1. Delayed or abolished depolarization because sodium stays out. 2. Membrane stabilization
What are the three main uses for sodium channel blockers?
"1. Local anesthetics 2. Anti-Arrhythmic 3. Anti-Epileptics"
Local anesthetics end in
One "i" in the name of a local anesthetic indicates:
Two "i"s in the name of a local anesthetic indicates:
First ester local anesthetic invented
Natural ester local anesthetic
Cocaine does something that no other local anesthetic does:
Cocaine vasoconstricts. All other local anesthetics are vasodilators.
How cocaine acts and achieves vasoconstriction
It stimulates the central nervous system by causing the release and blocking the reuptake of neurotransmitters, specifically epinephrine (beta activation),norepinephrine (alpha activation), and dopamine.
First synthetic amide local anesthetic
Lidocaine (cannot give orally due to strong 1st pass effect)
Main difference between local anesthetics is
Their duration of action
Shortest acting amides
Prilocaine and Lidocaine (both 90 mins)
Longest acting amides
Bupivacaine and Etidocaine (both 360 mins) and Ropivacaine (420 mins).
In general which are the longest acting amides or esters?
Amides are longer acting than esters. They have a longer half life.
Duration of action of Procaine (an ester)
How does the metabolism of esters compare to that of amides?
Ester metabolism is rapid and occurs in the plasma; amide metabolism is more complex and occurs in the liver.
How do the allergic reactions of esters compare to that of amides?
Allergic reactions are possible for esters but almost non-existent for amides.
How does the toxicity of esters compare to that of amides?
Esters have low toxicity compared to amides. Amides have a higher, dose dependent toxicity.
The action potential of a ventricular myocardial cell has
5 phases from 0 to 4
Sodium goes in and cell depolarizes (QRS)
Potassium channels open and potassium goes out (early repolarization)
Why is Phase 1 quickly aborted?
Because during phase 2 calcium starts coming in and cancels the effect of potassium going out. Plateau ST is reached during phase 2.
We "run out of" calcium and potassium keeps going out repolarizing the cell (late repolarization (T wave))
Calcium in (slow spontaneous depolarization)
Vaughan-Williams-Singh classification of antiarrhythmic drugs has
4 classes of drugs (I to IV)
Na channel blocker
K channel blocker
Ca channel blocker
Not part of the Vaughan-Williams classification but corresponds to antiarrythmic drugs that are Vagus Boosters (vagus nerve slows down heart).
Names you can call sodium channel blockers
Antiarrhythmics, local anesthetics, membrane stabilizers, Vaughan-Williams class I drugs.
Vaughan-Williams Class I (Na channel blockers) are subdivided in
Class IA, Class IB, Class IC.
All Vaughan-Williams Class I (Na channel blockers) A, B and C affect what phase of action potential?
Phase 0. They prevent influx of sodium thus preventing depolarization.
What do Class IA Na blocking drugs do to potassium channel during action potential
They block them, thus decreasing the outflow of potassium during phase 3
What do Class IB Na blocking drugs do to potassium channel during action potential
Opening effect on potassium channels that does not matter much clinically.
What do Class IC Na blocking drugs do to potassium channel during action potential
No effect on potassium channels. Clean Na channel blockers.
What is the effect on the ECG of blocking potassium channels?
Prolonged duration of QT interval.
Too much blocking of potassium channels and prolongation of QT interval leads to
Torsade de pointes (a polymorphic ventricular tachycardia).
What class of Na channel blockers can cause Torsade?
What other Vaughan-Williams Class drug besides class IA is torsadogenic
Class III: the potassium blockers
Treatment of choice for torsade?
Magnesium (Intra venous )
Example Class IA sodium channel blockers
Quinidine, Procainamide and Disopyramide
Example Class IB sodium channel blockers
Example Class IC sodium channel blockers
Atropine like effects (dry mouth, bronchodilation, large pupil) due to blockage of muscarinic receptors. Cinchonism (blurred vision, tinnitus, headache). Arrhythmia upon overdosing. Torsadogenic. Important: Increases digoxin levels in patients.
Rather clean Na channel blocker in spite of being class IA but it is metabolized to N-acetyl-procaine-amide (NAPA) a Class III drug (K channel blocker). If you are a rapid metabolizers you may get torsade.
To slow down brain in patient with seizure you can
Give a GABA agonist or a NMDA antagonist or a Na and Ca channel blocker.
If you block Na channels in brain you get
If you block Ca channels in brain you get
Blockage of neurotransmitter release
First sodium channel blocker for brain
"Carbamazepine (similar in structure to tricyclic antidepressants) and therefore it has same side effects as tricyclic antidepressants: H1-receptor blocker = sedation M-receptor blocker = dry mouth Na-channel-blocker = arrhythmia K-channel-blocker = arrhythmia Alpha-R-blocker = hypotension It is also a CYP P450 3A4 inducer.
Another way of saying muscarinic receptor blockade is
Atropine like effect
Both a sodium and a calcium channel blocker
Effects of phenytoin
"Gum hyperplasia and also Megaloblastic anemia (folate deficiency) Peripheral neuropathy Skin rash Hirsuitism Coarsening of facial features CNS symptoms"
Kinetics of phenytoin
First order kinetics at low doses but due to saturable hepatic hydroxylation it switches to zero order kinetics.
Substances that deplete folate reservoirs in human body: