Digitalis

5. Foxgloves or purpurea
Foxgloves or purpurea
Growing in England
cultivated in India
Roots , leaves , seeds
contains several
poisonous glycosides

7. +
+
Genin ( active part )
(steroid nucleus + lactone ring)
Sugar
( physical properties)
The term digitalis is
used to refer to entire
group of cardiac
glycosides.
The most important
are: Digoxin, digitoxin
and ouabain

10. Increase contractility
Of cardiac cell
by
increasing free Ca++
concentration
BY
Inhibition of Na+/K+ ATPase
increase in intracellular Na+
increase intracellular Ca++
It directly facilitates entry
of Ca++ to cardiac cells
Increase release of
Ca++ from sarcoplasmic
reticulum
1
2
3

13. Vagal actions Sympathetic actions
Sensitization of baroreceptors
in aortic arch & carotid sinus
Stimulation of central
vagal nuclei
Sensitization of cholinergic
receptors in the heart
Decrease sensitivity
of SAN and AVN to
-stimulation
β
but in
toxic doses
increase
sympathetic activity
Autonomic action

15. Contractility: strong positive inotropic effect
Cardiac output
Heart rate : due to
Vagal causes:
- Reflex vagal stimulation due to
sensitization of baroreceptors.
-Central vagal stimulations.
- Inhibition of A-V conduction.
Extravagal causes:
-Bainbridge reflex is abolished due to
relieved venous congestion.
-Direct effect on conducting system
-The relative hypoxia

16. Excitability
•Small dose enhance cardiac excitability,
•large dose ….depress it.
Automaticity
•large dose, increase ability to develop
ectopic foci .. Extrasystole
•Effect of digitalis on E.C.G
•Depression of S-T segment and inversion of
‘T’ wave (the earliest changes).
•prolonged P-R interval , short Q-T interval
•Arrhythmias of different types.

17. Blood pressure:
•in heart failure with hypotension digitalis
normalizes blood pressure.
Effect on veins and venous pressure:
•reduces venomotor tone and increases the
venous capacity.
•reduces venous pressure in patient with CHF
secondary to positive inotropic action.
Effect on coronary circulation:
•Toxic doses may produce coronary constriction

19. Heart failure not
respond to diuretics
Absolute Indications
Chronic congestive heart failure
associated with atrial fibrillation
Atrial fibrillation
Atrial flutter
Paroxysmal atrial
tachycardia
Relative Indications

25. Accidental Sucidal Homocidal
overdosechildren
Eating plant
By mistake
Chronic
toxicity

26. Therapeutic dose
Fatal dose
Fatal period
0.5 – 2
ng\ml
2-4 mg
digoxin
0.5 - 24
H

27. Risk factors
•Decreased tolerance to the drug
•Hypokalemia , hypernatremia ,
hypomagnesemia
•Medications that interact with digitalis such as
quinidine, verapamil, amiodarone, and others.
•Reduced kidney function will cause digitalis to
build up in the body rather than be removed
normally through urine.
•Advanced age > 80

29. GIT
Nausea vomiting
diarrheaanoroxia
Abdominal pain
The earliest

30. cvs
Dysrhthmia associated
With increase automaticity
and decrease AV conduction
( torsade de points )
-Premature ventricular contraction
- sinus bradycardia
- variable degrees of heart block
- atrial fibrillations
- ventricular tachycardia
- cardiac arrest on systole

31. CNS
headache Malaise
confusion muscle weakness delirium
drowsiness parasthesia
hallucination

32. VISUAL changes
halos
blurred vision amblyopia
Yellow vision scotoma
diplopia

34. Investigations
•ECG is done to check for irregular heart
beats.
•Blood tests will be done to check:
•BUN and creatinine (which help reveal
kidney function)
•Digoxin and digitoxin levels
•Potassium level
•Magnesium level

36. Emergency & supportive measures
Stop it
Lidocaine
for arrhythemia
Maintain open airway
Maintain patient at least
for 12-24 H
Atropine 0.5-2 mg IV
for bradycardia

37. Decontamination
* Syrap ipecac within
Few minutes
* activated charcoal
After 60 minutes
Activated charcoal
I gm\kg
To decrease intestinal
absorption of diditalis
Pre-hospital Hospital Cholestyramine

38. Specific drugs & Antidotes
( FAB)
What is FAB ?
- sterile, purified, lyophilized
preparation of
digoxin-immune ovine Fab
(monovalent) immunoglobulin
fragments
- obtained from the blood of healthy
sheep immunized with a digoxin
derivative
- have a molecular weight of
approximately 46,000 Da.

