Foxgloves or purpureaFoxgloves or purpurea

Growing in England cultivated in India

Roots , leaves , seeds contains several

poisonous glycosides

+

+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

Increase contractilityOf cardiac cell

by increasing free Ca++

concentration

BY

Inhibition of Na+/K+ ATPaseincrease 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

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

β-stimulation but in toxic doses

increase sympathetic activity

Autonomic action

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

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.

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

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

Accidental Sucidal Homocidal

overdose children Eating plant By mistake

Chronic toxicity

Therapeutic dose

Fatal dose

Fatal period

0.5 – 2 ng\ml

2-4 mg digoxin

0.5 - 24 H

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

GIT

Nausea vomiting

diarrhea anoroxia

Abdominal pain

The earliest

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

CNS

headache Malaise

confusion muscle weakness delirium

drowsiness parasthesia

hallucination

VISUAL changes

halos

blurred vision amblyopia

Yellow vision scotoma

diplopia

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

Emergency & supportive measures

Stop it

Lidocaine for arrhythemia

Maintain open airwayMaintain patient at least

for 12-24 H

Atropine 0.5-2 mg IV for bradycardia

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

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.

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.

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.

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

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

* Useful only in digitoxin toxicity due to low volume of distribution

* Not effective in digoxin toxicity due to high volume of distribution

Enhanced Elimination

• 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.

MedicationsMetoprolol, 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.

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 diagnosisDigoxin toxicity.

- Toxicology book of mansoura univerisity

- pharmacology book of mansoura univerisity

- Health guide website- Medscape website

Referances