Forensic Chemistry

Second Semester
2022-2023

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Antidotes

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Definition
• Antidotes are substances that act specifically to prevent, reverse or
relieve the action or poisonous effect of a toxic agent.

Kaushik, Y., & Patel, D. (2019). INTERNATIONAL ROLE OF ANTIDOTES IN POISONING - A REVIEW.
http://www.iamj.in/posts/2019/images/upload/602_608.pdf
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Physiological antidote need to be used when
1. The poison may not have been completely removed by emesis or
gastric lavage.
2. When the gastric lavage is contra-indicated like in corrosives and
volatile poisons as petroleum distillates.
3. The poison is already absorbed.
4. The poison has been administered by route other than ingestion.

Kaushik, Y., & Patel, D. (2019). INTERNATIONAL ROLE OF ANTIDOTES IN POISONING - A REVIEW.
http://www.iamj.in/posts/2019/images/upload/602_608.pdf
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The Ideal Antidotes
• A good and utilizable antidote is expected to be cheap, safe and
readily and widely available.

ATC code for Antidotes

• V Various
• V03 All other therapeutic products
• V03A All other therapeutic products
• V03AB Antidotes
https://www.whocc.no/atc_ddd_index/?code=V03AB
Aruwa, C. E., Mukaila, Y. O., Ajao, A. A. N., & Sabiu, S. (2020). An appraisal of antidotes’ effectiveness: Evidence of the use of phyto-antidotes
and biotechnological advancements. Molecules, 25(7), 1–27. https://doi.org/10.3390/molecules25071516
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Classes of Antidotes
• Antidotes have been classified based on their efficacy, mechanisms of
action , the group of poisons they are used against.

• Based on their mode of action, antidotes are classified as:

1. Mechanical or physical antidotes.
2. Chemical antidotes.
3. Physiological or pharmacological antidotes.
4. Chelating Agents.

Aruwa, C. E., Mukaila, Y. O., Ajao, A. A. N., & Sabiu, S. (2020). An appraisal of antidotes’ effectiveness: Evidence of the use of phyto-antidotes
and biotechnological advancements. Molecules, 25(7), 1–27. https://doi.org/10.3390/molecules25071516
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Mechanical (physical) antidote
• It neutralizes poisons by preventing their absorption.

• For Example: Activated charcoal

• Fine, black, odorless powder produced by
destructive distillation of various organic materials,
usually wood pulp and high temperature with a
variety of activating agents, such as steam or CO2, to
increase its adsorptive capacity.

Kaushik, Y., & Patel, D. (2019). INTERNATIONAL ROLE OF ANTIDOTES IN POISONING - A REVIEW.
http://www.iamj.in/posts/2019/images/upload/602_608.pdf
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Activated charcoal
• Activated charcoal is also usually called a universal antidote as it is
indicated for most poisons.

• Universal Antidote:
It is an antidote that is used in those cases where the nature of the ingested
poisons is unknown or where it is suspected that a combination of two or more
poisons has been taken

Aruwa, C. E., Mukaila, Y. O., Ajao, A. A. N., & Sabiu, S. (2020). An appraisal of antidotes’ effectiveness: Evidence of the use of phyto-antidotes
and biotechnological advancements. Molecules, 25(7), 1–27. https://doi.org/10.3390/molecules25071516
8
Activated charcoal
• It is used in cases of poisoning with strychnine, morphine, atropine,
nicotine and phenobarbital.

• Activated charcoal prevents the absorption of poisons from the

stomach and intestine by binding the poison and interrupting
enterohepatic circulation, though it must be administered within the
first hour of the ingestion of poison for this to be possible.

Kaushik, Y., & Patel, D. (2019). INTERNATIONAL ROLE OF ANTIDOTES IN POISONING - A REVIEW.
http://www.iamj.in/posts/2019/images/upload/602_608.pdf
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Chemical Antidote
• It neutralizes the poison chemically within the GIT.

