Study Notes on Cardiovascular Disease and Drugs by Sanjay Chand, MD

Cardiovascular Disease and Drugs

Professor Sanjay Chand, MD
Integrated Biomedical Sciences, University of Detroit Mercy

America’s Burden

High Blood Pressure Statistics:
  - Approximately 1 in 3 U.S. adults (about 150 million people) have high blood pressure.
  - Consequences of high blood pressure:
    - Heart Attack: 69% of first heart attacks occur in individuals with high blood pressure.
    - Stroke: 77% of first strokes occur in individuals with high blood pressure.
    - Heart Failure: 74% of heart failures are linked to high blood pressure.
  - High blood pressure was a primary or contributing cause of death for about 690,000 Americans in 2025.
  - Direct costs attributable to high blood pressure: $131 billion annually.
  - Only 46% of individuals with high blood pressure have it under control.
  - Worldwide prevalence of hypertension is projected to be as high as 1 billion.

Hypertension

Definition: A condition characterized by elevated blood pressure.
Classification of Blood Pressure Levels:
- Normal:
Causes of Hypertension:
  - Primary (Essential): Unknown cause, >95% of cases.
  - Secondary: Result from other diseases:
    - Pheochromocytoma
    - Renovascular disease (e.g., renal artery stenosis)
    - Aldosteronism
    - Coarctation of the aorta

Guidelines for Hypertension Management

AHA/ACC 2025 Recommendations:
  - Initiate treatment at blood pressure 130/80 mm Hg rather than 140/90 mm Hg.
  - Lifestyle changes recommended for managing high blood pressure.
  - Medication consideration for Stage I hypertension if there is:
    - A history of cardiovascular events (Myocardial Infarction (MI) or Cerebrovascular Accident (CVA)).
    - High risk factors such as age, diabetes mellitus, chronic kidney disease, or atherosclerotic risk (high cholesterol).
    - Patients may need multiple medications, which can be combined into a single pill for compliance.
  - Consider socioeconomic and psychosocial stress as risk factors for high blood pressure.

Signs of Secondary Hypertension

Clinical Clues on Exam:
  - Pallor, edema, and other signs of renal disease.
  - Abdominal bruit (diastolic component indicates renovascular issues).
  - Signs of hypercortisolism: truncal obesity, purple striae, buffalo hump.
Laboratory Tests May Indicate:
  - Increased creatinine levels or abnormal urinalysis.
  - Unexplained hypokalemia indicative of hyperaldosteronism.
  - Impaired blood glucose levels observed with hypercortisolism.
  - Impaired TFT indicating hypo/hyperthyroidism.

Target Organ Damage from Hypertension

Involves the Following Organs:
  - Heart:
    - Left ventricular hypertrophy
    - Myocardial Infarction (MI)
    - Previous coronary revascularization (CABG)
    - Heart failure
  - Brain:
    - Stroke or transient ischemic attacks
  - Kidneys:
    - Chronic kidney disease
  - Peripheral Vascular:
    - Peripheral arterial disease
  - Eyes:
    - Retinopathy

Hypertensive Crisis

Description: Acute elevation of blood pressure associated with end organ damage.
Criteria for Hypertensive Crisis:
  - BP readings of ≥180/120 mm Hg on two consecutive measurements.
  - Risks of potential organ damage can result in:
    - Hypertensive encephalopathy
    - Acute aortic dissection
    - Acute MI
    - Acute CVA (Cerebrovascular accident)
Common Causes Include:
  - Withdrawal from antihypertensive drugs.
  - Autonomic hyperactivity (specific drugs identified).
  - Collagen vascular diseases (e.g., systemic lupus erythematosus).
  - Renal diseases (e.g., acute glomerulonephritis).
  - Head trauma.
  - Neoplasia (e.g., tumors secreting catecholamines).
  - Pre-eclampsia leading to further complications.
  - Recreational drugs (e.g., cocaine, amphetamines).

Identifiable Causes of Hypertension

Examples:
  - Sleep apnea
  - Drug-induced hypertension
  - Chronic kidney disease
  - Primary aldosteronism
  - Renovascular disease
  - Cushing's syndrome
  - Pheochromocytoma
  - Coarctation of the aorta
  - Thyroid/parathyroid disease
  - Dietary and lifestyle factors

Management of Hypertension

Blood Pressure Control:
  - Achieved through:
    - Baroreceptor reflexes that modulate sympathetic stimulation of cardiac output (CO) and peripheral resistance (PR).
    - Renin-angiotensin-aldosterone system (RAAS) controlling plasma volume over the long term.
  - Effective regulation of blood pressure to maintain it in a narrow range.

