Calcium Channel Blockers Flashcards
What is the prototype Phenylalkylamine CCB for this course?
Verapamil
What is the prototype benzothIAZEpine CCB for this course?
diltIAZEm
What is the prototype 1,4-Dihydropyridine CCB for this course? (2 items)
Nifedipine
Amlodipine
What are the therapeutic uses of CCBs? (3 items)
Angina pectoris
HTN
Treatment of supraventricular arrhythmias (A-flutter, A-fib, SVT)
What type of CCs do CCBs bind to?
L-type Ca2+ Channel
Describe an L-type Ca2+ channel. Which part of the channel do the CCBs bind?
Polymer of 6 transmembrane domains. CCBs bind between the 5th and 6th domains
What are the two types of binding to Ca channels?
Use dependent binding
Voltage dependent binding
What does use dependent binding mean? What drugs work this way and why?
The channel must be open for drug to bind. More effective at higher rates because channels are open more often. This targets cardiac cells. Diltiazem and Verapamil work this way because of their size.
What does voltage dependent binding mean? What does this mean for targeting of drug? What drug works this way?
The greater the depolarization the more effective the drug is. Smooth muscle is more depolarized than cardiac. Nifedipine works this way, and is more effective on vascular smooth muscle.
What is the pattern of calcium channel activity?
Closed –> Open –> Inactive. Must return to closed before it can open again.
Which channel state do the Phenylalkylamine and Benzothiazepines work?
Open state
Which channel state do the Dihydropyridines work?
Inactive state
Why aren’t different classes given together?
That have an allosteric binding effect. They don’t have entirely exclusive binding activity. This can either increase or decrease each drugs activity.
What are the specific vasodilitory effects of CCBs? (2 items)
- Relaxation of arterial smooth muscle but not venous smooth muscle
- Significant reduction in afterload but not preload
Why do CCBs act selectively on Cardiac and Vascular Muscle and not on skeletal muscle? (3 items)
They have L-type selectivity.
Neuromuscular channels are N-type and P-type channels.
Skeletal muscle relies on intracellular Ca2+ for contraction not external entry of Ca2+.
How do cardiac cells rely on L-type Ca2+ channels? (2 items)
For contraction and for upstroke of the AP in slow response cells.
How do smooth muscle cells rely on L-type Ca2+ channels?
For influx of Ca2+ for contraction
What primary effects do dihydropyridines like Nifedipine have and why?
What sides effects do they have and what contraindication does this create?
Peripheral vasodilation of arteries due to voltage dependent activity.
Can cause reflex tachycardia, myocardial contractility, and O2 demand. These are contraindicated in tachyarrhythmias as a result.
What effect does Verapamil have on Peripheral vasodiltation, coronary vasodilation, preload, afterload, contractility, heart rate, and av conduction
Peripheral Vasodilation + Coronary Vasodilation ++ Preload none Afterload - - Contractility - - - Heart rate - - - AV conduction - - -
What effect does Diltiazem have on Peripheral vasodiltation, coronary vasodilation, preload, afterload, contractility, heart rate, and av conduction
Peripheral Vasodilation + Coronary Vasodilation ++ Preload none Afterload - - Contractility - - Heart rate - - - AV conduction - -
What effect does Nifedipine & Amlodipine have on Peripheral vasodiltation, coronary vasodilation, preload, afterload, contractility, heart rate, and av conduction
Peripheral Vasodilation ++ Coronary Vasodilation +++ Preload none Afterload - - - Contractility +/- Heart rate +/none AV conduction none
What is the Oral absorption, Bioavailability, Protein binding and Half-life of Verapamil?
Oral absorption - 90%
Bioavailability - 10-35%
Protein binding - 83-92%
Half-life - 2.8-6.3 hours
What is the Oral absorption, Bioavailability, Protein binding and Half-life of Diltiazem?
Oral absorption - 90%
Bioavailability - 41-67%
Protein binding - 77-80%
Half-life - 3.5-7 hours
What is the Oral absorption, Bioavailability, Protein binding and Half-life of Nifedipine?
Oral absorption - 90%
Bioavailability - 45-86%
Protein binding - 92-98%
Half-life - 1.9-5.8 hours
What is the Oral absorption, Bioavailability, Protein binding and Half-life of Amlodipine?
Oral absorption - 90%
Bioavailability - 64-90%
Protein binding - 97-99%
Half-life - 30-50 hours
What are the adverse effects of Diltiazem? (5 items)
Moderate hypotension Moderate peripheral edema Mild CHF worsening Mild AV block Potentiates Beta blockers
What are the adverse effects of Verapamil? (7 items)
Moderate hypotension Mild headaches Moderate peripheral edema Moderate constipation Moderate CHF exacerbation Moderate AV Block Moderate caution with Beta blockers
What are the adverse effects of Dihydropyridines (Nifedipine, Amlodipine)? (3 items)
Significant hypotension
Significant headaches
Significant Peripheral edema
What components need to be monitored when using CCBs? (5 items)
Heart rate Blood pressure Anginal symptoms Signs of CHF Adverse effects
What are contraindications for Diltiazem admin? (4 items)
Hypotension
Bradycardia
AV conduction defects
Severe cardiac failure
What are contraindications for Verapamil admin? (4 items)
Hypotension
Bradycardia
AV conduction defects
Severe cardiac failure
What are contraindications for Nifedipine & Amlodipine admin? (2 items)
Hypotension
Severe cardiac failure
How are CCBs generally metabolized?
Cytochrome p450.
