Fentanyl distribution

G. Duarte, and S.P. da Cunha. Pharmacokinetics and transplacental distribution of fentanyl in epidural anesthesia for normal pregnant women. Eur I Clin Pharmacol. 61 517-522 (2005). 

The interior volume of the theater, estimated from illustrations, was probably less than three hundred thousand cubic feet, i.e., about 10,000 cubic meters. Based on doses used for anesthesia, a concentration of as little as 2-3 mg per cubic meter of a super-potent Fentanyl derivative might be sufficient for a building that size, if instantaneous incapacitation is not required. This assumes continuous inhalation for about 30 minutes. Thus, if evenly distributed, the total amount of drug required might be in the range of a few dozen grams - almost certainly less than a pound. If the Russian authority pumped in 5x the effective dose (as it claimed), its uneven distribution in the air would likely have caused many deaths. But only one in six died. 

Fentanyl is highly lipophilic. It is rapidly distributed to tissues such as the brain, heart, kidneys, and lungs, followed by slower movement into muscle and fat. 

It is known that the abuse of prescription fentanyl is on the rise, but the degree of increase is difficult to distinguish. Doctors are increasingly wary of turning down requests for pain medication for fear of lawsuits if the patient truly is in a lot of pain. Determining how much pain a patient feels is nearly impossible for the doctor, so they must rely on what the patient tells them. This has led to an increase of people illicitly getting pain relievers for personal use or distribution. Some patients lie to their doctors about their conditions in order to get painkillers others have gone to several doctors to get several prescriptions. 

This is not true. Fentanyl was designed for use in humans and only later used in connection with animals. It is true that fentanyl is widely distributed by veterinarians for use with animals, and that it has similar effects on animals as on people. Because of this similarity, veterinarians may administer fentanyl because human reports of drug effects can be helpful in dealing with animal patients, who cannot tell doctors when they are in pain. 

Anyone who sells or distributes fentanyl or one of its analogs, regardless of whether it is pharmaceutically or clandestinely created, can face criminal charges. This includes giving someone else some of a legally prescribed dosage. Any doctor who falsely prescribes fentanyl to someone can face criminal charges. 

Immunoassay detection of drugs in horses. I. Particle concentration fluoroimmunoassay detection of fentanyl and its congeners. Research Communications in Chemical Pathology and Pharmacology 57 389-407 MacDonald E, Scheinin M 1995 Distribution and pharmacology of a2-adrenoceptors in the central nervous system. Journal of Physiology and Pharmacology 46 241-258... 

Meuldermans WEG, Hurkmans RMA and Heykants JJP, Plasma protein binding and distribution of fentanyl, sulfentanil, alfentanil and lofentanil in blood. Arch. Int. Pharmacodyn., 257, 4-19 (1982). Cited in Lombardo E, Obach RS, Shalaeva MY and Gao E, Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics, /. Med. Chem., 47, 1242-1250 (2004) ref. 276. 

Ref. 276 Meuldermans WEG, Hurkmans RMA, Heykants JJP, Plasma protein binding and distribution of fentanyl, sulfentanil, alfentanil and lofentanil in blood. Arch. Int. Pharmacodyn., 257, 4-19 (1982) Potentiometric titration. 

B. Pharmacokinetics. Usually, peak effects occur within 2-3 hours, but absorption may be slowed by their pharmacologic effects on gastrointestinal motility. Most drugs have large volumes of distribution (3-5 Ukg). The rate of elimination is highly variable, from 1-2 hours for fentanyl derivatives versus 15-30 hours tor methadone. See also Tables 11-43 and 11-59. 

Umenhofer WC, et al. Comparative spinal distribution and clearance kinetics of intrathecally administered morphine, fentanyl, alfentanil, and sufentanil. Anesthesiology 2000 92 739-753. 

In a 31-year-old woman scheduled for laparoscopic myomectomy a thoracic epidural catheter was placed at T12/L1 and elicited pain in the leg. The catheter was drawn back 3 cm. The pain subsided, no blood or CSF was aspirated, and a test dose of 2 ml of lidocaine 2% was injected. Within minutes she developed symptoms of spinal analgesia and a second aspiration proved that the catheter was in the intrathecal position. Therefore, only 20 micrograms of fentanyl in 2 ml of saline were given, and the catheter was removed afterwards. After an uncomplicated perioperative period, she developed severe pain extending from the left buttock to the tips of the toes in a radicular distribution from L2 to L5. It was treated with a lumbar epidural infusion for the first 13 days and afterwards with carba-mazepine and amitriptyline for 12 more days. The pain and allodynia abated by 25 days after insertion of the catheter. An MRI scan showed a small area of high intensity in the ipsilateral dorsal column. 

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