Pharmacology Assignment on Fentanyl: Hazards, Exposure Assessment, Risk Characterisation and Management
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This assignment discusses the hazards, exposure assessment, risk characterisation and management of Fentanyl, a synthetic, lipophilic phenylpyridine opoid with analgesic and anaesthetic properties.
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0PHARMACOLOGY ASSIGNMENT Pharmacology Assignment Name of the student University name Author’s note
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1PHARMACOLOGY ASSIGNMENT Table of Contents Summary.................................................................................................................................2 Full report...............................................................................................................................3 Hazard identification..................................................................................................................3 Exposure assessment..................................................................................................................4 Risk characterisation..................................................................................................................5 Management of risk....................................................................................................................6 Data gaps and experimental plans for filling them up...............................................................6 References..................................................................................................................................8
2PHARMACOLOGY ASSIGNMENT Summary In the current assignment a particular drug has been selected for discussion that is fentanyl. It used as an active component in Ionsys and is generally prescribed by experienced medical professionals in hospitals experienced in the use of opoids such as fentanyl. Fentanyl is a depressant drug, which slows down the messages travelling between the brain and the body. It belongs to the class of drugs known as opoids and is prescribed for the management of chronic pain as a result of cancer, nerve damage, back injury, trauma and other causes (Zhouet al.2015). In Australia fentanyl is a schedule drug and comparatively 80 to 100 times stronger than morphine (Sheinet al.2016). The exposure to the chemical can be though airborne mode or though oral ingestion. They are often used for pain management in hospitals under expert supervision. However, as reported byKuipet al.(2017), many people have been using fentanyl as an alternative form of pain management without expert supervision. The medicine initially relieves stress in the body and makes one feel less pain by reducing the rate of neurotransmission between brain and body. Over gradual and continuous usage one many become addicted to it as it often leaves one feeling euphoric. Reports and evidences have proved that fentanyl exposure over prolonged period of time may make develops symptoms such as respiratory distress, chest pain, skin rashes etc. In many cases, a severe respiratory distress could lead to death. In large doses whether accidental or illicitly taken it can activate the mast cells producing large amount of histamines and interleukins which can result in acute hypersensitive reactions (Barashet al.2018).
3PHARMACOLOGY ASSIGNMENT Full report Hazard identification Fentanyl is a synthetic, lipophilic phenylpyridine opoid with analgesic and anaesthetic properties. It selectively binds to themu-receptorin the central nervous system and mimics the effects of the endogenous opiates. As reported byKuipet al.(2017), the binding of the fentanyl reduces the release of neurotransmitters such as acetylene, Substance P, GABA, dopamine and reduces the sensation of pain.Sublingual mode of delivery of fentanyl as spray allows more rapid absorption compared to transmucosal preparations (Bäckberget al.2015). This has been confirmed though a number of studies and research methods. The toxicity produced by the drug could be further differentiated based upon acute versus chronic symptoms.The drug in less doses may producenausea, constipation , reduced appetite, rashon the body, drowsiness, fatigue, slurred speech,low blood pressure etc. In high doses the drug may produce some of the symptoms such as chest pain, slow breathing, seizures and coma. In most extreme cases due to drug overdose there could be death in the patient. The overdose of fentanyl has often been seen to produce some adverse clinical effects in the patient such as pain in the chest and breathing difficulties. This had been further associated with the development of other clinical conditions such as coughing. As reported by Adelgaiset al.(2017), the coughing occurs as fentanyl constricts the tracheal smooth muscleswhichstimulatestheirritantreceptors.Thedevelopmentofrashorother hypersensitivities could be attributed to the release of histamine, interleukins and other inflammatory substances from the mast cells.
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4PHARMACOLOGY ASSIGNMENT Exposure assessment Fentanyl class of compounds are often used for the treatment of pain due to cancer, injury, trauma and other causes. It reduces the sensation of pain by slowing down the rate of transmission between the brain and the body. There are a number of sources of exposure to fentanyl such as it can be absorbed in the body via inhalation, through oral exposure or ingestion, or through skin contact. Fentanyl acts as an anti-depressant and has been recently marked as an unscheduled drug. As reported byRaucket al.(2017), 31.4% of the Australians have been using fentanyl to relieve pain and stress. Most of the consumption have been done under unsupervised medications and is legaly prohibited. Fentanyl contaminated drugs has raised the interest of the users to effectively mitigate risk management strategies. In 50% of the cases the users have been seen to be less aware of the consequences of fentanyl over long term and have only been taking them as normal opoids (cdc.gov 2018). The exposure to fentanyl by the oral route is most common where people had been prescribed fentanyl for controlling the overwhelming sensation of pain. The medicine acts similar to heroine by giving a feeling euphoria to the users. They act similar to heroines by making one addicted to the use of it over long run. As mentioned byZecca,et al.(2017), the withdrawal of the medicine can produce stronger effects such as respiratory distress. Risk assessment to fentanyl in pregnancy has also been carried during the first trimester with little or no adverse impact upon the mother or foetus (Raucket al.2017).As mentioned byMacmaduet al.(2017), data regarding altered neurodevelopment in the child has also been ruled out. However, use of opoid at the time of delivery has been related with n neonatal respiratory depression. The use of fentanyl in combination with other opoids may
5PHARMACOLOGY ASSIGNMENT further aggravate the symptoms of respiratory distress along with other side effects such as intestinal coiling followed by extreme pain. Risk characterisation Fentanyl is 30 to 50 times more potent than heroine and just 2 milligrams of the medicine is considered to be a deadly dose for than 95% of the Australian public. As mentioned byGeddeset al.(2018), a small amount of spread of the powdery form of fentanyl in the environment mainly through air can increase the chances of coming in contact with it manifold times. It is available in powder, tablet or liquid form and only a small amount inhaled through the nose or absorbed by the mucous membrane can cause severe reactions. The overdose of the drug can result in the onset of severe respiratory depression. The drug possesses huge risks for the ones who may come in contact with it in their daily course of duty such as the police officers. As mentioned byKenneyet al.(2018), gradual exposure to the drug may cause to develop addiction for the same over longer terms. The correctional officers who are assigned with the duty of checking and controlling of narcotic activities are the most prone to be come in contact with the drug accidentally. Some of the effective precautionary measures could be taken over here such as nitrile gloves. There is a lack of precautionary measures, which could be implemented by the police department for controlling the rate of exposure to the deadly chemical (policeone.com 2018). In higher doses it can affect the synthesis of adrenaline in the body, which slows down the senses for the reception of any forms of stress or pain (Kenneyet al.2018). As reported byIbachet al. (2017), in excessive doses it shuts down the normal responses of the body causing a feeling of choking or suffocation.
6PHARMACOLOGY ASSIGNMENT Management of risk The risk management is very crucial for reducing the ill effects of exposure to fentanyl. The risk management could be broken down into number of important components such as general precautions, dermal precautions, respiratory precautions, airway management and reducing the chances of splash exposure. For example, the correctional or police officers are at increased risk of coming in contact with the fentanyl. The workers should be trained over recognising the signs of fentanyl intoxication (Jafariet al.2017). They should be providedwithreadilyavailablenaloxoneandthedosesinwhichtheyshouldbe administered to control the adverse effects of fentanyl. The use of nitrile gloves can act as sufficient precautionary measures reducing the chances of skin contact with the powdered form of the drug. As argued byScheuermeyeret al.(2018), use of alcohol base hand sanitizers need to be avoided as they further enhance dermal drug absorption. Under unusual circumstances of airborne exposure to fentanyl properly fitted N95 respirator could be used to giveprotection.Theoccupationalhealthandsafetyadministration(OSHA)approved protection for eyes and face needs to be used during tasks where there lays a possibility of contact (Raucket al.2017). Additionally, naloxone should be administered on expressivity of the signs of hypoventilation. Data gaps and experimental plans for filling them up It has been repeated many times and over that in large doses fentanyl has been seen to produce much lethal consequences by slowing the down the rate of respiration. However, the exact mechanism is unclear. The focus has been shifted upon the release of components such as Substance P, GABA which is secondary messengers and produces serious impact upon the signal transduction pathway. Though the manner in which the respiratory depression is brought about is unclear.
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7PHARMACOLOGY ASSIGNMENT Inordertounderstandtheeffectsoffentanyluponthehumanphysiologya randomised control trial could be set up in order to compare the impact upon the exposure to minute doses of fentanyl with other opiods. However, care needs to be taken that they are not continued for long term as prolonged administration of the medication can produce much severe consequences.
