By

Ali alalawi
Arrhythmia
 Cardiac arrhythmia (also dysrhythmia) is a term
for any of a large and heterogeneous group of
conditions in which there is abnormal electrical
activity in the heart.

 The heart beat may be too fast or too slow, and

may be regular or irregular.

 Normal sinus rhythm (60-90bpm), SA node

pacemaker
Symptoms
Some arrhythmias are life-threatening medical emergencies
that can result in cardiac arrest and sudden death.

Others cause symptoms such as an abnormal awareness of

heart beat (palpitations), and may be merely annoying.

Still others may not be associated with any symptoms at all,

but predispose toward potentially life-threatening stroke or
embolus

Occurrence:
 80% of patients with acute myocardial infarctions
 50% of anaesthetized patients
 About 25% of patients on digitalis
Normal electrical activity in the heart
Each heart beat originates as an
electrical impulse from a small
area of tissue in the right atrium
of the heart called the sinus node
or Sino-atrial node or SA node.
The impulse initially causes both
of the atria to contract, then
activates the atrioventricular (or
AV) node which is normally the
only electrical connection
between the atria and the
ventricles , which can be called
as main pumping chambers.

The impulse then spreads through both ventricles via the Bundle of His
and the Purkinje fibres causing a synchronised contraction of the heart
.muscle, and thus, the pulse
Classification of arrhythmia
1. Characteristics:
 a. flutter – very rapid but regular contractions
 b. tachycardia – increased rate
 c. bradycardia – decreased rate
 d. fibrillation – disorganized contractile activity

2. Sites involved:
 a. ventricular
 b. atrial
 c. sinus
 d. AV node
 e. Supraventricular (atrial myocardium or AV node)
Unidirectional Block
Damaged tissue is usually depolarized → ↓ conduction velocity
Strategy of Antiarrhythmic Agents
Suppression of dysrhythmias
A. Alter automaticity
i. decrease slope of Phase 4
depolarization
ii. increase the threshold potential
iii. decrease resting (maximum
diastolic) potential

B. Alter conduction velocity

i. mainly via decrease rate of
rise of Phase 0 upstroke
ii. decrease Phase 4 slope
iii. decrease membrane resting
potential and responsiveness

C. Alter the refractory period

i. increase Phase 2 plateau
ii. increase Phase 3 repolarization
iii. increase action potential duration
antiarrhythmic agents:
There are five main classes in the Vaughan
Williams classification of antiarrhythmic agents:
1.Class I agents interfere with the sodium (Na+)
channel.
2.Class II agents are anti-sympathetic nervous
system agents. Most agents in this class are beta
blockers.
3.Class III agents affect potassium (K+) efflux.
4.Class IV agents affect calcium channels and the
AV node.
5.Class V agents work by other or unknown
mechanisms
Class I agents interfere with the sodium
(Na+) channel.
 These drugs bind to and block the fast sodium
channels that are responsible for the rapid
depolarization (phase 0) .

 blocking these channels decreases the slope of

phase 0, which also leads to a decrease in the
amplitude of the action potential.
Class I agents interfere with the
sodium (Na+) channel.
 Quinidine (Class IA prototype)
Other examples: Procainamide, Disopyrimide
1. General properties:
a. D-isomer of quinine
b. As with most of the Class I
agents
- moderate block of sodium channels
- decreases automaticity of pacemaker
cells
- increases effective refractory
period/AP duration
Actions of Quinidine
Cardiac effects:
a. ↓ automaticity, conduction velocity and excitability of
cardiac cells.

b. Preferentially blocks open Na channels

c. Recovery from block slow in depolarized tissue; lengthens

refractory period (RP)

d. All effects are potentiated in depolarized tissues

e. Increases action potential duration (APD) and prolongs AP

repolarization via block of K channels; decreases reentry

f. Indirect action: anticholinergic effect (accelerates heart), which

can speed A-V conduction.
Actions of Quinidine:
Extracardiac
a. Blocks alpha-adrenoreceptors to yield vasodilatation.
b. Other strong antimuscarinic actions

