A Clinical discussion on organophosphorus poisoning! A glance at how actually a prescription must be! finding rational and irrational prescriptions!

1. CLINICAL CASE DISCUSSION
- Dr Nikita Ingale
- JR2
- Dept of Pharmacology
- GMCH Nagpur
PG GUIDE
- Dr Vijay Motghare
- Professor & head
- Dept of Pharmacology
- GMCH Nagpur

2. PATIENTS PROFILE
29-07-2019ORGANOPHOSPHORUS POISONING 2
• Name – xyz
• Age – 27 yrs
• Sex- Male
• Registration no - ------
• Ward – ward --
• Date of admission – 16/06/2018 at 1:00 am

3. ADMISSION NOTES
29-07-2019ORGANOPHOSPHORUS POISONING 3
- Pt admitted to wd [ MICU] through casualty reference from Rural hospital with
history of consumption of CHLORPYRIFOS at 7 pm last night
- Patient relatives were unaware of the amount of substance consumed
- Chief complaints  5 episodes of vomiting
-  frothy saliva in the mouth

4. 29-07-2019ORGANOPHOSPHORUS POISONING 4
- No history of alcohol consumption
- No history of seizures
- No history of psychiatric illness
- No history of diabetes mellitus / hypertension
ADMISSION NOTES

5. 29-07-2019
ORGANOPHOSPHORUS POISONING
5
MICU Registrar notes on 16/06/18 at 1:00 am
On examination:-
 General condition – not stable
 Afebrile
 Conscious, irritable
 Pulse – 110/min
 BP – 130/90 mm hg
 RR – 30/min
 SPO2 – 95%
 Liver, spleen – not palpable
 RS- clear
 Air entry – normal
 Pin point pupil – present
 Fasciculations +
 Smell of organophosphorus +

6. 29-07-2019
ORGANOPHOSPHORUS POISONING
6
Treatment notes on 16/06/18 at 1:00 am by
registrar
- Folleys catheter and Ryles tube inserted under aseptic condition
- Patients Clothes changed
- Gastric lavage done stat
 Inj. Atropine 2 cc every 2 mins for 15 mins till atropinisation
 Inj PAM 2 g stat f/b 0.5g/hr till 12g
 Inj Taxim 1 g IV TDS
 Inj. Rantac 50 mg IV BD
 Inj. Emset 4 mg IV TDS
 IV fluids – DNS 1 pint & NS 2 pint & RL 2 Pint
ADVISED-
MLC
CBC, KFT , LFT
ECG
Consent
Serum cholinesterase
BP 2 hrly

7. REPORTS OF THE ADVISED INVESTIGATIONS
29-07-2019ORGANOPHOSPHORUS POISONING 7
- Sr Cholinestrase 391.7 IU/L
- Hb = 11.7 gm %
- Platelets= 3.05 lakhs
- TLC = 10.1 x 10-3/ mm3
- SGOT = 96
- SGPT = 52
- Na+ = 144
- K+ = 45
- Total protein = 6.7 gm %
- Total bilirubin =0.8 gm %

8. ORGANOPHOSPHORUS POISONING
Treatment notes on 16/06/18 at 8:00 am by
registrar
 Inj. Atropine 2 cc every 15 mins
 Inj PAM 2 g stat f/b 0.5g/hr till 12g
 Inj Taxim 1 g IV TDS
 Inj. Rantac 50 mg IV BD
 Inj. Emset 4 mg IV TDS
 IV fluids – DNS 1 pint & NS 2 pint & RL 2 Pint
 Gastric lavage done again
- General condition = fair
- BP = 116/70 MM Hg
- RBS = 108
- Urine output = 1500 ml overnight
- SP02 = 98%
- Resp rate = 26/ min
- Pulse = 84/ min
- Systemic examination = irritable
Fasciculations +, mid-dilated pupils+

9. ORGANOPHOSPHORUS POISONING
Treatment notes on 16/06/18 at 2:00 pm by lecturer
 Inj. Atropine 2 cc every 15 mins
 Inj PAM 2 g stat f/b 0.5g/hr till 12g
 Inj Taxim 1 g IV TDS
 Inj. Rantac 50 mg IV BD
 Inj. Emset 4 mg IV TDS
 IV fluids – DNS 1 pint & NS 2 pint & RL 2 Pint
 Gastric lavage done again
- General condition = fair
- BP = 116/70 MM Hg
- RBS = 108
- Urine output = 1500 ml overnight
- SP02 = 98%
- Resp rate = 33/ min
- Pulse = 82/ min
- Systemic examination = irritable
Fasciculations +, mid-dilated pupils+

10. 29-07-2019ORGANOPHOSPHORUS POISONING 10
Treatment notes on 16/06/18 at 8:00 pm by
registrar
 Inj. Atropine 2 cc every 15 mins - General condition = fair
- BP = 126/70 mm Hg
- RBS = 110
- Urine output = 1500 ml overnight
- SP02 = 98%
- Resp rate = 28/ min
- Pulse = 80/ min
- Systemic examination = irritable
Fasciculations +, mid-dilated pupils+

11. 29-07-2019ORGANOPHOSPHORUS POISONING 11
Treatment notes on 17/06/18 at 8:00 am by
registrar
Fasciculations +, mid-dilated pupils+
- General condition = fair
- BP = 110/70 mm Hg
- RBS = 110
- Urine output = 1300 ml overnight
- SP02 = 98%
- Resp rate = 20/ min
- Pulse = 78/ min
- Systemic examination = irritable
 Inj. Atropine 2 cc every 15 mins
 Inj Taxim 1 g IV TDS
 Inj. Rantac 50 mg IV BD
 Inj. Emset 4 mg IV TDS
 IV fluids – DNS 1 pint & NS 2 pint & RL 2 Pint

12. 29-07-2019ORGANOPHOSPHORUS POISONING 12
Treatment notes on 17/06/18 at 11:00 am by
lecturer
Fasciculations +, mid-dilated pupils+
- General condition = fair
- BP = 118/70 mm Hg
- RBS = 118
- Urine output = 1300 ml overnight
- SP02 = 98%
- Resp rate = 20/ min
- Pulse = 74/ min
- Systemic examination = irritable
 Inj. Atropine 2 cc every 15 mins stat

13. 29-07-2019ORGANOPHOSPHORUS POISONING 13
Treatment notes on 17/06/18 at 2:00 pm by
registrar
Fasciculations +, mid-dilated pupils+
- General condition = fair
- BP = 110/70 mm Hg
- RBS = 118
- Urine output = 1300 ml overnight
- SP02 = 98%
- Resp rate = 20/ min
- Pulse = 72/ min
- Systemic examination = irritable
 Inj. Atropine 2 cc every 15 mins
 Inj Taxim 1 g IV TDS
 Inj. Rantac 50 mg IV BD
 Inj. Emset 4 mg IV TDS
 IV fluids – DNS 1 pint & NS 2 pint & RL 2 Pint

14. 29-07-2019ORGANOPHOSPHORUS POISONING 14
Treatment notes on 17/06/18 at 8:00 pm by
registrar
Fasciculations +, mid-dilated pupils+
- General condition = fair
- BP = 118/70 mm Hg
- RBS = 120
- Urine output = 1300 ml overnight
- SP02 = 98%
- Resp rate = 12/ min
- Pulse = 80/ min
- Systemic examination = irritable
 Inj. Atropine 2 cc every 15 mins
 Inj Taxim 1 g IV TDS
 Inj. Rantac 50 mg IV BD
 Inj. Emset 4 mg IV TDS
 IV fluids – DNS 1 pint & NS 2 pint & RL 2 Pint

15. 29-07-2019ORGANOPHOSPHORUS POISONING 15
Treatment notes on 18/06/18 at 8:00 am by
registrar
Fasciculations +, mid-dilated pupils+
- General condition = fair
- BP = 120/70 mm Hg
- RBS = 108
- Urine output = 1200 ml overnight
- SP02 = 98%
- Resp rate = 12/ min
- Pulse = 78/ min
- Systemic examination = irritable
 Propped up position
 Inj. Atropine 2 cc every 15 mins
 Inj Taxim 1 g IV TDS
 Inj. Rantac 50 mg IV BD
 Inj. Emset 4 mg IV TDS
 IV fluids – DNS 1 pint & NS 2 pint & RL 2 Pint

16. 29-07-2019ORGANOPHOSPHORUS POISONING 16
Treatment notes on 18/06/18 at 6:00 pm by
registrar
Fasciculations +, mid-dilated pupils+
- General condition = fair
- BP = 122/70 mm Hg
- RBS = 108
- Urine output = 1200 ml overnight
- SP02 = 98%
- Resp rate = 24/ min
- Pulse = 74/ min
- Systemic examination = irritable
 Propped up position
 Inj. Atropine 2 cc every 15 mins
 Inj Taxim 1 g IV TDS
 Inj. Rantac 50 mg IV BD
 Inj. Emset 4 mg IV TDS
 IV fluids – DNS 1 pint & NS 2 pint & RL 2 Pint

17. 29-07-2019ORGANOPHOSPHORUS POISONING 17
Treatment notes on 19/06/18 at 2:00 am by
registrar
Fasciculations +, mid-dilated pupils+
- General condition = fair
- BP = 120/70 mm Hg
- RBS = 108
- Urine output = 1200 ml overnight
- SP02 = 98%
- Resp rate = 28/ min
- Pulse = 78/ min
- Systemic examination = irritable
 Propped up position
 Inj. Atropine 2 cc every 15 mins
 Inj Taxim 1 g IV TDS
 Inj. Rantac 50 mg IV BD
 Inj. Emset 4 mg IV TDS
 IV fluids – DNS 1 pint & NS 2 pint & RL 2 Pint

18. 29-07-2019ORGANOPHOSPHORUS POISONING 18
Treatment notes on 19/06/18 at 10:00 am by Associate
professor
Fasciculations +, mid-dilated pupils+
- General condition = fair
- BP = 110/70 mm Hg
- RBS = 110
- Urine output = 1300 ml overnight
- SP02 = 98%
- Resp rate = 28/ min
- Pulse = 70/ min
- Systemic examination = irritable
 Propped up position
 Inj PAM 2 g stat f/b 0.5g/hr till 12g
 Inj. Atropine 2 cc every 15 mins
 Inj Taxim 1 g IV TDS
 Inj. Rantac 50 mg IV BD
 Inj. Emset 4 mg IV TDS
 IV fluids – DNS 1 pint & NS 2 pint & RL 2 Pint

19. 29-07-2019ORGANOPHOSPHORUS POISONING 19
Treatment notes on 19/06/18 at 8:00 pm by
registrar
Fasciculations -, mid-dilated pupils+
- General condition = fair
- BP = 108/70 mm Hg
- RBS = 115
- Urine output = 1300 ml overnight
- SP02 = 98%
- Resp rate = 30/ min
- Pulse = 76/ min
- Systemic examination = irritable
 Propped up position
 Inj PAM 2 g stat f/b 0.5g/hr till 12g
 Inj. Atropine 2 cc every 15 mins
 Inj Taxim 1 g IV TDS
 Inj. Rantac 50 mg IV BD
 Inj. Emset 4 mg IV TDS
 IV fluids – DNS 1 pint & NS 2 pint & RL 2 Pint

20. 29-07-2019ORGANOPHOSPHORUS POISONING 20
Treatment notes on 20/06/18 at 8:00 am by
registrar
Fasciculations -, mid-dilated pupils+
- General condition = fair
- BP = 112/70 mm Hg
- RBS = 110
- Urine output = 1300 ml overnight
- SP02 = 98%
- Resp rate = 22/ min
- Pulse = 76/ min
- Systemic examination = irritable
 Propped up position
 Inj PAM 2 g stat f/b 0.5g/hr till 12g
 Inj. Atropine 2 cc every 15 mins
 Inj Taxim 1 g IV TDS
 Inj. Rantac 50 mg IV BD
 Inj. Emset 4 mg IV TDS
 IV fluids – DNS 1 pint & NS 2 pint & RL 2 Pint

21. 29-07-2019ORGANOPHOSPHORUS POISONING 21
Treatment notes on 20/06/18 at 11:00 am by
registrar
Fasciculations -, mid-dilated pupils+
- General condition = fair
- BP = 110/70 mm Hg
- RBS = 110
- Urine output = 1300 ml overnight
- SP02 = 98%
- Resp rate = 22/ min
- Pulse = 72/ min
- Systemic examination = normal
 Patient vitals stable
 Transferred to ward 23
 Inj. Atropine 2 cc stat
 Inj. Midaz 2cc stat

22. 29-07-2019ORGANOPHOSPHORUS POISONING 22
Treatment notes on 20/06/18 at 8:00 pm by
registrar
Fasciculations -, mid-dilated pupils+
- General condition = fair
- BP = 110/80 mm Hg
- RBS = 110
- Urine output = 1200 ml overnight
- SP02 = 98%
- Resp rate = 24/ min
- Pulse = 70/ min
- Systemic examination = normal
 Inj. Atropine 2 cc stat

23. 29-07-2019ORGANOPHOSPHORUS POISONING 23
Treatment notes on 21/06/18 at 11:00 am by
registrar
Fasciculations -, mid-dilated pupils+
- General condition = fair
- BP = 110/70 mm Hg
- RBS = 110
- Urine output = 1300 ml overnight
- SP02 = 98%
- Resp rate = 22/ min
- Pulse = 72/ min
- Systemic examination = normal
 Inj. Atropine 2 cc stat

