NAME THAT DRUG SUBMITTED BY QUEST DIAGNOSTICS
Long on History, Short on Pain T
his edition of Name Tat Drug in- volves a synthetic drug of World War II origins. Its roots in Nazi Germany
should narrow the list of potential suspects. Originally developed by Max Bockmuhl
and Gustav Ehrhart at IG Farben, this group of scientists, and others involved in the German war effort, experimented with many different combinations of drugs that led to a variety of unique discoveries. Many did not meet the objective of aiding the war effort and were filed away. Te drug in question is one such “forgoten” discovery. With the onset of WWII, morphine
and other analgesics were needed to treat injured soldiers coming in from the front lines. Unfortunately, the supply of mor- phine was unsteady during war-time and Germany needed something that could be manufactured from easily obtained precursors. Tested as a morphine sub- stitute, this compound was found to be lacking the same morale-boosting affects as plant-derived morphine even though its analgesic properties were very good. Be- cause of the poor initial results, this drug was tossed aside. Aſter the war was over, the Allies went through all the German records and began experimenting with the “spoils of war”. Tis drug was found and eventually sold to Eli Lily who began selling it in 1947. Although now available in generic forms, it was originally sold in 5 mg and 10 mg dosages. Te mystery drug belongs to the opioid
family even though its two-dimensional structure bears litle similarity to any of the classical poppy plant alkaloids. It is very similar in structure and composition to another familiar and troublesome drug, propoxyphene (Darvon®). Te pharmacological effects, analgesic
effects and duration of action are extraordi- narily similar to morphine. Like morphine,
54 datia focus
this drug causes an increase in intestinal tone with a corresponding decrease in intestinal motility. Unlike morphine, this drug has considerable analgesic effective- ness when administered orally. Te half-life of this drug is approximately 24-36 hours but is highly variable. It is oxidatively me- tabolized to a stable metabolite, 2-ethyli- dene-1,5-dimethyl-3,3-diphenylpyrrolidine by cytochrome P450 2B6, 3A4, and 2C19. Tese enzyme isoforms do not metabolize the isomers of the drug at the same rate, ac- counting for the widely variable metabolite profiles and concentrations found in indi- vidual users. It is thought that this could be a possible explanation for the variable dose- response observations seen in patients administered the drug. Tese variations have led to the prescribing guidance of “start low, go slow” approach. Metabolism is extensive with only about 20–25 percent of the drug excreted unchanged in the urine. Te rate of urinary elimination can be increased by urinary acidification. Te parent drug is extensively bound to plasma proteins and various tissue proteins, includ- ing the brain. Tis is thought to explain the persistence of low plasma concentrations of the drug aſter cessation of treatment. Te drug is primarily used for its analge-
sic properties for the relief of pain and the treatment of opioid abstinence syndrome. It is seldom used for its effects on the gas- trointestinal tract (antiperistaltic) or its ef- fects on cough (antitussive). Te treatment of opioid withdrawal is based on the drug’s ability to bind to the µ-opioid receptors in the brain and suppress the symptoms of withdrawal in physically dependent individuals. Its outstanding property of oral efficacy and extended duration of action make it suitable for use in outpatient type setings. It is supplied in tablets, solutions for oral administration and as a solution for
spring 2013
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