Side Effects:
 "Quinidine syncope"(fainting)- due to disorganized ventricular
 tachycardia
 Associated with greatly lengthened Q-T interval; can lead to Toursades de
Pointes (precursor to ventricular fibrillation)
 Negative inotropic action (decreases contractility)
 GI :diarrhea, nausea, vomiting
 CNS effects: headaches, dizziness, tinnitus (quinidine “Cinchonism”)
Pharmacokinetics/therapeutics
1. Oral, rapidly absorbed, 80% bound to membrane proteins
2. Drug interaction: displaces digoxin from binding sites; so
avoid giving drugs together
3. Effective in treatment of nearly all dysrhythmias, including:
a) Premature atrial contractions
b) Paroxysmal atrial fibrillation and flutter
c) Intra-atrial and A-V nodal reentrant dysrhythmias
d) Wolff-Parkinson-White tachycardias (A-V bypass)

4. Especially useful in treating chronic dysrhythmias requiring

outpatient treatment
Procainamide (Class 1A)
Cardiac effects
a Similar to quinidine, less muscarinic & alpha-adrenergic blockade
b. Has negative inotropic action also

Extracardiac effects
a. Ganglionic blocking reduces peripheral vascular resistance

Toxicity
a. Cardiac: Similar to quinidine; cardiac depression
b. Noncardiac: Syndrome resembling lupus erythematosus

Administered orally, i-v and intramuscularly

Class IB prototype:
Examples: Lidocaine Mexiletine, Phenytoin,
Tocainide
General:
a. Commonly used antidysrhythmic agent in emergency
care (decreasing use)
b. Given i-v and i-m; widely used in ICU-critical care units
(old DOC, prior 2001)
c. Low toxicity
d. A local anesthetic, works on nerve at higher doses
Lidocaine Actions
Cardiac effects
a. Exclusively acts on Na channels in depolarized tissue by blocking
open and inactivated Na channels
b.Potent suppresser of abnormal activity.

Toxicity:
least cardiotoxic, high dose can lead to hypotension
tremors, nausea, slurred speech, convulsions

Pharmacokinetics/therapy
a. IV, IM since extensive first pass hepatic metabolism
b. T1/2 = 0.5-4 hours
c. Effective in suppressing dysrhythmia associated with depol. tissue
(ischemia; digitalis toxicity); ineffective against dysrhythmias in
normal tissue (atrial flutter).
d. Suppresses ventricular tachycardia; prevents fibrillation
Phenytoin (Class IB)
1. Non-sedative anticonvulsant used in treating epilepsy
2. Limited efficacy as antidysrhythmic (second line
antiarrythmic)
3. Suppresses ectopic activation by blocking Na and Ca
channels
4. Especially effective against digitalis-induced
dysrhythmias
5. T1/2 = 24 hr - metabolized in liver
6. Side Effect: Gingival hyperplasia (40%)
 Propranolol (Class II, beta
adrenoreceptor blockers)
Other agents:
Metoprolol, Esmolol (short acting), Sotalol (also Class III), Acebutolol

Cardiac effects (of propranolol), a non-selective beta blocker

a. Main mechanism of action is block of beta receptors; ↓ Ph 4 slope.
Which decreases automaticity under certain conditions

b. Some direct local anesthetic effect by block of Na channels (membrane

stabilization) at higher doses

c. Increases refractory period in depolarized tissues

d. Increases A-V nodal refractory period

 Propranolol (Class II, beta
adrenoreceptor blockers)
Non-cardiac: Hypotension

Therapeutics
a. Blocks abnormal pacemakers in cells receiving excess catecholamines

(e.g. pheochromocytoma) or up-regulated beta-receptors (ie.

hyperthyroidism)

b. Blocks A-V nodal reentrant tachycardias; inhibits ectopic foci

c. Propranolol used to treat supraventricular tachydysrhythmias

d. Contraindicated in ventricular failure; also can lead to A-V block.

