antiarrhytmic drugs Flashcards
Drug therapy of Cardiac Arrhythmias is based on:
1- Knowledge of the — , — and— of the arrhythmia (see Syncope lecture)
- The response of an arrhythmia to drugs is as much a function of the pathophysiological condition as it is of the drug action.
3-A clear understanding of the — of the drugs to be used
-Knowledge of the effect of the drug on the electrophysiological properties of the normal and abnormal cardiac tissue
-The effects of the drug on the mechanical properties of the heart & vasculature
-The interactions of the drug with the autonomic nervous system (ANS)
3-A broad knowledge of the — of each agent is required, and their potential interactions with other drugs, is necessary to monitor therapy
mechanism, consequences , natural history
pharmacology
adverse effects
-Arrhythmias = broad category of conditions where the — or — is abnormal.
-Arrhythmias can range from incidental, asymptomatic clinical findings to life-threatening abnormalities. Some are inherited as —- syndrom and — syndrome
-For some human arrhythmias, precise mechanisms are known, and treatment can be targeted specifically to those mechanisms.
Often due to cardiac — secondary to — or a —
In other cases, mechanisms can only be inferred, and the choice of drugs is based largely on results of prior — .
Antiarrhythmic drug therapy has 3 goals:
1- — of an ongoing arrhythmia
2- or — of future arrhythmias
3- and interventions to reduce the — of thrombosis (associated with —- ).
-Unfortunately, antiarrhythmic drugs not only may help control arrhythmias but also can — them, even during –therapy.
-Thus, prescribing antiarrhythmic drugs requires that precipitating factors be excluded or minimized, that a precise diagnosis of the type of arrhythmia (and its possible mechanisms) be made.
heart rate or rhythm
Wolff-Parkinson-White syndrome
Brugada syndrome
cardiac scarring
2ndary to atheroscolrosis or MI
experience
termination
prevention
risk
arterial fibrillation
cause
ling term
cardiac action potential types:
SA node:
Resting potential —-
Upstroke generated by —-
Voltage-sensitive Na+ channels would be—
AV node:
— conduction.
Upstroke generated by —
Voltage-sensitive Na+ channels would be —
Ventricle:
Cardiac action potential duration— .
Shorter duration at the — of the heart.
Repolarisation wave moves from — to —
more +ve
ca+2 influx
inactivated
slow
ca+2 influx
inactivated
varies
base
bottom to top
electrical coupling to contraction and ECG:
1- an electrical impulse moves from – to the walls of – causing them to —
2- the impulse reaches – which – it by — seconds
3- bundle branches carry signals from — to —
4- the signal spread through – causing them to —
- info: threshold voltage is required to trigger AP in adjacent cells
SA
atria
contract
AC
delays
0.1 second
AV
apex
ventricle
contract
refractory period - natural protection:
-Na+ channels move from – to
— very quickly (time dependent)
-Once inactivated, have to move
to closed before can reopen
-Move from inactivated to closed
needs exposure to — voltage
-While Na+ channels inactivated
heart is –
open to inactivated
-ve voltage
refractory
types of arrhythmia:
Clinically, arrhythmias are classified according to:
the — of — of the abnormality – atrial (—- ) or — ;
whether the — is increased ( — ) or decreased ( — ).
