ABSTRACT
Tacrine was initially synthesised in 1945 as part of a project seeking antibacterial drugs to treat infected wounds in soldiers. However, it was inactive in vitro against common strains of bacteria. Serendipitously, it was injected in vivo into dogs anaesthetised with chloroform and morphine and noted to immediately counter the respiratory rate depression caused by morphine but not block analgesia. Subsequent studies showed that tacrine was an acetylcholinesterase inhibitor. When combined with morphine in ampoules it was possible to inject larger doses of morphine without causing respiratory depression and it was marketed for 10 years in Australia. Tacrine was also used alone for treating acute anticholinergic syndrome in the 1980s. Shortly after this, it was hypothesised by William Summers that it could be of benefit in treating the early stages of Alzheimer's dementia and an IND was granted by the US Food and Drug Administration and a use patent awarded to Summers. It was the first of four anticholinesterases to be approved for treating this condition although its variable pharmacokinetics was a disadvantage.
Subject(s)
Alzheimer Disease/drug therapy , Anticholinergic Syndrome/drug therapy , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/therapeutic use , Tacrine/pharmacology , Tacrine/therapeutic use , Animals , Humans , United States , United States Food and Drug AdministrationSubject(s)
Anticholinergic Syndrome/etiology , Datura/poisoning , Delirium/chemically induced , Social Media , Adolescent , Anticholinergic Syndrome/drug therapy , Anticholinergic Syndrome/physiopathology , Australia , Delirium/diagnosis , Delirium/drug therapy , Eating , Emergency Service, Hospital , Humans , Internet , Male , Risk AssessmentSubject(s)
Anticholinergic Syndrome , Biperiden/adverse effects , Delirium , Indans/administration & dosage , Muscle Rigidity , Physostigmine/administration & dosage , Piperidines/administration & dosage , Risperidone/adverse effects , Anticholinergic Syndrome/drug therapy , Anticholinergic Syndrome/etiology , Antiparkinson Agents/administration & dosage , Antiparkinson Agents/adverse effects , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/adverse effects , Biperiden/administration & dosage , Burns/complications , Burns/metabolism , Burns/physiopathology , Burns/therapy , Cholinesterase Inhibitors/administration & dosage , Delirium/diagnosis , Delirium/drug therapy , Delirium/etiology , Delirium/psychology , Diagnosis, Differential , Donepezil , Drug Administration Routes , Drug Synergism , Humans , Male , Middle Aged , Muscle Rigidity/chemically induced , Muscle Rigidity/drug therapy , Risperidone/administration & dosage , Treatment OutcomeABSTRACT
Sometimes it is suspected that people have been involuntary exposed to drugs, usually by spiked drinks. A young woman was transported to an emergency department by ambulance. Her clinical symptoms (decreased consciousness, mydriasis, confusion, hallucinations and urine retention) indicated anticholinergic syndrome that was effectively treated with the antidote physostigmine. A urine sample tested negative for common narcotic drugs and alcohol, but an extended toxicological analysis of the urine revealed the presence of the alkaloid scopolamine. Scopolamine occurs naturally in Solanaceae plants and is used in some medications. The woman reported that the symptoms had appeared soon after she was offered tea by a male acquaintance. The analytical results along with the woman's story indicated that she had been subjected to a drug-facilitated crime. The results further demonstrate that in suspected cases of involuntary drug exposure, testing should cover a wide panel of relevant drugs, otherwise poisoning may be missed.