1. Acids neutralize alkalis.

• Weak solutions should be given e.g. vinegar.
• Neutralization of acids with strong alkalis and vice versa must be avoided,
because the antidote may itself be injurious and strong exothermic reactions
cause further injury.
• Neutralization of acid by sodium carbonate Na2CO3 is avoided because of
excessive release of CO2 which may cause perforation of the weakened
stomach walls.
Kaushik, Y., & Patel, D. (2019). INTERNATIONAL ROLE OF ANTIDOTES IN POISONING - A REVIEW.
http://www.iamj.in/posts/2019/images/upload/602_608.pdf
10
Chemical Antidote
2. Albumin
Can be given in Cu poisoning (forms insoluble copper albuminate).

3. Iodine
A solution of tincture iodine or Lugol’s iodine will precipitate lead, mercury and
silver.

Kaushik, Y., & Patel, D. (2019). INTERNATIONAL ROLE OF ANTIDOTES IN POISONING - A REVIEW.
http://www.iamj.in/posts/2019/images/upload/602_608.pdf
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Physiological (Pharmacological) Antidote
• These agents act on the tissue of the body.

• They are classified as following:

1. Competitive Antagonists.
2. Acceleration of Detoxification.
3. Reduced Toxicity.
4. Receptor Site Blocker.

Kaushik, Y., & Patel, D. (2019). INTERNATIONAL ROLE OF ANTIDOTES IN POISONING - A REVIEW.
http://www.iamj.in/posts/2019/images/upload/602_608.pdf
12
Physiological (Pharmacological) Antidote
1- Competitive Antagonists
• Antagonists are chemical substances (drugs) that binds to receptors
without producing a notable stimulation of the receptor.

• This is the most common mechanism where the antidotes bind

reversibly to cellular receptors, competing with and ultimately
displacing the poisons from binding with active receptors, thereby
reducing the amount of effective poisons.

Aruwa, C. E., Mukaila, Y. O., Ajao, A. A. N., & Sabiu, S. (2020). An appraisal of antidotes’ effectiveness: Evidence of the use of phyto-antidotes
and biotechnological advancements. Molecules, 25(7), 1–27. https://doi.org/10.3390/molecules25071516
13
Physiological (Pharmacological) Antidote
1- Competitive Antagonists
• For example: Naltrexone and Naloxone, are antidotes for most
narcotic analgesics poisoning like Heroin, competes against the
poison molecules at the opioid receptor.

Naltrexone: Naloxone:
Heroin
ATC code: N07BB04 ATC code: V03AB15
Aruwa, C. E., Mukaila, Y. O., Ajao, A. A. N., & Sabiu, S. (2020). An appraisal of antidotes’ effectiveness: Evidence of the use of phyto-antidotes
and biotechnological advancements. Molecules, 25(7), 1–27. https://doi.org/10.3390/molecules25071516
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Physiological (Pharmacological) Antidote
2- Acceleration of Detoxification
• Some antidotes help to speed up the process of conversion of the
poison to a non-toxic substance.
• First example is the action of N-acetylcysteine in accelerating the
detoxification of potentially toxic metabolites during paracetamol
poisoning.

N-acetylcysteine (NAC): Carbocisteine

ATC code: V03AB23 ATC code: R05CB03
Aruwa, C. E., Mukaila, Y. O., Ajao, A. A. N., & Sabiu, S. (2020). An appraisal of antidotes’ effectiveness: Evidence of the use of phyto-antidotes
and biotechnological advancements. Molecules, 25(7), 1–27. https://doi.org/10.3390/molecules25071516
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Physiological (Pharmacological) Antidote
2- Acceleration of Detoxification
• NAC is a glutathione donor that
acts in the liver by the conjugation
of glutathione with N-acetyl-P-
benzoquinoneimine.

https://en.wikipedia.org/wiki/Paracetamol_poisoning
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Physiological (Pharmacological) Antidote
2- Acceleration of Detoxification

H-γGlu-Cys-Gly-OH
XCG

https://www.psychiatrictimes.com/view/exploring-n-acetylcysteine-in-psychiatry
https://pubchem.ncbi.nlm.nih.gov/compound/Glutathione#section=Biologic-Description
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Physiological (Pharmacological) Antidote
2- Acceleration of Detoxification
• Thiosulphate (ATC code: V03AB06) accelerates the conversion of
cyanide to thiocyanate, a non-toxic substance.

