This document discusses antiarrhythmic drugs. It begins by defining arrhythmias as abnormal heartbeats that can be too slow, fast, irregular or early. It then discusses the sites in the heart where arrhythmias can originate, such as the sinus node or ventricles. The mechanisms of arrhythmia are described as automaticity, reentry, after depolarization or enhanced pacemaker activity. The document reviews the Vaughan-Williams classification system for antiarrhythmic drugs and provides examples of drugs from each class. It also discusses specific antiarrhythmic drugs like amiodarone, beta blockers, lidocaine, calcium channel blockers and more.

1. Antiarrhythmic Drugs
Dr Seebat Masrur
D-card Student
Cardiology Department
SZMCH

2. Arrhythmia
Arrhythmias are abnormal beats which may be too slow, too rapid, too
irregular, or too early.
The term arrhythmia refers to any change from the normal sequence of
electrical impulses, causing abnormal heart rhythms.

3. Sites of Arrhythmias
• Sinus Node
• Atrial cells
• AV Node
• Ventricular Cells
Mechanism of Arrhythmia
• Automaticity
• Reentry
• After depolarization
• Enhanced/Ectopic pacemaker
activity

4. Normal
Rhythm

5. Arrhythmia

6. Types of Arrhythmias
• Sinus Origin-Sinus Tachycardia, Sinus Bradycardia, Sinus Arrhythmias
• Atrial Origin-SVT, Atrial Fibrillation, Atrial Flutter
• Av Nodal or Junctional origin- Junctional rhythm, Junctional
tachycardia
• Ventricular origin-Ventricular Tachycardia, ventricular fibrillation

7. Ionic Basis of Membrane Electrical Activity
• The transmembrane potential of cardiac cells is determined by the
concentrations of several ions.
-Sodium
-Potassium
-Calcium
-Chloride
On either side of the membrane and the permability of the membrane to
each ion
• These ions move across cell membranes in response to their gradients only
at specific times during the cardiac cycle when these ion channels are
open.

9. Vaughan-Williams
Classification of
Antiarrhythmic Drugs
Some drugs such as digoxin, ivabradine and adenosine have
no place in this classification, while others such as
amiodarone have properties in more than one class
Class Action Example
I Sodium channel blockade
Ia Block Na+ channel and prolong action potential Quinidine, disopyramide
Ib Block Na+ channel and shorten action potential Lidocaine, mexiletine
Ic Block Na+ channel with no effect on action potential Flecainide, propafenone
II β-Adrenergic receptor blockade Atenolol, bisoprolol, metoprolol
III Potassium channel blockade and/or inward current
enhancer.
Amiodarone, dronedarone, sotalol
IV Calcium channel blockade. Verapamil, diltiazem

10. An Updated Classification of Current Antiarrhythmic Pharmacological Drugs
Circulation. 2018;138:1879–1896. DOI: 10.1161/CIRCULATIONAHA.118.035455
Class Pharmacological Target Example
0 HCN channel– mediated pacemaker
current (I f ) block
Ivabradin
Ia Voltage-gated Na+ channel blockers Quinidine, ajmaline,
disopyramide
Ib Voltage-gated Na+ channel blockers Lidocaine, mexiletine
Ic Voltage-gated Na+ channel blockers Propafenone, flecainide
Id Voltage-gated Na+ channel blockers Ranolazine

11. An Updated Classification of Current Antiarrhythmic Pharmacological Drugs
Circulation. 2018;138:1879–1896. DOI: 10.1161/CIRCULATIONAHA.118.035455
Class Pharmacological Target
(Autonomic inhibitors and activators)
Examples
IIa Nonselective β- and selective β1-adrenergic
receptor inhibitors
Atenolol, Bisoprolol, Betaxolol,
Celiprolol, Esmolol, Metoprolol
IIb Nonselective β-adrenergic receptor
activators
Isoproterenol
IIc Muscarinic M2 receptor inhibitors Atropine, Anisodamine,
Hyoscine, Scopolamine
IId Muscarinic M2 receptor activators Carbachol, Pilocarpine,
Methacholine, Digoxin
IIe Adenosine A1 receptor activators Adenosine, Aminophylline

12. An Updated Classification of Current Antiarrhythmic Pharmacological Drugs
Circulation. 2018;138:1879–1896. DOI: 10.1161/CIRCULATIONAHA.118.035455
Class Pharmacological Targets Examples
IIIa Voltage dependent K+ channel blockers Amiodarone, Dronedarone,
Ibutilide, Sotalol
IIIb Metabolically dependent K+ channel
openers
Nicorandil, pinacidil
IIIc Transmitter dependent K+ channel
blockers
Blocker under regulatory review for
management of atrial fibrillation:

13. An Updated Classification of Current Antiarrhythmic Pharmacological Drugs
Circulation. 2018;138:1879–1896. DOI: 10.1161/CIRCULATIONAHA.118.035455
Class Pharmacological targets Examples
IVa Nonselective surface membrane Ca2+ channel blockers Bepridil, Verapamil, Diltiazem
IVb Intracellular Ca2+ channel blockers Flecainide, propafenone
IVc Sarcoplasmic reticular Ca2+-ATPase activators No clinically approved drugs in use
IVd Surface membrane ion exchange inhibitors No clinically approved drugs in use
IVe Phosphokinase and phosphorylase inhibitors No clinically approved drugs in use

14. An Updated Classification of Current Antiarrhythmic Pharmacological Drugs
Circulation. 2018;138:1879–1896. DOI: 10.1161/CIRCULATIONAHA.118.035455
Class Pharmacological Targets Examples
V Mechanosensitive channel
blockers
No clinically approved drugs
in use
VI Gap junction channel blockers Carbenoxolone
VII Upstream target modulators ACEI, ARBs, Omega 3 fatty
acids, Statins

15. Ivabradine
Ref Drugs for heart; Circulation. 2018;138:1879–1896. DOI: 10.1161/CIRCULATIONAHA.118.035455
• Ivabradine is a blocker of the pacemaker current If, It likely acts through
hyperpolarization activated cyclic nucleotide-gated channel block.
• There is no negative inotropic effect nor BP reduction as with b-blockers, nor
any rebound on cessation of therapy.
• The downside is that the current If is also found in the retina, so that there
may be disturbance of nocturnal vision with flashing lights (phosphenes) that
could impair driving at night and is often transient.
• Ivabradine, is used to reduce heart rates in situations of inappropriate sinus
tachycardia or when sinus tachycardia accompanies cardiac failure.

16. Ivabradine
Ref Drugs for heart; Circulation. 2018;138:1879–1896. DOI: 10.1161/CIRCULATIONAHA.118.035455
• The treatment of chronic heart failure New York Heart Association level II to
IV with systolic dysfunction in patients in sinus rhythm and whose heart rate
is 75 bpm or more, in combination with standard therapy including b-blocker
therapy or when b-blocker therapy is contraindicated or not tolerated.
• Ivabradine can cause Sinus bradycardia by depressing sinus node
automaticity by blocking of If.

17. Lidocaine
• Lidocaine acts preferentially on the ischemic myocardium and is more
effective in the presence of a high external potassium concentration.
• Lidocaine can be used when tachyarrhythmias or very frequent premature
ventricular contractions seriously interfere with hemodynamic status in
patients with AMI.
• Lidocaine should not be used prophylactically or when there is bradycardia or
bradycardia plus ventricular tachyarrhythmias.
• Dose-IV 75-200 mg; then 2-4 mg/min for 24-30 h. (No oral use). T1 ⁄2
approximately 2 h.
• Side effects- drowsiness, numbness, speech disturbances and dizziness,
bradycardia, hypotension.

18. Beta-
Adrenoceptor
Antagonist
• Noncardioselective-Propranolol,
Sotalol
• Cardioselective-Metoprolol,
Bisoprolol
• Vasodilatory b-Blockers,
Nonselective-Labetalol,
Carvedilol
• Vasodilatory b-Blockers,
Selective-Nebivolol

19. Beta-Blocking Agents
Ref Drugs For Heart
Indications for b-Blockade FDA-Approved Drugs
Ischemic Heart Disease Atenolol, metoprolol, Carvedilol, Bisoprolol
Hypertension Labetalol, Bisoprolol, Nebivolol, Atenolol, Esmolol
Arrhythmias Metoprolol, Esmolol, Propranolol, Acebutalol
Congestive Heart failure Carvedilol, metoprolol, bisoprolol, Nebivolol
Hypertrophic obstructive cardiomyopathy Propranolol
POTS Propranolol low dose
Anxiety
Essential tremor
Migraine prophylaxis Alcohol withdrawal
Propranolol, nadolol, timolol
Endocrine Thyrotoxicosis (arrhythmias) Propranolol
Gastrointestinal Esophageal varices Propranolol
Glaucoma (local use) Timolol

20. Cardiac effects
of beta-
adrenergic
blocking drugs

21. Effects of
beta-
blockade on
ischemic
heart

22. ROUTE OF
ELIMINATION
Ref-Drugs for heart

23. Side Effects of Beta-Blockers
Ref-Drugs for heart
1. Smooth muscle spasm (bronchospasm and cold extremities)
2. Exaggeration of the cardiac therapeutic actions (bradycardia, heart
block, excess negative inotropic effect)
3. Central nervous system penetration (insomnia, depression), and
4. Adverse metabolic side effects(B-blockers to increase new diabetes)
5. In a large group with mean age 48 years, erectile problems took place
in 11% given a b-blocker, compared with 26% with a diuretic and 3%
with placebo.

24. Beta-Blockade: Contraindications and
Cautions Ref-Drugs for heart
Cardiac
Absolute: Severe bradycardia, high-degree heart block, cardiogenic
shock, overt untreated left ventricular failure (versus major use in early
or stabilized heart failure).
Relative: Prinzmetal’s angina (unopposed a-spasm), high doses of other
agents depressing SA or AV nodes (verapamil, diltiazem, digoxin,
antiarrhythmic agents); in angina, avoid sudden withdrawal.

25. Pulmonary
Ref-Drugs for heart
Absolute: Severe asthma or bronchospasm. Must question for past or
present asthma. Risk of fatalities.
Relative: Mild asthma or bronchospasm or chronic airways disease. Use
agents with cardioselectivity plus b2-stimulants (by inhalation).

26. Central Nervous
Ref-Drugs for heart
• Absolute: Severe depression (especially avoid propranolol).
• Relative: Vivid dreams, Visual hallucinations, Fatigue, Erectile
dysfunction, Psychotropic drugs (with adrenergic augmentation) may
adversely interact.

27. Peripheral Vascular, Raynaud Phenomenon
Ref-Drugs for heart
Absolute: Active disease: gangrene, skin necrosis, severe or worsening
claudication, rest pain.
Relative: Cold extremities, absent pulses, Raynaud phenomenon. Avoid
nonselective agents (propranolol, sotalol, nadolol); prefer vasodilatory
agents.

28. Diabetes Mellitus
Ref-Drugs for heart
Relative: Insulin-requiring diabetes: nonselective agents decrease
reaction to hypoglycemia; use selective agents. Note successful use of
atenolol in type 2 diabetes in prolonged UK trial at cost of weight gain
and more antidiabetic drug usage.

29. Metabolic Syndrome or Prediabetes
Ref-Drugs for heart
Beta-blockers may increase blood sugar by 1-1.5 mmol/L and impair
insulin sensitivity especially with diuretic co-therapy; consider use of
carvedilol or nebivolol.

30. Renal Failure
Ref-Drugs for heart
• Relative: As renal blood flow falls, reduce doses of agents eliminated
by kidney.

31. Liver Disease
Ref-Drugs for heart
• Relative: Avoid agents with high hepatic clearance (propranolol,
carvedilol, timolol, acebutolol, metoprolol). Use agents with low
clearance (atenolol, nadolol, sotalol).

32. Pregnancy Hypertension
Ref-Drugs for heart
Beta-blockade increasingly used but may depress vital signs in neonate
and cause uterine vasoconstriction. Labetalol and atenolol best tested.

33. Others
Ref-Drugs for heart
Surgical Operations-may be maintained throughout, provided indication is not
trivial; otherwise stop 24 to 48 hours beforehand. May protect against
anesthetic arrhythmias and perioperative ischemia. Preferred intravenous
drug: esmolol. Use atropine for bradycardia, b-agonist for severe hypotension.
Age-Helps to reduce BP, but lacks positive outcome data. Watch
pharmacokinetics and side effects in all older adult patients.
Smoking- Is less effective
Hyperlipidemia-Triglycerides increase and HDL-cholesterol falls

34. Amiodarone
Ref-Drugs for heart
• Amiodarone is a complex antiarrhythmic agent, predominantly class III, that
shares at least some of the properties of each of the other three EP classes of
antiarrhythmics.
• Amiodarone has a very long tissue half-life (25–110 days)
• Indication- Recurrent VF or hemodynamically unstable VT
-Atrial Fibrillation(acute conversion of chronic AF)
-Preventing recurrences of paroxysmal atrial fibrillation or flutter
• Amiodarone has been regarded as one of the most effective agents available,
yet is now being replaced by ICDs

35. Ref-Drugs for heart
• Amiodarone also has a cytotoxic effect on thyroid follicular cells and inhibits
conversion of T4 to T3 (increasing the ratio of T4 :T3). Most patients receiving
amiodarone have normal thyroid function but up to 20% develop
hypothyroidism or thyrotoxicosis, and so thyroid function should be
monitored regularly. TSH provides the best indicator of thyroid function.
• The pathophysiology of amiodarone-induced hypothyroidism (AIH)
is thought to be due to the high iodine content of amiodarone causing a
Wolff-Chaikoff effect.
• AIT Type 1-Excess iodine-induced thyroid hormone synthesis.
• AIT Type 2-Amiodarone-related destructive thyroiditis

36. Adverse Effects of
Amiodarone
• Thyroid Dysfunction-Both
Hypothyroidism and
Hyperthytroidism
• Corneal Deposits
• Pulmonary Fibrosis/Pneumonitis
• Liver Fibrosis/Hepatitis
• Peripheral Neuropathy
• Photosentivity
• Slate grey appearance
• Thrombophlebitis
• LQTS, Bradycardia

37. Nondihydropyridine
. Ref-Drugs for heart
Examples-Diltiazem, Verapamil
Indications
• Angina
• Hypertension
• Verapamil for SVT

38. Verapamil- non-DHP agent
Ref-Drugs for heart
Electrophysiology-Verapamil inhibits the action potential of the upper and
middle regions of the AV node where depolarization is calcium mediated.
Pharmacokinetics and interactions- Oral verapamil takes 2 hours to act and
peaks at 3 hours. Therapeutic blood levels (80 to 400 ng/mL) are seldom
measured. The elimination half-life is usually 3 to 7 hours.
Verapamil doses-The usual total oral daily dose is 180-360 mg daily, no more
than 480 mg given once or twice daily (long-acting formulations) or three
times daily for standard short-acting preparations

39. Side effects-Verapamil
Ref-Drugs for heart
• Headaches
• Facial flushing
• Dizziness
• Constipation
• Rare side effects may include pain in the gums, facial pain, epigastric
pain, hepatotoxicity, and transient mental confusion

40. Diltiazem
Ref-Drugs for heart
Pharmacokinetics-The onset of action of short-acting diltiazem is
within 15 to 30 minutes , with a peak at 1 to 2 hours. The elimination
half-life is 4 to 7 hours; hence, dosage every 6 to 8 hours of the short-
acting preparation is required for sustained therapeutic effect. The
therapeutic plasma concentration range is 50 to 300 ng/mL.
Diltiazem doses- The dose of diltiazem is 120 to 360 mg, given in four
daily doses of the short-acting formulation or once or twice a day with
slow-release preparations. Cardizem SR permits twice-daily doses

41. Side effects-Diltiazem
Ref-Drugs for heart
• Headache
• Dizziness
• Ankle Oedema
• Constipation
Contraindications-Contraindications resemble those of verapamil

42. NON-DHP
CONTRAINDICATIONS
Ref-Drugs for heart

43. Digoxin
Ref-Drugs for heart
• It has weak positive inotropic effect,
it slows the ventricular rate, which
allows better ventricular filling in CHF,
especially with atrial fibrillation.
• Sodium pump inhibitionDirect
calcium uptake
• Renin release from the kidney is
inhibited because digoxin decreases
the activity of the renal sodium pump
with a natriuretic effect.
• Blood half-life approximately 36 hr

44. Digoxin use
Ref-Drugs for heart
1. Chronic atrial fibrillation without overt CHF.
2. In chronic atrial fibrillation with heart failure.
3. In CHF with sinus rhythm the limited benefits found in the large DIG
trial.
Contraindications include hypertrophic obstructive cardiomyopathy,
some cases of Wolff-Parkinson-White syndrome with atrial fibrillation ,
significant AV nodal heart block, and diastolic dysfunction.
Relative contraindications are renal failure and older age (reduce
doses).

45. Digoxin Toxicity
https://www.passmedicine.com/v7/textbook/textbook.php#
The BNF advises that the likelihood of toxicity increases
progressively from 1.5 to 3 mcg/l.
Features-
• Lethargy, nausea & vomiting, anorexia, confusion, yellow-green
vision
• Arrhythmias (e.g. AV block, bradycardia)
• Gynecomastia
Precipitating factor
Hypokalemia, renal failure, elderly, myocardial ischemia etc
Drugs-Amiodarone, verapamil, diltiazem, Thiazide and loop
diuretics.

46. ECG Feature
• Down-sloping ST depression ('reverse tick',
'scooped out’)
• Flattened/inverted T waves
• Short QT interval
• Arrhythmias e.g. AV block, bradycardia
Management
•Digibind
•Correct arrhythmias
•Monitor potassium
https://www.passmedicine.com/v7/textbook/textbook.php#

47. Adenosine
• It has multiple cellular effects mediated by opening of the adenosine-
sensitive inward rectifier potassium channel, with inhibition of the
sinus and especially the AV node.
• Adenosine is most commonly used to
terminate supraventricular tachycardias.
• It should be avoided in asthmatics due to
possible bronchospasm.
• Other side effects-Chest discomfort, Flushing, Nausea.
• Adenosine's half-life is 10-30 seconds

49. Thank You