CARDIOACTIVE

DRUGS
CARDIOACTIVE DRUGS
• Also known as cardiotropics or cardiovascular drugs
• Major classification: Cardiac glycosides, Antiarrhythmics
• Commonly used for patients with arrhythmias and congestive heart failure
Classification of Antiarrhythmics:
• Class I (Rapid sodium channel blockers)
• Quinidine, procainamide, lidocaine
• Class II (Beta receptor blockers)
• Propanolol, Esmolol, Metoprolol
• Class III (K+ channel blockers)
• Amiodarone
• Class IV (Calcium channel blockers)
• Verapamil, Nitrates and Nitrites
ARRHYTHMIAS
• Cardiac arrhythmia; Greek word: “rhymos” = rhythm; “a” = loss of
• A condition in which a heart beats an irregular or abnormal rhythm
• Conditions associated are: Bradycardia, Tachycardia
• Also known as dysrhythmia

CONGESTIVE HEART FAILURE

• A chronic progressive condition that occurs when your heart muscle doesn't
pump blood as well as it should
• Caused by fluid leak to the blood vessel walls resulting to inability or failure to
meet organs the need for oxygen and nutrients
• Common causes of heart failure: Coronary artery disease, Congenital heart
disease, Cardiomyopathy, Endocarditis, Myocarditis, Diabetes, Kidney failure,
Anemia
BRADYCARDIA
• Slow heart rate: <60 BPM
• <50 BPM: Symptomatic resulting to dizziness, shortness of breath and fainting
• <40 BPM: Absolute bradycardia
• Due to abnormalities in supplying oxygen-rich blood to the parts of the body

TACHYCARDIA
• Fast heart rate: 100 - 400 BPM
• Due to insufficient pumping of oxygen-rich blood towards the body parts
• Fibrillation – fine, rapid, irregular contraction of skeletal and/or cardiac muscle
- Atrial fibrillation vs Ventricular fibrillation
CARDIAC GLYCOSIDES
• 3000 years ago since Egyptians, Romans and early
Europeans used it
• Found in plants such as Milkweed, Lilly of the Valley, the
Oleander plant, and Foxglove plant
• Sources are:
• Digitalis lanata (Digoxin)
• Digitalis purpura (Digitoxin)
• Stropanthus gratus (Stropanthin)
• Stropanthus kombe (Ouabain)
DIGOXIN
• Also known as Lanoxin (brand name)
• Cardiac glycoside for treatment of arrhythmia and CHF
• Therapeutic actions and toxicities can be influenced by serum
electrolytes
• Inhibits membrane Na-K ATPase which decreases intracellular K+
and increases intracellular Na resulting in decreased activity of
the Na-Ca exchanger, which normally imports three extracellular Na+
ions into the cell and transports one intracellular Ca2+ ion out of the
cell. This change results to an increase in the intracellular Ca2+
concentration which leads to improved muscle contractility (positive
inotropic effect)
• Hyperthyroid individuals are resistant to action of digoxin
DIGOXIN
• Elimination: renal filtration of the
plasma free form
• Peak serum level: 8 hours after an
oral dose
• Half life: 38 hours on an average
adult
• Therapeutic level: 0.5 - 2 ng/mL
• Toxic level: >2 ng/mL
• Toxic effects: nausea, vomiting,
visual disturbances, premature
ventricular contractions,
atrioventricular node blockage
ANTI-ARRHYTHMICS
• available for nearly 100 years and remain a mainstay in
the management of atrial fibrillation (AF)
• used to control various types of fast arrhythmias include
atrial flutter, supraventricular tachycardia, ventricular
tachycardia and premature heart beats
• used only to treat rapid heart rhythms
• They alter the excitability of cardiac cells by changing the
duration of the effective refractory period, suppress
abnormal automaticity
ANTI-ARRHYTHMICS
• Class I: drugs that block voltage-sensitive sodium channels inhibiting
the influx of sodium, thereby diminishing the rate of depolarization
• Class II: β-adrenoceptor antagonists which block β-adrenergic
(epinephrine and norepinephrine) stimuli, diminishing the rate of
diastolic depolarization
• Class III: drugs that substantially prolong the cardiac action potential
by blocking potassium channel which thereby results in reduction of
potassium efflux and slowing down repolarization
• Class IV: calcium antagonists which blocks the calcium channels
which thereby prolonging the action potential
CLASS I: SODIUM CHANNEL BLOCKERS
1. QUINIDINE
• Naturally-occurring drug for treatment of arrhythmia
• Also used to treat malaria
• Usually in various formulations such as quinidine sulfate and
quinidine gluconate in which GIT absorption is more rapid and
complete for sulfate
• 85% bound to serum protein
• Elimination of these drugs happened through hepatic metabolism
CLASS I: SODIUM CHANNEL BLOCKERS
1. QUINIDINE
• Route of Administration: Oral; Intravenous (IV)
• Half-Life: 5 - 12 hours
• Peak Serum Level: 2 hours after an oral dose (sulfate);
4 - 5 hours (gluconate)
• Therapeutic Level: 2.3 – 5 ug/mL
• Toxic Level: >5ug/mL
• Adverse Effects: nausea, vomiting, diarrhea, stomach pain and cramps,
dizziness or lightheadedness, headache, fatigue, weakness, rash, vision
changes, difficulty sleeping
• Measurement: Fluorometry, Immunoassay and Chromatography
CLASS I: SODIUM CHANNEL BLOCKERS
2. PROCAINAMIDE (PRONESTYL)
• A cardiac depressant used as the hydrochloride salt in the treatment of
cardiac arrhythmias specifically ventricular arrhythmia
• Absorption in gastrointestinal tract and is 20% protein bound
• Major side effects: increased refractoriness of the atria and decreased
myocardial excitability by blocking open sodium channel and outward
potassium current both which prolong action potentials and increased
refractoriness
• Drug elimination is possible through renal filtration and hepatic
metabolism
• Hepatic metabolite: N-acetyl procainamide (NAPA)
CLASS I: SODIUM CHANNEL BLOCKERS
2. PROCAINAMIDE
(PRONESTYL)
• Route of Administration: Oral;
Intravenous (IV); Intramuscular (IM)
• Peak Serum Level: 1 hour after an oral
dose
• Therapeutic Level: 4 - 10 ug/mL
• Toxic Level: >12 ug/mL
• Adverse effects: Lupus-like
syndrome, upset stomach, loss of
appetite, vomiting, bitter taste,
dizziness or lightheadedness
CLASS I: SODIUM CHANNEL BLOCKERS
3. LIDOCAINE (XYLOCAINE)
• Drug of choice for emergency treatment of cardiac arrhythmias
• Commonly used to correct ventricular arrhythmia and for treatment of
acute myocardial infarction
• Also used as local anesthetics
• It is not protein-bound and not stored in tissues
• Due to almost complete hepatic removal of absorbed drug, it is not
administered orally but rather administered by continuous IV infusion or
transdermal
• Monoethylglycinexylidide (MEGX) is the the primary product of hepatic
metabolism
CLASS I: SODIUM CHANNEL BLOCKERS
4. FLECAINIDE 
• Used as the acetate salt in the treatment of life-threatening arrhythmias.
• Also used for the prevention of paroxysmal atrial fibrillation/flutter associated with
disabling symptoms and paroxysmal supraventricular tachycardia.
• Half-Life: 16 - 20 hours
• Therapeutic Level: 200 - 300 mg / day
• Toxic Level: > 400 mg
• Adverse Effects: headache, dizziness, blurred vision, and nausea.

