Killam MD on Hypertension Part 3
By Dr. Ronald Killam
June 22, 2015
Category: Hypertension
Tags: Hypertension   HCTZ   ACEI  

    In the early 1980’s, while I was in medical school, another class of blood pressure (BP) medicine was developed called angiotensin-converting enzyme inhibitors (ACEI), based on improved understanding of how the kidneys regulate BP. The kidneys can sense when the system is not full which decreases renal blood flow and causes the production of angiotensin. Meaning: angio-vessel, tensin-squeeze. The arterial constriction raises blood pressure and increases renal blood flow making the system seem fuller. ACEI block this effect and relax blood vessels, which reduces BP. Angiotensin also causes aldosterone to be released from the adrenal gland, which causes salt, and water retention, which does make the system more full. At last we completely understood HTN and had a new wonder drug, captopril, an ACEI that could be used as a single agent, in theory! What we discovered, in practice, ACEI alone only worked transiently. When used alone BP nearly always returned to pre-treatment levels as the kidneys strive to maintain the volume of fluid in the system. The combination of Hydrochlorothiazide (HCTZ) to clamp the volume at a lower level, and ACEI to relax blood vessels, proved to be a potent way to treat HTN, and remains the most common initial therapy. The most commonly used ACEI is the Lisinopril/HCTZ 20/25, $4/30 days at Wal-Mart. ACEI have also shown to reduce the risk of kidney damage in diabetics, reduce the risk of CHF after a heart attack, and improve outcome in patients with CHF. Angiotensin Receptor Blockers (ARB) were developed in the 1990’s for people with adverse reactions to ACEI and work by a similar mechanism. There are a few other BP medications, but these are the most commonly used ones.

    Lasix is another fluid pill that is used for patients with a weak heart or systolic CHF, which reduces blood flow in their kidneys, or in patients where the kidneys are weak. This can be viewed as when the hole in the side of the bucket is too small and smaller than the faucet. Even with fluid draining out that hole more fluid is being added faster, and so the bucket will fill up. Lasix is like drilling a hole in the bottom of the bucket, the higher the dose, the bigger the hole. The aim is to use just the right dose/hole to make up for the difference in the size of the hole in the side of the bucket and the size of the faucet. Too big a hole and the bucket runs dry, and the kidneys fail. It is not a substitute for HCTZ because the hole in the bottom drains at a constant rate, so the volume in the bucket goes up and down according to how much is being added. HCTZ and the hole in the side of the bucket is still frequently needed to regulate the fluid level at a constant volume and allows for a lower and safer dose of Lasix.

    In conclusion, JNC-7 guidelines referred to in Part 1 states that: “certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (ACEI, ARB, BB, CCB).” However as stated at the beginning, when 2 or more BP meds are required, one of them should be HCTZ. 

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