Cardiotonics

Pharmacology for Nurses

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

4. Cardiac glycosides

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

7. Pharmacological Actions Cardiac actions Extracardiac actions

8. 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 .

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

10. 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.

11. 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.

12. 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 .

13. 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

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

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

16. 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

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

18. 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

19. 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

20. 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.

21. 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

22. Phosphodiesterase -3 inhibitors

23. Cardiotonic agents Eg : inamrinone , milrinone , levosimendan , enoximone

24. Mechanism of action Phosphodiesterase -3 isoenzyme (PDE-3) degrades cyclic adenisine monophosphate ( cAMP ) in heart, blood vessels and bronchial smooth muscles.

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

26. 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.

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

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

29. 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.

30. 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

31. Thank you