This document discusses cardiotonic drugs, which increase the contractility of the cardiac muscle without increasing oxygen demand. It focuses on two main types - cardiac glycosides like digoxin, and phosphodiesterase inhibitors. Digoxin increases calcium levels in cardiac cells, strengthening contractions. It has a positive inotropic effect and is used to treat heart failure and arrhythmias. The document outlines the mechanisms, effects, dosing, interactions, toxicity and nursing considerations for digoxin and phosphodiesterase inhibitors.

1. Cardiotonics
Dr. Binu Babu
Ph.D., M.Sc. (N), MBA
Mrs. Jincy Ealias
M.Sc. (N)

2. • Cardiotonics are the drugs which increase the
contractility of the cardiac muscle without
increase in the myocardial oxygen demand.
• Also called as ionotropic drugs.
• Commonly used for patients with heart failure.

3. Types
Cardiac glycosides
Eg: digoxin, digitoxin, oubain
Phosphodiesterase -3 inhibitors
Eg: inamrinone, milrinone, levosimendan,
enoximone

5. Introduction
• The word digitalis is used to mean cardiac
glycosides.
• William Withering, an English physician first
described the clinical effects of digitalis in CCF in
1785.
• Obtained from the foxglove plant family.
• Digoxin is the only cardiac glycoside used
clinically, because of its favorable pharmacokinetic
properties.

6. Mechanism of action
Inhibit the enzyme Na+K+ATPase (also called sodium
pump) present on the cardiac myocytes
Accumulation of intracellular Na+
Prevents extrusion Increase Ca++ entry
of Ca++ through Ca++ channels
Increase intracellular Ca++
Increase force and velocity of contraction
Positive ionotropic effect

9. Pharmacological Actions
1. Cardiac actions
2. Extracardiac actions

10. 1. Cardiac actions
• Positive inotropic effect:
▫ Increases force of contraction of heart increases
stroke volume increases cardiac output.
▫ The systole is shortened and the diastole is prolonged
which allows more rest to the heart.
▫ The ventricles are more completely emptied because of
more forceful contractions.
• Heart rate is reduced.
• Effects on electrophysiological properties
▫ Digitalis depresses AV conduction and enhances
automaticity of the ventricles and the Purkinje cells.
• Blood pressure:
▫ No significant effects in CCF patients.
▫ Pulse pressure may increase.
• Improves Coronary circulation
▫ Due to increased cardiac output and prolonged
diastole during which the coronaries get filled better.

11. 2. Extracardiac actions
• Kidney
▫ Diuresis occurs which relieves edema in CCF
patients.
• CNS
▫ High doses stimulate CTZ resulting in nausea and
vomiting.

12. Pharmacokinetics
• Digoxin can be given both oral and parenteral route.
• Digoxin is well-absorbed orally.
• Rapid onset of action within 30-120 minute (orally)
and 5-30 minutes (IV).
• Presence of food in the stomach delays absorption.
• Widely distributed throughout the body and gets
concentrated in heart, skeletal muscles, liver and
kidney.
• Primarily excreted unchanged in the urine, so
precautions to be taken for renal impairment patients.

13. Dose
• The loading dose is 0.75 – 1.25 mg orally or
0.125 – 0.25 mg IV, followed by the maintenance
dose of 0.125 – 0.25 mg/day, orally.

14. Administration
Dilution of digoxin injection:
• Digoxin injection can be administered undiluted
or diluted. Dilute 1 mL of digoxin in 4 mL of
sterile water for injection, D5W, or 0.9% NaCl.

15. Loading dose
• One-half the loading dose given immediately IV
or PO
• One-fourth the loading dose given 8 to 12 hours
later IV or PO
• The remaining one-fourth loading dose given
after an additional 8 to 12 hours IV or PO
• Administer IV slow push over 5 to 10 minutes
• Obtain ECG 6 hours after digitalizing dose to
assess for toxicity
Maintenance dose
• should be started 12 hours after the loading dose
is completed

16. Indications
• CCF
• Arrhythmias
▫ Atrial flutter - reduces the ventricular rate
▫ Atrial fibrillation - reduces the ventricular rate
▫ Atrial tachycardia- digoxin is an alternative to
verapamil.

