LECTURE NOTES – ANTIARYTHMIC AGENTS 1

COMMON CARDIOVASCULAR CONDITIONS

Chest pain
- Myocardial ischemia; myocardial infarction (no blood supply or
decreased supply)
o LAD – ST elevation
o Inferior wall affected – give fluids
Increased blood pressure
- Primary or secondary hypertension
o If in young adults – usually primary (essential hypertension)
o Kidney or adrenal problems
Palpitations
- Arrythmias
Shortness of breathing
- Myocardial ischemia, Myocardial infarction, CHF

ARRYTHMIA o Made up of Sodium, Potassium, and Calcium

- Refers to any change in normal sequence of electrical impulse Different phases of Cardiac Action Potential:
- Fast, slow or erratic Phase 0 Phase 1 Phase 2 Phase 3 Phase 4
- 60-100 bpm – normal Depo Repo Depo and Rapid Resting
o Anything in between is still abnormal if rate is not equal Repo repo
- Occurs when normal sequence of impulse initiator becomes Influx of Na Closure of Inward Ca & Outward Inward K
disorganized Na outward K current current
(delayed
CARDIAC ELECTROPHYSIOLOGY K/rectifier)
- Inherent generator – pacemakers Upstroke Plateau
1. Cardiac action potential (SA node)
2. Action potential conducted to right atrial muscle to Left
atrium
3. Signal: AV node
4. His-Purkinje fiber system
5. Signals to (muscles) ventricles
Normal Rhythm
- P – atrial depolarization
- QRS – ventricular depolarization
- T – ventricular repolarization
- Atrial repolarization is not seen because of the small current
Pacemakers – spontaneous time dependent depolarization of the cell Why do arrythmias occur?
membrane - Disturbance in impulse formation
SA Node AV node Purkinje fibers o Especially when duration of impulse formed is shortened
Main Pacemaker Secondary site of Origin: AV node w/ o There is a rhythm in normal heart
origin bundle of is splits to - Disturbance in Impulse Conduction
R and L bundle o “Tamang landas”
branch o SA  AV  Purkinje
RA: primary site of Potassium, Calcium RBV or LBV – block o “Distorbo sa buhay; Road blocks”
electrical signal, and pacemaker in Bundle Bunch o Pathway is blocked
fastest normal current - Can be both
pacemaker
Rate: 60b/min Rate: 40b/min Rate: 20B/min MECHANISMS OF ARRYTHMIA
Can still survive Can still survive Not enough to - Enhanced automaticity
sustain life - After depolarizations and triggered automaticity
- Re-entry
CARDIAC ACTION POTENTIAL ENHANCED AUTOMATICITY
- There is a flat phase in the cardiac potential - Seen in cells that normally display spontaneous diastolic
- Made up of several currents depolarizations: SA and AV nodes and His-Purkinje system
Time dependent, voltage gated membrane currents - B-adrenergic stimulation, hypokalemia, mechanical stretch of
- Sodium current – rapid depolarization phase cardiac muscles: Accelerate pacemaker rate
- Calcium current – rapid depolarization phase SA and AV node. o Too much stretching of atrium/ventricle  make it more
Contraction of cardiac myocytes sensitized
- Potassium current – repolarizing phase: cardiac myocytes - Acetylcholine – dec heart rate by decreasing phase 4 slope and
- Pacemaker current – SA AV nodal cells and purkinje fibers hyperpolarization
Cardiac Action Potential AFTER DEPOLARIZATION AND TRIGGERED AUTOMATICITY
- Depolarization and repolarization of cardiac cells - Interruptions of normal cardiac action potential in any of the
- Shape and duration: activity of ion channels protein complexes phases
- Transmembrane current - B-adrenergic stimulation, hypokalemia, mechanical stretch of
cardiac muscles: Accelerate pacemaker rate
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LECTURE NOTES – ANTIARYTHMIC AGENTS 2
- Acetylcholine: dec heart rate by decreasing phase 4 slope and o 3rd and 4th hour – disappears
hyperpolarization - Establish treatment goals
REENTRY o Treatment is not always necessary – remove first triggering
- Cardiac impulse travel in a path, reactivate original site rapid factor
reactivation independent of normal sinus node o Choose appropriate therapeutic approach – one atrial
- Two types: fibrillation is not the same as the next one
