PA1-_Antihypertensive_therapy

Centrally Acting Alpha-2 Agonists

• Commonly Used Agents:

  • Clonidine

  • Guanfacine

  • Alpha-methyldopa

• Mechanism of Action (MoA):

  • Stimulate α2 adrenoreceptors in the medulla.

  • Inhibit sympathetic vasomotor centers.

• Effects:

  • Reduced peripheral resistance

  • Lowered blood pressure (BP)

  • Minimal effects on heart rate and cardiac output (CO)

• Clonidine Indications:

  • Hypertension refractory to treatment

  • Hypertension complicated by renal disease (does not significantly affect renal blood flow or glomerular filtration rate (GFR))

  • Supportive therapy in alcohol withdrawal and opioid withdrawal patients

  • Treatment of hypertensive urgency (e.g., BP >210/110 without functional impairment)

• Alpha-methyldopa Indication:

  • Primarily used for gestational hypertension, shown to be safe for the fetus.

• Adverse Effects of Centrally Acting Drugs:

  • Sedation, depressive mood

  • Dry mouth

  • Impaired mental acuity

  • Rebound hypertension if abruptly discontinued

  • Alpha-methyldopa:

    • Can cause hemolytic anemia and autoimmune hepatitis

• Drug-Drug Interactions:

  • Especially with tricyclic antidepressants

Hypertensive Crisis

• Definition:

  • Hypertensive crisis occurs when:

    • Systolic BP >179 mmHg

    • Diastolic BP >109 mmHg

• Hypertensive Emergency:

  • End-organ damage is evident (e.g., stroke, intracranial bleeding).

  • Specific areas affected include:

    • Central Nervous System (CNS): stroke, encephalopathy

    • Heart: acute heart failure, cardiac decompensation, acute coronary syndrome (ACS)

    • Lungs: pulmonary edema

    • Eyes: retinopathy

    • Kidneys: acute renal failure

    • Eclampsia: seizures in pregnant patients

• Hypertensive Urgency:

  • No end-organ damage, often presents with:

    • Headache without neurological deficits

    • Light-headedness, dizziness

    • Facial flushing, restlessness

Treatment of Hypertensive Crisis

• Assessment:

  • Conduct a thorough physical exam to distinguish between emergency and urgency.

• Hypertensive Emergency Treatment:

  • Immediate initiation of antihypertensive medications is essential.

  • Do not lower BP >30% in the first hour to avoid the risk of stroke or myocardial infarction (MI), with exceptions for lung edema and aortic dissection.

  • First-line treatments include:

    • Glyceroltrinitrat nebulizer (0.4 mg, max of 1.2 mg total)

    • ACE Inhibitor (Captopril 12.5-25 mg orally)

    • For definitive BP lowering: Urapidil IV (12-15 mg, max 50 mg total) or Clonidine SC (0.075 mg)

• Hypertensive Urgency Management:

  • Aim to lower BP within 24-48 hours.

  • Calming the patient and addressing stressors.

  • If on antihypertensive medications, consider an additional dose or another long-term agent like an ACE inhibitor or sartan.

Treatment Goals and Guidelines

• Effective BP Control:

  • A 10 mmHg reduction in systolic BP is associated with a 20% reduction in major cardiovascular events, a decrease in all-cause mortality by 10-15%, and reductions in stroke and heart failure rates.

• BP Targets:

  • Ideal BP: <140/90 mmHg

  • For well-tolerated treatment: <130/90 mmHg

  • Patients with diabetes mellitus should aim for <130/80 mmHg

• Lifestyle Modifications:

  • Smoking cessation

  • Salt intake management (max 5g/day)

  • Alcohol reduction, weight loss, and endurance training can help achieve BP reductions.

• Medicinal Treatment Sequencing:

  • Initial Dual-Combination Therapy (single pill preferred):

    • ACE Inhibitor or ARB + Thiazide or Calcium Channel Blocker (CCB)

    • Beta-blockers are used only when indicated.

  • Therapy intensification can lead to triple or quadruple combinations if necessary to control BP effectively.