From mercury injections in early syphilis and heart failure patients to the discovery of carbonic anhydrase and the rise of sulfa drugs, we follow how physicians first learned to manipulate fluid balance. We also explore the development of acetazolamide and the eventual breakthrough of thiazide diuretics—revealing how observation and experimentation reshaped the treatment of heart failure and high blood pressure.

• (00:01:18) - What are diuretics?
• (00:02:28) - Mercury for congenital syphilis & surprise diuresis
• (00:08:46) - Mercury’s problems & the need for safer diuretics
• (00:10:26) - Sulfa drugs & penicillin’s first patient
• (00:12:24) - Sulfanilamide, acidosis, and the first kidney clues
• (00:15:01) - Discovery of carbonic anhydrase and its significance
• (00:17:36) - Designing better carbonic anhydrase inhibitors (Acetazolamide)
• (00:19:55) - Chlorthiazide and the thiazide era
• (00:21:26) - Wrap-up

Dive into the first real medications used to treat dangerously high blood pressure. From muscle poisons and anti-malarials to a plant root used for centuries, we trace how hydralazine and reserpine emerged as early antihypertensive therapies. We also explore the landmark VA Cooperative Study, which proved that lowering blood pressure could prevent strokes, heart failure, and kidney damage—and began changing modern medicine.

• (00:00:00) - Introduction: Hypertension Pharmacological Options
• (00:02:48) - Sodium Thiocyanate: The First BP-Lowering Medication
• (00:04:58) - Landmark Study: VA Cooperative
• (00:08:12) - Anti-Malarials: The Accidental Hypertension Treatement
• (00:10:29) - Pentaquine: The First Proof
• (00:13:42) - Hydralazine: An Anti-Malarial That Became a Blood Pressure Drug
• (00:15:04) - Reserpine: The Plant That Lowered Blood Pressure
• (00:19:09) - Turning Point: The Beginning of Modern Hypertension Care
• (00:22:03) - Outro: What Comes Next

Before thiazides and ACE inhibitors, clinicians relied on bleeding, low-salt diets, metabolic experiments, and even nerve-cutting surgeries to manage dangerous blood pressure. This episode explains how these early interventions—and key discoveries about volume, salt, and baroreceptors—shaped our understanding of hypertension and paved the way for pharmacologic breakthroughs.

• (00:00:00) - Introduction: Early Battles With Blood Pressure
• (00:02:08) - Bloodletting: The First “Therapy”
• (00:04:53) - Patient Story: “Mom, I Don’t Want to Die”
• (00:06:59) - Sponsor Break: Dr. Clay’s Drainage Kit
• (00:08:43) - Enter Salt: The Oldest Dietary Culprit
• (00:14:05) - Diets & The Rise of the “Rice Houses”
• (00:21:09) - Baroreceptors: The Nervous System’s Pressure Sensors
• (00:25:11) - Sympathectomies: Cutting Nerves to Cut Pressure
• (00:26:41) - Recap & What Comes Next