o Anatomic pathway: Accessory pathways o AF: Decrease ventricular response
o Functionally defined re-entry: Localized ischemia, slow o Relive symptoms due to arrythmia e.g. dyspnea
conduction occurs and may be re-excitable o Restore normal rhythm
- Trigger  instead of spreading a certain way it goes back - Consider Cardiac Electrical wiring as dynamic: influenced by
- Heart rates that are very fast (common) several factors
o IHD  resting potential more negative  dec Na current 
FAST RHYTHMS dec slow conduction
VENTRICULAR TACHYCARDIA - Minimize risk
- Atrium has its own rhythm while ventricle has no rhythm o Anti-arrhythmic agents causing arrythmia
o Identify the patient specific contraindications (History is
important)
o Check plasma concentration
VAUGHAN WILLIAMS CLASSIFICATION
CLASS
CLASS I Block Na Slow rate and
channel rise of action
potential
- Variant – torsades de pointes IA Prolong Inc QRS Quinidine,
o Long QT phenomenon (problem in repolarization) repolarization Duration, QT Procainamide
o Main problem is potassium channels IB Shorten AP Minimal Lidocaine
VENTRICULAR FIBRILLATION effect on PR, Mexilitene
- No cardiac output QT, QRS Hydrochloride
- Chaotic depolarization IC Slow Prolong QRS Flecainide
- Afterwards  flat line conduction Propafenone
ATRIAL FLUTTER velocity
- Ventricle has rhythm but atrium does not contract properly II Beta Slow sinus Esmolol,
ATRIAL FIBRILLATION adrenergic rhythm, AV Propanolol,
- Atrium fibrillates (chaotic) antagonist nodal Atenolol
- There is still blood going to the ventricle conductance,
- Can trigger slow, moderate, or fast ventricular response Reduce
sympathetic
SLOW RHYTHMS activity
AV BLOCK III Block outward Lengthen, Sotalol,
- First degree – PR interval is prolonged K current repolarization, Amiodarone
- Second degree – one P no QRS; one or two Ps and no QRS refractoriness
Book discusses fast rhythms most IV Ca Channel Slow inward Verapamil,
- Give atropine for slow heart rates or pacemaker blocker CA current, Diltiazem
prolong PR
PRINCIPLES IN THE USE OF ANTI-ARRYTHMIC DRUGS interval
- Identification and Removal of Precipitating Factors Dec rate – neg chronotropic
o Increased HR by drinking coffee – remove coffee Dec contractility – neg inotropic
o Chocolate can sometimes trigger or tea – caffeine content Dec action potential – neg dromotropic
o Alcoholic beverage
o Someone in your life – adaptation; stress management Class ii DRUGs (eg propranolol hydrochloride and other B-adrenergic
- Hypoxia – give oxygen blocking agents) are B-adrenergic antagonists
- Anti-arrhythmic agents – drug itself is pro-arrhythmic - Slows sinus rhythm and slows AV nodal conduction w/o
o Always monitor substantially changing the Q-T or QRS interval (ventricular depo
o Start with long-acting drugs  ventricular repo)
- Hypokalemia Class III drugs (eg sotalol hydrochloride and amiodarone) – blocks
- Ischemia outward potassium current
- Erythromycin – not all - lengthens repolarization and refractoriness
- Anti-Psychotic agents Class IV drugs (eg verapamil hydrochloride and diltiazem
- Analgesics: Celecoxib (Celebrex) hydrochloride) are primarily calcium channel-blocking agents
o When it first came out  Few years after it came with a - slows inward calcium current and thereby prolong P-R interval
black box label (CAUTION)  it can trigger cardiac events without changing QRS or Q-T interval
- Bronchodilators – agonist CLASS I Na Channel Blocker
o Asthmatic (Salbutamol) – tachycardia MOA:
o Dose-dependent and the half-life is short - Blocks fast Na channel (Non-nodal cardiomyocytes)
o 1st and 2nd hour with nebulization – tachycardia
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LECTURE NOTES – ANTIARYTHMIC AGENTS 3
- Prolong action potential duration Indications
o Problem in upstroke - Ischemic arrythmias/ventricular arrythmias
- Decrease conductivity Generic: Lidocaine Hydrochloride
- Increase refractoriness - Injection, Solution
- Dose: LD 50-100mg IV in 25-50mg/min
- Maintenance dose: 1-4mg/min IV
Adverse Effect
- Pro-arrhythmic
- Large doses: Seizures
- Tremors, altered level of consciousness

