PA1-_Antihypertensive_therapy

Antihypertensive Therapy Notes

Definition of Arterial Hypertension

  • Hypertension: Defined as the level of blood pressure (BP) at which the benefits of treatment (with lifestyle interventions or drugs) clearly outweigh the risks, as supported by clinical trials (Source: https://doi.org/10.1093/eurheartj/ehy339).

Blood Pressure Categories

  • Ambulatory Blood Pressure Monitoring (ABPM) and Blood Pressure (BP) classifications are used to diagnose and assess hypertension severity.

Renin-Angiotensin-Aldosterone System (RAAS)

  1. Components:

    • Juxtaglomerular complex in the kidneys releases Renin via:

      • Decrease in renal perfusion

      • Decrease in NaCl concentration in renal tubules

      • Stimulation of adrenergic receptors (β1)

  2. Renin Mechanism:

    • Renin converts Angiotensinogen (synthesized in the liver) into Angiotensin I.

    • Angiotensin I is converted by ACE (Angiotensin Converting Enzyme) into Angiotensin II in the lungs.

  3. Effects of Angiotensin II:

    • Causes vasoconstriction of small arteries, leading to increased BP.

    • Stimulates secretion of Vasopressin/ADH and Aldosterone:

      • ADH: Causes vasoconstriction and promotes water retention.

      • Aldosterone: Causes reabsorption of sodium (Na+) and water, increasing blood volume, thus increasing BP.

  4. Additional Effects of Angiotensin II:

    • Increases thirst, promotes cardiac hypertrophy, enhances norepinephrine release, decreases renal blood flow, and affects central nervous system activity.

ACE Inhibitors (End -pril)

  • Examples: Ramipril, Lisinopril, Captopril.

  • Indications:

    • Arterial hypertension, heart failure, myocardial infarction, diabetic nephropathy, chronic kidney disease.

    • Often used with thiazide diuretics or calcium-channel blockers as first-line therapy.

  • Mechanism of Action:

    • Decrease arterial and venous pressure, prevent sodium and water retention.

    • Additional benefits: Cardiac remodeling, nephroprotection.

  • Side Effects:

    • Dry cough (10-20%), angioedema, hyperkalemia, taste changes, hypotension, and peripheral edema.

  • Contraindications:

    • Pregnancy, lactation, history of angioedema, bilateral renal artery stenosis.

Angiotensin Receptor Blockers (ARBs; End -sartan)

  • Examples: Losartan, Valsartan, Candesartan.

  • Indications:

    • Used if ACE inhibitors cause cough, or as alternatives.

  • Mechanism:

    • Block AT1 receptors without affecting bradykinin levels.

  • Side Effects & Contraindications:

    • Similar to ACE inhibitors but lower risk of cough and angioedema; contraindicated in pregnancy.

Renin Inhibitors

  • Aliskiren: Only available renin inhibitor.

  • Indications: Only for arterial hypertension.

  • Mechanism of Action:

    • Inhibits renin, reducing angiotensin I formation.

  • Side Effects:

    • Teratogenicity, diarrhea, drug-drug interactions (CYP3A4).

Beta-Blockers (End -lol)

  • Types: Cardioselective (β1) vs. Non-selective (β1 and β2).

    • Examples: Metoprolol (β1), Carvedilol (α and β blocker).

  • Indications:

    • Hypertension, supraventricular arrhythmias, previous myocardial infarction, chronic heart failure.

  • Mechanism:

    • Reduces heart rate, myocardial contractility, and renin secretion; beneficial for hypertension management.

  • Side Effects:

    • Hypotension, bradycardia, AV block, exacerbated heart failure, and potential adverse metabolic effects (hypoglycemia).

Alpha-1 Blockers

  • Examples: Prazosin, Doxazosin, Terazosin.

  • Mechanism:

    • Cause arterial and venous dilation, decreasing peripheral resistance and BP.

  • Adverse Effects:

    • Reflex tachycardia, orthostatic hypotension, fluid retention.

  • Indications:

    • Resistant hypertension cases.

Calcium Channel Blockers (CCBs)

  • Classes: Dihydropyridines (e.g., Amlodipine), Non-dihydropyridines (e.g., Verapamil).

  • Mechanism:

    • Block L-type calcium channels, leading to smooth muscle relaxation and vasodilation.

  • Indications:

    • First-line treatment for hypertension, angina.

  • Side Effects:

    • Headaches, peripheral edema.

Direct Vasodilators

  • Examples: Hydralazine, Minoxidil (used in conjunction with other antihypertensive agents).

  • Mechanism:

    • Directly relax arterial smooth muscles, reducing peripheral resistance and BP.

  • Adverse Effects:

    • Reflex tachycardia, risk of angina exacerbation due to increased heart workload.

Diuretics

  • Types: Thiazide (first-line), loop diuretics, potassium-sparing diuretics.

  • Mechanism: Increase renal sodium excretion leading to decreased blood volume and BP.

  • General Considerations: Use lowest effective doses to minimize adverse effects and be mindful of sodium intake in patients.