https://study.com/academy/lesson/what-is-sodium-thiosulfate-formula-properties.html
Aruwa, C. E., Mukaila, Y. O., Ajao, A. A. N., & Sabiu, S. (2020). An appraisal of antidotes’ effectiveness: Evidence of the use of phyto-antidotes
and biotechnological advancements. Molecules, 25(7), 1–27. https://doi.org/10.3390/molecules25071516
18
Cyanide poisoning management
• The United States standard cyanide antidote kit first uses a small
inhaled dose of amyl nitrite (ATC code: V03AB22), followed by
intravenous sodium nitrite (ATC code: V03AB08), followed by
intravenous sodium thiosulfate (ATC code: V03AB06).

Amyl nitrite Sodium nitrite Sodium thiosulfate

https://en.wikipedia.org/wiki/Cyanide_poisoning
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 Cyanide poisoning management
• The nitrites oxidize some of the
hemoglobin's iron from the ferrous state to
the ferric state, converting the hemoglobin
into methemoglobin.

• Cyanide binds to methemoglobin, forming

cyanmethemoglobin, thus releasing
cyanide from cytochrome oxidase.
https://en.wikipedia.org/wiki/Cyanide_poisoning
Shepherd, G., & Velez, L. I. (2008). Role of Hydroxocobalamin in Acute Cyanide Poisoning. Annals of Pharmacotherapy, 42(5), 661–669.
https://doi.org/10.1345/aph.1K559

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 Cyanide poisoning management
• Hydroxocobalamin (ATC code: V03AB33) is a form of vitamin B12
which binds with cyanide to form the harmless cyanocobalamin
(another form of vitamin B12).

Hydroxocobalamin Cyanocobalamin

https://en.wikipedia.org/wiki/Cyanide_poisoning
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Physiological (Pharmacological) Antidote
3- Reduced Toxicity
• There are antidotes that reduce the toxicity of poisons by either
facilitating the conversion of the poison to a less toxic substance or
inhibiting the conversion to a potentially toxic substance.

• For example: in methanol poisoning, ethanol (ATC code: V03AB16)

inhibits the conversion of methanol to toxic metabolites by competing
with the methanol for alcohol dehydrogenase, the enzyme that is
required for the process.

Aruwa, C. E., Mukaila, Y. O., Ajao, A. A. N., & Sabiu, S. (2020). An appraisal of antidotes’ effectiveness: Evidence of the use of phyto-antidotes
and biotechnological advancements. Molecules, 25(7), 1–27. https://doi.org/10.3390/molecules25071516
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Physiological (Pharmacological) Antidote
3- Reduced Toxicity

https://theskepticalchemist.com/methanol-toxic-ethanol/
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Physiological (Pharmacological) Antidote
4- Target Site Blocker
• Some antidotes bind to the target site before the toxin,
thereby blocking the site and preventing the toxin from
binding.

• Fomepizole (ATC code: V03AB34) is an alcohol

dehydrogenase blocker that could reverse toxic alcohol
(methanol and ethylene glycol) poisoning.
Fomepizole

Aruwa, C. E., Mukaila, Y. O., Ajao, A. A. N., & Sabiu, S. (2020). An appraisal of antidotes’ effectiveness: Evidence of the use of phyto-antidotes
and biotechnological advancements. Molecules, 25(7), 1–27. https://doi.org/10.3390/molecules25071516
24
Chelating Agents
• These are antidotes that react with the poison to form an inert
complex which is not immediately harmful to the body and is later
removed from the body through excretion as it is more water-soluble
than the metal itself, resulting in higher renal excretion of the
complex.