CLASS IC Na CHANNEL BLOCKER

- Prolongs upstroke
- Markedly depress phase 0 repolarization
Drugs: - Minimal to NO effect on AP duration or in ventricular AP
- Procainamide, Disopyramide, aquinidine - Inc QRS duration on ECG with NO effect on QT interval
- Procainamide – primary drug - Dec conductivity
- Use: in all types of arrythmia
- Specifically: Acute MI
- Affects atria, purkinje fibers, and ventricular tissues

Procainamide
- Analog to procaine; better tolerated than quinidine
- Pharmacologic effects: prolong cardiac AP, dec automaticity, inc
refractory period and slows down conduction
- Indication: VTACH
Generic: Procainamide hydrochloride
- Injection, solution
CLASS IC FLEICANIDE
- Dose: LD 50—600mg IV in 20mg/min
- Maintenance dose: 2-6m/IV - With local anesthetic activity
Adverse effect: - Belongs to membrane stabilizing group of anti-arrhythmic agents
Pharmacologic Effects:
- Pro-arrhythmic
- Main: Hypotension and marked decrease in conduction - Blocks Na current, and delayed rectifier K current
- Decreases Intracardiac Conduction in all parts of the heart: His
CLASS IB Na Channel blocker Purkinje System
- Indication: Prevent paroxysmal supraventricular tachycardia,
MOA
- Fast effects at fast heart rates paroxysmal atrial flutter and fibrillation
Generic: Flecainide acetate
- Shorten AP duration
- Reduce refractoriness (dec effective refractory period) - Preparation: Oral tablet form
o 50mg, 100mg, and 150mg
- Increase Refractoriness
o Dose: 50-100 mg q 12 hours
Adverse effect
- Dose related
- Blurring of vision
- Trigger arrhythmia

CLASS IA CLASS IB CLASS IC

SVT, VTACH, VTACH,
VTACH, Prevent VFIB, VFIB,
Prevent VFIB, Symptomatic PVC Atrial fibrillation
Includes Mexelitine and phenytoin Symptomatic PVC
- Selectively acts on ischemic or depolarized cells Quinidine, Lidocaine Fleicainide
- Little to no effect on atrial or normal tissues Procainamide, Mexilitine Propafenone
o Ischemic arrythmias Dysopryramide, Tocainide
Phenytoin – digitalis induced arrythmia moricizine Phenytoin
Mexilitene – chronic arrythmia and neuropathic pain
CLASS II BETA BLOCKERS
Class IB Lidocaine - Normally do not reduce blood pressure in patients with normal
- Local anesthetic, may be used IV for cardiovascular indications BP
- Not routinely administered - Renin release usually by sympathetic NS via B1 receptors may be
Pharmacologic Effects: blocked by this drug
- Blocks open and inactivated Na channel, alter threshold - Act on slow rise of action potential
excitability MOA
- Decrease automaticity (phase 4) - Blocks B1 and B2 receptors primarily in the heart where B1>B2