Normal heart Rhythm = — bpm
Bradycardia is a slow heartbeat – bpm
Tachycardia is a fast heart — bpm
If this occurs for more than 5 consecutive beats, & lasts for more than 30 seconds, it becomes a —
—- when it starts and stops abruptly
—- when it occurs most of the time
Ectopic beat: A cardiac contraction initiated somewhere other than the —
- arrhythmia are generated – the level of ventricle
check slide 12,13
site of origin
supravneticular or ventricular
rate
tachycardia
bradycardia
60-100
<60
>100
sustained tachycardia
paroxysmal
incessant
SA node
above
mechanisms of arrhythmia generation - cardiac arrthymia:
1- — disturbances :
which can be from — ( substrate + trigger ) which can cause —- , —- , —
or can be from — which can cause—-
2- —- formation :
- — disturbances as — causing— or —- causing —
- — activity which can cause —-
conduction disturbances
reentry
atrial fibrillation , AVRT/AVNRT , ventricular tachycardia
conduction block
AV conduction block/delay
abnormal impulse formation
automaticity disturbances
enhances automaticity causing sinus tachycardia
reduced automaticity causing sinus bradycardia
( both of these sinuses are disturance of normal ANS function )
triggered acitvity as DAD or EAD causing premature complexes
premature beats - delayed afterdepolarization DAD:
-Afterdepolarizations are depolarizations caused by excessively — currents carried by the —
-If afterdepolarizations are large enough to reach — , premature — action potentials result before the next expected normal action potential
-Excessive intracellular – drives Na+/Ca2+ exchange
- Net — of charge – — current
-Added to If can attain threshold — next sinus beat
- Causes → — nervous system — or —
- premature beats - early afterdepolarization EADS:
- HERG channel + drugs , normal action potential
-slowing of — rate and – ADP
- one or more triggered beats
- — QT
- triggered beats causing — de pointes in 1 sc
- causes – induced block of – channel , — , — , — , —
large inward currents
na+2/ca+2 exchanger
threshold
ectopic
ca+2
+1
depolarising
before
sympathetic
overtstimulation or digotoxin
repolarisation
increase
prolonged
torsades
drug , HERG channel
old age
heart attacks
hyperkalaemia
genetics
visualisation of EAD leading to ectopic beat:
1- normal wave of AP –> — sinus rhythm
2- failure of repolarisation failing within refractory period —> — sinus rhythm
3- failure of repolarisation failing outside refractory period —> —
normal
abornmal
extra beat
heart block:
Damage to the — system in the heart
– most usually in —
There may be— of conduction through the AV node
[1st degree AV block]
There may be —
[2nd degree AV block]
There can be — of conduction between the atria and ventricles
[3rd degree block]
In 3rd degree block, the ventricle would be driven by — pacemaker, “—”. Much— than normal heart rate (30-40 BPM)
Causes → Drug-induced block of HERG channel, old age, heart attacks, hyperkalaemia, genetics
conduction
AV node
slowing
missed beat
complete breakdown
intrinsic
ventricular escape
slower
pls check slide 18,19 for pics
treating arrhythmia;
- Arrhythmia treatment may include — ,— procedures, implanted— or — to control or eliminate fast, slow or irregular heartbeats.
- — is now used extensively for most varieties of SVT, and patient-reported outcome measures have shown that patients experience significant improvements in their quality-of-life following ablation
-Implantable Cardioverter Devices (ICDs) effectively end most episodes of — or—
-Automatic external defibrillator (AED) devices becoming more common. Detect —and delivery — if appropriate.
-Antiarrhythmic drugs and catheter ablation have important roles in reduction of — arrhythmias
medication , catheter procedures , implanted device or surgery
catheter ablation
ventricular tachycardia or fibrillation
heart rhythm and electrical shock
symptomatic
automatic external defibrillator AED:
-Defibrillators apply — to the heart
-Causes all cardiac voltage-sensitive Na+ channels to — – open and then inactivate.
-Allows the — to restart, stops – cardiac currents
-If cause of arrhythmia not resolved, — can reoccur
electrical shock
synchronise
electrical acitvity
self sustaining
fibrillation
Implantable Cadioverter defibriallator (ICD):
-Animplantable cardioverter-defibrillator(ICD is a device,implanted inside the body, able to perform — , — , and — of the heart.
-The device is therefore capable of correcting most — cardiac arrhythmias.
-The ICD is the — treatment and — therapy for patients at risk forsudden cardiac deathdue toventricular fibrillationandventricular tachycardia.
-Current devices can be programmed to detectabnormal heart rhythmsand deliver therapy via programmable anti-tachycardia pacing, in addition to low-energy and high-energy shocks to restore normal cardiac rhythm.
-Procedural complications occur in 3-6% of patients.
