Agents used in cardiac arrhythmias Flashcards
Principal effects of stimulation of sympathetic nerves to the heart
Activation of beta-1-adrenoreceptors
- increase rate –> + chronotropic effect
- increase automaticity –> + bathmotropic effect
- increase AV conduction –> + dromotropic effect
- increase contractile force –> + inotropic effect
Principal effects of stimulation of parasympathetic nerves to the heart
Activation of M2- cholinoreceptors
- decrease rate –> - chronotropic effect
- decrease automaticity –> - bathmotropic effect
- decrease AV conduction –> - dromotropic effect
- contractile force –> NO EFFECT
Places in the heart where parasympathetic innervation is present
ONLY IN THE ATRIA
NOT IN THE VENTRICLES
Cardiac arrhythmia
-Cause
Deactivation of cardiomyocytes is not synchronized
The cardiac action potential
-phases and what happens in each one
Phase 0 –> depolarization, Na+ ions go to inside of the cell. Cell charge becomes +
Phase 1 –> very short phase, Na+ stops to flow and K+ channels open
Phase 2 –> plateau phase, calcium flows to inside
Phase 3 –> Ca2+ flow stops, K+ leaves the cell. This happens in order to make cell negative again
Phase 4 –> back to resting potential, cell is negative
SA node action potential (3)
- it is different
- only 0,3,4 phases
- less K+ leaves the cell, more positive ions will be left intracellularly
Effective refractory period (ERP)
time needed to restore capability of Na+ channels
Cardiac rate and rhythm
- electrical impulse originates in the SA node
- Atria
- Atrioventricular node - conduction is slow
- His-Purkinje system
- Ventricles
The cardiac action potential
- Refractory period of sodium-dependent cardiac cells depends on:
- Refractory period of calcium-dependent AV node depends on:
- the membrane potential, extracellular potassium concentration, actions of drugs that bind to the sodium channel
- on the rate of recovery from inactivation of calcium channels
Effect of potassium
Hyperkalemia –> arrthythmia, bradycardia, may cause total asystole –> increase K+ will increase K+ conduction during phase 3 = K+ going out, it will leave the cell with a very negative charge
Hypokalemia –> prolonged action potential duration, increased pacemaker rate, increased pacemaker arrhythmogenesis –> decrease K+ extracellularly –> it will leave the cell with a positive charge
Types of arrhythmias
- disturbances in impulse formation –> abnormal automaticity
- ectopic pacemaker activity, delayed after-depolarization - disturbances in impulse conduction –> abnormal conduction
- re-entry, heart block
Delayed after-depolarization (5)
- prolongation of the QT interval in the ECG
- occur in late phase 3 or early phase 4 - something wrong with K+ flow channels
- abnormally high amounts of Ca2+ intracellulary
- increase Ca2+ levels –> pump becomes more active –> sodium-calcium pump brings 1 additional charge to the INSIDE –> influx of + charges = membrane depolarization
SOLUTION: beta blockers
Re-entry (5)
- might occur in small bifurcating branches of the Purkinje system
- an area of unidirectional block develops in one of the branches
- 1 branch is damaged –> signals go through the other side –> signals come back through the damaged zone, it cannot go up but goes in circle –> causes tachycardia
- refractory period is shorter than conduction time
SOLUTION: drugs that extend ERP –> class 1a or class 3
Anti-arrhythmic drug classification
Class 1 - sodium channel block
Class 2 - sympatholytic - inhibit transmission of nerve impulse to sympathetic nervous system
Class 3 - prolong action potential duration
Class 4 - block cardiac calcium current
Class 1 drugs
- mechanism of action
- classes and names
-reduce phase 0 and 4 sodium currents
Class 1a - QUINIDINE
Class 1b - LIDOCAINE
Class 1c - PROPAPHENONE
Unwanted effects of class 1 drugs
LIDOCAINE
- CNS actions –> drowsiness, disorientation, convulsions
Class 2 drugs
- mechanism of action
- indications
- names
- unwanted effects
- reduce b-adrenergic activity in the heart
- decrease inward ions currents during phase 2 and 4
- pacemaker depolarization is slowed, conduction velocity is slowed in AV node, RP is prolonged
- prevent recurrence of tachy-arrhythmias, reduce mortality following myocardial infarction
- PROPRANOLOL, METOPROLOL, ESMOLOL
- worsening bronchospasms (asthma), negative inotropic effects, bradycardia, fatigue
Class 3 drugs
- mechanism of action
- name
- block K+ channels
- prolong action potential duration by reducing outward phase 3 K+ current –> prolongs plateau
- prolong ERP –> decrease the ability of the heart to response to rapid tachycardias
-AMIODARONE
AMIODARONE
- class
- mechanism of action
- indication
- pharmacokinetics
- unwanted effects
- class 3
- prolong cardiac action potential, increases refractory period
- supraventricular and ventricular tachyarrhythmias, Wolf-Parkinson-White syndrome
- high volume of distribution - so initially a high dose is necessary
- microcrystalline deposits in cornea and skin, thyroid dysfunction, paresthesia’s, tremor, pulmonary fibrosis, QT interval prolongation
Class 4
- names
- mechanism of action
- indication
- contraindication
- unwanted effects
-VERAPAMIL, DILTIAZEM
- decrease inward calcium in phase 2 and 4 –> slow conduction in SA and AV nodes,
- act on L-type channels causing a state and use dependent selective depression of calcium current,
- shorten plateau and reduce force of contraction
- reduce ventricular rate, prevent recurrent of paroxysmal supra-ventricular tachycardia
- Wolf-Parkinson-white syndrome
- headache, negative effects –> constipation, ankle edema
Verapamil vs. Diltiazem
V –> mainly acts on the heart
D –> has a balanced effect on heart and blood vessels
Adenosine
- mechanism of action
- indications
- dosing,metabolism
- unwanted effects
- produce endogenously
- act on cardiomyocytes –> decrease CAMP –> increase amount of K+ channels open –> causes a much stronger repolarization
- hyperpolarizes tissue and slows the rate of rise of the pacemaker potential
- supraventricular tachycardia
- effects last 20-30s, metabolized by enzymes on the luminal surface of vascular endothelium
- related to parasympathetic system activation –> chest pain, shortness of breath, dizziness, nausea
Volume of distribution
- ability of the drug to bind to different tissues in our body
- high VOD –> higher dose is needed in order to fulfill all of the compartments and so the concentration remains in a good level
Classification of the drugs is based on:
- how class affects action potential duration
- how it affects the refractory period
- based on association and dissociation to Na+ channels
- to which stage Na+ channels it has the highest affinity
Class 1A drugs
- name
- function
- indication
-QUINIDINE
- prolong action potential duration = prolong ERP,
- dissociate from the channel with intermediate kinetics,
- block Na+ channels in open state,
- affect conduction velocity
-Indications : for atrial problems –> fibrillation, flutter, extrasystole
Class 1b drugs
- name
- function
- indication
-LIDOCAINE
- Shorten APD = short ERP,
- dissociate from the channel with rapid kinetics,
- block Na+ channels in inactive state,
- no effect on conduction velocity
-Indications: for ventricular problems –> fibrillation, tachycardia, extrasystole
Class 1c
- name
- function
- indication
-PROPAPHENONE
- minimal effects on APD,
- dissociate from the channel with slow kinetics,
- block Na+ channels in all states,
- affect conduction velocity
-Indications: for atrial problems –> fibrillation, flutter, extrasystole