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LECTURE NOTES – ANTIARYTHMIC AGENTS 4
- Affects SA, AV, His purkinje system and ventricles - timed-release – works for 24 hours
- EFECT: Dec heart rate and contractility
o Dec oxygen consumption CLASS III POTASSIUM CHANNEL BLOCKER
o HR usually 60-70bpm - prolong repolarization
- It also acts in the vascular tone – also used as hypertensive drug - increase ERP
o Also causes hypotension and decreased HR - prolong Action potential (AP) duration
- It also causes bronchoconstriction in asthmatic patients - No effect on NA channel
o Do not give Beta blockers - Conduction Velocity: no decrease
- Phase 0 – action - Inc Qt interval on ECG
- Inc refractoriness of cardiac myocyte
- At low HR: arrhthmogenic

Indications
- MI: dec myocardial O2 demand, redistribution of blood flow and
anti-arrhythmic action
- CHF: block sympathetic responses in heart failure; use with
caution
- Tachy arrythmias and palpitations
Non- B1 selective Non-selective B1 selective 3rd
selective 3rd gen gen
blocks b1 relative have vasodilator blocks both b1
and b2 selectivity action by adrenoreceptors
DRUGS:
but not in blockade of Vasodilator
Amiodarone/Dronedarone
higher doses alpha action via alpha
Sotalol
adrenoreceptors adrenoreceptors
- Beta-blocker
Propanolol Atenolol, Labetolol Nebivolol
- Chiral drug – mirror-image type
Pindolol metoprolol Carvedilol Betaxolol
o One part acts as a beta blocker the other acts as a class III
Timolol Esmolol
drug
o Beta-blocker action is not cardioselective
Beta blocker: Esmolol
Dofetilide/Ibutilide
- Reduce in cAMP  reduce Ca current - Prototypical drug
- Affects specifically AV node Bretylium
- ECG: may appear to have prolonged PR interval
o delayed AV node conduction or negative dromotrophy CLASS III AMIODARONE
Adverse Effects
- Structural analogue of thyroid hormone
- may exacerbate failure
- Exert varied pharmacologic action
- life threatening brady-arrhythmias – watch out for drug
- Most effective anti-arrhythmic agent
interactions
- Blocks Na, K, Ca channel, and also Beta blocker effects
- may increase symptoms of peripheral vascular disease
Pharmacologic Effects:
- abrupt discontinuation of drugs: exacerbate angina and increase
- Blocks inactivated Na channel
risk of sudden death
- Dec Ca current and inward potassium rectifier current;
Preparations and Dosages
- inhibits automaticity and prolong AP duration
Name of drug Generic Preparation Dosage
- Repolarization
name
Indication
Propanolol Propanolol 60mg, 80 mg, 60-180mg/day - Recurrent ventricular fibrillation and hemodynamically unstable
HCl 160mg extended ventricular tachycardia
release cap Generic: Amiodarone HCl
Metoprolol Metoprolol 1mg/mL IV 50-100mg PO Preparation
tartrate 50-100mg 5mg IV x 3 LD at - Oral tablet form 100mg, 200mg 400mg
intervals - Dose: 800-1600mg/day
Nebivolol Nebivolol 2.5, 5mg, 5 mmg OD up to - Maintenance dose: 400mg/day
10mg 40 mg OD - IV: 50mg/mL 1000mg/first 24 hours taper dose
Extended release – once a day dosage
Tablet – can only be halved if it has a scored in the center
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LECTURE NOTES – ANTIARYTHMIC AGENTS 5
Adverse Effects: OTHERS ANTIARRHTYMICS: GROUP 5
- Hypotension ADENOSINE
- Depressed cardiac contractility seen in IV form MOA – completely blocks AV conduction
- Serious chronic: pulmonary fibrosis - Membrane hyperpolarization
Amiodarone toxicity - Inc potassium current
- Pulmonary fibrosis – With multiple areas of microcrystalline - Shorten duration of AP