• Good chelators must be easily absorbed from the gastrointestinal

tract (GIT), show minimal toxicity, low affinity for essential metals
within the organism it is administered to.
Aruwa, C. E., Mukaila, Y. O., Ajao, A. A. N., & Sabiu, S. (2020). An appraisal of antidotes’ effectiveness: Evidence of the use of phyto-antidotes
and biotechnological advancements. Molecules, 25(7), 1–27. https://doi.org/10.3390/molecules25071516
25
Chelating Agents
• For example:
2, 3-dimercaptosuccinic acid (DMSA) for lead and mercuury poisoning

DMSA Complex

Aruwa, C. E., Mukaila, Y. O., Ajao, A. A. N., & Sabiu, S. (2020). An appraisal of antidotes’ effectiveness: Evidence of the use of phyto-antidotes
and biotechnological advancements. Molecules, 25(7), 1–27. https://doi.org/10.3390/molecules25071516
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Chelating Agents
• For example:
B.A.L. (British anti-lewisite; dimercaprol; dimercaptopropanol)
(ATC code: V03AB09)
It is used as a physiological antidote in arsenic, lead, bismuth, copper,
mercury.

Kaushik, Y., & Patel, D. (2019). INTERNATIONAL ROLE OF ANTIDOTES IN POISONING - A REVIEW.
http://www.iamj.in/posts/2019/images/upload/602_608.pdf
27
Chelating Agents
• For example:
E.D.T.A. (ethylenediaminetetraacetic acid)
(ATC code: V03AB03)
It is a chelating agent and is effective in lead, mercury, copper, cobalt,
cadmium, iron and nickel poisoning.
Complex
E.D.T.A.

Kaushik, Y., & Patel, D. (2019). INTERNATIONAL ROLE OF ANTIDOTES IN POISONING - A REVIEW.
http://www.iamj.in/posts/2019/images/upload/602_608.pdf
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Recent Blood Thinner Antidotes
• The FDA approved andexanet alfa (ATC code: V03AB38) on 2018 as
antidote to reverse bleeding in people taking direct factor Xa inhibitor
as apixaban, rivaroxaban and edoxaban.
• Andexanet alfa is a recombinant activated factor X.
• FXa inhibitors bind to andexanet alfa with the same affinity as to
natural FXa.
• As a consequence in the presence of andexanet alfa natural FXa is
partially free.
https://www.health.harvard.edu/diseases-and-conditions/more-antidotes-for-newer-blood-
thinners#:~:text=The%20FDA%20approved%20andexanet%20alfa,%2C%20or%20edoxaban%20(Savaysa).
https://en.wikipedia.org/wiki/Andexanet_alfa#Mechanism_of_action
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Andexanet alfa

https://www.who.int/medicines/publications/druginformation/innlists/PL110.pdf
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Recent Blood Thinner Antidotes
• Another recent blood thinner dabigatran (ATC code: B01AE07) already
has an approved antidote called idarucizumab (ATC code: V03AB37).

• Dabigatran reversibly binds to the active site on the thrombin

molecule, preventing thrombin-mediated activation of coagulation
factors.

• Dabigatran FDA approval on 2010.

• Idarucizumab FDA approval on 2015.
https://en.wikipedia.org/wiki/Dabigatran
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Idarucizumab

Eikelboom, J. W., Quinlan, D. J., Van Ryn, J., & Weitz, J. I. (2015). Idarucizumab the antidote for reversal of dabigatran. Circulation, 132(25),
2412–2422. https://doi.org/10.1161/CIRCULATIONAHA.115.019628
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Idarucizumab

https://www.who.int/medicines/publications/druginformation/innlists/RL71.pdf?ua=1
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Reversal Of Neuromuscular Blockade
• Sugammadex is a medication for the reversal of
neuromuscular blockade induced by
Rocuronium (ATC code: M03AC09) and
Vecuronium (ATC code: M03AC03) in general
anesthesia.
• Sugammadex (ATC code: V03AB35) is a modified
γ-cyclodextrin (8 glucose subunits) with a
lipophilic core and a hydrophilic periphery.
• This gamma cyclodextrin has been modified
from its natural state by placing eight carboxyl
thioether groups at the sixth carbon positions. Sugammadex

https://en.wikipedia.org/wiki/Sugammadex
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Sugammadex
• These extensions extend the cavity size allowing
greater encapsulation of the rocuronium molecule.
• These negatively charged extensions electrostatically
bind to the quaternary nitrogen of the target. Rocuronium

Vecuronium

https://en.wikipedia.org/wiki/Sugammadex
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