Chloroform water is still being used as a preservative, flavouring agent and antimicrobial in many pharmaceutical products such as 30% cod liver oil v/v emulsion which is used as a source of vitamin A&D , Arachis oil 40% v/v emulsion which is used as a nutritious, demulcent & is mildly laxative. (Christopher, L & Dawn, B (2012)). In 2014 an article was published that stated chloroform was going to be used as an excipient in intramuscular/subcutaneous vaccine for all mammalian food producing species.
Christopher, L & Dawn, B (2012). Pharmaceutical compound & dispensing. 2nd ed. London: Pharmaceutical press. p70-75 European medicines agency (2014), Committee for Medicinal Products for Veterinary Use. [online] London:Pharmaceutical press Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Maximum_Residue_Limits_-_Report/2014/02/WC500162068.pdf (accessed on 3rd January 2017)
Following the death of a three-week-old boy in 1998, after being given peppermint water containing an excessive amount of chloroform, an inquest was sparked into extemporaneous standards. One finding from the inquest was that university and pre-registration training, did not always stress to pharmacists the importance and risks of chloroform water dilution. In addition to this often concentrated chloroform bottles lacked labels containing any instructions. This would result in an increased risk of error, if the pharmacist was in any doubt, when attempting to dilute concentrated chloroform. Finally it was discovered that there were major differences between extemporaneous dispensing in hospitals compared to community pharmacies. In hospitals it was common practice to properly verify and check that worksheets had been completed; however in a community setting this was often found not to be the case. In conclusion I feel the findings from this case further highlight why extemporaneous dispensing, especially with regards to chloroform is becoming less common in a community setting.
The Royal Pharmaceutical Society (2000). Boots pharmacist and trainee were cleared of the baby's manslaughter, but fined for dispensing a defective medicine. The Pharmaceutical Journal, 264: 390-392. (This article outlines the case of a pharmacist and a trainee, who incorrectly dispensed excessive amounts of chloroforms in a child’s peppermint waters).
Since the death of Matthew Young in 1998, pharmacists now are now less willing to prepare and dispense extemporaneous preparations. Even though the dispensing of extemporaneous preparations is less frequently seen in modern pharmacy practice, there is still a need to avoid the risk of errors due to insufficient training in the required extemporaneous competencies. (Cox and McDowell, 2007) Chloroform used to be used as a general anaesthetic administered by inhalation, however there are now much safer drugs which are preferred in general anaesthesia. Chloroform depresses respiration and causes hypotension due to a reduction in cardiac output which can potentially result in cardiac arrest. Hepatic and renal toxicity can occur between 6—24 hours after a dose, and symptoms include abdominal pain, vomiting, and subsequent jaundice. (The Pharmaceutical Press, 2017) During the American Civil War, Chloroform was the choice of anaesthetic by surgeons due to its volatility, low cost, and amount required for doses. However, now it is used in the manufacturing of pesticides, dyes, and for the obtaining of penicillin. (VMSL, 2003)
Cox, A. and McDowell, S. (2007) Changing roles, changing risks - the paradox of pharmacist prescribing. Available at: http://www.pharmaceutical-journal.com/opinion/comment/changing-roles-changing-risks-the-paradox-of-pharmacist-prescribing/10003021.article (Accessed: 8 February 2017)
The Pharmaceutical Press (2017) Chloroform. Available at: https://www.medicinescomplete.com/mc/martindale/2009/3104-d.htm (Accessed: 8 February 2017)
VMSL (2003) General anesthetics. Available at: http://svmsl.chem.cmu.edu/vmsl/genanes/ga_bg3.htm (Accessed: 8 February 2017)
Chloroform is used in pesticide formulations, as a solvent and chemical intermediate in laboratories and industrial situations, as a cleansing agent, in fire extinguishers and in the rubber industry. It is also used in the manufacture of fluorocarbon plastics, resins and propellants. In the past, chloroform was extensively used to induce and maintain medical anaesthesia. Its use as an anaesthetic was discontinued due to the severe adverse health effects associated with its use.
Chloroform vapours can cause shortness of breath and mouth and throat dryness. Ingestion of chloroform may cause burning of the mouth and throat and vomiting. Skin or eye contact will lead to irritation and inflammation. More severe exposures to chloroform by inhalation or ingestion will cause dizziness, drowsiness, liver and kidney damage, convulsions, heart problems, unconsciousness and in some cases death. Long-term exposure to chloroform can cause liver damage.
