Transcript Anti-arrhythmic Drugs - Ipswich-Year2-Med-PBL-Gp-2

Anti-arrhythmic Drugs
A very quick overview
A few rules before prescribing
All anti-arrhythmic drugs can actually have proarrhythmic effects.
 increase in frequency or duration of the index arrhythmia
 development of a novel arrhythmia
 development of torsades de pointes (sotalol and amiodarone)
Treatment should never be instituted for benign symptoms such as
palpitations without an incriminating ECG.
Underlying abnormalities of electrolytes such as hypokalaemia
(especially in digoxin use - toxicity) should be corrected if
present.
Symptomatic hypoperfusion or hypotension associated with a
tachyarrhythmia should always be regarded as a medical
emergency - may require urgent electrical cardioversion.
VW Classification of Antiarrythmics
Class 1 – Na+ channel blocker, thereby inhibiting phase 0, or
depolarisation
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Class IC agents have the slowest binding and dissociation from the
receptor (quinidine, procainamide and disopyramide).
Class IB agents are the most rapid (lignocaine and mexilitine).
Class IA agents are intermediate (flecainide).
During faster heart rates, less time exists for the drug to dissociate from
the receptor, resulting in an increased number of blocked channels
and enhanced blockade; resulting in a progressive decrease in
impulse conduction velocity and a widening of the QRS complex.
This use dependence is frequently seen with the class IC agents, less
frequently with the class IA drugs, and rarely with the class IB agents
VW Classification of Antiarrythmics
Class 2 - Beta blockers which reducing sympathetic effects on heart
rate and force of contraction
Class 3 - Block potassium channels to prolong repolarization, and
the refractory period – which shows as prolongation of QT
(>450 msec) interval setting up platform for torsade de pointes to
take off (Sotalol and Amiodarone).
Class 4 - Non-selective calcium channel blockers which act on
channels in the AV nodes (Diltiazem and Verapamil)
The Vaughan Williams classification system does not include Digoxin,
Atropine or Adenosine.
The Ventricular AP
Phase 0 depolarization: Sodium channels open allowing sodium entry into the cells
Phase 1 Repolarization: Results after sodium channels are fully closed and potassium channels
are opened.
Phase 2 plateau: Reflects the slow entry of calcium into the cells, which counteracts the effect of
potassium exit.
Phase 4 recovery: Sodium leaves and potassium re enters the cells via the Na-K-ATPase
Shockable rhythms
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VT (sustained)
VF
AF
Atrial Arrythmia – Sinus Tachy
Metoprolol tartrate 25 to 100 mg orally twice daily
OR
Verapamil sustained-release 160 to 480 mg orally, daily
Atrial Arrythmia - Premature complexes
Metoprolol tartrate 25 to 100 mg orally twice daily
OR
Verapamil sustained-release 160 to 480 mg orally, daily
Atrial flutter definitions
 Usually 2:1 AV block and Ventricular rate of 150bpm with narrow QRS
 VR of 100 is 3:1 AV block
 VR of 75 is 4:1 AV block
 VR of 300 is 1:1 AV block
Atrial fibrillation definitions
Irregular VR btw 160 – 180bpm
Risk factors – mitral valve, ASD, thyrotoxicosis, HF, HTN
Atrial flutter and atrial fibrillation: rhythm control
BUT FIRST!!!! Anticoagulation is needed for at least 4 weeks prior to
cardioversion
 Enoxaparin 1 mg/kg BD
 Heparin 5000units bolus then infusion and monitor APTT
 Warfarin 5mg daily for 2 days then as per INR result
AF rhythm control
Cardioversion with Drugs
 Flecainide
 Amiodarone
Maintainance of sinus rhthym after cardioversion
 Flecainide
 Amiodarone
 Sotalol
AF rate control
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Digoxin (rarely used alone in younger pt’s)
Atenolol
Metoprolol
Diltiazem
Verapamil
Paroxysmal SVT
Conversion to sinus rhythm (after non-drug manoeuvres)
 Adenosine IV
 Verapamil IV
Prophylaxis of SVT
 Atenolol/ Metoprolol
 Sotalol
 Flecainide
 Verapamil SR
 Amiodarone if all above fail
Ventricular Tachycardia
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Lignocaine
Amiodarone
Sotalol
Flecainide
Atenolol/ Metoprolol only if significant
ventricular dysfunction is present
Torsades de pointes
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Atropine IV if underlying bradycardia present
Magnesium IV
Isoprenaline IV
Lignocaine IV
amiodarone, disopyramide, flecainide or sotalol should be avoided in
patients with torsades as long QT interval perpetuates arrythmia
Cardiac Arrest recipe
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(2 to VT, VF or Asystole)
0
CPR
DC Shock if 2 to VT/VF only
Adrenaline and atropine for asystole
Amiodarone/ Lignocaine for VT/ VF
NaCO3 for acidosis if resus takes <10min
0
Amiodarone
MOA
Decreases nodal automaticity, slows AV conduction and prolongs refractory period
of myocardial tissues; also has weak beta-blocker activity.
Precautions
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Contraidicated with allergy to iodine (200mg tablet is nearly 40% iodine).
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Thyroid dysfunction, including goitre or nodules—increases risk of hypo- or
hyperthyroidism.
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Lung disease (particularly with reduced diffusion capacity)—less reserve to
cope with pulmonary adverse effects.
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Contraindicated in 2nd/ 3rd degree block, symptomatic bradycardia or sick sinus
syndrome (when no pacemaker).
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Amiodarone is the least negatively inotropic antiarrhythmic and is therefore
usually well tolerated in HF.
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Check QT interval is <450 milliseconds before use as amiodarone may
increase risk of arrhythmia by prolonging the QT interval.
Amiodarone
ADE’s
 Metallic taste
 Increased LFT’s
 Blue/ grey skin pigmentation
 Pulmonary fibrosis/ Pulmonary inflammation
 Hypotention
 AV block
 Torsade de pointes
Amiodarone
Acute treatment of tachyarrhythmias
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Emergency, IV 150–300 mg over 1–2 minutes (monitor clinical signs and ECG
very closely).
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Loading, IV infusion 5 mg/kg over 20 minutes to 2 hours.
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Maintenance, IV infusion 15–20 mg/kg over 24 hours; begin oral treatment as
soon as possible, overlapping oral and IV treatment by 2 days.
Chronic treatment of tachyarrhythmias
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Oral, 200–400 mg 3 times daily for 1 week, followed by 200–400 mg twice daily
for 1 week.
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Maintenance, 100–400 mg once daily.
Concentration monitoring
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Therapeutic range 1–2.5 mg/L although rarely done.
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The maximum effect of dosage change is not seen for 1–3 months or more
because half-life is 27–107 days.
Atropine
MOA – Removes the PNS stimulation of heart
Precautions – Acute MI – may worsen ischemia
IV Dose
 1 mg; repeat prn until desired rate is achieved - Max 3mg
Intratracheal dose is venous route not available
 Bradycardia, 1 mg; repeat prn until desired rate is achieved to
3mg Max
 Asystole, 6 mg once only.
Adenosine
MOA – short acting drug (also endogenous) depresses sinus and AV
node activity/ conduction; also produces peripheral and coronary
vasodilation. Is blocked by caffeine!
Precautions - Contraindicated in 2nd/ 3rd degree heart block or sick sinus
syndrome (without pacemaker).
Dose for SVT, diagnostic aid for tachycardia
 Rapid IV bolus, initially 3 mg; if unsuccessful within 1–2 minutes, give
6 mg; if still unsuccessful within 1–2 minutes give 12 mg.
Flecainide
MOA - Slows cardiac conduction and to a lesser extent, increases refractory period
in all myocardial tissues (esp in the His-Purkinje conduction system). Also has
negative inotropic activity.
