3. A-RHYTHM –IA
• Defn- Arrhythmia is deviation of heart from
normal RHYTHM.
• RHYTHM
1. HR- 60-100
2. Should origin from SAN
3. Cardiac impulse should propagate through
normal conduction pathway
4. with normal velocity.
7. Types of cardiac tissue
(on the basis of impulse generation)
• AUTOMATIC/ PACEMAKER/ CONDUCTING
FIBRES
(Ca++ driven tissues)
Includes SA node, AV node, bundle of His,
Purkinje fibres
Capable of generating their own impulse
Normally SA node acts as Pacemaker of heart
• NON-AUTOMATIC MYOCARDIAL
CONTRACTILE FIBRES (Na+ driven tissues)
Cannot generate own impulse
Includes atria and ventricles
13. FAST CHANNEL AP SLOW CHANNEL AP
Occurs in atria, ventricles,
PF
Predominant ion in phase-
0 is Na+
Conduction velocity more
Selective channel blocker
is tetradotoxin , LA
Occurs in SA node, A-V
node
Predominant ion in
phase-0 is Ca2+
Less
Selective channel blockers
are calcium channel
blockers
14. COMMON TERMS
Automaticity
Capacity of a cell to undergo spontaneous
diastolic depolarization
Excitability
Ability of a cell to respond to external stimulus
by depolariztion
Threshold potential
Level of intracellular negativity at which abrupt
and complete depolarization occurs
15. COMMON TERMS
Conduction velocity of impulse
Determined primarily by slope of action
potential and amplitude of phase-0, any
reduction in slope leads to depression of
conduction
Propagation of impulse
Depends on ERP & Conduction velocity
18. Regulation by autonomic tone
Parasympathetic/Vagus Nerve
stimulation:
• Ach binds to M2 receptors
• Activate Ach dependent outward K+
conductance (thus hyperpolarisation)
• ↓ phase 4 AP
Sympathetic stimulation:
• Activation of β1 receptors
• Augmentation of L-type Ca2+ current
• Phase 4 AP slope increased
19. Phase 0
Phase 1
Phase 2
Phase 3
Phase 4
R.M.P
(Plateau Phase)
Class I:
Na + channel blockers.
- Pacemaker potential
-
-
-
Class III:
K + channel blockers
-
Class IV:
Ca ++ channel blockers
Class II:
Beta blockers
Classification of Anti-Arrhythmic Drugs
20. Classification of Anti-Arrhythmic Drugs
(Vaughan-Williams-Singh..1969)
Phase 4
Phase 0
Phase 1
Phase 2
Phase 3
0 mV
-
80m
V
II
I
III
IV
Class I: block Na+ channels
Ia quinidine, procainamide,
disopyramide (1-10s)
Ib lignocaine (<1s)
Ic flecainide(>10s)
Class II: ß-adrenoceptor
antagonists atenolol, sotalol
Class III: prolong action potential
and prolong refractory period
amiodarone, dofetilide, sotalol
Class IV: Ca2+ channel antagonists
verapamil, diltiazem
21.
22. • Bind to and block Na+ channels (and K+
also)
• Act on initial rapid depolarisation
(slowing effect)
• Do not alter resting membrane potential
(Membrane Stabilisers).
• Bind preferentially to the open channel
state
• USE DEPENDENCE : The more the
channel is in use, the more drug is bound
Class I: Na+ Channel Blockers
23.
24. Class I: Na+ Channel Blockers
• IA: Ʈrecovery moderate (1-10sec)
Prolong APD
• IB: Ʈrecovery fast (<1sec)
Shorten
• IC: Ʈrecovery slow(>10sec)
Minimal effect on APD
26. DRUG MOA AP USES DOSAGE ADVERSE
EFFECTS
DRUG
INTERACTIO
NS
Quinidine
Alkaloid –
cinchona ,
dextro
isomer of
quinine
Blocks
activated
na+
channels
and k+
channels
Antimusca
rinic and
alpha
blocking
property
INC
APD
INC
ERP
Conver
t/preve
nt
AF/VT
6–10
mg/kg at
0.3–0.5
mg/kg
per min
IV
300–600
mg q6h
orally
t1/2
6-8 hrs
Diarrhea,
nausea,
vomiting,
cinchonism,
thrombocytop
eniaLong QT
and torsades
des pointes,
1:1 ventricular
response to
atrial flutter;
increased risk
of some
ventricular
tachycardias
in patients
with
structural
heart disease
Rise in blood levels
and toxicity of
digoxin due to
displacement from
tissue binding and
inhibition of
Pglycoprotein
mediated renal and
biliary clearance of
digoxin.
