CALCIUM CHANNEL BLOCKERS Flashcards
Class 4 antidysrhythmic drugs are calcium channel blockers. What cant you call them?
Calcium channel antagonists as we aren’t dealing with a receptors
What is the structure of a Ca2+ or Na+ channel?
Large alpha subunit = channel forming
24 membrane spanning domains (grouped into 4 repeats with 6 TM domains. 4th has charged subunits so is a voltage sensor.
Between 4th and 6th is a membrane dip and all the dips come together to form the lining of the channel
What is the mechanism of Ca2+ ion channels?
As membrane depolarises, the channels goes from open to inactive state
In open sate, Na+ and Ca2+ move into the cell
How do both Na+ and Ca2+ channels exist?
Resting state (majority), open state and inactive state
What do class 4 drugs do?
They act in specific subtypes: L-types Voltage sensitive calcium channel
If you block this channel (prominently expressed in the heart), you slow down SAN and AVN conduction so reduce after-depolarisation (which depends on Ca2+ build up in a muscle cell). Also, suppresses ectopic pacemakers.
Which 2 drugs are Ca2+ channel blockers?
Verapamil
Diltiazem
What is the clinical use of verapamil and dilitazem?
Paroxysmal supraventricular tachycardia (PSVT)
To decrease ventricular rate in atrial fibrillation
When is it DANGEROUS to use verapamil and dilitazem?
Dangerous to use in ventricular dysrhythmias
Dangerous in 🐺 Wolff-Parkinson-White syndrome
Dangerous in cardiodepression
Dangerous in hypotension
Dangerous in AVN block
Dangerous in oedema (swollen ankles)
Dangerous in headache
Dangerous in constipation 💩
How are calcium channel blockers classified?
L (late)
T (transient)
N (neuronal)
P (purkinje)
The system us based upon the functional properties of the tissues these things are expressed in.
What type (L,N,T or P) is verapamil and dilitazem?
L
Nifedipine is a dihydropyridine class of drugs. What are they used for?
Although they block L-type Ca2+ channels very effectively and are used for hypertension and angina, they are not used for dysrhythmias due to USE DEPENDENCE - they doesn’t show use dependence and tend to be more selective for the vasculature than the heart.
They have much less use dependence than verapamil
An example of a dihydropyridine is?
Nifedipine
How involved are n- type calcium channels in pain?
N-type calcium channels are neuronal so are expressed in nervous system. These are involved in pain. Some types of pain are very resistant to even strong opioids (nerve damage/neuropathic pain).
Blocking N-type Ca2+ = block pain transmission if applied to spinal cord
If we inhibit N-type calcium channels selectively, potentially, we are doing something about?
Pain
