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Transcript of © Assoc. Prof. Ivan Lambev E-mail: [email protected] ANTIARRHYTHMIC DRUGS (Summary) Medical...
![Page 1: © Assoc. Prof. Ivan Lambev E-mail: itlambev@mail.bg ANTIARRHYTHMIC DRUGS (Summary) Medical University of Sofia, Faculty of Medicine Department of Pharmacology.](https://reader036.fdocuments.us/reader036/viewer/2022062716/56649dfe5503460f94ae6b12/html5/thumbnails/1.jpg)
© Assoc. Prof. Ivan LambevE-mail: [email protected]
ANTIARRHYTHMICDRUGS(Summary)
Medical University of Sofia, Faculty of MedicineDepartment of Pharmacology and Toxicology
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Myocardial cells maintain transmembraneion gradients by movement of the Na+, Ca2+
and K+ through membrane channels.
The resting potential of a cardiac cell is– 85 mV compared to the extracellular environment.
Depolarization is initiated by a rapid influxof Na+ (phase 0).
BASIC ELECTROPHYSIOLOGY
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Depolarization
Rapid repolarization
Final repolarization
Plateau
Resting potential Spontaneousdepolarization
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In the AV node depolarization isdue to the slower influx of calcium ions.This results in slower conduction of the impulse through the AV node than in other parts of the heart.
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During the period between phase 0 and theend of phase 2, the cell is refractory to thefurther depolarization (absolute refractoryperiod) since the sodium channels are inactivated.
During phase 3, a sufficiently large stimuluscan open enough sodium channels to over-come the potassium efflux. This is therelative refractory period.
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Rapid repolarization
Plateau
Depolarization
Final repolarization
Spontaneous depolarization
Absoluterefractory periodRelative refractory period
Threshold potential
Resting membrane potential
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The cardiac action potential
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MECHANISMS OF ARRHYTHMOGENESIS
Arrhythmias can arise as the result ofabnormal impulse generation or abnormalimpulse conduction. The main mechanisms:
RE-ENTRY (the most frequently): if animpulse arrives at an area of tissue whenit is refractory to the stimulus, this impulsewill be conducted by an alternative route.
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If the impulse again reaches the “blocked”tissue distally when it has had sufficienttime to recover, the same impulse will beconducted retrogradely (re-entry).
This retrogradeconductionis slow, becauseto initiate a circuitof electrical acti-vity, the healthy tissue has to be given timeto repolarize.
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Such a mechanism can initiate a self-
perpetuating “loop” of electricalactivity which acts as a pacemaker.
The re-entry circuit can be localized
within the small area of myocardiumor it can exists as large circuit, for example between the atria and ventricles.
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•AUTOMATICITY. Subsidiary (or ectopic) pacemakers may develop when a sitein the myocardiumdevelops a more rapid phase 4 depolarizationthan the SA node, e.g. as a result of ischaemia.
Sp
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Threshold potential
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ANTIARRHYTHMIC DRUGS (AAD)
I. AAD used in tachyarrhythmias
The Vaughan WilliamsClassification of AAD
is based on their effects on the cardiac action potential (AP).
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Class I (membrane stabilizers)These AAD slow the rate of raise of phase 0of AP by inhibiting fast sodium channels.The class is subdivided according to theeffects of drugs on duration of AP.Ind.: SV and ventricular arrhythmias.
IA IB ICIncreasethe duration of AP
Decreasethe duration
No effect onthe duration
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IA IB IC
DisopyramideProcainamideAjmaline- weak negative inotropic effectQuinidine
LidocaineMexiletinePhenytoin
PropafenoneFlecainide
ARs: Bradycardia, AV block, () inotropiceffect, disturbances of GIT, rashes
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Rauwolfia serpentina•Ajmaline•Reserpine
Cinchona succirubra•Quinidine•Chinine
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Ventricular fibrillation, characterizedby irregular undulations without clear ventricular complexes.
Treatment: Lidocaine or electrostimulation
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Class II (-adrenoceptor antagonists)
Reduce the rateof spontaneous depo-larization of sinusand AV nodal tissueby indirect blockadeof calcium channels.Ind: SV and ventri-cular arrhythmias.
( cAMP)
pindolol, propranololatenolol, esmolol
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Atrial flutter with a 4:1 conduction ratio.
Esmolol(short action)
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Class IIIThese AAD prolongthe duration of the APand increase the abso-lute refractory period.This is the result ofreduced influx of K+
into the cell. Ind: SV and ventri-cular arrhythmias.
Amiodarone t1/2 5060 days ARs: hypo/hyperthyroidism, pulmonary fibrosis
Sotalol, Bretylium
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Class IV (calcium channel antagonists)
Mainly verapamil(22% oral availability)and diltiazem (i.v.) fromcalcium antagonistshave specific actionon the SA and AVnodes. They decreasethe duration of AP.
Ind: SV arrhythmias.ARs: headache, edema,bradycardia, AV block
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Adenosine inhibits AV conduction. The duration of effect is less than 60 s.•used bolus i.v. in SV tachycardia with narrow QRS complex.•ARs24-h: bradycardia, AV block.
Other drugs used in tachyarrhythmias
Digoxin reduces conduction through AV node and is useful to control atrial flutter and atrial fibrillation.
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Atropine is givenby bolus i.v. inj.in sinus brady-cardia and AVblock. It blocksM2-receptors andincreases conductionthrough the AV node.Isoprenalineis used in AV block
II. AAD used in bradyarrhythmias
Atr
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.
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Digitalis purpurea(foxglove)
Dig
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Digitoxin Digoxin
III. AAD used in Digitalis arrhythmia
PhenytoinPotassium chlorideMagnesium aspartate
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PROARRHYTHMIC ACTIVITY OF AAD
All AAD have the potential to precipitateserious arrhythmias, particularly ventri-cular tachycardia or fibrillation.
Mainly the AAD from class IA prolong the QT interval which predisposes to develop a polymorphic ventricular tachy-cardia known as “torsades de pointes”.
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Polymorphic ventricular tachycardiawith a twisting axis on the ECG
Torsades de Pointes
After overdose of AAD from class IA: