Cardiac glycosides or cardiotonic

Cardiac glycosides class lecture ppt for pharmacy students

1. Cardiotonic drugs Or Cardiac glycosides PREPARED BY- Suresh Kumar Ghritlahare Assist. Professor SRU, Raipur, (C.G.)

2. Cardiac Glycosides These are glycosidic drugs having cardiac inotropic properties and occuring in naturally having both beneficial and toxic effect on the heart and have played oustanding role in the therapy of congestive heart failure (C.H.F.). Cardiac glycosides are found in several plants and in toad skin ( Bufotoxin ). Digitalis lanata is the source of Digoxin , the only glycoside that is currently in use. Others like Digitoxin (from Digitalis purpurea ) and Ouabain (from Strophan thus gratus ), etc. are no longer clinically used or marketed. By convention the term, ‘Digitalis’ has come to mean ‘a cardiac glycoside’.

3. Chemistry The cardiac glycosides consist of an aglycone ( genin ) to which are attached one or more sugar (glucose or digitoxose ) moieties. DIGOXIN Theaglycone consists of cyclopentanoperhydrophenanthrene (steroid) ring to which is attached a 5 or 6 membered unsaturated lactone ring.

4. Source of Cardiac Glycosides S. No. Source Glycosides 1. Digitalis Purpurea (Leaf) Digitoxin , Gitoxin , Gitalin 2. Digitalis lanta (Leaf) Digitoxin , Gitoxin , Digoxin 3. Strophanthus gratus (Seed) Strophanthin -G 4. Thevetia (Nut) Thevetin 5. Convalleria Majalis Convallotoxin 6. Bufo Vulgaris (Toad Skin) Bufotoxin

5. Mechanism of Action Cardiac glycosides basically target myocardium of heart. Cardiac glycosides selectively inhibit Na+/K+ ATpase and decrease availability of Na+ ion at extracellular sites. In response to decrease availability of sodium at extracellular site sodium exchanger get inhibited Increase Ca ++ ion concentration intracellularly also increase sarcolema Ca++ load. Increase force of cardiac contraction is positive inotropic effect.

6. Pharmacological Actions 1. Heart : Digitalis has direct effects on myocardial contractility and electrophysiological properties. Force of contraction: Digitalis causes a dose dependent increase in force of contraction of heart—a positive inotropic action. Rate Heart: rate is decreased by digitalis. Bradycardia is more marked in CHF patients. Electrophysiological properties: Action potential (AP ): The resting membrane potential (RMP) is progressively decreased (to less negative values) with increasing doses. Conduction: A-V conduction is demonstrably slowed by therapeutic doses. ECG : Therapeutic doses of digitalis produce changes in the ECG.

7. Fig: Effect of digitalis on Purkinje fibre action potential

8. Blood vessels: Digitalis has mild direct vasoconstrictor action—peripheral resistance is increased in normal individuals. 3. Kidney: The retained salt and water is gradually excreted. No diuresis occurs in normal individuals or in patients with edema due to other causes. 4. CNS: Digitalis has little apparent CNS effect in therapeutic dose. Higher doses cause CTZ activation → nausea and vomiting.

9. Pharmacokinetics Absorption: Bioavailability of digoxin tablets from different manufacturers may differ. Presence of food in stomach delays absorption of digoxin . Distribution: The volume of distribution of digoxin is large (6–8 L/Kg). It is concentrated in the heart (~20 times than plasma), skeletal muscle, liver and kidney. Metabolism: Metabolized by liver Excretion: Digoxin is primarily excreted unchanged by the kidney:

10. Adverse Effects Extracardiac : Anorexia, nausea, vomiting and abdominal pain are usually reported first: are due to gastric irritation, mesenteric, CTZ stimulation. Fatigue, malaise, headache , mental confusion, restlessnessetc . Cardiac: Almost every type of arrhythmia can be produced by digitalis: pulsus bigeminus , nodal and ventricular extrasystoles , ventricular tachycardia and terminally ventricular fibrillation.

11. Contraindications Hypokalemia Elderly, renal or severe hepatic disease Myocardial ischaemia Myxoedema : Ventricular tachycardia Acute myocarditis

12. Uses 1 . Congestive heart failure: Systolic dysfunction: The ventricles are dilated and unable to develop sufficient wall tension to eject adequate quantity of blood. Diastolic dysfunction :The ventricular wall is thickened and unable to relax properly during diastole; ventricular filling is impaired because of which output is low. 2. Cardiac arrhythmias Atrial fibrillation (AF) Atrial flutter (AFI) Paroxysmal supraventricular tachycardia (PSVT)

13. REFERENCES Tripathi KD, “Essentials of Medical Pharmacology” published by Jaypee Brothers Medical Publishers (P) Ltd, Seventh Edition: 2013, New Delhi, p.p. no-512-519.

14. Thank you.. !!