–>These are tamponade, stroke, heart block and vascular access complications
cardioversion , defibrillation , pacing
most life threatening
first line and prophetic therapy
Catheter ablation for VT:
-Delivery of – energy (microwave) to problem tissue using a —
Tissue dies and ceases conducting signals
-Success rate of 80-90% in idiopathic VT
-May be used to reduce the frequency of symptomatic — that triggers ICD shocks
-Procedural complications occur in 3-6% of patients
–>These are tamponade, stroke, heart block and vascular access complications
radio frequency
catheter
ventricular tachycardia
antiarrythmic agents:
-The main goal of drug therapy to maintain — is to reduce — by decreasing the — and — of episodes using antiarrhythmic drugs.
-For patients with AF, a second major goal is the prevention of — .
Prevention of thrombo-embolism is treated with — drugs
-Antiarrhythmic drugs are classified using the Vaughan Williams classification (1970s)
-classes I and III are used in — control as medical — agents, while classes II and IV are used as —-control agents.
-Long-term outcomes, such as survival or rate of thromboembolism, are similar with either rhythm or rate control strategies in patients with atrial fibrillation (AF)
-Classification of antiarrhythmic drugs is generally done by their predominant – and —. Note that nearly all clinically used drugs act on multiple targets.
sinus rythym
symptoms
frequency and duration
thromboembolism
anti platet
rhythm control
cardioversion
rate control
action and target
1- class Ia: interfere with the— channel Reduce — slope and peak of action potential. Class 1a Moderate inhibition of Na+ channel ->reduction in phase 0 slope
examples: Disopyramide, (Quinidine), Procainamide
2- class Ib: is a – inhibitor examples (Lignocaine), Mexiletine
3- class Ic: is a — imhibitor as Propafenone, Flecainide
4- class II : are — nervous systemagents. Most agents in this class are— as Beta blockers ((Carvediol); propranolol, atenolol)
5- class III: affects — as (Amiodarone), (Dronadarone), Dofetilide, Bretylium, (Sotalol)
6- class IV: affects — and — as Calcium Channel Blockers: Verapamil, Diltiazem
7- unclassified : regulates — and stimulates —- as Digoxin, Adenosine, MgSO4
sodium (Na+) channel
phase 0
weak
strong
anti-sympathetic
beta blockers
potassium (k+) efflux
calcium channels and AV node
AV node
adenosine A1
check slide 26 ,27
Class Ia drugs (— channel blockers):
-Preferentially block – channels in the — or — state
—> decrease the rate of the — depolarization, & — conduction velocity.
-Moderate block of K+ channels
—> — duration of cardiac AP
-Used for —
-Used less and less
-They are — in that they – the QT interval but, by — conduction, they may promote — .
-There are no large-scale outcome trials that demonstrate that class I agents decrease mortality
Quinidine :
administered —.
Adverse effects : GI side effects, tinnitus, hearing loss, visual disturbances, confusion and psychosis (=Cinchonism*).
