Digitalis purpurea, also known as foxglove, contains cardiac glycosides including digoxin. It increases the force of heart contractions and is used to treat heart failure and irregular heartbeats. Its mechanism of action involves inhibiting the sodium-potassium pump in cardiac cells, increasing intracellular calcium levels and strengthening muscle contractions. It has a narrow therapeutic window, and signs of toxicity include nausea, vomiting, fatigue and arrhythmias at higher serum concentrations above 1.2 ng/mL.

2.  Prepared by
DR ABDUL SAMI
MPHIL EASTERN MEDICINE
THE ISLAMIA UNIVERSITY OF BAHAWALPPUR
PAKISTAN

3. Digitalis

4.  biological name:
Digitalis purpurea
 English name:
foxglove,purple foxglove ,
fairygloves,folia digitalis.

5.  Family:
scrophulariaceae
 Taste:
bitter
 Odour
distinct,characteristic

6.  Digitalis is a cardiac glycoside.it increases the force
of systolic contraction.
 Chemical constituents:
 there are 35 glycosides present in digitalis.
 Digitoxin
 Gitoxin
 Gitaloxin
 Purpurea glycoside A & B
 Inositol,luteolin,digitoflavon,digitonin.

7.  Chemical structure of digitoxin:

8. pharmacological action
 Digoxin is used to treat heart failure.
 used to treat a certain type of irregular heartbeat
(chronic atrial fibrillation).
 Treating heart failure may help maintain your ability
to walk and exercise and may improve the strength
of your heart.
 Treating an irregular heartbeat can decrease the risk
for blood clots, an effect that may reduce your risk
for a heart attack or stroke.
 This reduces strain on the heart and helps it
maintain a normal, steady, and strong heartbeat.

9. Therapeutic Uses
 Heart failure
 Digitalis compounds have been used in the treatment of
chronic heart failure owing to their cardiotonic effect.
digoxin, when used in conjunction with diuretics and
vasodilators, improves cardiac output and ejection
fraction, and reduces filling pressures and pulmonary
capillary wedge pressure (this reduces pulmonary
congestion and edema); heart rate changes very little.
 Digitalis compounds have a small direct diuretic effect
on the kidneys, which is beneficial in heart failure
patients.

10.  Atrial fibrillation and flutter:
 Atrial fibrillation and flutter lead to a rapid
ventricular rate that can impair ventricular filling
(due to decreased filling time) and reduce cardiac
output.
 Digitalis compounds, such as digoxin, are useful for
reducing ventricular rate.
 The mechanism of this beneficial effect of digoxin is
its ability to activate vagal efferent nerves to the
heart (parasympathomimetic effect).

11.  Vagal activation can reduce the conduction of
electrical impulses within the atrioventricular
node to the point where some of the impulses will be
blocked. When this occurs, fewer impulses reach the
ventricles and ventricular rate falls. Digoxin also
increases the effective refractory period within the
atrioventricular node.

12. Mechanism of action
 Digitalis compounds are potent inhibitors of cellular
Na+/K+-ATPase. This ion transport system moves
sodium ions out of the cell and brings potassium ions
into the cell. This transport function is necessary for
cell survival because sodium diffusion into the cell
and potassium diffusion out of the cell down their
concentration gradients would reduce their
concentration differences (gradients) across the cell
membrane over time. Loss of these ion gradients
would lead to cellular depolarization and loss of the
negative membrane potential that is required for
normal cell function.

13.  Cardiac myocytes, as well as many other cells, have a
Na+-Ca++ exchanger (not an active energy-requiring
pump) that is essential for maintaining sodium and
calcium homeostasis. The exact mechanism by which
this exchanger works is unclear. It is known that
calcium and sodium can move in either direction
across the sarcolemma. By inhibiting the Na+/K+-
ATPase, cardiac glycosides cause intracellular
sodium concentration to increase.

14.  This then leads to an accumulation
of intracellular calcium via the Na+-Ca++ exchange
system. In the heart, increased intracellular calcium
causes more calcium to be released by
the sarcoplasmic reticulum, thereby making more
calcium available to bind to troponin-C, which
increases contractility (inotropy). Inhibition of the
Na+/K+-ATPase in vascular smooth muscle causes
depolarization, which causes smooth muscle
contraction and vasoconstriction.

16. Pharmacokinetics
 Absorption:
 Following oral administration, peak serum
concentrations of digoxin occur at 1 to 3 hours.
 Patients with malabsorption syndromes (e.g., short
bowel syndrome, celiac sprue, jejunoileal bypass)
may have a reduced ability to absorb orally
administered digoxin.
 Distribution:
 Following drug administration, a 6-to 8-hour tissue
distribution phase is observed.

17.  Digoxin crosses both the blood-brain barrier and the
placenta. At delivery, the serum digoxin
concentration in the newborn is similar to the serum
concentration in the mother.
 Metabolism:
 Only a small percentage (13%) of a dose of digoxin is
metabolized in healthy volunteers. The metabolism
of digoxin is not dependent upon the cytochrome P-
450 system, and digoxin is not known to induce or
inhibit the cytochrome P-450 system.

18.  Excretion:
 Elimination of digoxin follows first-order kinetics
(that is, the quantity of digoxin eliminated at any
time is proportional to the total body content).
 Digoxin is not effectively removed from the body
by dialysis, exchange transfusion, or
during cardiopulmonary bypass because most of the
drug is bound to extravascular tissues.

19.  Side Effects and Warnings:
 The major side effect of digitalis compounds is
cardiac arrhythmia, especially atrial tachycardias
and atrioventricular block.
 Lean, elderly patients are more susceptible to
digitalis toxicity because they often have reduced
renal function, and their reduced muscle mass
increases plasma digoxin levels at a given dose
because muscle Na+/K+-ATPase acts as a large
binding reservoir for digitalis.

20.  Dosing:
 Traditional dosage starts at 1.5 g of leaf divided into
2 daily doses. Purified digoxin is typically used at
daily doses of 0.125 to 0.25 mg.
 Contraindications:
 In pregnancy and lactation.
 Hypokalemic pt.
 pt. who have atrioventricular block.
 Do not allow children to come into contact with the
potentially lethal plant.

21. toxicity
 Digoxin toxicity is related to serum concentration. As
digoxin serum levels increase above 1.2 ng/mL, there
is a potential for increase in adverse reactions.
 In adults with heart disease, clinical observations
suggest that an overdose of digoxin of 10 to 15 mg
results in death of half of patients.
 The most common signs and symptoms of digoxin
toxicity are
 nausea & vomiting
 anorexia and fatigue

22. Specific preparations