There was an incident where, in Boots Pharmacy, two pharmacists had dispensed a peppermint solution which had killed a four-day-old baby, which has created doubts in pharmacists and other people's minds over extemporaneous standards. The element of risk/error means that extemporaneous dispensing has become less frequent and almost non-existent in community pharmacies. The medicine given to Matthew Young, from Runcorn, Cheshire, contained 20 times too much chloroform. He suffered a heart attack and brain damage, and died in hospital 18 days later.
International Programme on Chemical Safety (IPCS). Chloroform. Environmental Health Criteria 163. 1994, WHO: Geneva. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/338529/Chloroform_info_incid_mgment_tox.pdf
Additional Information: How is chloroform being used in the laboratory today? It is used as a laboratory reagent for the detection of primary amines, bromides, and iodides. Chloroform is a solvent of many organic compounds which is why it's used in analytical chemistry to isolate such compounds. It is also used for the preservation of organic tissues in laboratories, such as anatomical specimens, as it prevents their decay. An example would be the euthanasia and preservation of laboratory insect specimens without damage. Chloroform containing deuterium, an isotope of hydrogen, is used as a solvent in Nuclear Magnetic Resonance (NMR Spectroscopy, as it is invisible to the NMR spectrometer. This means that the spectrometer will only analyse the sample, and not the solvent.
Chloroform has many applications in molecular biology, which include: DNA extraction from cells, using an extraction buffer. Extraction of mineral oil from polymerase chain reaction samples. DNA recovery from polyacrylamide gels, using phenol. Storage of lambda cDNA, lambda plaques, and plasmid DNA extraction.
How is chloroform used in industries today? Chloroform is used as a heat transfer medium in fire extinguishers, where it lowers the temperature of carbon tetrachloride. It serves as an intermediate in the production of dyes and pesticides like chloropicrin, and is used as a fumigant of stored-grain crops. It destroys bacteria, viruses, and pests by chlorination. It is used as an industrial solvent for fats, waxes, resins, oils, greases, adhesives, in photography, and dry cleaning.
It is used to manufacture a refrigerant called HCFC-22 or R-22 (hydrochlorofluorocarbon 22), which is used in air conditioners, supermarket freezers, fluoropolymer production, and polystyrene foam insulation. However, R-22 is rapidly being replaced by other refrigerants because it damages the atmospheric ozone layer.
It is used in the manufacture of plastics like vinyl chloride and aerosol propellants.It is also used in the manufacture of organic chemicals like cyclopropane, and tetrafluoroethene, which is an intermediate in the manufacture of the non-stick polymer Teflon.
A.Chavan, 2016. Chemistry: The Varied Uses of Chloroform That You Never Knew Existed. Last Updated: August 23, 2016 Assessed on 04/09/17
Additional Information: From viewing the British Pharmacopoeia it is stated that the use of Chloroform water has now been banned under the European conventions which is why it is currently no longer used. As stated from the previous blog entry, it was the peppermint water case which resulted in the death of 4 year old, Matthew Young which caused the decline in extemporaneous dispensing, and the manufacturing of medicines in the pharmacy setting, as the quality assurance become doubted. However, this case was not the deciding case for the withdrawal of chloroform water. Cartwright, A. (2014). The British pharmacopoeia, 1864 to 2014. 1st ed.
Extemporaneous preparation carries risk. As it was more often dispensed to vulnerable groups such as young children or patients who have difficulty taking tablets/capsules, errors occurred in extemporaneous preparation may lead to very serious harm (Pharmaceutical Press, 2010). The UK ‘peppermint water case’ was an example of serious incidents, which resulted in patient’s death. The use of a wrong strength of chloroform water and toxic ingredients caused this tragedy (Pharmaceutical Press, 2010). Death of patients could be caused by a thousand-fold overdose/underdose, because of mistakes made during calculating or measuring. Inadequate development and uniformity in extemporaneous preparation led to errors and therefore the products were in a lower quality than that were manufactured in large pharmaceutical industries/MHRA-licensed facilities (Pharmaceutical Press, 2010).
Pharmaceutical Press (2010) Standard: Introduction. Handbook Of Extemporaneous Preparation. Page 3-4. This article was useful providing incidents happened in different countries and showed the danger of dispensing extemporaneous preparation in hospital or community pharmacies.