Can cause a —
Na+ and K+ channel blockers
sodium channels
open and inactivated state
phase 0
slow
increasing
arterial fibirllation
proarrhtymic
prolong
depressing
reentry
orally
thrombocytopenia
Class Ib drugs (— channel blockers):
-Preferentially bind to — channels & have rapid — kinetics
-Little effect on — rate of depolarization, peak slightly reduced; shorten the duration od the action potential
-Dissociate – next sinus AP
-Use dependent (Na+ channels inactivated more of the time)
-Prevent — by reducing chances of Na+ channel opening outside sinus beats
Lidocaine / Lignocaine:
Standard treatment for ventricular arrhythmias associated with – and cardiac —
Acts preferentially on – myocardium
Administered – only, Rapidly metabolized /Half-life = 30 mins
Side effects: High plasma levels cause drowsiness, paresthesia and seizure activity
na+ channel
inactivated na+
dissociation
phase 0
before
extra beat
AMI , surgery
ischemic
IV
class Ic drugs ( – channel blocker)
Preferentially bind to -channels & have – dissociation kinetics
Decrease – rate of depolarization
Have little or no effect on the duration of the Action Potential
Use dependent (Na+ channels open more of the time)
— conduction speed (can exacerbate re-entry in ischaemic tissue)
Increase — of ventricle & His-Purkinje system
Flecainide:
No effect on — duration
Use in life threatening VT and in SVT
Given orally
Major SE: Proarrhythmic, given by electrophysiologist
Dizziness, blurred vision & Nausea
na+
open na+ channels
slow
phase 0
slow
electrical threshold
action potential
class ii ( —- ) ;
Antagonists of —
Reduce — -mediated activation of If current
Slow conduction through —
Slow heart rate & reduce force of contraction
Side effects
Bronchoconstriction: block beta-2 mediated smooth muscle relaxation in the bronchi. Thus relatively contra-indicated in reversible airways disease e.g., asthma
Mask symptoms of hypogylcaemia
May precipitate heart failure
Bradycardia
Exacerbate peripheral vascular disease
Somnolence, Depression
Impotence
Adversely alter lipid profile
Bisoprolol:
Clinical uses: – &— , heart failure, angina, AMI
“—- ” affinity for β1 > β2
beta blocker
b1 andrenorecpetor
b1 adreneorecptor mediated
AV node
SVT , ventricular arrhtymias
cardioselective
class iii agents ( — channel blocker ) :
Blockade of the cardiac — channel carrying the rapid component of the – rectifier — current. Act by slowing — (phase–), prolonging the — duration
-Include Amiodarone, Dronadarone, Dofetilide, Sotalol, Bretylium,
Some have additional effects on sodium channels, adrenergic alpha- and beta-receptors.
-mainly effects the — and— cells
-Rx: Both SVT and Ventricular arrhythmias
-Used in — cases, iv load followed by oral
S.Es: Thyroid disorders, photosensitivity, liver damage and pulmonary alveolitis
Amiodarone:
Clinical uses: SVT & ventricular arrhythmias, heart failure, angina, AMI
“cardioselective” affinity for β1 > β2
k+
ion
delayed
potassium
repolarisation ( phase 3)
action potential
purkinjie fibres and ventiucalr muscle
life threatening
Amiodarone( class iii)is used to treat and prevent a number of types ofcardiac dysrhythmias: ventricular tachycardia(VT),ventricular fibrillation(VF), andwide complex tachycardia, as well asatrial fibrillation (AF) andparoxysmal supraventricular tachycardia
It prolongs —- of thecardiac action potential, the— phase, where there is normally decreased – permeability and increased — permeability.
-Amiodarone also blocks— , — channels,— and— receptors
-After absorption, it distributes slowly but extensively to — tissue due to its — solublility,
-Very – elimination: up to —
-Excreted through lachrymal glands, skin and biliary tract
causes an — action due its large amount of — in its molecule
- — is a main cause of toxicity (10% fatal)
phase 3 , repolarisation
calcium
potassium
sodium , calcium , alpha and beta
adipose tissue
lipid
slow
6 months
anti thyroid
iodine
lung scarring
dronedarone ( class iii) : —- effect resembles —
-Structural changes to reduce — thus — half life and reduce accumulation in tissue
-Changes made to reduce risk of amioderone-associated thyroid-related and pulmonary disease
-Large trial 4,628 patients, dronedarone reduced the incidence of cardiovascular events or death in patients with atrial fibrillation (NEJM 2009;360:668)
dofetilide ( class iii) :
Dofetilide also blocks – channels carrying the rapid component of the delayed rectifier potassium current
has no effect on sodium channels, adrenergic alpha-receptors, or adrenergic beta-receptors.
It increases the — action potential duration due to — .
