Transcript 124207846-Cardiotropic

Cardiotropic Drugs
Cardiotropic Drugs
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used for Congestive
Heart Failure and for
Cardiac Arrhythmia
I. Digitalis Glycosides
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Digoxin
Digitoxin
Digoxin
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Half-life
35 – 40 h
Therapeutic Range 0.5 – 2 ng/mL
Toxic Level
>2 ng/mL
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Mechanism of Action
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Functions by inhibiting membrane Na+, K+ -ATPase (causes a
decrease in intracellular potassium, resulting in increased
intracellular calcium in cardiac contractility)
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Toxic Adverse Effects
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Nausea
Vomiting
Visual disturbances
Cardiac effects (premature ventricular contractions
– PVC and atrioventricular node blockage)
Route of Administration (oral)
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Important comments
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elimination of digoxin occurs primarily by renal
filtration of the plasma free form
in circulation, 25% is protein-bound and the rest is
sequestered into muscle cells
its therapeutic actions and toxicities is influenced by
the concentration of serum electrolytes (low serum
potassium and magnesium potentiate digoxin
actions)
Thyroid status also influence the action of digoxin:
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Hyperthyroid patients: resistance
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Hypothyroid patients: more sensitive
Digitoxin
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Half-life
4–6h
Therapeutic Range 9-25 ng/mL
Toxic Level
>25 ng/mL
Important comments
Converted to active metabolite (digoxin) in the liver
II. Procainamide (Prontesyl)
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Half-life
Therapeutic Range
Toxic Level
Route of Administration (oral)
3–5h
4 – 10 ng/mL
>12 ng/mL
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Important comments
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Undergoes N-acetylation in the liver to form Nacetylprocainamide (NAPA) which is the active
metabolite
Toxic side effects related to Systemic Lupus
Erythematosus (SLE)
Gastrointestinal absorption is rapid and complete
Absorbed procainamide is about 20% bound to
plasma proteins
Its active metabolite can be measured by
immunoassay
III. Quinidine
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Toxic Adverse Effects
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Half-life
5 – 12 h
Therapeutic Range 2.3 – 5 ng/mL
Toxic Level
>5 ng/mL
Nausea
Vomiting
Abdominal discomfort
Route of Administration (oral)
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Important comments
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Measured fluorometrically (common)
May also be determined by chromatography and
immunoassay
Undergoes hydroxylation in the liver
Two most common formulations:
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Quinidine sulfate (gastrointestinal absorption is complete
and rapid)
Quinidine gluconate
Absorbed quinidine is 70 – 80% bound to serum
proteins
Elimination is through hepatic metabolism
IV. Lidocaine (Xylocaine)
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Half-life
2h
Therapeutic Range 1.2 – 5.5 µg/mL
Toxic Level
>5.5 µg/mL
Important comments
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A local anesthetic
Undergoes N-dealkylation in the liver
Not protein-bound
Not stored in tissues
V. Propanolol (Indiral)
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Half-life
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Therapeutic Range
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Toxic Level
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Important comments
Toxic effect: Raynaud’s type
3h
50 – 100 ng/mL
>100 ng/mL
VI. Disopyramide
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Important comments
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Commonly used as quinidine substitute when
quinidine adverse effects are excessive
Orally administered
Gastrointestinal is complete and rapid
Eliminated by renal filtration, and to a lesser extent,
by hepatic metabolism
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Toxic Adverse Effects
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Anticholinergic effects (>4.5 µg/mL)
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Dry mouth
Constipation
Cardiac Effects (>10 µg/mL)
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Bradycardia
Atrioventricular node blockage
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