39. Mechanism of Action of digifab
-DigiFab has an affinity for digoxin in the
range of 109 to 1010 M-1, which is greater
than affinity of digoxin for its sodium
pump receptor, the presumed receptor for
its therapeutic and toxic effects.
- When administered to the intoxicated
patient, DigiFab binds to molecules of
digoxin reducing free digoxin levels, which
results in a shift in the equilibrium away fro
binding to the receptors, thereby reducing
cardio-toxic effects.
- Fab-digoxin complexes are then cleared
by kidney and reticuloendothelial system.

40. indications of DigiFab
•Known suicidal or accidental consumption of fatal doses of digoxin,
including ingestion of 10 mg or more of digoxin in previously
healthy adults, 4 mg (or more than 0.1 mg/kg) in previously healthy
children, or ingestion causing steady state serum concentrations
greater than 10 ng/mL
•Chronic ingestions causing steady-state serum digoxi concentrations
exceeding 6ng/mL in adults or 4 ng/mL in children
•Manifestations of life-threatening toxicity due to digoxin overdose,
including severe ventricular arrhythmias (such as ventricular
tachycardia or fibrillation), progressive bradycardia, and second or
third degree heart block not responsive to atropine, serum
potassium levels exceeding 5.5 mEq/L in adults or 6 mEq/L in
children with rapidly progressive signs and symptoms of digoxin
toxicity.

41. Side effects of digifab
•Exacerbation of low cardiac output states
and congestive heart failure due to
withdrawal of inotropic effect of digitalis.
•Hypokalemia due to reactivation of the
sodium-potassium ATPase
•Rapid ventricular response in patients
with atrial fibrillation due to withdrawal
of effects of digitalis on the
atrioventricular node.
•Rare allergic reactions in Patients with a
history of allergy, especially to antibiotics,
appear to be at particular risk

42. Calculation of Dose
In Digoxin ..
Dose =
(Serum digoxin concentration in ng/mL)
(weight in kg)

100 In Digitoxin ..
Dose =
(Serum digitoxin concentration in ng/mL) (weight in kg)
1000

43. * Useful only in digitoxin toxicity due to
low volume of distribution
* Not effective in digoxin toxicity due to
high volume of distribution
Enhanced Elimination

45. •A 96-year-old African American female (AAF) was admitted from a
nursing home with complaints of abdominal pain, nausea and vomiting
(N/V), dizziness, confusion and double vision for 5 days. She was
discharged from the hospital just 4 days ago. Digoxin was started
during that previous hospitalization for control of tachycardia in atrial
fibrillation. One day prior to discharge, digoxin level was 1.8 mg/mL
and digoxin dose was decreased to 125 mcg PO Q 48 hr.
Past medical history (PMH)
Hypertension, atrial fibrillation, coronary artery disease, stroke, congestive
heart failure.
Medications
Metoprolol, digoxin, (aspirin), lisinopril, furosemide (warfarin), esomeprazole
Physical examination
In pain, combative and confused.
Chest: Occasional bibasilar crackles.
Cvs : Clear S1 and S2, irregularly irregular rhythm, HR 101 bpm.
Abdomen: Soft, epigastric tenderness, no rebound, + BS.
Extremities: No edema.

46. What would you do?
Stop digoxin.
Monitor digoxin levels.
Control symptoms.
Sitter in the room.
What happened?
The initial digoxin level was elevated at nearly twice the upper
therapeutic level. All symptoms resolved as digoxin level decreased
to therapeutic range. Heart rate was controlled by increasing
metoprolol dose.
She was discharged back to the nursing home in good condition.
Final diagnosis
Digoxin toxicity.

47. -Toxicology book of mansoura univerisity
-pharmacology book of mansoura
univerisity
-Health guide website
-Medscape website
Referances