Pharmacology Notes on Vasodilators and Calcium Channel Blockers

Intended Learning Outcomes (ILOs)

• Understand the actions, mechanisms, and sites of action of calcium channel blockers (CCBs) and miscellaneous vasodilators.
• Recognize the application of these medications in treating hypertension, antiarrhythmics, and angina.
• Learning objectives include:
  • Risk factors for hypertension.
  • Cardiovascular consequences of untreated hypertension.
  • Mechanism of action for calcium channel blockers.
  • The NICE algorithm for choosing calcium channel types for clinical use.

Risk Factors for Hypertension

• In 2019, key contributors to mortality included:
  • High blood pressure: 10.85 million deaths
  • Smoking: 7.69 million
  • Air pollution: 6.67 million
  • High blood sugar: 6.5 million
  • Obesity: 5.02 million

Defining Hypertension

• NICE Guidelines (2019):
  • Determining blood pressure readings with clinic facilities and lifestyle advice.
  • Blood pressures are classified as:
  • Normal: Under 140/90 mmHg
  • Stage 1 Hypertension: 140/90 to 179/119 mmHg
  • Stage 2 Hypertension: 180/120 mmHg or more
  • Patients with Stage 1 hypertension should be followed up every five years.

Causes of Hypertension

• Primary (Essential) Hypertension: accounts for 90% of cases and develops gradually over time due to:
  • Genetics, smoking, obesity, sedentary lifestyle, and high sodium intake.
• Secondary Hypertension: accounts for 10% of cases and occurs suddenly due to:
  • Heart defects, kidney disease, and certain medications.

Mechanism of Calcium Channel Blockers

• CCBs work by:
  • Blocking L-type voltage-gated Ca2+ channels which results in:
  • Reduced Ca2+ entry leading to coronary and peripheral vasodilation.
  • Three classes of CCBs that block L-type channels:
  1. Phenylalkylamines (e.g., Verapamil)
  2. Benzothiazepines (e.g., Diltiazem)
  3. Dihydropyridines (e.g., Nifedipine)

Tissue Selectivity of CCBs

• Tissue selectivity:
  • Smooth muscle: Nifedipine > Diltiazem > Verapamil
  • Cardiac muscle: Verapamil > Diltiazem > Nifedipine
  • Important in the context of arterial resistance and myocardial oxygen demand.

Rate-Limiting vs Non-Rate Limiting CCBs

• Rate-limiting drugs (e.g., Verapamil & Diltiazem):
  • Directly affect heart rate, conduction, and contractility.
• Non-rate limiting agents (e.g., Dihydropyridines):
  • More effective vasodilators, leading to potential indirect tachycardia due to reflex responses.

Uses of L-type Blockers

• L-type CCBs are used for:
  • Hypertension: Dihydropyridines are preferred.
  • Anti-anginals: Cardiac effect drugs are selected to reduce myocardial oxygen demand.
  • Anti-arrhythmics: Treatment of arrhythmias, effective in classifying their properties.

Adverse Effects of L-type Blockers

• Common adverse effects include:
  • Headache, constipation, heart block, and gingival hyperplasia.

Miscellaneous Vasodilators

• Hydralazine:
  • Directly relaxes arteriolar smooth muscle.
• Minoxidil:
  • Opens KATP channels to hyperpolarize vascular smooth muscle, used in hypertension treatment but may cause hypertrichosis.
• Diazoxide:
  • Induces relaxation and is primarily used in specific conditions such as hypoglycemia.

Unmet Needs of Current Therapy

• Nicorandil:
  • A K+ channel activator that combines nitrate-like action with K+ channel opening.
  • Effective in angina management without associated tolerance issues.