PHAR 340 Lecture Notes - Lecture 3: Median Lethal Dose, Median Toxic Dose, Stereospecificity
19 Sep 2019
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Dose that elicits response in 50% of individuals. Dose that elicits toxicity in 50% of individuals. Dose that is lethal in 50% of individuals. Want curves to be far apart so theres a high td50 with a large window for drug to be effective before toxicity. Want to be large, toxic dose much higher than therapeutic e. g. diazepam (ti = 70) and digoxin (ti = 2) Not all respond at dose that kills them. Drug structure, receptor distribution, drug distribution, interspecies differences. If the target receptor is found in another part of the body and causes a bad effect, not good. Often test drugs on other animals but there may be receptor differences, can"t extrapolate to humans e. g. antibiotics attack microbes but not patient. Stereospecificity, bulky groups/steric hindrance, molecular rigidity, polarity/charge, atom substitutions. One 3d structure has activity while another doesn"t. One stereoisomer won"t interact with the receptor properly. How were ace inhibitors developed? e. g. l vs d norepinephrine.
