Medical Pharmacology
Dose-Response Laboratory

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Determination of the ED50 and LD50 of d-tubocurarine

The purpose of this experiment is to have students acquire the data and construct a quantal dose-response curve. Indices of the relative safety of the compound are to be computed and explanations for differences in response to different routes of administration are to be provided.

The laboratory is a computer simulation of a "live" experiment which was performed in previous years.

Each group of students will determine the response to d-tubocurarine at several doses. Groups of five mice will be injected intraperitoneally with various doses of d-tubocurarine. Immediately after each injection, place the mouse at the top of the inclined screen. Observe the mice carefully and record the number of mice in each group which are unable to hold onto the screen. If the mice do not fall to the bottom by the end of the observation period, remove them from the screen and record these as showing no effect. Some of the mice which become paralyzed will also die. These should be recorded as both paralyzed and dead.

Place live mice in the recovery room. Place dead mice in the morgue. The experiment screen on the computer is shown below.

Record the number of mice that respond positively (paralyzed and/or dead) at each dose as well as the number of mice that were administered that dose. In order to obtain the most accurate information the entire class data will be pooled. Plot on linear and semilog graph paper the percent (%) responding at each dose level and determine the ED50. Plot the percent dying at each dose level and determine the LD50. Do this for entire class data.

DOSE	PARALYSIS			DEATH
mg/kg	Group Response (#/5)	Total Class Response (#/Total)	Total Class Percent	Group Response (#/5)	Total Class Response (#/Total)	Total Class Percent
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.8 (oral)

Below are four questions related to the laboratory. Answer each one of them to the best of your ability and return the report no later then the Friday following the laboratory.

1. After plotting the data, determine the Therapeutic Index and Safety Index for d-tubo-curarine.
2. Based on your determination of these indices evaluate the relative safety of this drug, i.e. do you think it is safe. Explain your answer.
3. Curare is used safely in certain medical procedures such as muscle relaxation during surgical anesthesia. Explain why it can be used safely in this circumstance.
4. The drug, d-tubocurarine, was discovered from its use as a poison put on arrows for hunting by native South Americans. Using informatin in the text book and any other appropriate resources explain the results that were obtained when a 0.8 mg/kg dose was given intrapereitoneally compared to when it was given orally.

Copyright © 1998-2004
Department of Pharmacology & Physiology
All rights reserved.
Revised: November 1, 2004