This document discusses anticholinesterase poisoning from organophosphorus compounds. It covers the clinical features of organophosphorus poisoning including signs and symptoms due to excessive acetylcholine levels. Management includes atropine to block muscarinic receptors, pralidoxime as an enzyme reactivator, and supportive care. Atropine has anticholinergic effects and specific contraindications. Some synthetic drugs are similar to atropine but have more selective effects and fewer side effects for uses like mydriasis, gastrointestinal spasms, asthma, and parkinsonism.

1. • DR BADAR UDDIN UMAR
DRUGS ACTING ON THE ANS
ANTICHOLINESTERASE POISONING
ANTICHOLINERGIC DRUGS
LECTURE - 2

2. LEARNING OBJECTIVES:
At the end of this session the we shall be able to –
• Discuss the clinical features and drug treatment
of organophosphorus poisoning
• Explain the role of enzyme reactivators in
organophosphorus poisoning
• List and explain the adverse effects and
contraindications of atropine
• Discuss the aspects of pharmacokinetics, routes and
dosage of clinically important/ commonly used
drugs

3. ORGANOPHOSPHORUS POISONING
• Poisoning with organophosphorus
compounds (OPCs) may occur by –
• Accidental exposure during spraying
insecticides or in industry
• Suicidal poisoning
• Homicidal poisoning (rare)
• War gas exposure

4. OPC POISONING
• Acetylcholine esterase enzymes (AChE) of the
body will be destroyed
• Covalent phosphorus-enzyme bond
• Phosphorylation
• There will be massive (Acetylcholine) ACh
accumulation in the body…….ACh toxicity

5. ORGANOPHOSPHORUS COMPOUNDS
• Organophosphates are pentavalent phosphorus
compounds containing a labile group such as -
• Fluoride (in dyflos) or an
• Organic group (in parathion and ecothiopate)
• This group is released, leaving the serine hydroxyl
group (-SH) of the enzyme phosphorylated

6. ORGANOPHOSPHORUS COMPOUNDS
• The inactive phosphorylated enzyme is usually
very stable
• When phosphorylated by OPCs, AChE have no
ability to hydrolyze ACh and
• Recovery of enzymatic activity depends on the
synthesis of new enzyme molecules
• This may take weeks
• With ecothiopate, slow hydrolysis occurs over the course of a
few days, so that their action is not strictly irreversible

7. ORGANOPHOSPHORUS COMPOUNDS
• Dyflos and parathion are volatile non-polar
substances of very high lipid solubility
• Are rapidly absorbed through mucous membranes
and even through unbroken skin and insect cuticles
• Due to this they can be used as war gases or
insecticides

9. SIGNS AND SYMPTOMS OF OPC POISONING:
 All s/s are due to ….excessive level of Ach in the
body
 Muscarinic actions will lead to-
 Eye - Constricted pupils (Miosis), blurred vision, eye ache,
conjunctival congestion, brow ache
 Glands - Profuse Sweating, Salivation, Rhinorrhea &
Lacrimation
  GIT movement… Nausea, Vomiting, Diarrhea with
abdominal cramps

10. S/S OF OPC POISONING CONT.….
DUE TO MUSCARINIC ACTIONS…..
 Genito urinary - Urgency for urination and
spontaneous voiding and penile erection (in severe
case)
 Bronchospasm, bronchial secretion Difficulty in
breathing
 Pulse rate/ Bradycardia
 Hypotension
 Collapse

11. SIGNS AND SYMPTOMS OF OPC POISONING
CONT.….
Nicotinic effects
• Fasciculation (early)
• Weakness (late)
• Paralysis
• Adrenomedullary discharge
(sympathetic, early and
transient)
CNS Effects
• Anxiety
• Insomnia
• Nightmares
• Confusion
• Tremors
• Convulsions
• Respiratory depression
• Circulatory collapse

12. S/S OF OPC POISONING FOR EASY REMEMBERING:
DUMBBELLS…… stands for
• Diarrhea
• Urgency for Urination
• Miosis
• Bradycardia
• Bronchospasm
• Emesis
• Lacrimation
• Laxation and
• Salivation

13. MANAGEMENT OF OPC POISONING:
The therapy of organophosphate poisoning is known
by the catchy acronym - AFLOP:
 Atropine
 Fluids
 Oxygen
 Pralidoxime

14. MANAGEMENT OF OPC POISONING:
General measures:
 Termination of exposure by -
 Removal of clothes etc. that are contaminated
 Washing the whole body
 Gastric lavage
 Cleaning the airways for easy respiration
 Oxygen therapy and artificial respiration if needed
 IV fluid for correction of dehydration and shock
 IV Diazepam for convulsion

15. MANAGEMENT OF OPC POISONING:
Drugs used in OPC poisoning:
A) Atropine:
 It is the antagonist of Ach
 It will block the MR &
 Will prevent the effects of Ach

16. MANAGEMENT OF OPC POISONING:
Dose of atropine:
1-2 mg IM or IV immediately
Repeated 5-15 min…..until signs of atropinization
 Dryness of mouth
 Reversal of miosis (mydriasis)
 HR: above 70/min

