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1. Presented by
S.Lakshmi Sravanthi
11AB1R0051
Vignan pharmacy college
(Approved by AICTE , PCI & Affiliated to JNTU kakinada)
Vadlamudi , Guntur (Dt)-522213
2. Electrophysiology of the heart
Arrhythmia: definition, mechanisms,
types
Drugs :class I, II, III, IV
Guide to treat some types of arrhythmia
3. CARDIAC
ARRYTHMIAS
Definition
Cardiac arrythmias results from alterations in the orderly
sequence of depolarisation followed by repolarization in the heart.
Cardiac arrythmias may result in alterations in heart rate or rhythm
and arise from alterations in simple generation or conduction.
8. 0 1 2 3 4
• Effective refractory period
• Absolute refractory period
• Relative refractory period
1
0
2
3
4
ARP RRP
9. Phase 4: pacemaker
potential
Na+ influx and K
efflux and Ca++ influx
until the cell reaches
threshold and then
turns into phase 0
Phase 0: upstroke:
Due to Ca++
influx
Phase 3:
repolarization:
Due to K+ efflux
Pacemaker cells (automatic cells) have unstable
membrane potential so they can generate AP
spontaneously
12. Abnormal impulse
generation
Depressed automaticity of SA node
Enhanced automaticity of SA node
Impulse from ectopic loci
Ischemia, digitalis, catecholamine's, acidosis, hypokalaemia
Less (-) resting membrane potential
More (-) TP
13. Triggered Activity
Extra abnormal depolarisation
- Due to abnormal intracellular Ca2+ regulation
- During or immediately after phase 3
- After depolarisation may be categorized in to
- Early after depolarisation
- Delay after depolarisation
14. After depolarizations
EADs prolonged APD
Clinical arrhythmia:
e.g., torsades de pointes
due to: long QT syndrome
genetic defects
DADs HR or [Ca2+]i
Clinical arrhythmia:
e.g., Ca2+ overload
due to: digoxin or
PDE inhibitor toxicity
16. Conduction Block
Due to depression of impulse conduction at AV node & bundle of
His, due to vagal influence or ischemia.
Types :
1st degree heart block – slowed conduction
2nd degree block – some supraventricular complex not conducted
3rd degree block – no supraventricular complex are conducted
17. Re-entry phenomenon
Due to abnormality of conduction , an impulse may recirculate
in the heart and causes repetitive activation without the need
for any new impulse to be generated. These are called
reentrant arrythmias.
Circus movement type:
A premature impulse temporarily blocked in one direction by
refractory tissue, makes a one-way transit around an obstacle
finds the original spot in an advanced state of recovery and
rexicites it, setting up recurrent activation of adjacent myocardium.
20. IMPORTANT CARDIAC
ARRHYTHMIAS
– premature beats
Due to abnormal automaticity or impulse arising from
ectopic focus.
– Sudden onset of AT 150-200/min
Due to circus movement type of Re-entry or accessory
pathway
– 200-300 / min
Due to re entry circuit in right atrium
21. ATRIAL FIBRILLATION
o 350-550/min
o Due to electrophysiological inhomogenesity
of atrial fibers.
22. – 4 or more consecutive ventricular extrasystoles
Due to either discharge from ectopic focus or reentry
circuits
Polymorphic VT with rapid asynchronous complex, twisting
along the baseline on ECG with long QT interval
Grossly irregular, rapid & fractionated action of ventrcles –
resulting in incoordinated contraction of ventricles with loss of
pumping function.
23. POSSIBLE MECHANISMS OF ANTIARRHYTHMIC DRUGS
1. Suppressing the Automaticity
↓ Rate of phase 0
↓ Slope of phase 0
Duration ERP ↑
TP less negative
Resting membrane potential more negative
2. Abolishing reentry
Slow conduction
↑ ERP
24. Pharmacological
goals
The ultimate goal of antiarrhythmic drug therapy:
o Restore normal sinus rhythm and conduction
o Prevent more serious and possibly lethal arrhythmias from
occurring.
Antiarrhythmic drugs are used to:
o Decrease conduction velocity
o Change the duration of the effective refractory period (ERP)
o Suppress abnormal automaticity
26. Anti arrythmic drugs
class mechanism action notes
I Na+ channel blocker
Change the slope of
phase 0
Can abolish
tachyarrhythmia
caused by reentry
circuit
II β blocker
↓heart rate and
conduction velocity
Can indirectly alter
K and Ca
conductance
III K+ channel blocker
1. ↑action potential
duration (APD) or
effective refractory
period (ERP).
2. Delay
repolarization.
Inhibit reentry
tachycardia
IV Ca++ channel blocker
Slowing the rate of rise
in phase 4 of SA node.