5. DISOPYRAMIDE 
• Used to treat cardiac arrhythmias
• Used as substitute for quinidine
• Has anticholinergic effects – dry mouth and constipation (> 4.5 ug/mL)
CLASS II: BETA BLOCKERS
1. PROPANOLOL 
• Also used as treatment of angina pectoris, coronary artery disease and
hypertension
• It suppresses the conversion of T4 to T3 as used in the treatment of
thyrotoxicosis.
• Route of Administration: Oral
• Half-life: 3 hours
• Therapeutic Range: 50-100 ng/mL
• Toxic Level: >100 ng/mL
• Adverse Effects: Raynaud’s type (arterial insufficiency), bradycardia,
platelet disorder
CLASS II: BETA BLOCKERS
2. ESMOLOL 
• Esmolol is a very short-acting β-blocker used for intravenous
administration in acute arrhythmias that occur during surgery or
emergency situations.

3. METOPROLOL 
• Metoprolol is the β-adrenergic antagonist that is most widely
used in the treatment of cardiac arrhythmias. Compared to
propranolol, it reduces the risk of bronchospasm.
CLASS III: POTASSIUM CHANNEL BLOCKERS
1. AMIODARONE (CORDARONE)
• an iodine containing drug that is highly effective to treat serious
ventricular arrhythmias.
• Its derivatives are commonly known as dronedarone and
celivarone.
• Route of Administration: Oral and Intravenous (IV)
• Therapeutic Level: 1.0-2.5 ug/mL
• Toxic Level: >2.5 ug/mL
• Adverse effects: gastrointestinal tract intolerance, dizziness,
hyper- or hypothyroidism, liver toxicity, photosensitivity,
neuropathy, muscle weakness, and blue skin discoloration
CLASS IV: CALCIUM CHANNEL BLOCKERS
1. VERAPAMIL
• For treatment of angina, hypertension and supraventricular arrythmias.
• Blocks both activated and inactivated L-type calcium channels
• Route of Administration: Oral
• Half-Life: 7 hours
• Therapeutic Range: 80-400 ng/mL
• Toxic Level: >400 ng/mL
• Adverse effects: Peripheral Edema, flushing, GI upset, constipation
and fatigue
CARDIOACTIVE DRUGS
DRUG PEAK LEVEL THERAPEUTIC TOXIC LEVEL
RANGE
Digoxin 8 hours after oral dose 0.5 – 2 ng/mL > 2 ng/mL
Lidocaine 1.5 – 4.0 ug/mL > 4.0 ug/mL
Quinidine 2 hours after oral dose (sulfate); 2.3 – 5 ug/mL > 5 ug/mL
4 - 5 hours (gluconate)

Procainamide 1 hour after oral dose 4 – 10 ug/mL > 12 ug/mL

Disopyramide 3 - 5 ug/mL 10 ug/mL
Propanolol 50 – 100 ng/mL
Amiodarone 1.0 – 2.5 ug/mL > 2.5 ug/mL
Verapamil 80 – 400 ng/mL > 400 ng/mL