deposits with fibrosis noted due to reaction to these deposits - Angiotensin II receptor blocker
o X-ray – webs going everywhere in the lung Administered as rapid IV bolus – very short half-life but it is very
- Corneal verticillate – hair-like structures in the cornea effective
- Metabolized by RBC
CLASS IV CALCIUM CHANNEL BLOCKERS Indication:
- Dromotropy: negative conduction velocity w/in heart - Acute termination of re-entrant supraventricular arrythmias
MOA: Preparation: 3mg/mL
- Bind to L-type Channel  decrease inward Ca current Dosage: 6mg/mL
- Vasodilation - 1-3 seconds with rapid flush of 200cc NSS
- Negative inotropic/Chronotropic (verapamil, diltiazem) - No conversion in 1-2 min: 12 mg/mL
o Some have positive chronotropic effect Adverse Effects
- Negative dromotrophy (AV node) - Chest pain like the wrath of God
- Usually shortening of AP - Transient loss of consciousness
- AV conduction velocity dec - Worst – transient flatline
- PR and ERP inc ACTION EFFECT DOSAGE ADVERSE
- Verapamil: cardiac drug Interaction Shortened AP As bolus Short
- Amlodipine: cardiac and vascular drug with G duration, adverse
o Also hypertensive agent protein hyperpolarization, Loading effect
- Nifedipine: vascular drug coupled slow normal dose: 6- Transient
o Not considered anti-arrhythmic agent Adenosine automaticity 12mg IV asystole
- Licardipine – for controlling hypertension receptors Less than 5
o NOT FOR ARRHYTHMIA sec
Effects Activate K Dec Calcium Chest
- Vascular smooth muscle relaxation current in the currents fullness
- Negative inotropy/chronotropy atrium and Dyspnea
Indication AV nodes
- HTN, variant angina, exertional angina, unstable angina,
reduction of ventricular rate in Aflutter and AFib CLASS V DIGOXIN (Lanoxin)
Dihydropyridines Non-dihydropyridines MOA:
most smooth muscle selective Selective for myocardium; - Hyperpolarization
agents vascular calcium channels - Shortens atrial AP
Nicardipine Verapamil - Increase AV refractoriness
Nifedipine Diltiazem Pharmacologic Effect:
Felodipine - Potent inhibitors of Na-K Atpase pump
Indications: Angina, SVT, - Inc cardiac contractility (positive inotropy)
Aflutter, AFib - Unknown mechanism: Affect vagal efferents (negative
Nifedipine and Amlodipine: cause reflex sympa discharge  not good chronotropy)
anti-arrhythmic agents Indication
- For chronic HF, AFib, Aflutter
PREPARATIONS AND DOSAGES Preparation Dosage Adverse
Name Generic name Preparation Dosage Effects
Nifedipine Nifedipine 10mg 1 tab TID .05mg/mL .6-1mg IV in Both IV and Arrythmias,
ER 30, 60, 90 Er 1 TAB OD solution IV 12-24 hours PO nausea
mg .125 mg PO .0625mg-.6mg Low Cognitive
Verapamil Verapamil 120 mg, 180 120- .25 mg PO 24 hours therapeutic dysfunction
hdyrochloride mg OD 360mg/day dose

SUMMARY OF DRUG ACTIONS IN CARDIAC POTENTIAL OTHERS:

CLASS V MAGNESIUM
- Drug of choice for torsades
- Usually IV 1-2 gm Magnesium Sulfate
CLASS V POTASSIUM
- Depress ectopic pacemakers
- An anti-arrhythmic but can also be pro-arrhythmic
- It can kill patients – no trace
o In the field of espionage – use potassium to kill someone
Mexilitene – Analogue of Lidocaine
- Used for chronic oral therapy
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LECTURE NOTES – ANTIARYTHMIC AGENTS 6

Procainide – blocks open Na channel

- Prolongs cardiac AP

NON-PHARMACOLOGIC MANAGEMENT
1. Radiofrequency Catheter Ablation – applying heat to the part
causing arrythmia
2. Cryoablation – instead of applying heat, apply cold
3. Implantable cardioverter-defibrillator or ICD detect
potentially fatal arrhythmias like VF

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