The increase in the QT interval is a function of prolongation of both effective and functional refractory periods in the His-Purkinje system and the ventricles
sotalol ( class iii) :
— which contains both beta-adrenoreceptor-blocking (Vaughan Williams Class II) and cardiac action potential duration — (Vaughan Williams Class III) properties
But it is still considered Class III
Exerts — inotropic effect only thru b-blocking action
Used to treat ventricular arrhythmias
Main SE: prolong QT interval, beta blocker SE
electrophysiological
amiodarone
lipohilicity
shorten
ion
monophonic
delayed repolairzation
beta blocker
prolongation
-ve
Bretylium is a — antiarrhythmic agent primarily used to treat — ventricular arrhythmias, such as ventricular fibrillation (VF) and ventricular tachycardia (VT) that are unresponsive to other treatments.
Its predominant mechanism of action is to Inhibit/ reduce—- Release:
Bretylium inhibits the release of — from nerve terminals, reducing — nervous system output.
— Channel Blocker:
It also blocks— channels, which helps — the cardiac action potential.
Clinical Use: Used for the prophylaxis and treatment of VF and VT.
Administration: Typically administered intravenously (IV) or intramuscularly (IM) in emergency settings.
Side Effects: Hypotension: Can cause significant drops in blood pressure.-Unsurprising - as it affects NorAdrenaline release throught the body!
May also cause dizziness, orthostatic hypotension, and interactions with other drugs affecting blood pressure or heart rate.
Discontinuation:
Bretylium was discontinued in many countries due to supply issues and unproven efficacy. However, it has been reintroduced in some regions.
Bretylium is typically reserved for use in intensive care or emergency settings due to its potent effects and potential side effects
class iii
life threatening
sympathetic
noradrenaline
noradrenaline
potassium
potassium
stabilise
class iv - — channel blocker:
Verapamil and Diltiazem
- —-
Block the – subtype of Ca++ channels;
slow sinoatrial (SA) and atrioventricular (AV) nodal conductions to reduce heart rate and depress contractility under physiological conditions.
impair conduction and prolong refractoriness in the AV node; Inhibits calcium ion from entering the “slow channels” or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization
used both acutely and chronically to slow the ventricular response in atrial fibrillation (AF)
Act on AV node (NB: Ca++ influx only)
Treatment of SVT only; not other arrhythmias
S.Es:
CHF, interacts with beta blockers
Lowers Blood Pressure
Can cause BradyCardia
May precipitate AV block
Headache, abdominal discomfort, nausea,
Peripheral Oedema
ca++
Non-dihydropyridines
L
class v agents as —
Activation of — receptors
—- effect (Gi protein-linked)
Increases — → —-
Reduces —-
Negative — and — , coronary vasodilator, decreased speed of conduction through AV node
Very – half-life
Clinical use: treatment for SVT
Contraindications
Heart block
Sinus disease
adenosine
adenosine A1 receptor
anti adrenginc
k+ efflux –> hyperpolarizatio
ca+2 influx
chronotropy and iontropy
short
check slide 43
summary:
TheVaughan-Williams classificationis a system used to categorizeantiarrhythmic drugsbased on their mechanisms of action. Developed by British pharmacologists in the 1970s, this classification helps physicians understand how these drugs affect heart rhythms.
Class I (Sodium-Channel Blockers):
IA: Moderately reduces theslope of phase 0(depolarization) in cardiac action potentials. Increasesaction potential duration (APD)andeffective refractory period (ERP).
IB: Weakly reduces phase 0 slope. Shortens APD and decreases ERP.
IC: Strongly reduces phase 0 slope without affecting APD or ERP.
Class II (Beta-Blockers): Block sympathetic activityby antagonizing beta-adrenergic receptors; Reducesinus rateandelectrical conduction.
Class III (Potassium-Channel Blockers): Delay repolarization (phase 3), leading to prolonged APD and increased ERP.
Class IV (Calcium-Channel Blockers): BlockL-type calcium channels, particularly effective at thesinoatrial (SA) and atrioventricular (AV) nodes. Reducesinus rateandelectrical conduction.
Class V (Additional proposed class includes mechanosensitive channel blockers and gap junction blockers, which have drugs under investigation).
Non-pharmacological surgical techniques are often preferred