Marked fall in BP in
patients receiving
vasodilators.
Risk of torsades de
pointes is increased
by hypokalaemia
caused by diuretics.
Synergistic cardiac
depression with β-
blockers, verapamil,
K+ salts.
Quinidine inhibits
CYP2D6:
27. DRUG MOA AP USES DOSAGE ADVERSE
EFFECTS
DRUG
INTERAC
TIONS
Procainam
ide
orally
active
amide
derivative
of the local
anaestheti
c procaine
Blocks
activated
na+
channels
and k+
channels
Antimusca
rinic
INC
APD
INC
ERP
Monom
orphic
VT,
WPW
Syndro
me,AF
15 mg/kg
over 60
min IV
with
maintainan
ce 1–4
mg/min
250–500
q3–6h
orally
t1/2
3-5 hrs
Lupus
erythematosus-
like syndrome
(more common
in slow
acetylators),
anorexia, nausea,
neutropenia
Long QT and
torsades des
pointes, 1:1
ventricular
response to atrial
flutter; increased
risk of some
ventricular
tachycardias in
patients with
structural heart
disease
28. DRUG MOA AP USES DOSA
GE
ADVERSE
EFFECTS
DRUG
INTERAC
TIONS
Disopyra
mide
Blocks
activated
na+
channels
and k+
channels
Antimusca
rinic
INC
APD
INC
ERP
The primary
indication of
disopyramide
is
as a second
line drug for
prevention of
recurrences of
ventricular
arrhythmia.
It may also be
used for
maintenance
therapy after
cardioversion
of AF .
100–
300 mg
q6–8h
orally
t1/2
4-10
hrs
Anticholinergi
c effects,
decreased
myocardial
contractilityLo
ng QT and
torsades des
pointes, 1:1
ventricular
response to
atrial flutter;
increased risk
of some
ventricular
tachycardias
in patients
with structural
heart disease
Contrain
dications
are—sick
sinus,
cardiac
failuren
29. Moricizine This Class IA drug delays Na+
channel recovery to a greater extent (also
classified as Class IC).
It has been used to suppress VE and WPW
arrhythmias, AF prevention
but the CAST II study has found it to
increase mortality in post-MI patients.
dosage100–400mg q8h orally t1/2 3–13hrs
31. LIGNOCAINE
Blocks inactivated sodium channels more than open
state
Relatively selective for partially depolarized cells
Selectively acts on diseased myocardium
Rapid onset & shorter duration of action
Useful only in ventricular arrhythmias , Digitalis
induced ventricular arrnhythmias
× Lidocaine decreases APD in PF and ventricular muscle, but
has practically no effect on APD and ERP of atrial fibres
Atrial action potentials are so short that the Na+ channel
is in the inactivated state only briefly compared with
diastolic (recovery) times, which are relatively long
32. T ½ = 8 min – distributive, 2 hrs – elimination
Used in:
Ventricular arrhythmia
Digoxin induced arrhythmia
Dose=1–3 mg/kg at 20–50 mg/min maintainance 1–4 mg/min iv
Adverse effects
The main toxicity is dose related neurological effects:
Drowsiness, nausea, paresthesias, blurred vision, disorientation,
nystagmus, twitchings and fits.
Lidocaine has practically no proarrhythmic potential and is the least
cardiotoxic antiarrhythmic.
Only excessive doses cause cardiac depression and hypotension
33. Local anaesthetic
Inactive orally
Given IV for antiarrhythmic action
Na+ channel blockade which occurs
Only in inactive state of Na+ channels
CNS side effects in high doses
Action lasts only for 15 min
Inhibits purkinje fibres and ventricles but
No action on AVN and SAN so
Effective in Ventricular arrhythmias only
34. MEXILETINE
Oral analogue of lignocaine
Mexiletine is almost completely absorbed
orally, 90% metabolized in liver and excreted
in urine; plasma t½ 9–12 hours.
