PHARMACOLOGY

 What are arrhythmias?

 Normalcardiac contraction originates at the
SA node at 60-100 bpm.

 Spreads through atria into the AV node →

propagates over the His-Purkinje system to the
ventricles
 Arrhythmia-
abnormal pacemaker activity or
abnormal impulse propagation.
 Arrhythmiaactivity is divided into two
general categories:
 Those resulting from an abnormality in impulse
generation (aka autonomic arrhythmias)
 Those resulting from an abnormality in impulse
conduction (reentrant arrhythmias)
 Whenan arrhythmia is present heart rate
may be:
 Too slow (bradycardia)
 Too quick (tachycardia)
 Irregular
 Thereare many different types of
arrhythmias e.g.:
 Atrial fibrillation or flutter
 Atrioventricular nodal reentry tachycardia
(AVNRT)
 Heart block or atrioventricular block
 Multifocal atrial tachycardia
 Paroxysmal supraventricular tachycardia
 Sick sinus syndrome
 Ventricular fibrillation
 Ventricular tachycardia -- a fast heart rate that
originates in the lower chambers (ventricles)
 Wolff-Parkinson-White syndrome
 Risk factors???

 Possible causes??
 Therisk of getting a tachycardia or
bradycardia varies greatly, depending on:
 Blood chemistry imbalances, such as abnormal
potassium levels
 Cardiomyopathy -- a weakening of the heart
muscle or a change in the heart muscle
 Heart failure
 Overactive thyroid gland
 Past heart attacks
 Arrhythmiasmay also be caused by some
substances or drugs, including:
 Amphetamines
 Caffeine
 Cocaine
 Beta blockers
 Psychotropics
 Sympathomimetics
 Symptoms??
 Arrhythmia symptoms may be present all of the
time, they may come and go or may be
asymptomatic.
 Common symptoms include:
 Chest pain
 Fainting
 Fast or slow heartbeat (palpitations)
 Light-headedness, dizziness
 Paleness
 Shortness of breath
 Skipping beats - changes in the pattern of the pulse
 Sweating
 Thefollowing tests may be performed to
identify arrhythmias:
 Ambulatory cardiac monitoring
 Coronary angiography
 ECG
 Echocardiogram
 Electrophysiology study
 Goals for treatment:
 Reduce ectopic pacemaker activity
 Modify conduction.

 Normal conduction can be restored by:

 Electrical "shock" therapy (defibrillation or
cardioversion)
 Implanting a temporary pacemaker to interrupt
the arrhythmia
 Medications given through a vein (intravenous)
 Howwould you prevent arrhythmias from
occuring?
 Toprevent development of arrhythmias,
patients must be advised to take steps to
prevent coronary artery disease.
 Eating a well-balanced, low fat & salt diet
 Exercising regularly
 Not smoking
 Cut alcohol
 Comply with treatment
 Achieved with:
 Sodium channel blockers
 Blocking sympathetic autonomic effects in the
heart
 Prolonging the effective refractory period
 Calcium channel blockers
Four classes:
 Class 1- sodium channel blockade- (NB:
subclasses reflect effects on the APD and
the kinetics of Na blockade)

 1A: prolong action potential duration (APD) and

dissociate from the Na channel with intermediate
kinetics.

 1B: shorten APD and dissociate from the Na channel

with rapid kinetics.

 1C: minimal effects on APD and dissociate from the

Na channel with slow kinetics.
 Class 2 action is sympatholytic- drugs reduce
β-adrenergic activity in the heart.

 Class 3 action manifests as prolongation of the

APD.

 Class4 action is blockade of the cardiac Ca

current.
 Procainamide, quinidine, and disopyramide.
Quinidine
 Blocks Na channels thus slowing down action
potential upstroke, conduction and the QRS
duration on the ECG.
 It also blocks the K channels.

Indications: atrial and ventricular arrhythmias.

 A/E-Excessive action potential prolongation,
QT interval prolongation, torsade de pointes
arrhythmia and syncope, headache,
dizziness, tinnitus.

 70-80% systemic bioavailability when given

orally, 80% bound to albumin, eliminated via
hepatic metabolism.
 “twisting the points”-
 Procainamide- prolongs QRS duration of the
ECG by blocking sodium channels.

