verapamil question
Started by surgok
"Ca2+ channel block by calcium antagonists: Like other voltage-gated cation channels, Ca2+ channels exist in at least three states. A resting state stabilized at negative potentials (such as the resting potentials of most electrically excitable cells) which is a closed state from which the channel can open. The open state is induced by depolarization. Channels do not stay open indefinitely because they are “turned off” during prologend depolarization by transition into an inactivated state. Once the cell repolarizes inactivated channels return to the resting state and are now again available for opening. Ca2+ channel blockers inhibit Ca2+ flux mainly by “allosterically” stabilizing the inactivated closed state. By delaying its transition to the resting state after repolarization some blockers can also increase the refractory period of these channels"
Source: http://calcium.ion.ucl.ac.uk/l-type-pharmacology.html
Source: http://calcium.ion.ucl.ac.uk/l-type-pharmacology.html
QUICK HIT: VERAPAMIL and DILTIAZEM are the NON DIHYDROPERIDINE CALCIUM CHANNEL BLOCKERS (NDHPCCB). Only NONDHPCCBs work at the heart.
QUICK HIT: Reverse BB and NON DHP CCB OD (OVERDOSE) with GLUCAGON or CALCIUM or ATROPINE
BEST LUCK!
QUICK HIT: Reverse BB and NON DHP CCB OD (OVERDOSE) with GLUCAGON or CALCIUM or ATROPINE
BEST LUCK!
Do you know why Glucagon is used for BB overdose? I read a few things here and there, but don't really understand how it works exactly.
http://www.ncbi.nlm.nih.gov/m/pubmed/6144498/: "Glucagon increases heart rate and myocardial contractility, and improves atrioventricular conduction. These effects are unchanged by the presence of beta-receptor blocking drugs. This suggests that glucagon's mechanism of action may bypass the beta-adrenergic receptor site."
Wiki: "Anecdotal evidence suggests a benefit of higher doses of glucagon in the treatment of overdose with beta blockers; the likely mechanism of action is the increase of cAMP in the myocardium, in effect bypassing the β-adrenergic second messenger system."
This was already answered, but keep in mind both glucagon and BB's act by Gs 2nd messenger systems, so if BB's cause blockade of that then glucagon will in place increase cAMP.
I love the connection. Thanks!
To add to this, I believe the thinking on Glucagon for BB overdose is that you cannot give a B1 agonist (epi) because the receptors are so potently blocked that to reach a high enough concentration to overcome you would reach a toxic level of epi. Instead, it is assumed that although most of your glucagon is present on hepatocytes, there are sparse amounts on cardiac myocytes. If you give enough glucagon (I don't know the dosing for this drug, but I believe you give more than the suggested dose for hypoglycemia) you can theoretically increase cAMP levels enough to prevent severe cardiotoxicity.
This is the theory anyways; and although I believe glucagon is given for a BB overdose still, the last I read the actual data on its effectiveness has yet to prove a great benefit.
This is the theory anyways; and although I believe glucagon is given for a BB overdose still, the last I read the actual data on its effectiveness has yet to prove a great benefit.