Chloroform is able to depress the central nervous system, which can result in deep coma and depression of the respiratory centre. Chloroform was used as an anaesthetic to replace ether as it increased the movement of potassium ions in nerve cells. (Lazdunski et al.) However, the use of chloroform has been discontinued due to several deaths due to respiratory failure and cardiac arrhythmias. (Baxter et al.) The first reported death that occurred due to the use of chloroform was Hannah Greener, a 15 year old girl who died on January 28, 1848. At the time, it was unsure as to why the death occurred but there were suspicions as to whether the complications were due to respiratory disturbance or if there were specific effects that occurred on the heart. In 1911, Levy discovered that chloroform can cause cardiac fibrillation, this was recognized by conducting experiments with animals. (Wawersik, J.) In 1998, a four-day-old baby died due to an error made by a pharmacist’s assistant who prepared and supplied an incorrect medicine which was incorrect due to the medicine being given in the undiluted form. The infant died following cardiac arrest due to the inhalation of chloroform. This case was followed by the Royal Pharmaceutical Society issuing a warning that pharmacists should always check their work to prevent this happening in the future. (BBC News, 2000.) Currently, chloroform use has been discontinued in anesthesia due to its side effects. (Baxter et al.)
Baxter, Peter J et al. Hunter's Diseases Of Occupations, Tenth Edition. 10th ed. London: CRC Press, 2010.
BBC News, 2000. Chemists fined after baby death. [online]. London: BBC. Available from: http://news.bbc.co.uk/1/hi/health/660055.stm [Accessed 17th February 2017]
Lazdunski, Michel et al. "Inhalational Anesthetics Activate Two-Pore-Domain Background K+ Channels". Nature Neuroscience 2.5 (1999): 422-426. Available from: https://www.ncbi.nlm.nih.gov/labs/articles/10321245/ [Accessed 17 February 2017]
Wawersik, J. (1997-01-01). "History of chloroform anesthesia". Anaesthesiologie Und Reanimation. 22 (6): 144–152. PMID 9487785. Available from: https://www.ncbi.nlm.nih.gov/pubmed/9487785 [Accesssed 17th January 2017]
Chloroform water is still being used as a preservative, flavouring agent and antimicrobial in many pharmaceutical products such as 30% cod liver oil v/v emulsion which is used as a source of vitamin A&D , Arachis oil 40% v/v emulsion which is used as a nutritious, demulcent & is mildly laxative. (Christopher, L & Dawn, B (2012)).
ReplyDeleteIn 2014 an article was published that stated chloroform was going to be used as an excipient in intramuscular/subcutaneous vaccine for all mammalian food producing species.
Christopher, L & Dawn, B (2012). Pharmaceutical compound & dispensing. 2nd ed. London: Pharmaceutical press. p70-75
European medicines agency (2014), Committee for Medicinal Products for Veterinary Use. [online] London:Pharmaceutical press Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Maximum_Residue_Limits_-_Report/2014/02/WC500162068.pdf (accessed on 3rd January 2017)
Following the death of a three-week-old boy in 1998, after being given peppermint water containing an excessive amount of chloroform, an inquest was sparked into extemporaneous standards.
ReplyDeleteOne finding from the inquest was that university and pre-registration training, did not always stress to pharmacists the importance and risks of chloroform water dilution.
In addition to this often concentrated chloroform bottles lacked labels containing any instructions. This would result in an increased risk of error, if the pharmacist was in any doubt, when attempting to dilute concentrated chloroform.
Finally it was discovered that there were major differences between extemporaneous dispensing in hospitals compared to community pharmacies. In hospitals it was common practice to properly verify and check that worksheets had been completed; however in a community setting this was often found not to be the case.
In conclusion I feel the findings from this case further highlight why extemporaneous dispensing, especially with regards to chloroform is becoming less common in a community setting.
The Royal Pharmaceutical Society (2000). Boots pharmacist and trainee were cleared of the baby's manslaughter, but fined for dispensing a defective medicine. The Pharmaceutical Journal, 264: 390-392. (This article outlines the case of a pharmacist and a trainee, who incorrectly dispensed excessive amounts of chloroforms in a child’s peppermint waters).
Since the death of Matthew Young in 1998, pharmacists now are now less willing to prepare and dispense extemporaneous preparations. Even though the dispensing of extemporaneous preparations is less frequently seen in modern pharmacy practice, there is still a need to avoid the risk of errors due to insufficient training in the required extemporaneous competencies. (Cox and McDowell, 2007)
ReplyDeleteChloroform used to be used as a general anaesthetic administered by inhalation, however there are now much safer drugs which are preferred in general anaesthesia.
