Cardiac Glycosides in Heart Failure Treatment

Study Notes

Cardiac Glycosides

Cardiac glycosides are plant sterol derivatives that affect myocardial contraction and atrioventricular conduction.
They can be toxic in large doses, causing cardiac arrest in systole, but are important drugs in the treatment of congestive heart failure in lower doses.
They have a diuretic activity, which improves circulation and relieves edema often associated with heart failure.

Properties of Cardiotonic Glycosides

General properties:
- Amorphous powders
- Soluble in water
- Bitter in taste
- Insoluble in organic solvents
- Odourless compounds
- Generally toxic compounds
Physical and chemical properties:
- Soluble in H2O and EtOH
- Aglycones are soluble in organic solvents
- Increase in glycosides increases solubility
- Enzyme & acid hydrolysis
- Elevated temperature results in dehydration of the –OH at C14 with the production of an inactive anhydro-form

Cardiotonic Scaffold

Two types of genin can be distinguished:
- Five-membered lactone ring (cardenolides)
- Six-membered lactone ring (bufanolides/bufadienolides)
Sugar moieties are attached by a C3,β-linkage and composed of up to four sugar units, including glucose, rhamnose, and other deoxy-sugars.

Structural Diversity and Structure-Activity Relationship

Naturally occurring deoxy-sugars (except rhamnose) are unique to cardiac glycosides and relevant to phytochemical testing.
Deoxy sugars associated with cardiac glycosides include:
- 6-deoxy hexose (methyl pentose): rhamnose, fucose, allomethylose
- Methyl pentose-3-methyl-ether: digitalose
- 2,6-deoxy hexose: digitoxose, boivinose
- 2,6-deoxy hexose-3-methyl-ether: cymarose, sarmentose, oleandrose
Cardioactivity is due to aglycone moiety, while pharmacokinetic behavior is influenced by glycone moiety.
The α,β-unsaturated lactone ring is responsible for activity, but saturation decreases potency by 10-fold, and opening results in complete loss of activity.
The cis junction of rings C/D and A/B is necessary for activity, with A/B cis fused rings being more potent than A/B trans.

Description

This quiz covers the effects of cardiac glycosides on the heart, their toxicity, and their role in treating congestive heart failure. It also touches on their diuretic activity and how it improves renal secretion, relieving edema.