1. CARDIOVASCULAR SYSTEM
PHARMACOLOGY

2. ANTIARRHYTHMIC DRUGS
Antiarrhythmic drugs are used to prevent recurrent arrhythmias and restore sinus rhythm in patients
with cardiac arrhythmias.
These drugs are classified based on their electrophysiological effect on the myocardium.
Antiarrhythmic drugs do not improve the survival of patients with non-life-threatening arrhythmias and may
increase mortality, particularly in patients with structural heart disease.
They are associated with severe adverse effects, primarily due to their proarrhythmic effects on
the myocardium.
Patients who have received an intravenous antiarrhythmic should be monitored closely with serial ECGs.
Several classes of antiarrhythmics, including beta blockers, calcium channel blockers, amiodarone, cardiac
glycosides, and lidocaine.

4. Blue (if): Hyperpolarization triggers
the opening of funny channels (if),
resulting in an influx of cations into the
cell and their depolarization to the
threshold potential of -40 mV.
Violet (iCa): Voltage-gated calcium
channels (iCa) open at approx. -40 mV,
resulting in an influx of calcium cations
into the cell and their depolarization to
the threshold potential of approx. +20
mV.
Repolarization:
Green (iKs+Kr): The calcium channels close
and the delayed outward rectifier
potassium channels open (iKs+Kr). This
causes an outflow of potassium ions out
of the cell until it returns to -60 mV again.
This leads to the closure of the potassium
channels and the opening of funny
channels, thus initiating a new excitation
cycle.
Action potentials of pacemaker cells in the sinus node

5. Action potential and ion flux in myocardial contractile cells
Resting potential (approx. -90mV) relies
primarily on potassium channels (inward-
rectifier potassium channels), ensuring a
steady potassium efflux (iK1).
Phase 0 (depolarization): Neighboring cells
stimulate voltage-gated sodium channels
within the cell, causing them to open briefly.
This results in a sodium influx (iNa ), and,
consequently, the membrane potential
increases just beyond 0 mV (overshoot).

6. Phase 1 (partial repolarization): The brief influx of chloride and efflux
of potassium (not shown here) causes membrane potential to
decrease.
Phase 2 (plateau): The opening of voltage-gated L-type calcium
causes an influx of calcium ions (iCa), counteracting the repolarization
and keeping the membrane potential at approximately 0mV.
Phase 3 (repolarization): Rapid repolarization occurs via the opening
outward-rectifier potassium channels, resulting in a net efflux of
potassium.
Phase 4 (resting potential): A steady efflux of potassium (ik1) occurs
the cell is stimulated again and the process begins again at phase 0.

11. CLASSES OF ANTIARRHYTHMIC DRUGS

13. CLASS I - Fast sodium channel blockers – features of all
class I antiarrythmics
•Reduce or even block conduction(negative dromotropy), particularly in
depolarized tissue (e.g., during tachycardia)
•State-dependent: the faster the heart rate (e.g., tachycardia), the greater the
effect
• Shorter diastole
• Sodium channels spend less time in resting state
•Decreases the slope of phase 0 depolarization
•Stabilize membrane
•Categorized into 3 subgroups based upon their effects on the Na+ channel and
the action potential (AP) duration

14. CLASS IA ANTIARRHYTHMICS
•Moderate blockage of Na+ channels (intermediate association/dissociation)
•Prolong action potential(AP) duration (right shift)
•Slow conduction velocity
•Prolong effective refractory period (ERP) in ventricular APs
•Weak blockade of the K+ channel
•Paroxysmal supraventricular tachycardia (PSVT): AVNRT and AVRT
•Ectopic SVTs
•Antidromic AVRT and WPW(procainamide)
•Atrial fibrillation (AFib) and atrial flutter
•Ventricular arrhythmias
•Quinidine
•Procainamide – WPW
•Disopyramide
•Ajmaline

15. •QT prolongation →torsade de pointes(TdP)
•Cinchonism: headache, hearing/vision
loss, tinnitus, psychosis and cognitive impairment, associated
with quinidine use
•Thrombocytopenia
•Procainamide
• Drug-induced lupus erythematosus (reversible)
• Drug fever
•Disopyramide
• Heart failure
• Anticholinergic effects
Adverse Effects:

17. CLASS IB ANTIARRHYTHMICS
•Weak blockade of Na+ channels (fast association/dissociation)
•Shorten AP duration
•Slow conduction velocity
•No effect on or slight prolongation of ERP
•Strongest effect on ischemic or depolarized cardiac Purkinje
cells and ventricular myocardium
•Lidocaine
•Mexiletine
•Phenytoin
•Ventricular arrhythmias(especially
following myocardial infarction)
•Digitalis-induced cardiac
arrhythmias

18. ADVERSE EFFECTS OF TYPE IB ANTIARRYTHMICS
•CNS: possible depression or
excitation
• Dizziness, nausea
• Seizures
•Cardiovascular: AV conduction
block, ventricular extrasystoles

19. •Strong blockage of Na+ channels (slow
association/dissociation) →QRS
prolongation
•No to minimal effect on AP duration (no
shift)
•Slow conduction velocity
•Extend duration of effective refractory
period in both AV node and accessory tracts
•ERP unaffected in cardiac Purkinje cells and
ventricular myocardium
Class IC antiarrhythmics
•Flecainide
•Propafenone
•PSVT
•AFib(cardioversion)
•Atrial flutter
•Last resort in
refractory VT

20. ADVERSE EFFECTS OF CLASS IC ANTIARRHYTHMICS
•PSVT
•AFib(cardioversion)
•Atrial flutter
•Last resort in refractory VT

21. Class II antiarrhythmic drugs
•Beta blockers
•Inhibit β-adrenergic activation of adenylate
cyclase →↓ cAMP → ↓ Ca2+ → ↓ SA node and AV
node activity
•Prolong AV node repolarization (AV node is highly
sensitive to beta blockers) → prolongation of PR
interval
•Decrease slope of phase 4 in cardiac pacemaker
cells→ suppression of aberrant pacemakers
•Slow conduction velocity
•Metoprolol
•Esmolol(short acting)
•Propranolol
•Atenolol
•Timolol
•Carvedilol
•Sotalol

22. •AFib (rate control)
•Atrial flutter
•PSVT
•Premature ventricular contractions
•Ventricular arrhythmias
•Atrial premature beats

23. ADVERSE EFFECTS OF BETA BLOCKERS
•AV block, bradycardia, heart failure
•Exacerbation of asthma, COPD
•Sedation, CNS depression, sleep alterations
•Impotence
•Hypoglycemia (can mask symptoms of hypoglycemia)
•Hyperkalemia
•Dyslipidemia (metoprolol)
•Propanolol: may intensify vasospams in patients with preexisting vasospastic angina
•Avoid in patients with concurrent cocaine use or pheochromocytoma.
• Unopposed α1agonism →↑ blood pressure, coronary and systemic vasoconstriction
• Except for labetalol and carvedilol, which are nonselective α- and β-antagonists

25. Class III antiarrhythmic drugs
•Potassium channel blockers
•Inhibit delayed rectifier potassium currents
•Prolong QT interval
•Prolong AP duration (reverse use dependence) and ERP
•No effect on conduction velocity
•Amiodarone(has class I, II,
III, and IV
properties; lipophilic)
•Dronedarone
•Sotalol
•Bretylium
•Ibutilide
•Dofetilide
•AFib (cardioversionand rhythm control)
•Atrial flutter
•Sotalol and amiodarone can be used to treat:
• Supraventricular arrhythmias
• Ventricular arrhythmias, e.g., tachycardia

26. •QT prolongation → TdP
•Amiodarone
• Cardiovascular
• May cause heart failure, heart block, bradycardia, hypotension
• Lowest risk of ventricular arrhythmia compared to other drugs in its
class
• Pulmonary fibrosis
• Thyroid dysfunction(hypo- or hyperthyroidism)due to high iodine content
• Liver dysfunction
• Neurologic side effects (e.g., peripheral neuropathy)
• Can act as a hapten →bluish-gray deposits
in cornea and skin →photosensitivity →photodermatitis
• Constipation

27. CLASS IV ANTIARRHYTHMIC DRUGS
•Calcium channel blockers
•Inhibit slow calcium channels
•Decrease slope of phase 0 and 4 → slower
conduction velocity → increased ERP
•Prolong AV node repolarization
•Prolong PR interval
•Verapamil
•Diltiazem
•Nifedipine
•AFib (rate control)
•Atrial flutter
•Prophylaxis of
nodal arrhythmias, e.g., PSVT
•Multifocal atrial tachycardia
•Hypertension(nifedipine)

28. ADVERSE EFFECTS OF CLASS IV ANTIARRHYTHMICS
•Verapamil
• AV block
• Bradycardia
• Depression of sinus node
• Heart failure
• Constipation
• Flushing
• Edema
•Nifedipine
• Headache
• Flushing
• Pitting edema
• Reflex tachycardia
•Diltiazem: adverse effects similar to those of both verapamil and nifedipine, but less
prominent

30. CLASS V ANTIARRHYTHMIC DRUGS

31. •Diagnosis and termination of
certain forms
of PSVT (e.g., AVNRTand orthodrom
ic AVRT)
ADENOSINE
•Activates Gi protein → ↓ cAMP → deac
tivation of L-type Ca2+ channels
→ ↓ Ca2+ and ↑ K+ efflux →transient AV
node block
•Very short acting (∼ 15 sec)
•Administration
• Rapid bolus IV (very
short half-life: < 10
seconds)
• May be administered
repeatedly if the
previous dose was
unsuccessful

32. ADVERSE EFFECTS
•Chest pain
•Flushing
•Hypotension
•Bronchospasm
•Sense of impending doom
•Effect weakened
by adenosine receptor
antagonists (e.g., theophylline, caffei
ne)
•Contraindications to adenosine
• Pre-
excitation syndromes: antidromic
AVRT, WPW
• AV block
• Asthma
•Interactions: Theophylline and caffeine
weaken the effects of adenosine because
they are adenosine receptor antagonists.

33. MAGNESIUM SULFATE
•Decreases calcium influx
→ prevents
early afterdepolarizations (EADs)
Adverse Effects:
• Hypotension
•Asystole
•Drowsiness
•Flushing
•Loss of reflexes
•Respiratory depression
•Indications
• Torsade-de-pointes
• Refractory ventricular
tachyarrhythmias (e.g., polymorphic VT)
• Digoxin intoxication
• Eclampsia
• Constipation
• Tocolysis

34. DIGOXIN
•Inhibits Na+/K+-ATPases → higher
intracellular Na+ concentration
→ reduced efficacy of Na+/Ca2+ exchangers → hi
gher intracellular Ca2+ concentration
→ increased contractility and decreased heart
rate
•AFib
•Atrial flutter
•Chronic systolic heart failure
•Nausea, vomiting
•Abdominal pain
•Blurry vision with a
yellow tint and halos

38. IVABRADINE
•Selectively inhibits If channel in the
pacemaker cells of the SA node → prolongs
slow depolarization(phase 4) → slows heart
rate
•Chronic stable coronary heart
disease in patients who cannot
tolerate beta blockers
•Chronic HFrEF
Adverse effects:
Vision changes:
luminous
phenomena
(enhanced visual
brightness)
•Bradycardia
•Hypertension

39. IVabradine slows depolarization in phase IV.

40. “I am Ambivalent about the QUEEn PROofreading
my DISsertation”: Class IA antiarrhythmic drugs are QUEEnidine, PROcainamide, DISopyramide.
“LInDO MEXIco Is the Best”: LIDOcaine and MEXIletine are class IB antiarrhythmic drugs.
“I Can't Fail, Please”: Class IC antiarrhythmics are Flecainide, Propafenone.
“I Am Sober, Doctor, for III days”: Ibutilide, Amiodarone, Sotalol, and Dofetilide
are class III antiarrhythmic drugs.
Class IB antiarrhythmic drugs work Best after myocardial infarction; class
IC antiarrhythmic drugs are Contraindicated.
All antiarrhythmic drugs are also potentially proarrhythmic!
Intravenous administration should only be performed
with continuous cardiac monitoring!