Amiodarone contains iodine and is structurally related to thyroxine. It shows the affects of all classes i.e. class I, II, III and IV.
Mechanism of action:
Amiodarone blocks the sodium channels in inactivated state. It also blocks the calcium channels but to a less extent. It also noncompetitively inhibits α- and β- adrenoceptors.
Actions:
Its dominant action is the increase in duration of action potential. It also causes an increase in effective refractory period in the atrial and ventricular muscles.
It causes an increase in PR, QRS and QT intervals.
It causes a decrease in sinus rate and AV conduction as well as systemic and coronary vasodilation.
Pharmacokinetics:
It is not well absorbed orally. It has a prolonged half life of about 20-100 days and distributes mostly into adipose tissues. Its full effects are seen after 6 weeks of start of treatment.
Therapeutic uses:
It is used in
1. Angina
2. Premature ventricular contractions
3. Ventricular tachyarrhythmia
4. Refractory supraventricular arrhythmias
5. Arrhythmias in patients with wolf Parkinson white syndrome
Adverse effects:
It may cause gastrointestinal intolerance (nausea, vomiting, and constipation), headache, dizziness, paresthesias, pulmonary fibrosis and blue skin discoloration (due to the increased concentration of iodine in the skin).
Sunday, March 6, 2011
Saturday, March 5, 2011
Disopyramide
Mechanism of action:
Similar to quinidine
Actions:
It also possesses properties of class III agents.
It has same actions as that of quinidine but it is more pronounced in causing anti-muscarinic actions. It causes peripheral vasoconstriction and produces negative inotropic effects.
It causes a prominent decline in myocardial contraction in patients whose left ventricular function has already been impaired.
Therapeutic uses:
Ventricular arrhythmias
Pharmacokinetics:
It is taken orally and about 50 percent of the drug is excreted without any change through the kidneys. It has been found that about 30 percent of the drug is metabolized in the liver into mono-N-dealkylated metabolite.
Adverse effects:
It causes anticholinergic effects such as constipation, dry mouth, retention of the urine and blurred vision. It may also cause hypotension.
Contraindications:
It is contraindicated for patients with
1. 2nd or 3rd degree AV block
2. cardiogenic shock
3. severe uncompensated cardiac failure
Dosage:
It is given 300-800 mg daily in divided doses.
Similar to quinidine
Actions:
It also possesses properties of class III agents.
It has same actions as that of quinidine but it is more pronounced in causing anti-muscarinic actions. It causes peripheral vasoconstriction and produces negative inotropic effects.
It causes a prominent decline in myocardial contraction in patients whose left ventricular function has already been impaired.
Therapeutic uses:
Ventricular arrhythmias
Pharmacokinetics:
It is taken orally and about 50 percent of the drug is excreted without any change through the kidneys. It has been found that about 30 percent of the drug is metabolized in the liver into mono-N-dealkylated metabolite.
It causes anticholinergic effects such as constipation, dry mouth, retention of the urine and blurred vision. It may also cause hypotension.
It is contraindicated for patients with
1. 2nd or 3rd degree AV block
2. cardiogenic shock
3. severe uncompensated cardiac failure
Dosage:
It is given 300-800 mg daily in divided doses.
Procainamide
It is a derivative of procaine which is a local anesthetic.
Mechanism of action:
Same as that of quinidine
Actions:
Cardiac effects:
Almost similar to quinidine.
It decreases ectopic pacemaker rate, conduction velocity (negative dromotropism) and excitability especially in depolarized tissue. By decreasing conduction velocity (negatively dromotropic) it causes a promoted effective refractory period in atrial, ventricular and Purkinje fibers.
However unlike quinidine it has less effecient antimuscarinic action.
Due to its ganglionic receptor blocking properties, it results in more pronounced negative inotropic effects than quinidine.
It instigates serious CCF in patients with already ventricular dysfunction.
Other effects:
It reduces peripheral vascular resistance and may cause hypotension due to its ganglionic blocking properties.
Procainamide is well-absorbed orally.
Its half life is 2 – 3 hours. Some of the procainamide is metabolized in the liver into N-acetylprocainamide (NAPA). NAPA has the same properties as that of class III agents as it prolongs the duration of action potential.