Antihypertensive Drugs

Classes:
  - Diuretics
  - ACE Inhibitors
  - Angiotensin II Receptor Blockers (ARBs)
  - Calcium Channel Blockers
  - Beta Blockers
  - Alpha Blockers
  - Centrally Acting Antihypertensives
  - Vasodilators

Diuretics

Function: Increase urine production by inhibiting sodium reabsorption in the nephron.
Classes of Diuretic Drugs:
  - High Ceiling (Loop) Diuretics: Furosemide (Lasix), Bumetanide, Ethacrynic acid.
  - Thiazide Diuretics: Hydrochlorothiazide.
  - Potassium-sparing Diuretics: Spironolactone, Triamterene.
  - Others: Carbonic anhydrase inhibitors, Osmotic diuretics.

Loop Diuretics

Key Drugs: Furosemide (Lasix) is the most effective.
Mechanism: Act on the ascending limb of the loop of Henle, inhibiting sodium, potassium, and chloride reabsorption.
Adverse Effects:
- Hypokalemia, ototoxicity, dehydration, hypotension.

Thiazide Diuretics

Key Drug: Hydrochlorothiazide (HCTZ)
Mechanism: Block reabsorption of sodium and chloride in the distal convoluted tubule.
Use: Effective for treating essential hypertension and edema, but not as a stand-alone for diuresis.
Adverse Effects: Hypokalemia, elevated uric acid levels, hyperlipidemia, elevating blood glucose levels.

Potassium-Sparing Diuretics

Function: Act in the distal tubule to decrease sodium reabsorption and potassium excretion.
Types: Epithelial sodium channel blockers (Amiloride, Triamterene) and Aldosterone receptor antagonists (Spironolactone).
Adverse Effects: Hyperkalemia, menstrual irregularities, gynecomastia.

Carbonic Anhydrase Inhibitors

Definition: Enzymes critical for bicarbonate reabsorption in the nephron.
Function: Block sodium bicarbonate reabsorption, causing enhanced diuresis.

Clinical Uses of Diuretics

Effective for managing:
  - Cardiovascular diseases
  - Hypertension
  - Renal diseases
  - Endocrine abnormalities
  - Glaucoma treatment
  - Managing increased intracranial pressure
  - Altitude sickness (Acetazolamide - Diamox).

ACE Inhibitors

Description: Popular antihypertensive agents responsible for inhibiting angiotensin II production.
Common Drugs:
- Enalapril, Ramipril, Lisinopril (all end in ‘-pril’).
Mechanism: Inhibit ACE leading to reduced angiotensin II, causing vasodilation and decreased blood pressure.
Uses: Treat hypertension, heart failure, and after myocardial infarction.
Adverse Effects: Rash, dry cough, risk of renal failure in patients with bilateral renal artery stenosis, contraindicated in pregnancy.

Angiotensin II Receptor Blockers (ARBs)

Function: Block angiotensin II receptors leading to vasodilation and decreased aldosterone secretion.
Key Drugs: Losartan, Olmesartan, Telmisartan, Valsartan.
Advantages over ACE Inhibitors: Lower incidence of cough or angioedema, no significant effect on potassium levels.

Beta Blockers

Function: Antagonists of beta receptors decreasing heart rate and workload, useful in hypertension management.
Key Drugs: Propranolol, Metoprolol, Atenolol (all end in “-olol”).
Adverse Effects: Can cause bronchoconstriction, delayed recovery from hypoglycemia, and mask symptoms of hypoglycemia.

Calcium Channel Blockers

Mechanism of Action: Prevent calcium entry into smooth muscle leading to vasodilation of arterioles and decreased heart contractility.
Key Types: Dihydropyridines (Amlodipine, Nifedipine), non-dihydropyridines (Diltiazem, Verapamil).

Pharmacological Management of Angina

Definition: Pain in chest syndrome due to ischemia of the heart muscle.
Symptoms: Substernal pain described as squeezing or constricting, possibly radiating to the neck, jaw, or left arm.
6 Classes of Drugs Used for Management:
  1. Organic Nitrates (Nitroglycerin)
  2. Calcium Channel Blockers (Nifedipine, Verapamil)
  3. Beta Blockers (Propranolol, Atenolol)
  4. Antiplatelets & Anticoagulants (Aspirin)
  5. Ranolazine (FDA approved for chronic angina)
  6. Trimetazidine (decreases oxidation of free fatty acids).

Non-Pharmacological Management

Strategies for Management:
- Control weight/diet, lifestyle changes, stop smoking, reduce blood pressure, exercise, surgical revascularization (CABG), stents, laser therapy.

Nitrates

Nitroglycerin:
  - Converted to Nitric oxide in smooth muscle leading to vasodilation.
  - Administration route: Sublingual for acute attacks.
  - Prophylactic patches available to prevent angina, applied in 12-hour cycles, requiring nitrate-free periods to avoid tolerance.
Side Effects: Headaches, dizziness, hypotension, increased effect with alcohol.

Conclusion

Monitoring and Management of Cardiovascular Health:
- Regular assessment of blood pressure, understanding the implications of hypertension, and effective therapeutic interventions are crucial to managing cardiovascular diseases and ensuring optimal patient outcomes.