Cardiotropic Drugs

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Cardiotropic Drugs
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Cardiotropic Drugs

• used for Congestive Heart Failure and for Cardiac
  Arrhythmia

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I. Digitalis Glycosides

• Digoxin
• Digitoxin

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Digoxin

• Half-life 35 40 h
• Therapeutic Range 0.5 2 ng/mL
• Toxic Level gt2 ng/mL
• Mechanism of Action
• 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
• Nausea
• Vomiting
• Visual disturbances
• Cardiac effects (premature ventricular
  contractions PVC and atrioventricular node
  blockage)
• Route of Administration (oral)

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• Important comments
• 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
• Hyperthyroid patients resistance
• Hypothyroid patients more sensitive

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Digitoxin

• Half-life 4 6 h
• Therapeutic Range 9-25 ng/mL
• Toxic Level gt25 ng/mL
• Important comments
• Converted to active metabolite (digoxin) in the
  liver

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II. Procainamide (Prontesyl)

• Half-life 3 5 h
• Therapeutic Range 4 10 ng/mL
• Toxic Level gt12 ng/mL
• Route of Administration (oral)

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• Important comments
• Undergoes N-acetylation in the liver to form
  N-acetylprocainamide (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

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III. Quinidine

• Half-life 5 12 h
• Therapeutic Range 2.3 5 ng/mL
• Toxic Level gt5 ng/mL
• Toxic Adverse Effects
• Nausea
• Vomiting
• Abdominal discomfort
• Route of Administration (oral)

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• Important comments
• Measured fluorometrically (common)
• May also be determined by chromatography and
  immunoassay
• Undergoes hydroxylation in the liver
• Two most common formulations
• Quinidine sulfate (gastrointestinal absorption is
  complete and rapid)
• Quinidine gluconate
• Absorbed quinidine is 70 80 bound to serum
  proteins
• Elimination is through hepatic metabolism

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IV. Lidocaine (Xylocaine)

• Half-life 2 h
• Therapeutic Range 1.2 5.5 µg/mL
• Toxic Level gt5.5 µg/mL
• Important comments
• A local anesthetic
• Undergoes N-dealkylation in the liver
• Not protein-bound
• Not stored in tissues

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V. Propanolol (Indiral)

• Half-life 3 h
• Therapeutic Range 50 100 ng/mL
• Toxic Level gt100 ng/mL
• Important comments
• Toxic effect Raynauds type

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VI. Disopyramide

• Important comments
• 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
• Anticholinergic effects (gt4.5 µg/mL)
• Dry mouth
• Constipation
• Cardiac Effects (gt10 µg/mL)
• Bradycardia
• Atrioventricular node blockage

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