 Oral (propranolol) or IV.

Clinical uses: Beta-Blockers
• Angina (non-selective or β1-selective)
- Cardiac: ↓O2 demand more than O2 supply
- Exercise tolerance ↑ in angina patients
• Arrhythmia (β1-selective, LA-action)
- ↓ catecholamine-induced increases in conductivity and automaticity
• Congestive Heart Failure
- caution with use
• Glaucoma (non-selective)
- ↓aqueous humor formation (Timolol)
• Other
- block of tremor of peripheral origin (β2-AR in skeletal muscle)
- migraine prophylaxis (mechanism unknown)
- hyperthyroidism: ↓cardiac manifestation (only propranolol)
β-Blockers: Untoward Effects,
Contraindications
• Supersensitivity:
 Rebound effect with β-blockers, less with β-
 blockers with partial agonist activity (ie. pindolol).
 Gradual withdrawal

• Asthma:
 Blockade of pulmonary β2-receptors increase in airway
resistance (bronchospasm)
• Diabetes:
 Compensatory hyperglycemic effect in insulin-induced
hypoglycemia is removed by block of β2-ARs in liver. β1-
selective agents preferred
Amiodarone (Class III)
General:
a. New DOC for ventricular dysrhythmias (Lidocaine, old DOC)

b. prolongs refractory period by blocking potassium channels

c. also member of Classes IA,II,III,IV since blocks Na, K, Ca channels

and alpha and beta adrenergic receptors

d. serious side effects (cardiac depression, pulmonary fibrosis)

e. effective against atrial, A-V and ventricular dysrhythmias

f. very long acting

Bretylium (Class III, K+ channel
blockers)
Others Amiodarone , Ibutilide, (Sotalol, also beta-blocker)

General: originally used as an antihypertensive agent

Cardiac effects:

a. Direct antidysrhythmic action

b. Increases ventricular APD and increases refractory period; decreases automaticity

e. Blocks cardiac K channels to increase APD

Extracardiac effects: Hypotension (from block of NE release)

Pharmacokinetics/therapeutics

a. IV or IM

b. Excreted mainly by the kidney

c. Usually for emergency use only: ventricular fibrillation when lidocaine and
cardioversion therapy fail. Increases threshold for fibrillation.

d. Decreases tachycardias
Verapamil (Class IV, Ca++ channel
blockers)
Other example: Diltiazem
 Blocks active and inactivated Ca channels, prevents Ca entry
 Increases A-V conduction time and refractory period; directly slows SA and A-V
node automaticity

Extracardiac
a. Peripheral vasodilatation via effect on smooth muscle
b. Used as antianginal / antihypertensive

 Side effects:
a. Cardiac
 Too negative inotropic for damaged heart, depresses contractility
 Can produce full A-V block
b. Extracardiac
 Hypotension
 Constipation, nervousness
 Gingival hyperplasia
Verapamil (Class IV, Ca++ channel
blockers)
Pharmacokinetics/Therapeutics

a. T1/2 = 7h, metabolized by liver

b. Oral administration; also available parenterally

c. Great caution for patients with liver disease

d. Blocks reentrant supraventricular tachycardia (“A-V nodal reentrant

tachycardia”), decreases atrial flutter and fibrillation

e. Only moderately effective against ventricular arrhythmias

Dysrhythmics – Others (class v)
1. Adenosine: i.v. (secs), activates P1 purinergic
receptors (A1) coupled to K channels, ↓CV, ↑refractory period

2. Potassium ions (K+): Depress ectopic pacemakers

3. Digoxin: used to treat atrial flutter and fibrillation

- AV node ↓conduction (vagal stimulation)
- myocardium ↓refractory period
- Purkinje fibers ↑refractory period, ↓conduction

4. Autonomic agents: used to treat A-V block

- β-agonists, anticholinergics

5. Anticoagulant therapy:
- prevent formation of systemic emboli & stroke