPW
- wide complex tachcardia: useful in assisting diagnosis. SVT with aberrant conduction will
usually terminate with adenosine whereas few VTs will revert
Dose
6 then 12 then 18 mg
Drug interactions
- antagonized by methylxanthines, especially aminophylline
- dipyridamole potentiates effect by blocking uptake
Adverse effects
- flushing, dyspnoea and chest discomfort may occur transiently
- may precipitate bronchospasm in asthmatic patients
Use in pregnancy
- minimal placental transfer and short duration of action make it suitable for use in pregnancy
Beta-blockers
Anti-arrhythmic properties appear to be a class effect with no one drug being intrinsically
superior
Mode of action
- reduce slope of phase 4 in pacemaker cells thus prolonging their refractoriness
- slow conduction in AVN
- refractoriness and conduction in the His-Purkinje system are unchanged
Clinical use

- most effective in arrhythmias associated with increased cardiac adrenergic stimulation (eg
TTX, phaeochromocytoma, exercise or emotion)
- SVT: may terminate re-entry tachycardias when the AVN is part of the re-entry circuit but less
effective than adenosine or verapamil. Slow ventricular response to other SVTs
- VT: generally ineffective for the emergency treatment of sustained VT. Role in VT prevention
not clear
Adverse effects
- cross placenta readily. Fetal bradycardia, hypoglycaemia, hyperbilirubinaemia and intrauterine
growth retardation are concerns. Most reports have not shown significant adverse fetal effects
but beta-blockers are probably best avoided in known intrauterine growth retardation
Digitalis: In atrial flutter or fibrillation digitalis slows AV conduction sufficiently to protect the
ventricles from the high rates.
Potassium ions: Hypokalemia is associated with an increased incidence of arrhythmias,
especially in patients receiving digitalis
Effects: decrease of the cardiac rate
- decrease of the conductibility
- decrease of the automatism
- coronarodilatation