Chloroform depresses respiration and causes hypotension due to a reduction in cardiac output which can potentially result in cardiac arrest. Hepatic and renal toxicity can occur between 6—24 hours after a dose, and symptoms include abdominal pain, vomiting, and subsequent jaundice. (The Pharmaceutical Press, 2017)
During the American Civil War, Chloroform was the choice of anaesthetic by surgeons due to its volatility, low cost, and amount required for doses. However, now it is used in the manufacturing of pesticides, dyes, and for the obtaining of penicillin. (VMSL, 2003)
Cox, A. and McDowell, S. (2007) Changing roles, changing risks - the paradox of pharmacist prescribing. Available at: http://www.pharmaceutical-journal.com/opinion/comment/changing-roles-changing-risks-the-paradox-of-pharmacist-prescribing/10003021.article (Accessed: 8 February 2017)
The Pharmaceutical Press (2017) Chloroform. Available at: https://www.medicinescomplete.com/mc/martindale/2009/3104-d.htm (Accessed: 8 February 2017)
VMSL (2003) General anesthetics. Available at: http://svmsl.chem.cmu.edu/vmsl/genanes/ga_bg3.htm (Accessed: 8 February 2017)
Chloroform is used in pesticide formulations, as a solvent and chemical intermediate in laboratories and industrial situations, as a cleansing agent, in fire extinguishers and in the rubber industry. It is also used in the manufacture of fluorocarbon plastics, resins and propellants.
ReplyDeleteIn the past, chloroform was extensively used to induce and maintain medical anaesthesia. Its use as an anaesthetic was discontinued due to the severe adverse health effects associated with its use.
Chloroform vapours can cause shortness of breath and mouth and throat dryness. Ingestion of chloroform may cause burning of the mouth and throat and vomiting. Skin or eye contact will lead to irritation and inflammation. More severe exposures to chloroform by inhalation or ingestion will cause dizziness, drowsiness, liver and kidney damage, convulsions, heart problems, unconsciousness and in some cases death.
Long-term exposure to chloroform can cause liver damage.
There was an incident where, in Boots Pharmacy, two pharmacists had dispensed a peppermint solution which had killed a four-day-old baby, which has created doubts in pharmacists and other people's minds over extemporaneous standards. The element of risk/error means that extemporaneous dispensing has become less frequent and almost non-existent in community pharmacies.
The medicine given to Matthew Young, from Runcorn, Cheshire, contained 20 times too much chloroform. He suffered a heart attack and brain damage, and died in hospital 18 days later.
https://www.theguardian.com/uk/2000/mar/02/helencarter
International Programme on Chemical Safety (IPCS). Chloroform. Environmental Health Criteria 163. 1994, WHO: Geneva.
https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/338529/Chloroform_info_incid_mgment_tox.pdf
Additional Information:
DeleteHow is chloroform being used in the laboratory today?
It is used as a laboratory reagent for the detection of primary amines, bromides, and iodides. Chloroform is a solvent of many organic compounds which is why it's used in analytical chemistry to isolate such compounds.
It is also used for the preservation of organic tissues in laboratories, such as anatomical specimens, as it prevents their decay. An example would be the euthanasia and preservation of laboratory insect specimens without damage.
Chloroform containing deuterium, an isotope of hydrogen, is used as a solvent in Nuclear Magnetic Resonance (NMR
Spectroscopy, as it is invisible to the NMR spectrometer. This means that the spectrometer will only analyse the sample, and not the solvent.
Chloroform has many applications in molecular biology, which include:
DNA extraction from cells, using an extraction buffer.
Extraction of mineral oil from polymerase chain reaction samples. DNA recovery from polyacrylamide gels, using phenol. Storage of lambda cDNA, lambda plaques, and plasmid DNA extraction.
How is chloroform used in industries today?
Chloroform is used as a heat transfer medium in fire extinguishers, where it lowers the temperature of carbon tetrachloride.
It serves as an intermediate in the production of dyes and pesticides like chloropicrin, and is used as a fumigant of stored-grain crops. It destroys bacteria, viruses, and pests by chlorination.
It is used as an industrial solvent for fats, waxes, resins, oils, greases, adhesives, in photography, and dry cleaning.