It reduces automaticity in PF, both by
decreasing phase-4 slope and by increasing
threshold voltage
Use:
chronic treatment of ventricular arrhythmias
associated with previous MI
Tremor is early sign of mexiletine toxicity
35. Bradycardia, hypotension and accentuation
of A-V block may attend i.v. injection of
mexiletine.
Neurological—tremor, nausea and vomiting
are common; dizziness, confusion, blurred
vision,ataxia can occur.
Dosage 150–300 mg q8–12h orally
36. TOCAINIDE
Structurally similar to lignocaine but can be
administered orally t1/2 – 11-23 hrs
Serious non cardiac side effects like
pulmonary fibrosis, agranulocytosis,
thrombocytopenia limit its use
37. Class I C drugs
Encainide, Flecainide, Propafenone
Have minimal effect on
repolarization
Are most potent sodium
channel blockers
Risk of cardiac arrest ,
sudden death so not
used commonly
May be used in severe
ventricular arrhythmias
38. PROPAFENONE
Structural similarity with propranolol & has -blocking
action
T ½ - 2 – 10 hrs
Undergoes variable first pass metabolism
USES Reserve drug for ventricular arrhythmias, re-
entrant tachycardia involving accesory pathway,to
maintain sinus rhythum in AF dosage 150–300 mg q8h
Adverse effects:nausea,vomiting,bitter taste,blurred
vision,constipation and is proarrhythmic
C/I in structural heart disease
39. Flecainde
Flecainide
Orally active antiarrhythmic
Metabolized by microsomal enzymes (t ½ - 20 hrs)
Used for ventricular tachyarrhythmias &
maintenance of sinus rhythm in patients with
paroxysmal atrial fibrillation and/or atrial flutter
& WPW
C/I in pts with structural heart disease
Adverse events :
Heart failure, dizziness, headache , Blurred vision
40. Flecainde
■ Cardiac Arrhythmia Suppression Test
(CAST Trial):
■When Flecainide & other Class Ic given
prophylactically to patients convalescing
from Myocardial Infarction it increased
mortality by 2½ fold. Therefore the trial had
to be prematurely terminated
41. Ia Ib Ic
Moderate Na
channel blockade
Mild Na channel
blockade
Marked Na channel
blockade
Slow rate of rise of
Phase 0
Limited effect on
Phase 0
Markedly reduces
rate of rise of phase
0
Prolong
refractoriness by
blocking several
types of K channels
Little effect on
refractoriness as
there is minimal
effect on K channels
Prolong
refractoriness by
blocking delayed
rectifier K channels
Lengthen APD &
repolarization
Shorten APD &
repolarization
No effect on APD &
repolarization
Prolong PR, QRS QT unaltered or
slightly shortened
Markedly prolong
PR & QRS
42. BETA BLOCKERS
Depress phase 4 depolarization of
pacemaker cells,
Slow sinus as well as AV nodal conduction
↑ ERP, prolong AP Duration by ↓ AV
conduction
Reduce myocardial oxygen demand
Well tolerated, Safer
43. β Adrenergic
Stimulation
β Blockers
↑ magnitude of Ca2+ current &
slows its inactivation
↓ Intracellular Ca2+ overload
↑ Pacemaker current→↑ heart
rate
↓Pacemaker current→↓ heart
rate
↑ DAD & EAD mediated
arrhythmias
Inhibits after-depolarization
mediated automaticity
44. • Major drugs
• Acebutolol & esmolol, more selective β1-adrenoceptor
antagonists Used to treat ventricular arrhythmias
• Propranolol, metoprolol, nadolol, and timolol frequently
used to prevent recurrent MI
• Esmolol 500 micro g/kg iv over 1 min maintainance 50
micro g/kg per min for AF/AFL rate control
• Metoprolol 5mg over 3 to 5 min iv 3 doses maintainance
1.25 to 5 mg 6th hrly for SVT,AF rate control,exercise
induced VT, long QT