24. 29-07-2019ORGANOPHOSPHORUS POISONING 24
Treatment notes on 22/06/18 at 8:00 pm by
registrar
Fasciculations -, mid-dilated pupils+
- General condition = fair
- BP = 110/80 mm Hg
- RBS = 110
- Urine output = 1200 ml overnight
- SP02 = 98%
- Resp rate = 24/ min
- Pulse = 70/ min
- Systemic examination = normal
 Inj. Atropine 2 cc stat

25. 29-07-2019ORGANOPHOSPHORUS POISONING 25
Treatment notes on 23/06/18 at 11:00 am by
registrar
Fasciculations -, mid-dilated pupils+
- General condition = fair
- BP = 110/70 mm Hg
- RBS = 110
- Urine output = 1300 ml overnight
- SP02 = 98%
- Resp rate = 22/ min
- Pulse = 72/ min
- Systemic examination = normal
 Inj. Atropine 2 cc stat

26. 29-07-2019ORGANOPHOSPHORUS POISONING 26
Treatment notes on 23/06/18 at 8:00 pm by
registrar
Fasciculations -, mid-dilated pupils+
- General condition = fair
- BP = 110/80 mm Hg
- RBS = 110
- Urine output = 1200 ml overnight
- SP02 = 98%
- Resp rate = 24/ min
- Pulse = 80/ min
- Systemic examination = normal
 Inj. Atropine 2 cc stat

27. 29-07-2019ORGANOPHOSPHORUS POISONING 27
Treatment notes on 24/06/18 at 11:00 am by
registrar
Fasciculations -, mid-dilated pupils+
- General condition = fair
- BP = 110/70 mm Hg
- RBS = 110
- Urine output = 1300 ml overnight
- SP02 = 98%
- Resp rate = 22/ min
- Pulse = 72/ min
- Systemic examination = normal
 Inj. Atropine 2 cc stat
 Folley removed
 Patient requested for DAMA

28. CURRENT STATUS OF THE PATIENT
29-07-2019ORGANOPHOSPHORUS POISONING 28
- Patient was discharged as per DAMA request on 24/06/18 at 2:00 pm
- Patient had stable vitals, mid dilated pupils, no fasciculations

29. 29-07-2019ORGANOPHOSPHORUS POISONING 29
Discussion

30. 29-07-2019ORGANOPHOSPHORUS POISONING 30
AGRICULTURAL
POISONS
INSECTICIDAL
ORGANOPHOS-
PHOROUS
ORGANOCHLO-
RINES
CARBAMATES
MISCELLANEOUS:
PYRETHRINES &
PYRETHROIDS
HERBICIDAL RODENTICIDAL FUNGICIDAL

31. ORGANOPHOSPHOROUS COMPOUNDS:
 Comprise of the ester, amide or thiol derivatives of phosphoric acid
 Most commonly used as pesticides in commercial agriculture, field sprays and as
household chemicals.
Chemically classified as :
 A) ALKYL
 B) ARYL
 C) OTHERS 31

32. 29-07-2019ORGANOPHOSPHORUS POISONING 32
A) ALKYL
Chem. Constituent Trade Names
1) Malathion Malathion
2)Chloropyriphos Blase, Durshbnnan, Hyban, Pyriban, Trishul 20 EC,
Chlorguard
B) ARYL :
C) OTHERS :
Chem. Constituent Trade Names
1) Methyl Parathion Paradol, Paradol 2 DP, Dhanumar
2) Others : Paraoxon, Chlorotion, Diazinon ,Parathion
Chem. Constituent Trade Names
1) Phorate Thimet
2) Methyl Demeton Metasystox

33. There are more than a hundred organophosphorus compounds in common use, classified
according to their toxicity and clinical use:
1. Highly toxic organophosphates :
(e.g. Tetra-ethyl pyrophosphates, Parathion) mainly used as agricultural insecticides.
2. Intermediately toxic organophosphates :
(e.g. Coumaphos, Chlorpyrifos, Trichlorfon used as animal insecticides.
3. Low toxicity : (e.g. Diazinon, Malathion, Dichlorvos) used for household application
and as field sprays.
33
CLASSIFICATION

34.  Highly lipid soluble compounds
 Well absorbed by: transdermal, transconjunctival, inhalational, across g.i. and g.u. mucosa
& through direct injection.
 Rapidly redistributed to all body tissues.
 Highest concentrations : in the liver and kidneys.
 Cross the blood/brain barrier, produce potent effects on the CNS.
34
PHARMACOKINETICS