Precautions
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Contraindicated in 2nd/ 3rd degree heart block, increased risk of 1st degree block
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Increased risk of ventricular arrhythmias in structural heart disease or chronic
AF.
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Increases risk of significant bradyarrhythmia in sick sinus syndrome.
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Heart failure may worsen.
Dose
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IV, 2 mg/kg/dose over at least 10 minutes to a maximum of 150 mg.
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Oral, 50–100 mg twice daily; increase by 50 mg every 4 days up to a maximum
of 400 mg daily.
Lignocaine
MOA - Reduces automaticity of myocardial tissue with little effect on cardiac
conduction. It has a mild negative inotropic effect and weak neuromuscular blocking
activity.
Precautions
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Safe to use in pregnancy
 Contraindicated in 2nd/ 3rd degree heart block or severe SA block (without
pacemaker).
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Bradycardia or cardiogenic shock increases risk of arrhythmia; correct before
starting treatment if possible.
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Heart failure may worsen
Dose
Initially, IV injection 1 mg/kg (in adults usually 75–100 mg) over 1–2 minutes, repeated
after 5 minutes if necessary.Maintenance, IV infusion 10–50 micrograms/kg/minute.
Lignocaine
ADE’s
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Headache
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Dizziness
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Drowsiness
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Paraesthesia
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Hypotension
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Bradycardia
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Cardiac arrest
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Muscle twitching
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Seizures
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Coma
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Respiratory depression
Sotalol
MOA - nonselective beta-blocker (class 2) that ALSO prolongs the refractory period of
atria, ventricles and bypass tract (class 3). It has no significant intrinsic
sympathomimetic or membrane stabilising activity at therapeutic doses.
Precautions
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Phaeochromocytoma (may exacerbate hypertension since is not complete
antagonist)
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Diabetes (may cause hypoglycaemia)
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Heart failure (may worsen)
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Peripheral vascular disease – raynauds’
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Contraindicated in 2nd/ 3rd degree heart block or severe SA block (without
pacemaker)
Dose
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IV, initially 0.5–1.5 mg/kg (20–120 mg) over at least 10 minutes; repeat every
6 hours if necessary, or infuse 80–160 mg over 12 hours.
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Oral, initially 40–80 mg twice daily; increase according to response to 160 mg
twice daily.
Digoxin
MOA - Increases force of myocardial contraction and decreases AV nodal conduction,
predominantly by PNS effect on the heart, also slowing the heart rate. It can increase
the excitability of cardiac muscle, particularly at higher doses.
Precautions
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Contraindicated in 2nd/ 3rd degree heart block (without pacemaker), Wolff-ParkinsonWhite syndrome, VF/VT, cor pulmonale/ constrictive pericarditis and hypertrophic
obstructive cardiomyopathy.
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Predominately renally cleared (70%) so reduce dose in renal failure
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Safe is pregnancy (even used to treat some fetal arrythmias)
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Narrow therapeutic range; trough level (or at least 6 hours after dose) 0.8 –
1.2 micrograms/L. Steady state is reached after about 5 days if renal function is normal
(half-life is 36 hours).
 ECG effect is prolonged PR interval, ST depression or T wave inversion. Apart from the
effect on the PR interval, which is a sign of toxicity, the other ECG changes do not
necessarily indicate digoxin toxicity or myocardial ischaemia.
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Hypokalemia may lead to digoxin toxicity – monitor and correct K+
Digoxin
ADE’s
anorexia, N&V, diarrhoea, blurred vision, visual disturbances, drowsiness,
dizziness, nightmares, agitation, depression, acute psychosis,,
shortened QRS complex, atrial or ventricular extra systoles,
paroxysmal atrial tachycardia with AV block, ventricular tachycardia or
fibrillation, heart block, gynaecomastia (long-term use)
Dose
Loading, oral/IV 250–500 micrograms every 4–6 hours, to a maximum of
1.5 mg.
Maintenance, oral 125–250 micrograms once daily (rarely increased up to
500 micrograms daily).