• Acebutolol 200–400 mg q12h oral
• Atenolol 25–100mg per d oral
• Metoprolol 25–100 q6h oral
45. Control supraventricular arrhythmias
Atrial flutter, fibrillation, PSVT
Treat tachyarrhythmias caused by
adrenergic
Hyperthyroidism Pheochromocytoma,
during anaesthesia with halothane
Digitalis induced tachyarrythmias
Prophylactic in post-MI
Ventricular arrhythmias in prolonged QT
syndrome
USE’S
48. DRUG MOA AP USES DOSA
GE
ADVERSE
EFFECTS
DRUG
INTERACTION
S
Amioda
rone
Blocks
k+ and
inactivat
ed na+
channels
β blocking
action ,
Blocks
Ca2+
channels
INC
APD
INC
ERP
Resistan
t VT
Reccure
nt VF
For
sinus
rhythm
in AF
SVT
WPW
15mgmi
n for 10
min iv
then
1mgmin
for 6 hrs
maintena
nce 0.5-
1mg
Min
100-
400mg
qid
t1/2 3 to
8 wks
Tremor,
peripheral
neuropathy,
pulmonary
inflammation,
hypo- and
hyperthyroidism,
photosensitivity
Sinus
bradycardia, AV
block, increase in
defibrillation
thresholdRare:
long QT and
torsades des
pointes, 1:1
ventricular
conduction with
atrial flutter
digoxin and
warfarin levels
by reducing their
renal clearance.
Additive A-V
block can occur
in patients
receiving β
blockers or
calcium channel
blockers.
Inducers and
inhibitors of
CYP3A4
respectively
decrease and
increase
amiodarone
levels.
49. Antiarrhythmic
Multiple actions
Iodine containing
Orally used mainly
Duration of action is very long (t ½ = 3-8
weeks)
APD & ERP increases
Resistant AF, V tach, Recurrent VF are
indications
On prolonged use- pulmonary fibrosis
Neuropathy may occur
Eye : corneal microdeposits may occur
50. • Bretylium:
― Adrenergic neuron blocker used in resistant ventricular arrhythmias
― Major direct action is prolongation of APD and ERP, due to K+
channel blockade
• Sotalol:
– Beta blocker
– Also prolongs cardiac action potentials by inhibiting delayed
rectifier and possibly other K+ currents
– AF/VT prevention
– 80–160mg q12h with t1/2 of 12hrs
• Dofetilide, Ibutilide :
– Selective K+ channel blocker
– use in AF to convert or maintain sinus rhythm
– Dofetilide 0.125–0.5 mg q12h orally with t1/2 10hrs
– Ibutilide 1 mg over 10 min iv if over 60 kg
51. Dronedarone –used in AF/AFL,C/I in
CHF,LF 400 mg q12 hr orally
Vernakalant –under trials
Azimilide –under trials
Tedisamil-under trials
NEWER CLASS 3 DRUGS
52. Calcium channel blockers (Class IV)
• Inhibit the inward
movement of calcium
↓ contractility,
automaticity , and AV
conduction.
• Verapamil &
diltiazem
53. Verapamil
It blocks L type Ca2+ channels
The basic action of verapamil is to depress Ca2+ mediated
depolarization.
This suppresses automaticity or reentry dependent on
slow response
The most consistent action of verapamil is prolongation of
A-V nodal ERP.
As a result A-V conduction is markedly slowed and reentry
involving A-V node is terminated
54. • Uses:
– Terminate PSVT 5–10 mg over 3–5 min IV
maintainance 2.5–10 mg/h
– control ventricular rate in atrial flutter or fibrillation
80–120mg q6–8h orally
• Drug interactions:
– Displaces digoxin from binding sites
– ↓ renal clearance of digoxin
– CI in sick sinus and partial heart block
55. ×The direct cardiac actions of diltiazem are similar to those of
verapamil
×It is an alternative to verapamil for PSVT.
×For rapid control of ventricular rate in AF or AFl, i.v.
diltiazem is preferred over verapamil,because
it can be more easily titrated to the target heart rate,
causes less hypotension and myocardial depression
can be used even in the presence of mild-to-
moderate CHF.