It is used in atrial and ventricular arrhythmias and ventricular arrhythmias which comes with acute myocardial infarction.
Adverse effects:
It may cause mental confusion, anorexia, nausea, urinary retention and hepatitis. After prolonged use, it may cause reversible form of lupus erythematosus like syndrome in 20-30 percent of patients. Its toxic dose may cause asystole or instigation of ventricular arrhythmias.
Its effects on CNS include depression, hallucination and psychosis.
Contraindications:
It is contraindicated in patients with AV block or systemic lupus erythematosus.
Dosage:
It is given up to 50 mg/kg daily in divided doses every 3 to 6 hours.
Mechanism of action:
Same as that of quinidine
Actions:
Cardiac effects:
Almost similar to quinidine.
It decreases ectopic pacemaker rate, conduction velocity (negative dromotropism) and excitability especially in depolarized tissue. By decreasing conduction velocity (negatively dromotropic) it causes a promoted effective refractory period in atrial, ventricular and Purkinje fibers.
However unlike quinidine it has less effecient antimuscarinic action.
Due to its ganglionic receptor blocking properties, it results in more pronounced negative inotropic effects than quinidine.
It instigates serious CCF in patients with already ventricular dysfunction.
Other effects:
It reduces peripheral vascular resistance and may cause hypotension due to its ganglionic blocking properties.
Pharmacokinetics:
Procainamide is well-absorbed orally.
Its half life is 2 – 3 hours. Some of the procainamide is metabolized in the liver into N-acetylprocainamide (NAPA). NAPA has the same properties as that of class III agents as it prolongs the duration of action potential.
Therapeutic uses:
It is used in atrial and ventricular arrhythmias and ventricular arrhythmias which comes with acute myocardial infarction.
Adverse effects:
It may cause mental confusion, anorexia, nausea, urinary retention and hepatitis. After prolonged use, it may cause reversible form of lupus erythematosus like syndrome in 20-30 percent of patients. Its toxic dose may cause asystole or instigation of ventricular arrhythmias.
Its effects on CNS include depression, hallucination and psychosis.
Contraindications:
It is contraindicated in patients with AV block or systemic lupus erythematosus.
Dosage:
It is given up to 50 mg/kg daily in divided doses every 3 to 6 hours.
Pharmaceutical Management
The careful management and skillful administration of the business of pharmaceuticals is referred to as Pharmaceutical Management.
Quinidine
It is one of the alkaloids of cinchona also known as beta-quinine (it is an a C-9 epimer of quinine). Quinidine is also referred to as conquinine. It is the most primitive form of class IA drug.
Mechanism of action:
Its most important effect is on Phase 0 of the action potential causing a decrease in rapid depolarization by blocking the sodium channels.
It affects Phase 4 also when there is slow depolarization by slow opening of sodium channels.
Actions:
It causes the inhibition of ventricular arrhythmias, reentry arrhythmia and arrhythmias originating from other than normal place.
Quinidine decreases ectopic pacemaker rate, conduction velocity (negative dromotropism) and excitability especially in depolarized tissue. By decreasing conduction velocity (negatively dromotropic) it causes a promoted effective refractory period in atrial, ventricular and Purkinje fibers.
It increases duration of action potential which along with promoted effective refractory period decreases maximum reentry frequency.
Quinidine has α-adrenoceptor blocking properties which causes vasodilation and a reflex increase in SA nodal rate.
Other effects:
It has
1. antimalarial,
2. antipyretic and
3. oxytocic properties, so that increasing the contractions of the muscles of the womb during childbirth.
Pharmacokinetics:
Quinidine sulfate is well absorbed orally. It is metabolized in the liver by cytochrome p450 enzyme and excreted through the kidneys.
Therapeutic uses:
It is used for
1. Atrial, AV junctional and ventricular tachyarrhythmias
2. Premature atrial and ventricular contractions
3. It has the ability of maintaining sinus rhythm after sudden outburst of atrial fibrillations and flutter
4. Interatrial and atrioventricular nodal reentrant arrhythmias
5. Wolf Parkinson white tachycardia
Adverse effects:
Cinchonism (characterized by headache, tinnitus, photophobia, confusion), Anorexia, Gastrointestinal intolerance (Nausea), Rashes, Hepatitis
It may cause worsening of arrhythmia. It may block SA or AV nodes.
