# 13 - 2. Indices of safety and efficacy

# 2. Indices of safety and efficacy:

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2. Indices of safety and efficacy: 
Quantal or dose-response curves: Quantal curves plot the percentage of a population showing a 
specified, predefined categorical drug effect against the dose or log dose administered. The doseresponse curve plots the drug concentration against the continuous effects of the drug. 
Using these curves, the median effective dose, or median toxic doses can be determined. The 
median toxic dose is the dose at which 50% of patients experience a specific toxic effect, and the 
median effective dose is the dose at which 50% of patients have a specified therapeutic effect. 
In addition, using these curves the range of intersubject variability in drug response could be 
studied. Steep D-R curves reflect little variability; flat D-R curves indicate great variability in 
patient sensitivity to the effects of a drug. The therapeutic index can be determined using these 
curves. 
Therapeutic index: It is the relative measure of the toxicity or safety of a drug. It is defined as the 
ratio of the median toxic dose to median effective dose. In other words, it is the ratio of the 
minimum plasma concentration causing toxic effects to that causing a therapeutic effect. This can 
vary according to the toxic symptom specified for a given drug. For example, the gastrointestinal 
toxicity of lithium can occur at a lower plasma concentration than that for seizures. In the 
laboratory this is usually determined using the median lethal (LD50) and median toxic dose 
(TD50) in animal studies. In humans, this is identified using ‘minimal’ effective and ‘minimal’ 
toxic doses using trial data. Note that the term therapeutic index is only relevant when 
considering dose-dependent side effects; it is not useful when studying idiosyncratic reactions. 
Therapeutic index range: Certain drugs such as lithium, carbamazepine and phenytoin have a 
narrow range of plasma levels within which the efficacy is optimum and toxicity is less evident; 
crossing this range on higher side will increase toxicity while on the lower range will reduce 
efficacy. Drugs with the low therapeutic index or narrow therapeutic range will require plasma 
monitoring. 
Therapeutic window: This term is often confused with therapeutic safety range. In fact, this term 
is used to describe a specified plasma concentration value, only within which certain drugs 
appear to have a therapeutic efficacy. This does not concern the side effects or toxicity. 
Imipramine, nortriptyline, and desipramine have a curvilinear relationship when plasma levels 
are plotted against the therapeutic response, i.e. very high or very low levels do not help the 
patient.