PPT On Digoxin

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Digoxin Presentation Transcript:
1.Digoxin  , also known as digitalis, is a purified cardiac glycoside extracted from the foxglove plant, Digitalis lanata .Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin. Digoxin is widely used in the treatment of various heart conditions, namely atrial fibrillation, atrial flutter and sometimes heart failure that cannot be controlled by other medication. Digoxin preparations are commonly marketed under the trade names Lanoxin, Digitek, and Lanoxicaps.

2.Basics of kinetics:
Bioavailability
60 to 80% (Oral)
Protein binding capability
Hepatic (16%)
Half-life:
    36 to 48 hours(patients with normal renal function) 3.5 to 5 days(patients with impaired renal function)
Excretion:Renal
Routes:Oral, Intravenous

3.MECHANISM OF ACTION:
Digoxin binds to a site on the extracellular aspect of the a-subunit of the Na+/K+ ATPase pump in the membranes of heart cells (myocytes) and decreases its function. This causes an increase in the level of sodium ions in the myocytes, which leads to a rise in the level of intracellular calcium ions. This occurs because of a sodium/calcium exchanger on the plasma membrane, which depends on a constant inward sodium gradient to pump out calcium. Digoxin decreases sodium concentration gradient and the subsequent calcium outflow, thus raising the calcium concentration in myocardiocytes and pacemaker cells.
Increased intracellular calcium lengthens Phase 4 and Phase 0 of the cardiac action potential, which leads to a decrease in heart rate. Increased amounts of Ca2+ also leads to increased storage of calcium in the sarcoplasmic reticulum, causing a corresponding increase in the release of calcium during each action potential. This leads to increased contractility, the force of contraction, of the heart.
There is also evidence that digoxin increases vagal activity, thereby decreasing heart rate by slowing depolarization of pacemaker cells in the AV node. . This negative chronotropic effect would therefore be synergistic with the direct effect on cardiac pacemaker cells. Digoxin is used widely in the treatment of various arrhythmias

4.Today, the most common indications for digoxin are probably atrial fibrillation and atrial flutter with rapid ventricular response, but beta- or calcium channel- blockers should be the first choice.High ventricular rate leads to insufficient diastolic filling time. By slowing down the conduction in the AV node and increasing its refractory period, digoxin can reduce the ventricular rate. The arrhythmia itself is not affected, but the pumping function of the heart improves owing to improved filling.
The use of digoxin in heart problems during sinus rhythm . In theory the increased force of contraction should lead to improved pumping function of the heart. Digoxin is no longer the first choice for congestive heart failure, but can still be useful in patients who remain symptomatic despite proper diuretic and ACE inhibitor treatment. It has fallen out of favor because it was proven to be ineffective at decreasing morbidity and mortality in congestive heart failure

5.USE OF DIGOXIN IN HEART FAILURE:
Patients with more severe heart failure, a third heart sound gallop, left ventricular enlargement and a depressed left ventricular ejection fraction are more likely to respond to digoxin therapy.
Many compensatory mechanisms, including the sympathetic nervous system and salt- and water-retaining systems, become activated in the setting of a depressed cardiac output. The compensatory systems can maintain left ventricular function for days to months. However, when patients become overtly symptomatic, they begin to experience a striking increase in morbidity and mortality. The transition to symptomatic heart failure is accompanied by further activation of the neurohormonal system, including the sympathetic nervous system and a series of adaptive changes in the myocardium.
Digoxin-Induced Neurohormonal Modulation
In the past, digoxin was considered to be solely a positive inotropic agent. In patients with heart failure, digoxin exerts its positive inotropic effect by inhibiting sodium-potassium adenosine triphosphatase (ATPase). Inhibition of this enzyme in cardiac cells results in an increase in the contractile state of the heart.  it has been shown that digoxin exerts a positive inotropic effect at higher dosages (0.25 mg or more per day); however, at lower dosages (less than 0.25 mg per day), this drug exerts a mainly neurohormonal effect and has little inotropic activity.21
The neurohormonal effect of digoxin  showed that digoxin reduced plasma norepinephrine levels; these results were validated in other studies.The explanation for this effect was that digoxin improves impaired baroreceptor reflexes in heart failure.
Digoxin may also lower plasma renin levels, either because of a direct renal effect or secondary to inhibition of sympathetic activity. By inhibiting sodium-potassium ATPase in the kidney, digoxin decreases renal tubular reabsorption of sodium, thereby increasing delivery of sodium to the distal tubules and suppressing renin secretion.

6.DIGOXIN THERAPY IN CONGESTIVE HEART FAILURE:
Digoxin has been shown to improve morbidity without any benefit on mortality.
Digoxin may act by decreasing sympathetic activity.
Digoxin may not be effective in patients who have normal left ventricular systolic function.
The benefits of digoxin therapy are greatest in patients with severe heart failure, an enlarged heart and a third heart sound gallop.
Digoxin may be used in patients with mild to moderate heart failure if they do not respond to an angiotensin-converting enzyme inhibitor or a beta blocker.
Low dosages of digoxin can be effective.
Renal function and possible drug interactions must be considered in deciding on an appropriate dosage of digoxin.
In general, digoxin therapy should be avoided in the acute phase after myocardial infarction.

7.ATRIAL FIBRILLATION:
Atrial fibrillation (AF) is the most common type of heart arrhythmia. An arrhythmia is a problem with the rate or rhythm of the heartbeat.
Atrial fibrillation occurs when rapid, disorganized electrical signals cause the atria to fibrillate (contract very fast and irregularly). When this happens, the heart's upper and lower chambers don't work together as they should.

8.ATRIAL FLUTTER:
Atrial flutter refers to rapid and regular contractions (usually in the range of 120 to 350 times each minute) that is characterised on the ECG by a saw-tooth appearance. Not all atrial contractions are necessarily conducted to the ventricles due to a variable block within the atrioventricular node. When conduction to the ventricles does occur, the QRS complex morphology is regular but RR intervals may be random or follow a specific pattern.

9.DOSING AND TDM of Digoxin:

10.BIOAVALABILITY FACTOR (F)OF DOSAGE:

11.CRCL-BASED MAINTANCE DOSAGE AND INTERVAL ADJUSTMENT:

12. DOSING :
Digoxin may be taken with or without food. Digoxin is primarily eliminated by the kidneys; therefore, the dose of digoxin should be reduced in patients with kidney dysfunction. Digoxin blood levels are used for adjusting doses in order to avoid toxicity. The usual starting dose is 0.0625-0.25 mg daily depending on age and kidney function. The dose may be increased every two weeks to achieve the desired response.

13.Usual pediatric dose in atrial fibrillation:

14. DOSE ADJUSTMENTS:
If patients are switched from intravenous to oral formulations, allowances must be made for differences in bioavailability when calculating maintenance dosages. When changing from oral formulations to IM or IV therapy, dosage should be reduced by 20% to 25%.
Divided dosage of the capsule formulation is preferred in patients that require a daily dose greater than 300 mcg, those with a previous history of digitalis toxicity, and in patients who may be more likely to become toxic.

15. GENERAL ADVICE:
Calculate doses based upon lean (ideal) body weight.
Consider the differences in bioavailability between digoxin injection, tablets, and oral solution when changing patients from one dosage form to another.
For IV administration, digoxin injection may be diluted (4-fold or more) with normal saline, dextrose 5% in water, or sterile water for injection. Infuse slowly, 5 min or longer.
IM injection can lead to severe pain at the injection site. If the drug must be administered IM, inject it deeply into the muscle and follow with massage. Do not inject more than 2 mL (500mcg) into a single site.