Digoxin increases force but decreases rate of contraction of heart. So it is specifically a cardiotonic with opposite action on the rate. It inhibits Na+/K+-ATPase pump thereby increases intracellular calcium levels which are responsible for increase in the force of contraction. The inhibitory effect on cardiac rate by Digoxin is due to its vagal activity.
Howdy’s oxen access cardiotonic in heart failure digoxin is a correct glycoside so it is a natural glycoside coming from the digitalis species chemically it is having a structure like this and one of the important nucleus it is having is the sterile nucleus and this sterile nucleus is going to be connected with the five membered lactone ring which is unsaturated
And third important feature of this design because it is a glycoside it is going to be attached with a sugar moiety now this sugar is made up of the glue code dis dog sauce units in this way digoxin is a steroidal cardiac glycoside which is acting like a cardio tonic so in this video we will see how it is going to act as a cardio tonic and used in the treatment of
Heart failure so suppose this is the cardiac membrane and this is the outside of this membrane and is the inside of this membrane and during the action potential generation within the membrane sodium is going to enter into the membrane where it cause a depolarization of this cardiac cells so this phase what we call the phase zero and phase zero is followed by again
The entry of the calcium into the membrane which actually responds for the force of contraction of the heart this phase is called phase two plateau phase and finally the repolarization of this kartik membrane is mediated by the potassium ions which are going outside of this membrane this phase is called phase three complete repolarization phase in this way ions can
Enter into the cardiac membrane and go out of the cardiac membrane to bring the depolarization as well as the repolarization but once this action potential is complete how these ions are going to be restored we have seen that sodium and calcium are entering into the cardiac membrane and punishments going outside the membrane how they again be restored such that
Sodium and calcium are going again out of the membrane and potassium is coming inside the membrane so should happen in order to bring interaction potential because ions should be restored after the action potential but at the same time on restoring these ionic levels the membrane potential should not be changed this is carried by a few of the specialized systems
Electro neutral pumps such type of pump that is present on the cardig membrane is the sodium potassium atpase pump this pump fill from the sodium ions which are entered into the membrane during the phase zero to the outside of this membrane at the same time this pump can bring the potassium which is on the outside into the membrane where it is going to restore the
Potassium levels in this way sodium potassium atpase pump will work such that sodium is going outside and potassium is coming inside without any change in the membrane potential and this pump is also working in coordination with the ender pump that is the sodium calcium exchange pump this pump will bring few of the sodium ions again in into the membrane at the same
Time few of the cash my hands are going outside the membrane now these two pumps are working together so that they will bring the potassium inside and they will transport the sodium and calcium outside of the membrane to restore the ionic levels within the cardiac membrane and one of the interesting point is that these pumps will not change any membrane potential
And the membrane potential remains constant even these pumps are going to transport the ions across the membrane now here the digoxin is going to show its action on one of this pump that is a sodium potassium atpase pump so digoxin is going to bind to the potassium binding site on the sodium potassium atpase pump and inhibits the activity of this pump so dis auxin
Is competitively inhibiting this pump by competing with the potassium and because of this inhibition of this pump it increases the intracellular sodium levels so sodium is going to be accumulated as this pump is not working because of inhibition by dis oxen as the intracellular sodium levels are going to be accumulated this can inhibit the sodium cashman change
Pump which actually brings the sodium into the membrane has already intracellular sodium levels are more sodium cannot enter again into the membrane this pump is going to be inhibited now when this pump is going to be inhibited this results in the increased intracellular calcium levels within the membrane the razr indra seller cash rebels increase the force of
Contraction of the heart now let us see how dis oxen is going to act on the cellular level so dis oxen is going to increase the interest seller cash enables by inhibition of the sodium potassium atpase pump these calcium ions are going to be stored into the sarcoplasmic reticulum which is acting like a storage for the calcium ions within the cardiac membrane and
These calcium ions then go to enter into the sarcoplasmic reticulum where they are going to be stored and this sarcoplasmic reticulum is equipped with the fear of the receptors which are the rhino din receptors these reino de receptors when they are activated they can release the calcium out of this membrane in this way digoxin increase the intracellular calcium
Stores within the cardiac membrane now when the impulse is going to be achieved the cardiac membrane it activates the sodium channels so sodium channels are going to enter into the cardiac membrane which produces a depolarization during the phase zero and this phase zeros followed by phase two where the cash amounts are going to be entered into the membrane this
Calcium which is entered into the membrane is not directly respond the force of contraction of the heart but it is going to activate the rhino teen receptors which are present on the sarcoplasmic reticulum now when this cash max on the rhino d receptor it will release the calcium from the sarcoplasmic reticulum and by action of the calcium on the right note
Intercept are a large amount of the chasm is released into the cardiac membrane this released calcium can form a complex with the troponin to form the calcium troponin complex proponent is actually acting like a physiological block between the actin and myosin filaments and when this block is going to be removed the actin and myosin can slide on each other to bring
The cardiac contract in this way digoxin increased the intracellular calcium stores which are released sufficiently when an impulse achieves the cardiac membrane in this way detoxing can increase the force of contraction of the heart but why it is called as cardiotonic sodas aux-in hard we have seen it is going to increase the force of contraction but at the same
Time dis oxen is going to decrease the rate of contraction so that’s why digoxin is called as cardiotonic so increase the force of contraction what we call positive inotropic effect and decrease the rate of contraction is called negative corona tropic effect so here interesting point is that digoxin is increasing the force but quite obviously decrease in the rate
Of contraction the increase the force of contraction of the heart of by a sox in is because of the inhibition of the sodium-potassium atpase pump as hard we have seen by inhibition of this pump the intracellular cash levels increases which increase the force of contraction but at the same time this auction is going to decrease the rate of contraction of the heart
Because it increased the vagal activity that is a paris empathic activity by increase the parasympathetic activity it decreases the atrioventricular condition that is the av conduction thereby rate of contraction of the heart is going to be decreased in this way digoxin is really acting like a cardio tonic tonic is the drug which increase the force of contraction
It really increase the force of contraction but actually it is going to decrease the rate of contraction so it’s not a cardiac stimulant it is a cardio tonic which will increase the force of contraction has it increased the force of contraction it increased the cardiac output and blood supply to the system accordions so it can be used in the treatment of the heart
Failure so that’s about the mechanism of digoxin how it can be used in the treatment of heart failure
Transcribed from video
How Digoxin acts as Cardiotonic in Heart Failure? By egpat