Anti Arrhythmic Drugs Flashcards
1
Q
Properties of cardiac cells?
A
- excitability
- changes in resting membrane potential - Conduction
- slope of phase 0 (mass Na influx reaching threshold) - Refractory period
- phases 1-3 - Automaticity
- slope of phase 4
- increased slope = increase automaticity
2
Q
Factors that increase automaticity?
A
- Na/Ca influx
- sympathetic stimulation (beta receptor stimulation increases PKA and opening of calcium channels)
- ischemia
3
Q
Factors that decrease automaticity?
A
- K+ efflux
- parasympathetic stimulation (opens K+ channels causing hyperpolarization)
4
Q
Mechanisms of cardiac arrhythmias?
A
- abnormal automaticity
- sinus tachycardia at SA node
- sinus bradycardia at SA node
- latent pacemaker driven
- escape beats (ectopic) - triggered automaticity
- afterdepolarizations, AP triggered directly after effective refractory period (ERP) or before start of phase 4
- early afterdepolarizations (EAD) arise from plateau after ERP, class Ia and III antiarrhythmic drugs predispose person to EAD
- delayed afterdepolarization (DAD) arise from resting potential due to Ca build up in cell from Na/K ATPase inhibitor (Digoxin) - Reentry
- develop self sustaining electrical circuit with depolarization of surrounding tissue, leading to tachycardia
- conduction block (ischemia, fibrosis)
- bypass track (parkinson’s bypass AV node)
- treatment is ablation (burn excess track) - Supraventricular tachycardia
- paroxysmal atrial tachycardia (PAT) ectopic foci in atria
- beat is somewhere other than SA node
- HR increased - Premature ventricular contractions (PVC)
- beat arises from ectopic foci in ventricle - Ventricular tachycardia
- torsade de pointes
- treat with lidocaine or amiodarone
5
Q
What class of drugs predispose a person to EADs?
A
class III and Ia
6
Q
Why is digoxin used instead of Ouabain?
A
- Ouabain results in a bunch of DADs
- Digoxin stimulates PSNS via Vagus nerve slowing HR and contractility which offsets buildup of calcium
7
Q
Classification of Antiarrhythmic drugs?
A
- Na channel blockers (class Ia, Ib, Ic)
- decrease phase 0 upstroke rate and phase 4 slope, increase threshold - Beta blockers (class II)
- decrease phase 4 slope - K channel blockers (class III)
- increase action potential duration - Ca channel blocker (class IV)
- decreases phase 4 slope - Adenosine
- increase diastolic potential
- opens K channels
8
Q
Na channel characteristics?
A
- resting state is closed
- active state is open and Na comes in, reaching threshold
- inactivated channel, no ion conduction (occurs with lidocaine in system)
- USE-DEPENDENT BLOCKADE
- more channel is activated the more drug will block it
- antiarrhythmic effects faster during faster HR - drugs have high affinity for inactivated channels and low affinity for resting state channels
9
Q
Class 1 (a,b,c) anti arrhythmics?
A
- Na channel blockers minimize Na reentry for AP
- all depress phase 0 slope from Na block
- Ia and Ic bind active channels
- Ib bind inactive channels
- Ia increased refractory period due to K channel block
- Ib reduced refractory period b/c they bind inactive channels, do not block K channels
- Ic normal refractory period due to limited K block
10
Q
Class Ia anti arrhythmics common features?
A
- Quinidine, Procainamide, Disopyramide
- common features:
1. block fast influx of Na channels during phase 0 and block K channels to PROLONG REFRACTORY PERIOD
2. HYPERKALEMIA - increased K in blood
3. ECG effects: - increases QRS and QT intervals (block K channels)
- PR interval varies due to anticholinergic effects (increases HR and AV conduction)
4. anti cholinergic effects - initial HR increase
5. clinical use: - supraventricular (AV node and above) and ventricular arrhythmias
- procainamide is used most
11
Q
Quinidine?
A
- class Ia
- D isomer of antimalarial alkaloid Quinine
Clinical use:
- supraventricular and ventricular arrhythmias
- has some alpha adrenergic activity (PR)
- use PO, can cause hypertension with IV administration due to alpha blocking
ADR:
- diarrhea
- cinchonism (hearing disorders)
- torsades de pointes
- interact with Digoxin by decreasing Digoxing clearance, which increases toxicity of Digoxin
12
Q
Procainamide?
A
- class Ia
- less anticholinergic effects than Quinidine, no alpha block, safer for IV
Clinical use:
- ventricular arrhythmias
- good to take PO, short half life (3-4 hours), sustained release
- active metabolite produces class III antiarrhythmic effects (blocks K channel to prolong AP)
ADR:
- antinuclear antibody formation (ANA) in 80% of people, Lupus like symptoms in 15% of patients (blood disorder)
- rash, fever, hepatitis, arthralgia
- infrequent progress to pleural effusion and pericardial tamponade
- agranulocytosis
13
Q
Disopyramide?
A
- class Ia
- 2nd line drug only used when other drugs are not effective
clinical use:
- ventricular arrhythmias (life threatening)
- negative inotropic effects causing cardiac depression, CHF, and hypotension
14
Q
Lidocaine?
A
- class Ib anti arrhythmic
- must administer IV
Effects:
- acts on inactivated Na channels
- minimal K channel block
- decreases excitability, phase 4 automaticity and afterpotentials
ECG effects:
- PR and QRS unaffected
- QT and AP duration decreased
- ERP/APD ratio is increased (delay of AP)
Clinical use:
- ventricular arrhythmias
- one of two options for MI
ADR/Toxicity:
- cardiac depression (decreased contractility), this is good
- narrow therapeutic window, can cause mix of CNS stimulation and depression if above therapeutic levels, blocks Na in CNS (death from anaesthetic properties at high concentrations)
- generally safe
15
Q
Mexiletine/Tocainide?
A
- oral forms of lidocaine, similar effects
- does not undergo first pass effect
Tocainide
- associated with agranulocytosis, blood dyscriasias and pulmonary fibrosis, give only fro life threatening arrhythmias
- only for ventricular arrythymias and ventricular tachycardia
- has a higher incidence of agranulocytosis
ADR:
-GI and CNS disturbances