17. MANAGEMENT OF OPC POISONING:
B) Enzyme reactivator / regenerator
 Reactivate or regenerate AChE enzyme
 So AChE will be free again and metabolize ACh
Oximes -
 PAM (Pralidoxime) &
 DAM (Diacetylmonoxime)

18. MANAGEMENT OF OPC POISONING:
Oximes
 The oxime group (=NOH) has a high affinity for
phosphorous atom
 So, can hydrolyze the phosphorylated AChE enzyme
 Should be given within 12 hrs. of poisoning, after
that can‟t be reversed (stabilized by ‘aging’)

21. AGING
OF
ACETYLCHOLINESTERASE

22. LOSS OF AN ALKYL GROUP FROM PHOSPHORYLATED
ACHE “AGES” THE ENZYME
AChE, phosphorylated
and inhibited by DFP
“Aged” AChE

23. “AGING” OF PHOSPHORYLATED- ACHE

24. ADVERSE EFFECTS OF ATROPINE
ANTICHOLINERGIC DRUG

25. ADVERSE EFFECTS OF ATROPINE
• Dry mouth
• Blurred vision
• Tachycardia
• Constipation
• Urinary hesitancy and retention
• Atropine poisoning
25

26. CONTRAINDICATIONS OF ATROPINE….
• Glaucoma
• Elderly males with enlarged prostate
• Paralytic ileus
• Ulcerative colitis
• Gastroesophageal reflux
• Tachycardia
• Cardiac insufficiency
26

27. ATROPINE-LIKE DRUGS
• Atropine has got wide-spread effect
• So, it produces many side-effects
• There are some Atropine-like synthetic drugs
• which are used clinically for different conditions

28. Atropine-like synthetic drugs
• These drugs have got more effect in that
specific purpose &
• has less side-effects than atropine

29. ATROPINE-LIKE SYNTHETIC DRUGS
• Atropine-like Mydriatic drugs
• Atropine-like antispasmodic drugs
• Atropine-like antiasthmatic drugs
• Atropine-like antiparkinsonic drugs

31. ATROPINE-LIKE MYDRIATICS:
• Homatropine
• Eucatropine
• Cyclopentolate
• Tropicamide

32. ATROPINE-LIKE MYDRIATICS:
• Atropine-like synthetic drug
• Duration of action: shorter than atropine
• Effect of atropine lasts for about 1 week
• Effects are like atropine but less side effects

33. ATROPINE-LIKE MYDRIATICS:
Used in eye for …..
• Mydriasis for Funduscopic examination
• Accurate measurement of refractory error…. Specially
for un-cooperative patients & young children (ciliary
paralysis is required)
• Prevention of synechia (adhesion) formation in uveitis
& iritis

34. ATROPINE-LIKE MYDRIATICS:
Homatropine
Duration : duration about 2-3 days
Cyclopentolate
• Duration : duration about 1 day
Tropicamide
• More shorter duration of action: 6 hrs.

35. ATROPINE-LIKE MYDRIATICS:
• Now-a-days, antimuscarinics are less used for
opthalmoscopic examination if there is no need of
long lasting effect
• Alpha-adrenergic stimulants (e.g., phenylephrine)
are used for their short-lasting mydriatic effect,
specially for funduscopic examination

37. ATROPINE-LIKE ANTISPASMODICS:
• Dicycloverine (Dicyclomine)
• Oxybutynin
• Propantheline
• Hyoscine butylbromide

38. ATROPINE-LIKE ANTISPASMODICS:
Dicycloverine (Dicyclomine)
• Tertiary amine
• More lipid soluble
• More absorbed
• More CNS effect
• Has some direct action on smooth muscle

39. ATROPINE-LIKE ANTISPASMODICS:
Propantheline
Hyoscine butylbromide
• Quaternary ammonium compound
• Less lipid soluble
• Less absorbed
• Less CNS effect
• More appropriate as GIT antispasmodics

40. ATROPINE-LIKE ANTISPASMODICS:
These are selective … less side-effects
Mainly used for….
• Traveler's diarrhea
• Peptic ulcer disease
• Spasmodic pain in GIT
• IBS (irritable bowel syndrome)

42. ATROPINE-LIKE ANTIASTHMATIC:
• Ipratropium
• Tiotropium (longer duration of action)
Selective effect in bronchus
• Used in bronchial asthma
• Given by inhalation in bronchial Asthma

44. ATROPINE-LIKE ANTIPARKINSONIC DRUGS:
• Benztropine
• Orphenadrine
• Procyclidine
Selective effect in brain
• Decreases Ach effect in basal ganglia
• Decreases tremor, rigidity in parkinsonism

45. LEARNING OUTCOMES:
• At the end of this session the students will be able to –
• Discuss the clinical features and drug treatment of
insecticide (organophosphorus) poisoning
• Explain the role of enzyme reactivators and the
importance of „aging‟ in organophosphorus poisoning
• List the adverse effects and contraindications of
atropine and explain the reasons of the same
• Discuss the aspects of pharmacokinetics, routes and
dosage of clinically important/ commonly used drugs
like atropine