↓conduction velocity
in SA and AV node
27. Class I
IA IB IC
They ↓ automaticity in non-nodal
tissues (atria, ventricles, and purkinje
fibers)
They act on open Na+
channels or
inactivated only
Use dependence
Have moderate K+ channel
blockade
28. IA
Quinidine Procainamide Disopyramide Moricizine
Slowing the rate of rise in phase 0
They prolong action potential & ERP
↓ the slope of Phase 4 spontaneous depolarization
↑ QRS & QT interval
29. QUINIDINE
Antimalarial, antipyretic, skeletal muscle relaxant and atropine like
action.
Mechanism of action
• Quinidine binds to open and inactivated sodium channels
and prevents sodium influx, slowing the rapid upstroke during
phase o.
• It also decreases the slope of phase 4 spontaneous
depolarization and inhibits potassium channels.
31. Uses
• Ventricular tachyarrythmias
• Used in the termination of ventricular tachycardia
Drug interactions
• Quinidine can interact the plasma concentration of digoxin,
which may in turn lead to signs and symptoms of digitalis
toxicity.
• Cimitidine increases hepatic metabolism of quinidine
32. PROCAINAMIDE
Procaine derivative, quinidine like action
Mechanism of action
Procainamide binds to open and inactivated Na+ channels and
prevents sodium influx, slowing the rapid upstroke during
phase 0
Hypotension
Hypersensitivity reaction
A/E
33. Premature atrial contractions
Paroxysmal atrial tachycardia
Dose:1-1.5g rate of 20-50mg/min
• Procainamide
hypersensitivity
• Bronchial asthma
• Cimitidine inhibits the
metabolism of procainamide
Uses
C/I Drug Interactions
34. DISOPYRAMIDE
Mechanism of
action
Disopyramide produces a negative ionotropic effects
that is greater than weak effect exerted by quinidine and
procainamide, and unlike the latter drugs, disopyramide
causes peripheral vasoconstriction.
• Myocardial depression
• Urinary retention
• Constipation
A/E
35. • ventricular tachycardia
• AF & AFI
- CHF
Disopyramide
Uses
C/I
Drug Interactions
In the presence of phenytoin, the metabolism of disopyramide
is increased and the accumulation of its metabolite is also
increased, there by increasing the probability of
anticholinergic properties.
36. A/E
Nausea
Dizziness
A-V block
Uses
Ventricular
tachycardia
C/I
A-V block
Drug
hypersensitivity
MORICIZINE
Drug
interactions
No significant
interactions
Mechanism of action
Moricizine reduces the maximal
upstroke of phase 0 and shortens
the cardiac transmembrane action
potential.
The phenomenon may explain
the efficacy of moricizine in
suppressing rapid ecotopic
activity.
37. They shorten Phase 3 repolarization
↓ the duration of the cardiac action potential
Prolong phase 4
IB
Lidocaine Mexiletine Phenytoin
38. LIDOCAINE
the duration of action potential decreases
It shorten phase 3 repolarization and decreases the
duration of action potential
• Drowsiness
• Slurred speech
• Confusion and convulsions
• VA
• Digitalis toxicity
A/E
Uses
Mechanism of action
39. C/I
Lidocaine is contraindicated
in the presence of second and
third degree heart block, since it
may increase the degree of block
and can abolish the
idioventricular Pacemaker
responsible for maintaining the
cardiac rhythm.
Drug interactions
• Proponolol increases its
toxicity.
• The myocardial depressant
effect of lidocaine is enhanced
by phenytoin administration.
40. PHENYTOIN
Phenytoin was originally introduced for the control of
convulsive disorders but now also been shown to be
effective in the treatment of cardiac arrythmias.
Uses
Anaesthesia
Open heart surgery
Digitalized induced and ventricular arrythmia in children
41. A/E C/I
Respiratory arrest Severe bradycardia
Hypotension Severe heart failure
AF & AFI
Drug Interactions
Plasma phenytoin concentrations are increased in
the presence of chloramphenicol, disulfiram, and
isoniazid, since the later drugs inhibit the hepatic
metabolism of phenytoin
42. MEXELETINE
Mechanism of action
It is a local anaesthatic and an active antiarrythmic by the
oral route; chemically and pharmacologically similar to lidocaine.
It reduces automaticity in PF, both by decreasing phase 4 slow
and by increasing threshold voltage.
By reducing the rate of 0 phase depolarization in ischemic
PF it may convert one-way block to two-way block.
43. A/E C/I
Tremor
Hypotension
Bradycardia
• Cardiogenic shock
• Second or third-degree
heart block
Uses Drug Interactions
• VA
• Congenital long
QT syndrome
• When mexiletine is administered with phenytoin
or rifampin, since these drugs stimulate the hepatic
metabolism of mexiletine, reducing its plasma
concentration.