17. Contraindications
• Hypokalemia - enhances toxicity
• MI, thyrotoxicosis patients and elderly - more
prone to arrhythmias.
• Acid base imbalance - prone to toxicity

18. Adverse effects
Extracardiac:
• First symptoms are;
▫ Anorexia
▫ Nausea
▫ Vomiting
▫ Diarrhea
• Other extracardiac symptoms;
▫ Weakness
▫ Confusion
▫ Hallucinations
▫ Blurred vision
▫ Gynecomastia
Cardiac toxicity
• Arrhythmias
▫ Bradycardia
▫ Ventricular tachycardia
▫ Ventricular fibrillation
▫ AV block
▫ Ventricular extra
systole
▫ Atrial flutter
▫ Atrial fibrillation
▫ Pulses bigeminy

19. Digoxin toxicity
• The usual therapeutic range is 1–2 ng/ml.
• Toxic plasma level is above 2.4 ng/ml.

20. Symptoms
• Anorexia
• Nausea
• Vomiting
• Diarrhea
• Palpitation
• Irregular heart block,
Bradycardia, Junctional
tachycardia
• Confusion
• Lethargy
• Visual changes
▫ Halos or rings of light
around objects
▫ Seeing lights or bright
spots
▫ Changes in colour
perception –especially
yellow, green
▫ Blind spots in vision

21. Treatment of digoxin toxicity
• Stop digitalis.
• Stop diuretics if given concurrently.
• Determine serum digoxin level
• Determine electrolytes, particularly serum K,
Mg, and Ca, and treat any abnormalities
• Oral or parenteral K+ supplements are given.
• Obtain continuous ECG monitoring and treat
arrhythmias

22. • Ventricular arrhythmias are treated with IV
lignocaine.
• Bradycardia is treated with IM/IV atropine.
• Supraventricular arrhythmias is treated with IV
propranolol.
• Gastric lavage for acute toxicity to limit digoxin
absorption.
• In severe toxicity - antidigoxin
immunotherapy (antidigoxin antibodies) IV
infusion (digoxin Fab - digibind) which is an
antidote.
• Digibind IV over 30 minutes.

23. Drug interactions
• Drugs that enhance digoxin toxicity
▫ Diuretics (due to hypokalaemia)
▫ Quinidine
▫ Calcium
▫ Verapamil
▫ Methyldopa
• Drugs that reduce digoxin levels
▫ Antacids, neomycin, metoclopramide- decrease
absorption
▫ Rifampicin, phenobarbitone - accelerate metabolism
due to enzyme induction

25. • Cardiotonic agents
• Eg: inamrinone, milrinone, levosimendan,
enoximone

26. Mechanism of action
Phosphodiesterase -3 isoenzyme (PDE-3)
degrades cyclic adenisine monophosphate (cAMP)
smooth
Increase in myocardial cell cAMP
Increases calcium levels in myocardial cells
Triggers myocardial contraction
Positive ionotropic effect
in heart, blood vessels and bronchial
muscles.
Phosphodiesterase -3 inhibitors block PDE-3

27. Pharmacokinetics
• Given only by IV route.
• Metabolized in the liver and excreted in the
urine.

28. Dose
• Inamrinone
▫ Loading dose is 0.5 mg/kg IV bolus, followed by the
maintenance dose of 5 – 10 μg/kg/min IV infusion,
(max 10 mg/kg in 24 hrs).
• Milrinone
▫ More potent & short lasting with fewer side effects.
▫ Loading dose is 50 mcg/kg IV bolus over 10
minutes, followed by the maintenance dose of
0.375 – 0.75 mcg/kg/min IV infusion.

29. Indications
• Short term management of severe heart failure
• Heart failure refractory to other treatments.

30. Adverse effects
• GIT
▫ Anorexia
▫ Nausea
▫ Vomiting
▫ Abdominal pain
• CVS
▫ Ventricular arrhythmias
▫ Hypotension
▫ Chest pain
• Blood
▫ Thrombocytopenia
• Hypersensitivity
reaction
▫ Vasculitis
▫ Pleuritis
▫ Pericarditis
▫ Ascites

31. Nursing implication
• Serum digoxin estimation at least 4 hrs after IV
dose and 6 hrs after oral dose.
• IV digoxin slowly over 5 minutes.
• Assess the manifestations of digoxin toxicity.
• Hold the digoxin if the heart rate below 60
beats/min.
• Assess electrolyte levels especially potassium,
magnesium.
• Monitor for drug interactions.

32. • Monitor apical pulse for 1 minute before
administering the drug to monitor for adverse
effects.
• Maintain emergency equipment ready.
• IM injection of digoxin should be discouraged,
as absorption is only 80% compared to IV; local
irritation, muscle damage, and necrosis may also
occur