 Italso indirectly blocks K channels, but has

less prominent antimuscarinic effects than
quinidine.

 Indications: atrial and ventricular

arrhythmias
 A/E:similar to quinidine, hypotension
(ganglion blocking effects), systemic lupus
erythematous (SLE), pleuritis, pericarditis.

 Rarely used but can be administered IV or IM

with 75% systemic bioavailability when given
orally.
 Disopyamide- effects similar to quinidine, with
greater antimuscarinic effects.

 Thus should be administered with a drug that

slows AV conduction esp. when treating atrial
flutter.

 Only available for oral use

 A/E:may precipitate heart failure in patients

with preexisting left ventricular depression,
urinary retention, dry mouth, blurred vision,
constipation, worsening of glaucoma.
 Lidocaine- inhibits fast sodium channels and
shortens APD→ inhibiting ectopic beats and
conduction in depolarized cells.

 Least cardiotoxic of all the sodium channel blockers.

 Indications-suppression of ventricular arrhythmias

associated with MI, cardiac surgery or other acute
situations.
 A/E:SA node arrest, worsening of impaired
conduction, vetricular arrhythmias,
paresthesias, tremor, nausea, slurred speech,
lightheadedness, convulsions.

 Extensive1st pass metabolism thus only 3% is

bioavailable, give parenterally
(rapid/immediate onset of action).

 Mexiletine- resistant to 1st pass metabolism

and is effective by the oral route
 Powerful sodium channel blockers,
manifested by QRS widening on the ECG,
with little effect on the QT interval.

 Theyallow 1:1 conduction to the ventricles

causing marked acceleration in the
ventricular rate.

 Thusin atrial flutter, they should only be

used with beta blockers or verapamil.
 Flecainide-potent Na and K channel blocker
with slow unblocking kinetics (used for patients
with otherwise normal hearts who have
supraventricular arrhythmias.)

 Effective
in suppressing premature ventricular
contractions.

 Negative inotropic effects but no β-blocking

action.

 A/E-may cause severe exacerbation of

arrhythmia in patients with preexisting
tachycardia.
 Propafenone- structurally similar to
propranolol, with weak β-blocking properties.

 Has negative inotropic effects with sodium blocking

linetics similar to those of flecainide.

 Used for supraventricular arrhythmias.

 A/E: metallic
taste, constipation, exacerbation of
arrhythmias might occur.
 β-blockers like propranolol belong to this class due
to their β-receptor blocking actions and direct
membrane effects.

 Cardiacβ1-receptor blockade, intrinsic

sympathomimetic activity, membrane effects
and prolonging cardiac AP.
 Prolong
action potentials via K channel
blockade in the cardiac muscle.

 Ultimately,
prolonging repolarisation→
manifested as an increase in the QT interval
on the ECG.

 Includes amiodarone, dronedarone, sotalol.

 Used for prophylaxis and treatment of
supraventricular and ventricular arrhythmias.

 A/E- torsades de pointes,

hyper/hypothyroidism, neurotoxicity,
photosensitivity, GI effects.

 35-60% bioavailability after hepatic

metabolism.
 Sotalol-
has class 2 (β-blocking) and class 3
properties (AP prolonging).

 Usedin arrhythmias that fail to respond to β-

blockers, in patients with high risk of
developing torsades de pointes.

 100%bioavailable (no hepatic metabolism

and no plasma binding).
 Examples: verapamil and diltiazem.

 Verapamil- blocks both activated and

inactivated L-type calcium channels and
slows SA node conduction.
 Indicated for supraventricular tachycardia.

 NB: bulk up these notes, add dosages…

 VSa 69-year-old retired teacher presents
with a 3-month history of palpitations,
intermittent shortness of breath, and
fatigue. She has a history of hypertension
and says she drinks at least 4 mugs of coffee
daily. An ECG shows an irregular heart rate.
The patient complains that she sweats a lot.
Upon physically examining the patient, you
also note that her paleness.
 At this stage, would you initiate treatment
with an antiarrhythmic drug to maintain
normal sinus rhythm?
 What drug would you choose?
 After initiating the patient on a class I
antiarrhythmic agent on a chronic basis, she
comes back complaining of fatigue, low-
grade fever and joint pain suggestive of
systemic lupus erythematosus (SLE). What
drug was issued?
 How would you counsel this patient?