Saturday, March 5, 2011

Anti-arrhythmic drugs

Arrhythmia:

The rhythmic activity of the heart is disturbed by any of the following phenomena:

Delayed after depolarization:
It is due to abnormally high level of calcium ions inside the cell.

Re-entry:
It is represented by the entry of the same impulse on a part of heart muscle that it has recently activated.

Here some of the parts of the muscles of the heart get abnormally depolarized. At this, conduction depends on slow calcium current.

For example Wolff-Parkinson White syndrome and AV reentry.

Abnormal pacemaker activity:
Under normal conditions, SA node is most prominent in Phase 4 depolarization and has higher rate of firing.

When there is generation of impulses from other than the SA node resulting in the competitive stimulation of the heart muscles. This causes arrhythmia.

This is promoted by sympathetic stimulation.

Heart block:
This results from the impairment of AV node or ventricular conduction.

Potential:
It is the work done (W) on a unit positive charge (+q) for its movement from a reference point, which is located somewhere outside of the field to a specific point in the field, against electric field (direction).

It is represented by “V” and its formula is

V = W/q

Potential difference:

It is the difference in potential energy between two points (suppose A and B) within an electric field.

It is represented by “ΔV” and its formula is

VA – VB = ΔV = W/q

Membrane potential:
Potential difference across the membranes is referred to as membrane potential. It is therefore a difference of potential (V) inside a nerve, cell membrane or some other tissue (which have the ability of excitation) and space or fluid outside the membrane or nerve cell.

It is negative in normal conditions i.e. resting potential and changes to positive value when excited or generating an impulse i.e. action potential.

Resting potential:
1. Potential difference is negative i.e. V = -75 to -70 milliVolts.

2. Inner side or surface is more negative than the outer side i.e. sodium ions (positive ions) are more on the outer side or surface and chloride ions (negative ions) are more inside. (minute amount of potassium ions (positive ions) are also there inside).

3. When the inner side is more negative than the outer; the cell membrane, neuron or the tissues at this place are referred to as polarized.

When, some condition or any disturbance, cause to make the inner side more negative than the normal state; at this place it is referred to as hyperpolarized.

Action potential:
1. Potential difference is positive i.e. V = +55 milliVolts

2. It is a temporary change in membrane potential due to a stimulus or excitation.

When some condition or any disturbance cause to make the inner side less negative than the normal state; at this place it is referred to as depolarized.

The action potential is declined by closing sodium channels and opening potassium channels, which helps to maintain approximately same amount of positive charge.

Phases of action potential:

Cells of cardiac muscles have somewhat long duration of action potential. So, it is divided into 5 phases:

Phase 0:
This is characterized by fast depolarisation.

On excitation, voltage gated sodium channels start opening resulting in the inward movement of sodium ions so that the inner side starts to become less negative.

Threshold potential:
At a certain point, potential difference reaches at -60 mV. This is referred to as threshold potential.

At this point, the sodium channels completely open resulting in the influx of a large amount of sodium ions. This depolarization cause the neighboring sodium channels to be activated resulting in the movement of impulse along with action potential.

After the inactivation of the sodium channels there is no flow of sodium ions.

Phase 1:
This is characterized by partial repolarisation.

Here the sodium channels are inactivated and potassium channels get activated resulting in the outward movement of potassium ions (positive ions). This outward movement of positive ions results and the concentration of positive ions inside the fiber or membrane remain same.

Phase 2:
This is characterized by the plateau phase.

Here calcium channels get opened resulting in the inward movement of calcium ions. So that the balance remains and not more positive ions get concentrated outside by the outward flow of positive ions.

Phase 3:
This is characterized by repolarisation.

At this stage calcium channels get inactivated. Potassium channels remain open resulting in the outward flow of potassium ions leading to membrane repolarisation. Here at this point there is an increase of sodium ions inside the membrane and decrease of potassium ions outside.

Phase 4:
This is characterized by the potential pacemaker in whom there is slow depolarisation.

At this stage, the sodium channels start opening again for another threshold potential. Depolarization again started for another action potential.

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