8PHARMACOLOGY ASSIGNMENT References Adelgais, K.M., Brent, A., Wathen, J., Tong, S., Massanari, D., Deakyne, S. and Sills, M.R., 2017.Intranasalfentanylandqualityofpediatricacutecare.JournalofEmergency Medicine,53(5), pp.607-615. Bäckberg, M., Beck, O., Jönsson, K.H. and Helander, A., 2015. Opioid intoxications involving butyrfentanyl, 4-fluorobutyrfentanyl, and fentanyl from the Swedish STRIDA project.Clinical Toxicology,53(7), pp.609-617. Barash, J.A., Ganetsky, M., Boyle, K.L., Raman, V., Toce, M.S., Kaplan, S., Lev, M.H., Worth, J.L. and DeMaria Jr, A., 2018. Acute Amnestic Syndrome Associated with Fentanyl Overdose.New England Journal of Medicine,378(12), pp.1157-1158. cdc.gov 2018,cdc.gov,Available at: https://www.cdc.gov/niosh/topics/fentanyl/risk.html [Accessed on 22April 2018] Geddes, L., Iversen, J., Memedovic, S. and Maher, L., 2018. Intravenous fentanyl use among people who inject drugs in Australia.Drug and alcohol review,pp.105-154. Ibach, B.W., Miller, J.L., Woo, S., Harrison, D., Standifer, K.M., Hagemann, T. and Johnson, P.N.,2017.Characterizationoftoleranceinchildrenduringfentanylcontinuous infusions.Journal of Pediatric Intensive Care,6(02), pp.083-090. Jafari, S., Buxton, J.A. and Joe, R., 2015. Rising Fentanyl-related Overdose Deaths in British Columbia.Canadian Journal of Addiction,6(1), pp.150-169.
9PHARMACOLOGY ASSIGNMENT Kenney, S.R., Anderson, B.J., Conti, M.T., Bailey, G.L. and Stein, M.D., 2018. Expected and actual fentanyl exposure among persons seeking opioid withdrawal management.Journal of Substance Abuse Treatment, pp.56-85. Kermanizadeh, A., Jacobsen, N.R., Roursgaard, M., Loft, S. and Møller, P., 2017. Hepatic hazard assessment of silver nanoparticle exposure in healthy and chronically alcohol fed mice.Toxicological Sciences,158(1), pp.176-187. Kuip, E.J., Zandvliet, M.L., Koolen, S.L., Mathijssen, R.H. and Rijt, C.C., 2017. A review of factors explaining variability in fentanyl pharmacokinetics; focus on implications for cancer patients.British journal of clinical pharmacology,83(2), pp.294-313. Macmadu, A., Carroll, J.J., Hadland, S.E., Green, T.C. and Marshall, B.D., 2017. Prevalence and correlates of fentanyl-contaminated heroin exposure among young adults who use prescription opioids non-medically.Addictive behaviors,68, pp.35-38. policeone.com2018,policeone.com,Availableat:https://www.policeone.com/police- products/Narcotics-Identification/articles/469108006-Fentanyl-What-are-the-exposure-risks/ [Accessed on 21 April 2018] Rauck, R., Oh, D.A., Parikh, N., Koch, C., Singla, N., Yu, J., Nalamachu, S. and Vetticaden, S., 2017. Pharmacokinetics and safety of fentanyl sublingual spray and fentanyl citrate intravenous: a single ascending dose study in opioid-naïve healthy volunteers.Current medical research and opinion,33(11), pp.1915-1920. Scheuermeyer, F.X., DeWitt, C., Christenson, J., Grunau, B., Kestler, A., Grafstein, E., Buxton, J., Barbic, D., Milanovic, S., Torkjari, R. and Sahota, I., 2018. Safety of a Brief
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10PHARMACOLOGY ASSIGNMENT EmergencyDepartmentObservationProtocolforPatientsWithPresumedFentanyl Overdose.Annals of emergency medicine, pp.56-87. Shein, S.L., Ferguson, N.M., Kochanek, P.M., Bayir, H., Clark, R.S., Fink, E.L., Tyler- Kabara, E.C., Wisniewski, S.R., Tian, Y., Balasubramani, G.K. and Bell, M.J., 2016. Effectiveness of pharmacological therapies for intracranial hypertension in children with severe traumatic brain injury–results from an automated data collection system time-synched to drug administration.Pediatric critical care medicine: a journal of the Society of Critical CareMedicineandtheWorldFederationofPediatricIntensiveandCriticalCare Societies,17(3), p.236. Zecca, E., Brunelli, C., Centurioni, F., Manzoni, A., Pigni, A. and Caraceni, A., 2017. Fentanyl sublingual tablets versus subcutaneous morphine for the management of severe cancer pain episodes in patients receiving opioid treatment: a double-blind, randomized, noninferiority trial.Journal of Clinical Oncology,35(7), pp.759-765. Zhou, M., Slaven, M., Forgione, A., Pasetka, M., Zeng, L., Lam, H., Holden, L., Pulenzas, N., Lao, N., Chow, E. and DeAngelis, C., 2015. Review of fentanyl formulations in the management of breakthrough cancer pain.Journal of Pain Management,8(1), p.7.