The drug’s Therapeutic Index (TI) identifies the margin of safety of the drug
and is a ratio between the therapeutic dose in 50% of persons/animals and the
lethal dose in 50% of animals. The therapeutic dose is notated as ED 50 and
the lethal dose in animals is noted as LD 50. The closer that the ratio is to 1, the
greater the danger of toxicity.
TI=LD 50 /ED 50Drugs that have a low TI are said to have a narrow margin of safety. These
drugs require that levels in the plasma be monitored and adjustments are made
to the dosage in order to prevent a toxic effect from occurring.
The plasma drug levels must be within the therapeutic range, which is also
known as the therapeutic window. The therapeutic range is between the mini-
mum effective concentration (MEC) for obtaining the desired pharmaceutical
response and the minimum toxic concentration (MTC). MEC is achieved by
administering a loading dose, which is a large initial dose given to achieve a
rapid plasma MEC.PEAK AND TROUGH LEVELS
The plasma concentration of a drug must be monitored for drugs that have a nar-
row margin of safety or low therapeutic index. The concentration is measured at
two points. These are the peak drug level and the trough level.
The peak drug level is the highest plasma concentration at a specific time.
Peak levels indicate the rate a drug is absorbed in the body and is affected by the
route used to administer the drug. Drugs administered intravenously have a fast
peak drug level while a drug taken orally has a slow peak drug level because the
drugs needs time to be absorbed and distributed. Blood samples are drawn at
peak times based on the route used to administer the drug. This is usually^1 ⁄ 2 to
1 hr after drug administration.
The trough level is the lowest plasma concentration of the drug and measures
the rate at which the drug is eliminated. Blood should be drawn immediately
before the next dose is given regardless of the route used to administer the drug.Side Effects
A drug can have a side effect in addition to its pharmaceutical response. A side
effect is a physiologic effect other than the desired effect. Sometimes side effects(^36) CHAPTER 2 Drug Action and Drug Interactions