How Verapamil and Diltiazem Work 🫀 Non-DHP Calcium Channel Blockers Explained

🧠 Description:
This video takes a deep dive into non-dihydropyridine calcium channel blockers like verapamil and diltiazem, exploring why they act specifically on cardiac tissue rather than vascular smooth muscle. We break down the Cav1.2 (L-type) calcium channel, explain how state-dependent binding works, and show how the drugs’ affinity for the inactivated state leads to powerful effects on heart rate, conduction, and contractility.

You’ll learn the structural and electrophysiological mechanisms behind:

S4-mediated channel opening
S5/S6 conformational shifts and calcium selectivity
Inactivation and its critical role in drug binding
Why these drugs do not significantly vasodilate
How they reduce automaticity, dromotropy, and inotropy
Who benefits from them—and who should avoid them
This is essential knowledge for clinicians and learners aiming to understand cardiac pharmacology, arrhythmia management, or rate control strategies.

Timestamps:
0:00 Introduction to non-DHP calcium channel blockers
0:20 Cav1.2 overview and state-dependent binding
0:50 Why they target cardiac tissue, not vascular smooth muscle
1:25 S4–S6 subunit mechanics and channel opening
2:30 Inactivation and cytoplasmic loop tension
3:10 Conformational shift of S6 and inactivation
4:00 Binding during inactivation—how drugs like verapamil fit
5:00 Why cardiac tissue sees more inactivation
6:00 Nodal effects: reduced automaticity and conduction
7:00 Myocardial effects: less RYR2 activation and contractility
8:00 Clinical outcomes: reduced HR, slowed conduction, weaker contraction
9:00 When to use: AFib, SVT, angina, hypertension
10:00 When to avoid: systolic dysfunction, AV blocks, combo with beta blockers
11:00 Recap: mechanism, binding preference, and clinical considerations

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