Antihypertensive drug
Thiazides Diuretics shorts notes by K.D.Tripathi
What
are Thiazides?
- Thiazides are mild diuretics (water pills) used
to treat high blood pressure (hypertension).
- Common examples:
🔹 Hydrochlorothiazide
🔹 Chlorthalidone
🔹 Indapamide (works similarly)
⏱️
Which is better – Hydrochlorothiazide or Chlorthalidone?
- Both are effective and used widely.
- Chlorthalidone
lasts longer (~48 hours) than hydrochlorothiazide (<
24 hours).
- That means chlorthalidone works better for 24-hour
blood pressure control.
🔍
How do they work?
Thiazides lower BP in 2 stages:
📉
Stage 1: Early Effect
- Increase urine output → reduce water and salt in
body → lowers blood volume → BP drops.
- Cardiac output (CO) drops first.
🧠
Stage 2: Long-Term Effect
- Body tries to compensate (salt & water
slowly return to normal).
- But BP remains low because blood vessels
become less tight (↓ Total Peripheral Resistance or TPR).
- This is due to a slight salt loss in tissues,
making blood vessels more relaxed.
🧪
Other Possible Mechanism:
- Might open potassium channels in vessels and cause
slight vasodilation.
- But this effect is weak or doubtful.
🕒
When does BP lowering happen?
- Takes 2–4 weeks
to fully work.
- Heart rate and cardiac output stay normal in long-term
use.
- Only TPR decreases, showing long-term benefit.
❤️ Safety & Special Points
- No effect on large veins (capacitance vessels).
- No major postural drop in BP (orthostatic hypotension is rare).
- Do not interfere with nervous reflexes.
📊
Effectiveness
- Thiazides reduce BP by ~10 mmHg on average.
- Work well alone in 30% of mild BP cases.
- Boost effects of other BP medicines (except some calcium channel blockers like DHPs).
- Prevent water retention, which helps avoid resistance to other drugs.
👴
Best Use
- Very effective in elderly people.
- Best dose: 25 mg/day
(Higher doses make more urine but don’t lower BP more).
⚠️
Things That Reduce Effect
- High salt diet
can reduce their effectiveness.
- NSAIDs
(like ibuprofen) can also block their BP-lowering action.
📌
Quick Recap Table
|
Feature |
Summary |
|
💊 Drugs |
Hydrochlorothiazide,
Chlorthalidone, Indapamide |
|
🩺 Use |
First choice for simple high BP |
|
⌛ Duration |
Chlorthalidone longer-acting |
|
⚙️ Mechanism |
Reduces blood volume → later
reduces vessel resistance |
|
⏳ Onset |
BP falls in 2–4 weeks |
|
🧠 Safe |
No major side effects on heart or
nerves |
|
➕ Combo Use |
Enhances most other BP drugs |
|
⚠️ Caution |
Less effective with high salt or
NSAIDs |
How They Reduce Cardiac Output (CO):
Cardiac Output (CO) = the amount of blood pumped by the heart per minute
🔽 Thiazides decrease cardiac output in two main ways:
1. Initial Phase (First Few Days)
o Thiazides make you lose water and sodium through urine.
o This reduces blood volume (less fluid in blood vessels).
o When blood volume drops, the heart pumps less blood → cardiac output drops.
o This also lowers blood pressure temporarily.
2. Later Phase (After Few Weeks)
o Even though blood volume returns to normal later, the blood vessels become less tight.
o This is due to a reduction in total peripheral resistance (TPR).
o So, blood pressure stays low without lowering cardiac output too much.
🌡️ What is TPR (Total Peripheral Resistance)?
✅ Simple Definition:
TPR = The resistance (friction) the blood faces while flowing through the body’s blood vessels.
🩸 Blood flows through arteries and arterioles (small arteries).
These arterioles can tighten (constrict) or relax
(dilate).
· Tight arterioles = high resistance = higher blood pressure
· Relaxed arterioles = low resistance = lower blood pressure
🧪 Example:
Imagine blood vessels as pipes and blood as water:
· Narrow pipes = more resistance = hard for heart to push blood
· Wide pipes = less resistance = easier blood flow
So:
· High TPR → heart has to work harder
· Low TPR → heart works easier
🧾 Summary Table
|
Term |
Meaning |
Effect |
|
Cardiac Output (CO) |
Amount of blood pumped per minute |
Thiazides reduce it early by lowering blood volume |
|
TPR (Total Peripheral Resistance) |
Resistance blood faces in vessels |
Thiazides reduce TPR later → help maintain low BP |