44. IC
flecainide Encainide Propafenone moricizine
markedly slow Phase 0 depolarization
slow conduction in the myocardial tissue
minor effects on the duration of action potential
and ERP
reduce automaticity by increasing threshold potential
rather than decreasing slope of Phase 4 depolarization.
45. FLECAINIDE &
ENCAINIDE
Mechanism of action
Flecainide suppresses phase 0 upstroke in purkinje
and myocardial fibers.
This causes marked slowing of conduction in all cardiac
tissues, with a minor effect on the duration of the action
potential and refractoriness.
Automaticity is reduced by an increase in the threshold
potential rather than a decrease in the slope of phase
4 depolarization
46. Proarrhythmogenic efffect on
patients with coronary artery
disease
Use- ventricular arrhythmia
A/E – torsades de point, visual
disturbances & headache
Digoxin toxicity
C/I- cardiogenic shock
48. MORICIZINE
Has all three subclass properties
Less proarrhythmogenic effect
Used in ventricular arrhythmias
200-400mg orally at 8hourly
49. CLASS II DRUGS – PROPRANOLOL,
METOPROLOL, ESMOLOL, ACEBUTOLOL
Depress phase 4 depolarization
depress automaticity
prolong AV conduction
↑ ERP
Prolong PR interval
HR
contractility
50. Hypoglycemia
(infants)
Asthma
Branchospasm
C/I
Asthma
Bradycardia
Severe CHF
PROPANOLOL
Mechanism of action
Propanolol decreases the slope of
phase 4 depolarization and
other ectopic foci.
Prolong the ERP of A-V node.
Uses
AF
Digitalis-induced arrythmias
A/E
51. Acebutolol is a cardioselective
β1-adrenoreceptor blocking agent
that also has some minor membrane
stabilizing effect on the action
potential.
Mechanism of action
Acebutolol reduces blood pressure in
patients with essential hypotension
primarily through its negative
ionotropic and chronotropic effects.
Acebutolol
A/E
Bradycardia
GI upset
Uses
• VA
• Angina pectoris
C/I
Cardiogenic shock
Severe bradycardia
ACEBUTOLOL
57. Sotalol Like – Amiodarone
Non cardioselective blocker
Has both class II & class III
actions
Oral dose 80mg twice daily
Proarrhythmic effect
C/I - hypokalaemia
Arrhythmic
death in post MI
Uses =VF, VT &
AF
A/E= fatigue,
Headache, chest
pain
Drug interactions
Drug with inherent
QT-Interval prolonging activity may
enhance the class 3 effects of sotalol.
58. NEWER CLASS III
Dronedarone
Vernakalant
Azimilide
Tedisamil
Without iodine, short t1/2, AF
Oral 400mg twice daily
Na+ & K+, atrial ERP, AF
Block both rapid & slow k+ channel
59. Verapamil Diltiazem
Mechanism
Class IV
• Block L-type calcium channels.
• Rate of phase 4 in SA / AV node
• Slow conduction – prolong ERP
• Phase 0 upstroke
60.
61. Verapamil
Stronger action on heart than smooth muscle
Used in supraventricular arrhythmia
80-120mg three times a day
A/E – ankle oedema, constipation
C/I – AV block, LVF, hypotention & WPW
It digoxin toxicity
Diltiazem
Mixed action
Oral dose 30-90mg 6hourly
62. WHICH OTHER DRUGS……
Adenosine
Naturally occurring nucleoside
Adenosine receptors – open GP-K+ & inhibits nodal conduction
Used in Reentry circuit, PSVTs & SVT
Ultra short t1/2 (10-20 sec)
A/E – facial flushing, short breath, bronchospasm, metallic taste
Dipyridamole it’s action
3mg IV bolus
63. Magnesium
Na+/K+ATPase, Na+, K+ & Ca++
VT, digitalis-induced & torsades de point
Potassium
Normal – conduction, ERP & automaticity
Hypokalaemia – EAD & DAD
66. REFERENCES
o Lippincotts,Pharmacology-IV Edition,Pg.no:196-207
o P.N.Bennet,M.J.Brown,Clinical Pharmacology-IX Edition,Pg no:497-519
o K .D. Tripathi,Essentials Of Medical Pharmacology, Pg.no:508-520
oRang/ dale,Pharmacology, V Edition , Pg no:277-280
o Charles R.Ciaig,Robert E. Stitzel,Modern Pharmacology With Clinical
Applications
67. ACKNOWLEDGEMENT
I thank principal sir Dr. P. Srinivasa Babu for giving me this
opportunity.
I Also thankful to my guide Mrs.B.DEEPTI M.Pharm(Ph.D)
for her constant guidance.