Mechanism of action:
Its most important effect is on Phase 0 of the action potential causing a decrease in rapid depolarization by blocking the sodium channels.
It affects Phase 4 also when there is slow depolarization by slow opening of sodium channels.
Actions:
It causes the inhibition of ventricular arrhythmias, reentry arrhythmia and arrhythmias originating from other than normal place.
Cardiac effects:
High concentration of Quinidine directly affects the cardiac cells whereas low concentrations of Quinidine causes indirect (anti-cholinergic) effects on the heart.Quinidine decreases ectopic pacemaker rate, conduction velocity (negative dromotropism) and excitability especially in depolarized tissue. By decreasing conduction velocity (negatively dromotropic) it causes a promoted effective refractory period in atrial, ventricular and Purkinje fibers.
Quinidine has α-adrenoceptor blocking properties which causes vasodilation and a reflex increase in SA nodal rate.
It has
1. antimalarial,
2. antipyretic and
3. oxytocic properties, so that increasing the contractions of the muscles of the womb during childbirth.
Pharmacokinetics:
Quinidine sulfate is well absorbed orally. It is metabolized in the liver by cytochrome p450 enzyme and excreted through the kidneys.
Therapeutic uses:
It is used for
1. Atrial, AV junctional and ventricular tachyarrhythmias
2. Premature atrial and ventricular contractions
3. It has the ability of maintaining sinus rhythm after sudden outburst of atrial fibrillations and flutter
4. Interatrial and atrioventricular nodal reentrant arrhythmias
5. Wolf Parkinson white tachycardia
Adverse effects:
Cinchonism (characterized by headache, tinnitus, photophobia, confusion), Anorexia, Gastrointestinal intolerance (Nausea), Rashes, Hepatitis
It may cause worsening of arrhythmia. It may block SA or AV nodes.
Classification of the anti-arrhythmic drugs
Detailed Classification of Anti-arrhythmic drugs
Class I (Na+ Channel blockers):Class IA drugs (Fast Channel Blockers):
Quinidine, Procainamide, Disopyramide, Imipramine, Amiodarone, Moricizine, Diphenylhydantoin, Ajmaline, Dronedarone, KB130015
Class IB drugs:
Lidocaine, Tocainide, Mexiletine, Phenytoin
Class IC drugs:
Flecainide, Encainide, Indecainide, Lorcainide, Propafenone
Class II Drugs (β-blockers):
Propranolol, Esmolol, Atenolol, Timolol, Metoprolol, Bisoprolol
Class III Drugs (K-Channel blockers):
Amiodarone, Sotalol, Bretylium, Dofetilide, Ibutilide, N-acetylprocainamide, Almokalant, Nibentan, Nifekalant, Azimilide, AVE0118, Ronalozine
Class IV drugs (Ca-Channel blockers or Slow Channel Blockers):
(V) Verapamil, Diltiazem, Bepridil, Nifedipine
Class V drugs:
Digitalis, Adenosine, Digoxin
Miscellaneous Drugs:
Magnesium, Potassium, BIIB-513, Cariporide, H345/52, SSR149744C, Tecadenoson, Tedisamil, ZP123
Further Reading:
Current Trends in Pharmacology by Ray, A.and Gulati, K. 2007, International Publishing house private Ltd.
Fundamental Approaches to the management of Cardiac Arrhythmias by Sung, R. J. and Lauer, M. R. 2000, Kluwer Academic Publishers.
Physiology and Pharmacology of the Heart by Brown, H.; Kozlowski, R. and Davey, P. 1997, Willey Blackwell.
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.
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.
Subscribe to:
Posts (Atom)
-
Q: What do you know about ergot alkaloids? Ans: These include alkaloids which we get from the ergot fungus Claviceps purpurea or derived ...
-
(For detailed study of Pharmaceutical Incompatibility Click here) Multiple Choice Questions (MCQs) from Pharmaceutical Incompatibility in ...
-
Multiple Choice Questions (MCQs) of Powders and Granules from Pharmaceutics 1. _______ powders consist of more than one ingredients. a. Si...
