Therapeutic Ratio

The therapeutic ratio is an index of the safety of a drug. The way to calculate the therapeutic ratio is to divide the lethal dose (LD50) by the effective dose (ED50) (Figure 2.10). The LD50 is the dose that produces death in 50% of the population. The ED50 is the dose that produces a desired therapeutic effect in 50% of the population. High therapeutic ratios indicate a substantial spread between the lethal dose and the dose required to produce the desired therapeutic effect. Therefore, higher therapeutic ratios usually reflect greater drug safety. For example, the LD50 for morphine is 80 mg in a nontolerant person. The ED50 for morphine to produce analgesia is 10 mg (intramuscularly). Therefore, the therapeutic ratio for morphine is 8, indicating the relative safety of using morphine to produce pain relief. By contrast, the therapeutic ratio for alcohol to produce anesthetic effects is 1. Alcohol's LD50 is a blood level of approximately 0.4% in a nontolerant person. Alcohol's ED50 to produce anesthesia is also 0.4%. Therefore, using alcohol to produce anesthesia for, say, tooth extraction in the 1800s would also have a good chance of killing the patient.

Figure 2.7 A typical example of a drug's dose–response curve. As the dose of the drug increases, its effect increases – up to a certain point.

Figure 2.8 A classic example of an inverted U-shaped dose–response curve. Increasing doses of cocaine progressively increase locomotor activity – up to a point. When the dose gets high enough, locomotor activity starts to decrease. With cocaine, high doses cause stereotyped behavior. [Modified with permission from Baladi MG, Koek W, Aumann M, Velasco F, France CP. Eating high fat chow enhances the locmotor-stimulating effects of cocaine in adolescent and adult female rats. Psychopharmacology, 2012, (222), 447-457.]

Figure 2.9 Comparisons of efficacy and potency between different analgesics. Notice that hydromorphone is more potent than morphine but has similar efficacy. Acetaminophen is both less potent and less effective than the opioid analgesics. [Modified with permission from Levine RR. Pharmacology: Drug Actions and Reactions, 2nd edition. Little, Brown and Company, Boston, 1978.]

Figure 2.10 Example of how to calculate a drug's therapeutic ratio.

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