Some Neurotoxic drugs

1. Neurotoxic
Drugs
Section 4

2. 03
Rotenone
01 Scopolamine
02
Organophosphates
TABLE OF CONTENTS

3. Rotenone
A natural compound, used as an
insecticide and a herbicide and for
lice and tick control on pets

4. Rotenone neurotoxicity
It causes blockade of oxidative phosphorylation with
limited synthesis of ATP
Rotenone causes oxidative stress and dopaminergic
neuronal loss (neurodegeneration and neuronal
apoptosis)
SO
increasing ROS production and
inhibiting mitochondrial respiration
Parkinsonism

5. Parkinson Disease

6. Rotenone toxicity management
N-acetylcysteine or antioxidants
Glutathione
precursor

7. Scopolamine
Is a drug used to prevent nausea and
vomiting caused by motion sickness
or postoperative
It is in a class of medications called
antimuscarinics

8. Scopolamine neurotoxicity
Alzheimer’s
disease
Scopolamine causes short-term and
long-term memory loss by blocking the
muscarinic cholinergic receptors in the
brain and interfering with learning
and memory.
Induces amyloid β (Aβ) deposition,
oxidative stress and
neurodegeneration

9. Scopolamine toxicity management
Physostigmine is recommended as an antidote
in cases of accidental overdosage of
anticholinergic drugs
It inhibits acetylcholinesterase, the enzyme
responsible for the breakdown of acetylcholine

10. Organophosphates
Organophosphates are the most
widely used insecticides today

11. Organophosphates neurotoxicity
Bind to AChE and prevent the breakdown of Ach
(cholinesterase inhibitor)
Accumulation of Ach and the continued stimulation of
its receptors causing cholinergic symptoms

13. Cholinergic symptoms

14. Organophosphates management
Gastric Lavage
Atropine Injection
PAM Injection [Pralidoxime injection]
PAM belongs to group of compounds called
oximes that bind to organophosphate
inactivated acetylcholinesterase
(regeneration)
1-2 gm for 15-30 minutes infusion repeat in 1
hour if necessary

15. Organophosphates management
Pralidoxime also should be given to affect the
nicotinic receptors since atropine only works on
muscarinic receptors
Pralidoxime is an effective antidote for
organophosphate poisoning only if the antidote is
administered before the “aging” process (i.e., within 24
hours of exposure), which stabilizes the
organophosphate-enzyme complex.

17. Case study

18. Case 1
A 27-year-old lady presented with blurring of vision in her right eye for
two days. She enjoyed good past health and had just returned to Hong
Kong after a trip to Korea.
On examination, the right pupil was dilated and non-reactive. She did
not have other symptoms and the rest of the examination was normal.
There was no history of recent use of any local eye medication. However,
on direct questioning, she gave the history of using a transdermal patch
for motion sickness given by the tour guide in Korea. She used the patch
for two days and her symptoms started on the second day after applying
the medication.

19. Case 1
She also recalled that she might rub the right eye after touching the
patch and therefore possibly acquire local contamination. We made the
diagnosis of scopolamine-induced mydriasis and treated her by
reassurance and follow up. Her symptom gradually subsided in about
three day

20. Case 2
A 28-year-old healthy lady who presented with acute confusion. She
suffered from motion sickness after a travel from China and consulted a
local general practitioner (GP) in Hong Kong. She received an
intramuscular injection for vomiting, oral diphenhydramine (50 mg) and
cinnarizine (25 mg). Four hours later, her husband brought her to
emergency department because of progressive confusion. Her vital signs,
including blood pressure (112/77 mmHg) and pulse (78 bpm), were
normal. On examination, we found dilated pupils, dry mucosa, as well as
decreased bowel sounds and made a provisional diagnosis of
anticholinergic poisoning. Although she had been given anticholinergic
agents (diphenhydramine and cinnarizine) by the GP, the dose was
normal and could not explain the clinical picture solely

21. Case 2
We looked particularly for the use of transdermal scopolamine patch
and found it behind the patient's left ear, which was initially covered by
hair. We removed the patch and treated her with slow intravenous
injection of physostigmine.
She responded promptly to normal mental status after 2 mg of
physostigmine without any cholinergic side effects. She remained
orientated and asymptomatic in the next eight hours and was discharged
from emergency department.

22. Question
What is the most likely explanation of the
patients toxicity symptoms?

23. Question
Why physostigmine was ordered to manage
the case?

24. Question
Why did scopolamine cause mydriasis in case 1?

25. Case 3
Presenting the case of 30 year old female patient admitted in new civil
hospital on 19/10/2016 at 10:40pm
The police was informed since poisoning was detected and it underwent
the case of Medico Legal Case.
History of ingestion of bug killing medicine.
On Examination
-Pupil was pin point

26. What is the most likely
toxicity reason?
Q1

27. What is a probable
management to this case?
Q2

28. What can be the reason of
pin point pupil
Q3

29. THANKS!