It is used to manufacture a refrigerant called HCFC-22 or R-22 (hydrochlorofluorocarbon 22), which is used in air conditioners, supermarket freezers, fluoropolymer production, and polystyrene foam insulation. However, R-22 is rapidly being replaced by other refrigerants because it damages the atmospheric ozone layer.
It is used in the manufacture of plastics like vinyl chloride and aerosol propellants.It is also used in the manufacture of organic chemicals like cyclopropane, and tetrafluoroethene, which is an intermediate in the manufacture of the non-stick polymer Teflon.
A.Chavan, 2016. Chemistry: The Varied Uses of Chloroform That You Never Knew Existed. Last Updated: August 23, 2016
Assessed on 04/09/17
Additional Information:
DeleteFrom viewing the British Pharmacopoeia it is stated that the use of Chloroform water has now been banned under the European conventions which is why it is currently no longer used. As stated from the previous blog entry, it was the peppermint water case which resulted in the death of 4 year old, Matthew Young which caused the decline in extemporaneous dispensing, and the manufacturing of medicines in the pharmacy setting, as the quality assurance become doubted. However, this case was not the deciding case for the withdrawal of chloroform water.
Cartwright, A. (2014). The British pharmacopoeia, 1864 to 2014. 1st ed.
Extemporaneous preparation carries risk. As it was more often dispensed to vulnerable groups such as young children or patients who have difficulty taking tablets/capsules, errors occurred in extemporaneous preparation may lead to very serious harm (Pharmaceutical Press, 2010). The UK ‘peppermint water case’ was an example of serious incidents, which resulted in patient’s death. The use of a wrong strength of chloroform water and toxic ingredients caused this tragedy (Pharmaceutical Press, 2010). Death of patients could be caused by a thousand-fold overdose/underdose, because of mistakes made during calculating or measuring. Inadequate development and uniformity in extemporaneous preparation led to errors and therefore the products were in a lower quality than that were manufactured in large pharmaceutical industries/MHRA-licensed facilities (Pharmaceutical Press, 2010).
ReplyDeletePharmaceutical Press (2010) Standard: Introduction. Handbook Of Extemporaneous Preparation. Page 3-4. This article was useful providing incidents happened in different countries and showed the danger of dispensing extemporaneous preparation in hospital or community pharmacies.
Chloroform is able to depress the central nervous system, which can result in deep coma and depression of the respiratory centre. Chloroform was used as an anaesthetic to replace ether as it increased the movement of potassium ions in nerve cells. (Lazdunski et al.) However, the use of chloroform has been discontinued due to several deaths due to respiratory failure and cardiac arrhythmias. (Baxter et al.) The first reported death that occurred due to the use of chloroform was Hannah Greener, a 15 year old girl who died on January 28, 1848. At the time, it was unsure as to why the death occurred but there were suspicions as to whether the complications were due to respiratory disturbance or if there were specific effects that occurred on the heart. In 1911, Levy discovered that chloroform can cause cardiac fibrillation, this was recognized by conducting experiments with animals. (Wawersik, J.) In 1998, a four-day-old baby died due to an error made by a pharmacist’s assistant who prepared and supplied an incorrect medicine which was incorrect due to the medicine being given in the undiluted form. The infant died following cardiac arrest due to the inhalation of chloroform. This case was followed by the Royal Pharmaceutical Society issuing a warning that pharmacists should always check their work to prevent this happening in the future. (BBC News, 2000.) Currently, chloroform use has been discontinued in anesthesia due to its side effects. (Baxter et al.)
ReplyDeleteBaxter, Peter J et al. Hunter's Diseases Of Occupations, Tenth Edition. 10th ed. London: CRC Press, 2010.
BBC News, 2000. Chemists fined after baby death. [online]. London: BBC. Available from: http://news.bbc.co.uk/1/hi/health/660055.stm [Accessed 17th February 2017]
Lazdunski, Michel et al. "Inhalational Anesthetics Activate Two-Pore-Domain Background K+ Channels". Nature Neuroscience 2.5 (1999): 422-426. Available from: https://www.ncbi.nlm.nih.gov/labs/articles/10321245/ [Accessed 17 February 2017]
Wawersik, J. (1997-01-01). "History of chloroform anesthesia". Anaesthesiologie Und Reanimation. 22 (6): 144–152. PMID 9487785. Available from: https://www.ncbi.nlm.nih.gov/pubmed/9487785 [Accesssed 17th January 2017]