Diltiazem
DOSAGE
0.25 mg/kg IV over 3–5 min (max 20 mg)
maintainance 5–15 mg/h
30–60 mg q6h orally
56. Other antiarrhythmics
• Adenosine :
– Purine nucleoside having short and rapid action
– IV suppresses automaticity, AV conduction and dilates
coronaries
– Drug of choice for PSVT 6–18 mg (rapid bolus) t1/2 10 sec
– Adverse events:
• Nausea, dyspnoea, flushing, headache ,bronchospasm
• All arrhythmias potentiated by profound pauses, atrial
fibrillation
Drug interactions -Dipyridamole potentiates its action by inhibiting
uptake, while theophylline/ caffeine antagonize its action by blocking
adenosine receptors
57. Adenosine
• Acts on specific G protein-coupled adenosine
receptors
• Activates AcH sensitive K+ channels channels in
SA node, AV node & Atrium
• Shortens APD, hyperpolarization & ↓
automaticity
• Inhibits effects of ↑ cAMP with sympathetic
stimulation
• ↓ Ca currents
• ↑AV Nodal refractoriness & inhibit DAD’s
59. Atropine: Used in sinus bradycardia ,av
block
Digitalis: Atrial fibrillation and atrial flutter
0.125–0.5mg qd orally
0.25 mg q2h iv until 1 mg
60. Magnesium
• Its mechanism of action is unknown but
may influence Na+/K+ATPase, Na+
channels, certain K+ channels & Ca2+
channels
• Use: Digitalis induced arrhythmias if
hypomagnesemia present, refractory
ventricular tachyarrythmias, Torsade de
pointes even if serum Mg2+ is normal
• Given 1g over 20mins
Editor's Notes
Deviation from the normal pattern of cardiac rhythm
May occur when there is disturbance in initiation or conduction of cardiac impulse
Range from asymptomatic to life threatening
Non automatic fibres: these are ordinary working myocardial fibres, cannot generate the impulse of their own, during diastole RMP remains stable -90mV inside. When stimulated they depolarize rapidly (Fast phase-0) with considerable overshoot (+30mV), rapid return to near isoelectric level 0mV (Phase-1), maintenance of membrane potential at this level for a considerable period of time (Phase-2) plateau phase during which calcium ions flow in and bring about contraction, then relatively rapid repolarization (Phase-3) mainly by continued extrusion of potassium via potassium channel, phase 4 resting phase, in this phase the final ionic reconstitution of cell is achieved by na-k+ exchange pump which actively pushes Na+ out of cell and K+ into the cell. The resting membrane potential once attained doesnot decay (stable- phase4).
Automatic fibres: they are present in SA node, AV node and his-purkinje system. i.e the specialized conducting tissue(in addition patches are present around interatrial septum, A-V ring and around openings of great veins. The most charecteristic feature of these fibres is the phae 4 or slow diastolic depolarization i.e after repolarizing to the maximum value membrane potential decays spontaneously when it reaches a critical threshold value –sudden depolariztion occurs automatically . Thus they are capable of generating their own impulse. The rate of impulse generation by a particular fibre depends upon the value of maximum diastolic potential , slope of phase 4 depolarization and value of threshold potential .
Why SA node acts as pacemaker: SA node has steepest phase-4 depolarization undergoes self excitation and propogates the implse to the rest of the heart- acts a pacemaker. Other fibres which also undergo phase 4 depolarization but at a slower rate receive propogated impulsebefore reaching threshold valueand remain as latent pacemakers.
