Anti-Anginal Agents

1
Anti-Anginal Agents

• Angina
• Disease, symptoms
• Types of Anti-anginal Agents
• Nitrovasodilators, calcium channel blockers and
  b-blockers
• Nitrovasodilators
• Structure, physical properties, biochemical
  mechanism of action, metabolism and
  pharmacokinetics
• Calcium channel blockers
• Types, structure, physical properties,
  biochemical mechanism of action
• Adverse Effects/Reactions

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Angina Pectoris

• Development of Angina

• Angina is a Symptom, not a disease

• Types of Angina

• Stable Angina (typical, atherosclerotic
  exertional)
• Unstable Angina (pre-infarction at rest)
• Variant Angina (transient vasospasmatic)

3
Nitrovasodilators
4
Structure
Nitrate Esters

• Some nitrate esters are wrongly named, e.g.,
  amylnitrite is actually isoamylnitrite,
  nitroglycerin is not a nitro compound
• Nitrate esters are susceptible to hydrolysis!
  Shelf life is a concern.

5
Pharmacokinetics of Nitrate Esters

• Nitrate esters act fast! Think about the size of
  these molecules.
• They are rapidly metabolized in the liver
  (glutathione-nitrate reductase). Yet, can be used
  in oral prophylactic therapy, especially ISDN,
  ETN and PETN
• Number of nitrate groups does not linearly
  correspond to potency
• Nitrate esters and possibility of explosion!
• Nitrovasodilators decrease the blood pressure of
  patients!!

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Biochemical Mechanism of Action
7
Mechanism of Action of __________!!

• Another less-known use of this drug is in the
  treatment of pulmonary arterial hypertension!!

8
Biochemical Mechanism of Action
9
Calcium channel blockers

• Types of Calcium Channel Blockers

• Dihydropyridines ? Nifedipine and others
• Phenylalkylamines ? Verapamil and Bepridil
• Benzothiazipines ? Diltiazem

10
Structure of Ca2 channel blockers
11
Protein Binding of Calcium Channels Blockers
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Adverse Effects of Calcium Channel Blockers

• Development of Arryhthmia Bepridil induces new
  arrhythmias
• Hypotension vasodilations side-effect
  especially with nitrovasodilators
• Rebound angina sudden stoppage of drug induces
  flow of Ca2 into cells causing coronary arteries
  to spasm
• Metabolism by liver use with caution in
  patients with hepatic dysfunction
• Mild to moderate edema due to vasodilation