Pharmacology Assignment on Fentanyl: Hazards, Exposure Assessment, Risk Characterisation and Management

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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Pharmacology Assignment
Name of the student
University name
Author’s note

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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

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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
(Zhou et al. 2015). In Australia fentanyl is a schedule drug and comparatively 80 to 100 times
stronger than morphine (Shein et 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 by Kuip et 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 (Barash et al. 2018).

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Full report
Hazard identification
Fentanyl is a synthetic, lipophilic phenylpyridine opoid with analgesic and anaesthetic
properties. It selectively binds to the mu-receptor in the central nervous system and mimics
the effects of the endogenous opiates. As reported by Kuip et 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 (Bäckberg et 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 produce nausea, constipation ,
reduced appetite, rash on 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
Adelgais et al. (2017), the coughing occurs as fentanyl constricts the tracheal smooth
muscles which stimulates the irritant receptors. The development of rash or other
hypersensitivities could be attributed to the release of histamine, interleukins and other
inflammatory substances from the mast cells.

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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 by Rauck et 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 by Zecca, 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 (Rauck et al. 2017). As
mentioned by Macmadu et 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

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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 by Geddes et 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 by Kenney et 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 (Kenney et al. 2018). As reported by Ibach et al.
(2017), in excessive doses it shuts down the normal responses of the body causing a feeling
of choking or suffocation.

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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 (Jafari et al. 2017). They should be
provided with readily available naloxone and the doses in which they should be
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 by Scheuermeyer et 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
give protection. The occupational health and safety administration (OSHA) approved
protection for eyes and face needs to be used during tasks where there lays a possibility of
contact (Rauck et 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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In order to understand the effects of fentanyl upon the human physiology a
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.

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References
Adelgais, K.M., Brent, A., Wathen, J., Tong, S., Massanari, D., Deakyne, S. and Sills, M.R.,
2017. Intranasal fentanyl and quality of pediatric acute care. Journal of Emergency
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 22 April 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. Characterization of tolerance in children during fentanyl continuous
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.

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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.com 2018, policeone.com , Available at : 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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Emergency Department Observation Protocol for Patients With Presumed Fentanyl
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
Care Medicine and the World Federation of Pediatric Intensive and Critical Care
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.