RMP IS -90 MV
Cardiac bounded by a lipoprotein membrane which has receptor channels crossing it
WHEN AN ATRIAL OR VENTRICULAR CELL RECIEVES An action potential it starts depolarising in response to it..and sodium starts entering it
Intracellular negativity starts diminishing
When such depolarisation reaches a threshold potential, the sodium channels open abruptly
Na enters cell in large quantities
CELL MEMBRANE ACTION POTENTIAL CHANGES FROM -90 TO ALMOST +30MV
Phase 0: rapid depolarisation…fast selective inflow of na ions
During latter part, ca ions also enter the cell via na channels
Frther in phase 1 and 2 ca ions enter thru slow ca channels
THE CONFORMATION OF THE SODIUM CHANNELS HENCE CHANGES TO INACTIVE STATE
The ca which enters the cell in dis manner causes release of ca from sarcoplasmic reticulumraising the conc of ca within the cells
This intracellular free ca interacts with actin myocin system and causes contraction of heart
Afetr this, phase 1: short rapid repolarisation due to beginning of outflow of potassium and entry of cloride ions into the cells, MEMBRANE CHARGE CHANGES FROM +30 TO ALMOST 0 MV IN VERY SHORT TIME
Phase 2 : prolonged plateau phase.. Balance bw ca enterin the cell and k leavin the cell..VOLTAGE SENSITIVE SLOW l type CA CHANNELS OPEN …SLOW INWARD CA CURRENT BALANCED BY SLOW OUTWARD K CURRENT..DEPOLARISATION = REPOLARISATION
Phase 3 : rapid repolarisation.. CA CHANNELS CLOSE…K CHANNELS OPEN..Contimued extrusion of k…RESUMES INITIAL NEGATIVITY
FROM PHASE 0 TO 3 THERE HAS BEEN A GAIN OF NA AND A LOSS OF K ..THIS IS NOW REVERTED AND BALANCED BY NA K ATPASE
Phase 4: resting phase..ELECTRICALLY STABLE… Ionic reconstitution of cell is reachieved by na k exchange pump
RMP MAINTAINED BY OUTWARD K LEAK CURRENTS AND NA CA EXCHANGERS
The cycle is then repeated
Inactivation gates of sodium channels in resting membranes close over the potential range of -75 to -55mv
Cardiac sodium channel protein shows 3 different conformations
Depolarisation to threshold voltage results in opening of the activation gates of sodium channel thus causing markerdly increased sodium permeability
Brief intense sodium current , conductance of fast sodium channel suddenly increases in response to depolarising stimulUs
Very large influx of na accounts for phase 0 depolarisation
Clusure of inactivation gates result
Remain inactivated till mid phase 3 to permit a new propagated response to external stimulus…refractory period..
Cardiac calcium channels are L type
Phase 1 and 2 : turning off nodium current, waxing and waning of calcium curent, slow development of repolarising potassium current, calcium enters ..potassium leaves..
Phase 3: complete inactivation of sodium and calcium currents and full opening of potassium
2 types of main potassium currents involved in phase 3 : ikr and iks
Certain potassium channels are open at rest also…”inward rectifier” channels
In addition there are 2 energy requiring exchange pumps in cardiac myocyte cell membrane…na k exchange pump…and and na-ca exchange pump
Normally na ions concentrated extracellularly and vice versa for k cions
Thus have a tendency odf diffusion along concentration gradient
This diffusion is opposed by na k pump
This pump operates contimuously and does not switch on and off during action potential of cardiac cells
Action potential in automatic tissues
less negative resting membrane potential ,Maximum diastolic potential lies near -60 mv
slow diastolic depolarization (phase 4), which generates an action potential as the membrane voltage reaches threshold
action potential upstrokes (phase 0) are slow(mediated by calcium rather than sodium current)
Action potential is longer
Conduction velocity is slow, Refractory period longer
Less overshoot low amplitude
RMP not stable and full repolarisation at -60mV
Phase 1 2 3 indistinguishable
Spontaneous Depolarisation occurs due to:
Slow, inward Ca2+ currents
Slow, inward Na+ currents called “Funny Currents”
Ca influx and not of na dominates the depolarisation and is largely responsible for initiation and propagation of ap
Thus cardiac automaticity is decreased by calcium channel blockers in case of slow channel AP
Steeper the diastolic depolarisation, higher is the pacemaker rate
SA node has the steepest phase 4 depolarisation
Other nodal cells can become pacemakers when their own intrinsic rate of depolarisation is greater than SA node(latent pacemakers)
In all pacemaker cells, the outward potassium current during phase 4 is smaller, which keeps the cell with automaticity in a less negative potential (near depolarisation state -60mv).
