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Even less safe are drugs such as digoxin, a cardiac glycoside; its therapeutic index is approximately 2:1. [12] Other examples of drugs with a narrow therapeutic range, which may require drug monitoring both to achieve therapeutic levels and to minimize toxicity, include dimercaprol, theophylline, warfarin and lithium carbonate.
The threshold dose is only a measure of acute toxicity since the drug or toxic substance investigated is administered at once. The consequence of long-term administration remains unknown. [ 27 ] As the threshold dose is the measured minimal response, its accuracy heavily depends on the machinery used.
The botulinum toxin as the most toxic substance known has an LD 50 value of 1 ng/kg, while the most non-toxic substance water has an LD 50 value of more than 90 g/kg; a difference of about 1 in 100 billion, or 11 orders of magnitude. As with all measured values that differ by many orders of magnitude, a logarithmic view is advisable.
Similarly, the MTD is the highest possible but still tolerable dose level with respect to a pre-specified clinical limiting toxicity. [5] In general, these limits refer to the average patient population. For instances in which there is a large difference between the MED and MTD, it is stated that the drug has a large therapeutic window.
Examination for toxidromes, drug testing, or laboratory test may be helpful. Other laboratory test such as glucose, urea and electrolytes, paracetamol levels and salicylate levels are typically done. Negative drug-drug interactions have sometimes been misdiagnosed as an acute drug overdose, occasionally leading to the assumption of suicide. [10]
Assignment to a toxicity class is based typically on results of acute toxicity studies such as the determination of LD 50 values in animal experiments, notably rodents, via oral, inhaled, or external application. The experimental design measures the acute death rate of an agent.
The most effective way to diagnose poisoning is by obtaining a blood paracetamol level. A drug nomogram developed in 1975, called the Rumack–Matthew nomogram, estimates the risk of toxicity based on the serum concentration of paracetamol at a given number of hours after ingestion. [10]
Therapeutic drug monitoring (TDM) is a branch of clinical chemistry and clinical pharmacology that specializes in the measurement of medication levels in blood. Its main focus is on drugs with a narrow therapeutic range, i.e. drugs that can easily be under- or overdosed. [1] TDM aimed at improving patient care by individually adjusting the dose ...