Cardiac glycosides INDEX

The higher the therapeutic index, the safer the drug the lower the therapeutic index, the greater the possibility of toxicity. The therapeutic index for barbiturate as a class is 10, whereas the therapeutic index for cardiac glycoside as a class is 3. Because the usual therapeutic dose of cardiac glycoside is 1 mg, death may result if only 3 mg has been administered. 

The most important and often-used drugs in the treatment of CHF are the cardiac glycosides, which may exist and occur naturally in the body. Unfortunately, the margin of safety for these drugs is very narrow (therapeutic index, 3.0). Toxicity can develop readily, and careful attention to pharmacokinetic principles is absolutely crucial (see Table 12). 

The ratio of the median lethal dose LD and the median effective dose gives the therapeutic index (TI = LD JED, which expresses how safe it is to use the dmg the higher the therapeutic index of a material is, the safer it is. In the case of diazepam (a common sedative), this value is around 100, while for digoxin (a cardiac glycoside), the TI is only 2-3, so the latter must be used very carefully. The actress Judy Garland died in 1969, at the age of 47, because she took too much Seconal, a sedative with small therapeutic index. 

Many aspects of the relationships between dose and effect, particularly as regards time and concentration, were analysed by Qark (1933, 1937). Further statistical analysis showed that the safety of a drug is better established by comparing with LDp namely the dose which cures 99 per cent of the hosts is compared with the dose which kills i per cent of them. Judged by these high standards, several drugs now in use, particularly the cardiac glycosides, are seen to require a substitute with a better Chemotherapeutic Index. 

Other inotropic drugs are necessary not to replace digitalis as much as to supplement in cases of severe heart failure refractory to the glycosides, and in situations where their efficacy is insufficient and the therapeutic index is too low. The clinical goal is to improve the symptoms of cardiac failure by improving left ventricular function or by reducing resistance to the heart s output against the peripheral circulation—or even better—to achieve both. 

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