The depolarising inward calcium currents are large enough to gradually depolarise the cell during diastole
Vagal discharge and beta blockers slow the phase 4 slope
Tachycardia is caused by increased paceamkers discharge ..due to increased phase 4 slope..reasons may be: hypokalemia, beta stimulation, positive chronotropic drugs, fibre strech, acidosis, partial depolarisation by currents of injury
Coronary sinus opening also
ERP< APD in fast channel, ERP> APD in slow channel , slow channel AP can occur in purkinje fibres also, but it has much longer duration with prominent plateu phase.
In normal heart automaticity is maximum in SA node (Pacemaker). In diseased heart, other areas of myocardium may may develop automaticity and become focus of ectopic impulse generation and arrhythmias.
Excitability: can be conceived in terms of minimum intensity of stimulus required to depolarize the cell membrane. It depends upon the level of resting(diastolic) intracellular negativity, if negeativity decreases eg from -90mV TO -70mV excitability of cell increases.
Threshold potential: if threshold potential is raised changed from -70 to -60 mV Automaticity of tissue is supressed.
A drug which reduces phase zero slope(at any given RMP) will shift membrane responsiveness curve to right and impede the conduction. Reverse occurs if a drug shifts curve to left. Normally purkinje fibres have highest conduction velocity 4000 mm/sec
Protective mechanism and keeps the heart rate in check, prevents arrhythmias and coordinates muscle contraction
It extends from phase 0 uptill sufficient recovery of Na channels.
Divided into:
Class Ib drug blocks sodium channels more in inactivated state than open state but do not delay the channel recovery they do not deprss AV condcution or prolong APD Even shorten
Than with long APD ( Na + channels remain inactivated for long period of time
Normal ventricular fibres are minmally affected , depolarized damaged fibres are significantly depressed
Brevity of AP and lack of lidocaine effect on channel recovery may explain its inefficacy in atrial arrhythmias
No significant hemodynamic effect
No significant autonomic actions
IV preparation must not contain preservative , symapthomimetic or vasoconstrictor
1-3 mg/min infusion
Clinical Pharmacokinetics
High first pass metabolism
half-life 1–2 hours
a loading dose of 150–200 mg administered over about 15 minutes
should be followed by a maintenance infusion of 2–4 mg/min
400 mg loading dose then 200 mg 8 hrly
Contraindicated in patients with AV block as it may accelerate AV block
450- 750 mg of mexiletine orally per day provides significant relief in diabetic neuropathy
Although uses are similar to lidocaine
3:1000
Can also cause nausea, dizziness, paraesthesia, numbness
Can precipitate CHF by depressing AV CONDUCTION and ALSO CAN CAUSE bronchospasm.
Dose = 200 mg tds
Morcizine has properties of all 3 classes but as it prolongs qrs it has been placed along with class Ic drugs
Usual dose = 100- 200 mg bd orally how ever these drugs are proarrhythmic even when normal doses are administered to patients with sick sinus syndrome pre exixting ventricular tachyarrhythmia, ventricular ectopy or previous MI
Currently reserved for life threatening refractory ventricular arrhythmias who do not have CORONARY ATRETY DISEASE. LIKELY HOOD OF DEVELOPING TORSADES DE POINTES IIS SERIOUS DRAWBACK OF THESE DRUGS, OTHER ADVERSE EFFECTS INCLUDE VISUAL DISTURBANCES , DIZZINESS, NAUSEA AND HEADACHE.
Slow sinus as well as av nodal conduction which results in decrease in HR and increase PR atrial depolarization, QT and QRS are not significantly altered.
Propranolol, acebutolol esmolol have been aprroved for antiarrhythmic use
Class III drugs block outward K+ channels during phase III of action potential
These drugs prolong the duration of action potential without without affecting phase 0 of action potential or resting membrane potential they instead prolong ERP
Bretylium became obsolete because of poor bioavailability and development of tolerance, reintroduced as antiarrhythmic for parenteral use. Main adverse effect is postural hypotension , nausea, vomiting . Long term use may result in swelling of parotid gland particularly at meal time. It is contraindicated in digitalis induced arrhythmias and cardiogenic shock.
Dronaderone: amiodarone like drug without iodine atoms so no pulmonary or thyroid toxicity. Has shorter half life 1-2 days compared to months
Vernakalant mixed sodium and potassium channel blocker
Azimilide: blocks rapid and slow components of potassium channels low incidence of torsades de pointes
Tedisamil:
