PHARMACOLOGY LECTURE

Melitza Campos-Cruz, M.D.

ARRHYTHMIAS
- sometimes called Dysrhythmias
- conduction dysfunctions caused by abnormalities in impulse generation or impaired
transmission of the impulses
- deviations from the normal rate or pattern of the heartbeat

Four things may happen during arrhythmias:

a) The heart will beat too FAST (tachycardia, either the atrium or the ventricle)
b) The heart will beat too slow (bradycardia)
c) The heart will respond to other impulses
generated by the cardiac cells (other than
the SA node)
d) The heart will respond to impulses
traveling along extra pathways.

ANTI-ARRHYTHMIC DRUGS
- given to modify impulse generation and conduction
- desired action is to restore the cardiac rhythm to normal
- affect the action potential of the cardiac cells, altering their automaticity or
conductivity
- but can also affect the conduction system, they also can produce ARRHYTHMIAS
(“Pro-Arrhythmics”)

The classes of anti-arrhythmic agents: (Vaughan Williams Classification)

Class 1 antiarrhythmics
- generally cause a decrease in excitability & conduction
 M.O.A.: These agents act by blocking fast acting voltage-sensitive sodium channels;
binding to open, inactivate channels.
The drug response is decreased conduction velocity in the cardiac tissues, suppression of the
automaticity that decreases the likelihood of ectopic foci, and increased recovery time
(repolarization or refractory period).

Class 1 (Moricizine)
 General Class I agent
 Has characteristics of all three subclasses
 Used for symptomatic ventricular and life-threatening dysrhythmias

3 subclasses of Class 1:
a) Class IA agents - Quinidine, Procainamide, Disopyramide
- fast SODIUM channel blockers that affects the depolarization phase;
delay repolarization
Used for atrial fibrillation, premature atrial contractions, premature ventricular
contractions, ventricular tachycardia, Wolff-Parkinson-White syndrome
Quinidine- highly protein-bound; can also cause heart block and neurologic/psychiatric
symptoms.

b) Class 1B agents- Lidocaine, Mexiletine, Tocainide, Phenytoin

 Block sodium channels
 Accelerate repolarization
 Decrease the APD
 Used for ventricular dysrhythmias only (premature ventricular contractions,
ventricular tachycardia, ventricular fibrillation)

c) Class 1C agents- Encainide, Flecainide, Propafenone

 Block sodium channels (more pronounced effect)
 Little effect on APD or repolarization
 Used for severe ventricular dysrhythmias
 May be used in atrial fibrillation/flutter

Therapeutic Uses of the Class 1

 The clinical indications are life-threatening VENTRICULAR ARRHYTHMIAS.
 Qunidine is specially used for ATRIAL ARRHYTMIAS.
 They have a local anesthetic effect.

Drug-Drug interactions:
 DIGOXIN and Beta blockers- Quinidine competes for the renal transport sites for
digoxin so that combination of these drugs leads to increase DIGOXIN levels and toxicity.
 Cimetidine- increase the serum levels of class 1
 Quinidine requires an acidic urine for excretion. Patients taking quinidine should
avoid foods that alkalinize the urine (may lead to increased quinidine levels and toxicity)

Class 2 anti-arrhythmics
- beta- blockers that cause a depression of the phase 4 of the action potential
- decrease the conduction velocity, automaticity and recovery time
Examples: Propranolol, Metoprolol, pindolol, acebutolol and esmolol
M.O.A.:
 Reduce or block sympathetic nervous system stimulation, thus reducing transmission
of impulses in the heart’s conduction system
 Depress phase 4 depolarization
These effects stabilize excitable cardiac tissue & dec.BP ------ dec. the heart’s workload
General myocardial depressants for both supraventricular and ventricular dysrhythmias.

Therapeutic uses (Class 2):

 Indicated for the treatment of supraventricular tachycardias and premature ventricular
contractions.
Contraindications and Precautions
 Presence of sinus BRADYCARDIA and AV block.
 CHF, asthma, respiratory depression and cardiogenic shock
 Precautions should be instituted if given to patients with diabetes and thyroid
dysfunctions.
Class 3 Anti-arrhythmics
- POTASSIUM channel blockers that diminish the outward potassium current during
repolarization of cardiac cells.
- increase the refractory period and prolong the action potential.
Examples are: sotalol, bretylium, amiodarone, ibutilide
M.O.A.:
Block potassium channels and slow the outward movement of potassium during phase 3 of
action potential. This action prolongs the action potential.
 Prolongs repolarization in phase 3

Clinical Indications:
 Used for dysrhythmias that are difficult to treat
 Life-threatening ventricular tachycardia or fibrillation, atrial fibrillation or flutter—
resistant to other drugs
 Sustained ventricular tachycardia

* Amiodarone has been associated with a potentially fatal liver toxicity.

Class 4 Anti-arrhythmias
- CALCIUM channel blockers that decrease the calcium influx into the specialized cardiac
muscle cells causing slowed conduction.
-increase the refractory period of the AV node, which decreases the ventricular response
Ex. diltiazem (paroxysmal supraventricular tachycardia)
Verapamil (for supraventicular tachycardia)
 Calcium channel blockers
 Depress phase 4 depolarization
M.O.A.:
Act to BLOCK calcium channels in the cell membrane---- depression of depolarization and
prolongation of repolarization---- slow automaticity and conduction.
Clinical Indications:
 Treatment of paroxysmal supraventricular tachycardia.
To control the ventricle response to rapid atrial rates (atrial fibrillation and flutter)-given I.V.)
Adverse Effects
 Vasodilatation of blood vessels throughout the body brings about the side-effects.
 Shock and arrhythmia

Other Antidysrhythmics (Miscellaneous Drugs)

 Have properties of several classes and are not placed into one particular class
digoxin, adenosine
Digoxin
 Cardiac glycoside
 Inhibits the sodium-potassium ATPase pump
 Positive inotrope—improves the strength of cardiac contraction
 Allows more calcium to be available for contraction
 Used for CHF and atrial dysrhythmias
 Monitor potassium levels, drug levels, and for toxicity

Adenosine (Adenocard)
 Slows conduction through the AV node
 Used to convert paroxysmal supraventricular tachycardia to sinus rhythm
 Very short half-life
 Only administered as fast IV push
 May cause asystole for a few seconds
 Other side effects minimal

SIDE EFFECTS (Anti-Arrhythmics)

 ALL antidysrhythmics can cause dysrhythmias
 Hypersensitivity reactions
 Nausea
 Vomiting
 Diarrhea
 Dizziness
 Blurred vision
 Headache

NURSING CONSIDERATIONS:
Emphasize the client to avoid:
a) Alcohol-can intensify the hypotensive effects
b) Caffeine- increases the cathecolamine levels
c) Tobacco- can promote vasoconstriction

Instruct the client to report side effects:

dizziness, faintness, N/V, respiratory depression,
sedation, hypotension, arrhythmias.

DRUGS FOR SHOCK

Dopamine
 A sympathomimetic drug often used to treat hypotension in shock states that are not
caused by hypovolemia.
 An immediate precursor of norepinephrine, occurs naturally in the CNS basal ganglia
where it functions as a neurotransmitter.

Pharmacodynamics: It can activate the alpha and beta adrenergic receptor depending upon
the concentration.
 It stimulates receptors to cause cardiac stimulation and renal vasodilation.
 The dose range is 1-20 micrograms/kg/min

Pharmacokinetics: Dopamine is administered IV, excreted in the urine. At low dose (1-2
micrograms), dopamine DILATES the renal and mesenteric blood vessels producing an
increase output (dopaminergic effect)
Dopamine:
 At moderate dose of 2-10 micrograms:
a) enhances cardiac output by increasing heart rate (beta 1-adrenergic effect)
b) elevates blood pressure through peripheral vasoconstriction (alpha adrenergic effect)
 At higher doses of more than 10 micrograms: vasoconstriction of all vessels -----can
lead to diminished tissue perfusion.
Clinical uses:
To treat hypotension
To increase heart rate
To increase urine output (giving less than 5mg/kg/min)

Side effects:
 Tachycardia, hypertension, ectopic beats, angina, dysrhythmias, myocardial
ischemia, nausea and vomiting.
Important Notes:
* Check the IV site hourly for signs of drug infiltration of dopamine, which can cause tissue
necrosis.

* Phentolamine should be infiltrated in multiple areas to reduce tissue damage.