35. CLINICAL PRESENTATION
Muscarinic Nicotinic effects CNS effcts
Salivation
Lacrimation
Urination
Diarrhoea
GI upset
Emesis
- Muscle weakness
and fasciculation
-Cramping of
skeletal muscle
-Tachycardia
Headache
Dizziness
Confusion
Drowsiness
Coma
Respiratory
depression
CCD- OP POISONING

36. 29-07-2019ORGANOPHOSPHORUS POISONING 36

37. DIAGNOSIS :
 Requires a high index of suspicion : history of exposure and typical clinical features.
 Helpful signs :
pungent garlic-like odour of organophosphorous in breath and vomitus,
miosis, bradycardia, muscle fasciculations.
 Excessive salivation, excessive respiratory tract secretions and lacrimation are other
helpful signs.
37

38. TREATMENT :
Decontamination :
 Remove all clothing
 Thorough skin wash with soap and water
 If ocular exposure has occurred, copious eye irrigation with normal saline
Gastric lavage :
 In case of ingestion, stomach wash is given
 Lavage is preferred to enforced emesis as emesis may lead to aspiration pneumonitis 38

39. Airway and respiration :
 Maintainence of airway & O2 inhalation.
 Place the patient in the left lateral position, ideally in a head-down position, to reduce the
risk of aspiration.
 Extension of the neck in this position helps to keep the airway patent.
Anticholinergics :
 Atropine: antagonizing the muscarinic effects of the organophosphate on the CNS,
gastrointestinal tract is the mainstay of treatment. 39
TREATMENT :

40. IV Atropine
- 2 mg/15 min (adult) &
0.05 mg/kg/15 min (children)
till full atropinisation.
Maintainance dose:-
 Start hourly atropine infusion at 20% of
total dose of atropine required for
atropinisation for 7 days 40
ATROPINE
Target end-points for Atropine
therapy :
- Clear chest on auscultation with no wheeze
- Heart rate > 80/min
- Pupils no longer pinpoint
- Dry axillae
- Systolic blood pressure > 80 mm Hg

41. ATROPINE TOXICITY
29-07-2019 41
Atropine toxicity :
- Blind as a bat (photophobia)
- Hot as a hare (hyperpyrexia)
- Dry as a bone (dry mouth, skin)
- Red as a beet (flushing)
- Mad as a wet hen/ hatter (hallucinations)

42. CHOLINESTERASE REACTIVATORS:
 Oximes reactivate acetylcholinesterase inhibition by Organophosphorus.
 AChE activating enzymes are PAM2, Obidoxime, diacetylmono-oxime [DAM]
 SHORTCOMINGS – 1] not useful if enzyme has undergone the process of ageing
 2] ineffective in carbamate poisoning
 3] cannot cross blood brain barrier
42

43. PAM2 reactivates AChE by attaching with the
anionic site in the phosphorylated enzyme
The oxime group attracts the phosphate group
(phosphate transfer to –NOH group of 2-PAM)
The oxime-phosphonate complex diffuses out,
leaving the regenerated AChE enzyme in active
form
PRALIDOXIME
H2O

44. 29-07-2019ORGANOPHOSPHORUS POISONING 44
WHO guidelines recommended
1] giving a 30 mg/kg loading dose of Pralidoxime over 10-20 min followed
by a continuous infusion of 8-10 mg/kg/hr until clinical recovery or seven
days

45. RATIONALITY
29-07-2019ORGANOPHOSPHORUS POISONING 45
 Inj Atropine = Life saving antidote
 Inj Pralidoxime - Cholinesterase reactivator
 Inj Taxim - To avoid hospital acquired infections
 IV Fluids- To compensate fluid loss due to vomiting

46. IRRATIONALITY
29-07-2019ORGANOPHOSPHORUS POISONING 46
- Injection Atropine – patient not monitored for signs of atropinisation
- maintaince dose used is not proper
- Injection Midaz- no indication for the use of this drug
- No monitoring of levels of Sr Cholinestrase enzyme
- Inj PAM2 = maintainance doses not given properly
- Brand names of the drug used

47. Suicide is never the
solution!
SAY NO TO SUICIDE!
Next PG Activity-
Clinical case disussion
By Dr Shubhangi Gawade

48. 29-07-2019ORGANOPHOSPHORUS POISONING 48

49. 29-07-2019ORGANOPHOSPHORUS POISONING 49

50. 29-07-2019ORGANOPHOSPHORUS POISONING 50

51. 29-07-2019 51
presynapti
c
presynapti
c
presynapti
c
postsynaptic postsynaptic
Acetyl choline cholinestrase
MECHANISM OF ACTION