Presemtation fulling covering the organosphosphate poisoning

1. SHANZA AMAAN
Postgraduate trainee FCPS-II
MEDCINIE UNIT 1
CMCH LARKANA

3. OBJECTIVES:
•INTRODUCTION
•TYPES
•EXPOSURE
•ABSORPTION ROUTE
•PHARMACOKINETICS
•MECHANISM OF ACTION
•Cholinergic receptors
•CLINICAL FEATURES
•DIAGNOSIS
•MANAGEMENT
•PREVENETION

4. INTRODUCTION
•Organophosphate compounds are a diverse group of
chemicals used in both domestic & industrial setting,
mainly in agriculture. They have been used as
insecticide world wide. There are no rules and
regulations in purchase of these compounds and
readily available over the counter despite being a
major cause of morbidity and mortality. Exposure to
Organophosphate to commit suicide is a key problem
in developing countries and is a more common cause
of poisoning than the chronic exposure experienced
by farmers in contact with pesticide.

7. INTRODUCTION
•Organophosphorus compounds (OP) are organic
derivate of phosphorus that have largely been used as
pesticides and nerve agents.
•OP pesticides are used in commercial agriculture to
control pests on fruits and vegetables crops.
•They are also used in home gardens , for flea control
on pets.
•some OP compounds are also used for Theraptic
purpose such as ecothiopate used in the treatment of
glaucoma to reduce Intraocular pressure.

8. •At the beginning of world war II the development of
OP substances switched to highly toxic compounds
used as warfare agents (e.g. Sarin , Tabun, Soman ).
•OP compounds are also present in ant, rat, cockroach
sprays, antilice shampoo, used as dewormers of pets
animals.

11. ABSORPTION ROUTE
• INGESTION ( accidental / Suicidal )
• INHALATION
• CUTANEOUS
• INJECTION

12. PHARMACOKINETICS
•most of organophosphates are highly lipid
soluble compounds and are well absorbed from
skin, oral mucous membranes, conjunctiva, and
the gastrointestinal and respiratory tract.
•Due to their high lipid solubility they easily
cross blood brain barrier and produce potent
effects on CNS.
•They are rapidly distributed in all body tissues.

13. • Metabolism occurs primarily by oxidation
in liver with conjugation and esterase
hydrolysis producing a half life of minutes
to hours.
• Elimination of organophosphates and it’s
metabolites occur mainly via urine, bile
and feaces.

14. ORGANOPHOSPHATES

15. •Organophosphates act as irreversible cholinesterase
inhibitors b/c the bond formed between OP-AchE is not
spontaneously reversible without pharmacologic
intervention.
•The inhibition of cholinesterase leads to accumulation
of acetylcholine causing overstimulation and subsequent
disruption of transmission in both central and peripheral
nervous system.

18. •In organic chemistry
organophosphates are esters of
phosphorus having • a central
phosphate molecule • a terminal
oxygen connected to phosphorus
by a double bond which is called
phosphoryl group, •2 lipophilic
groups bonded to phosphorus,
and• a leaving group bonded to
phosphorus .

22. REVERSIBILE

26. WHAT IS AGING?
•OP-AchE bond become irreversible after a reaction called
aging in which one of the R group leaves the phosphate
molecule and this OP-AchE bond become resistant to
hydrolysis. So Aging is DE alkylation reaction of
organophosphorus OP-inhibted acetyl choline esterase AchE.
•The extent of potential reactivation of Organophosphate-
inhibited acetylcholine esterase decreases with time, a
phenomenon called AGING.
•Different OP compounds have various aging time ranging
from 2 minutes for nerve agent soman to 72 hours for certain
insecticides.

27. ACETYLCHOLINE
RECEPTORS
• MUSCARINIC
• NICOTINIC

34. SING AND SYPMTOMS
Divided into
•MUSCARNIC effects
•NICOTINIC effects
•CNS effects

39. THREE CLINICAL PHASES
•ACUTE CHOLINERGIC SYNDROME
•INTERMEDIATE SYNDROME
• ORGANOPHOSPHATE INDUCED DELAYED
POLYNEUROPATHY

41. ACUTE CHOLINERGIC EXCESS
•Cholinergic symptoms within first 24 hours due to
persistent depolarization of neuromuscular junction due
to blockade of acetylcholine at all receptors.
•Features include muscarinic effects (miosis,
bradycardia,lacrimation,salivation,bronchorea,
bronchospasm,urination,emesis and diarrhea.
• Nicotinic effects include ( fasciculations,muscle
weakness and paralysis) via acetylcholine stimulation of
receptors at neuromuscular junction.

43. INTERMEDIATE SYNDROME
•10-40% of patients poisoned with organophosphorus
develop a distinct neurological disorder after 24 to 96 hrs
after exposure or resolution of cholinergic excess. This
excess acetylcholine at NM junction causes down
regulation of nicotinic receptors __ muscles are affected
•This disorder referred to as intermediate syndrome
consists of characteristic neurological findings including
neck flexion weakness, decreased deep tendon reflexes,
cranial nerve abnormalities, proximal muscle weakness
and respiratory insufficiency.

45. •Risk factors for development of intermediate syndrome
include exposure to highly fat soluble organophosphorus
agents and may be related to inadequate doses of
oximes.
•There is no specific treatment but with adequate
supportive care including prolonged mechanical
ventilation most patients have complete resolution of
neurologic dysfunction within 2 to 3 weeks.

46. OP-INDUCED DELAYED POLYNEUROPATHY
•OPIDN typically occurs 1 to 3 weeks after ingestion of
specific organophosphorus agents including chlorpyrifos,
due to degeneration of long myelinated nerve fibers.
•The mechanism may involve inhibition of neuropathy
target esterase (NTE) rather than alteration in RBC
acetylcholine esterase function. This enzyme NTE which
is found in brain, peripheral nerves & lymphocytes is
responsible for metabolism of various esters within the
cells.

47. •Affected patients present with painful glove and
stocking paresthesia followed by symmetrical motor
polyneuropathy characterized by flaccid weakness of
lower extremities which ascend to involve upper
extremities.
•Sensory disturbances are usually mild . Delayed
neurotoxicity primarily affect distal muscle groups but
in severe toxicity proximal muscle groups may also be
affected.

49. •The risk of developing OPIDN is independent of severity of
acute cholinergic toxicity. Some organophosphorus agents
such as parathion are potent cholinergic agents but not
associated with OPIND.
•Others such as triorthocresyl phosphate (TOCP) produce
few clinical signs of cholinergic excess but are frequently
implicated in OPIDN.
•Most cases of mild delayed neurotoxicity improve with
time; in severe cases an upper motor neuron syndrome with
spacity of lower extremities cause permanent disability.

50. CARDIAC ISSUES
•Cardiac arrhythmia including heart block and QT
prolongation are occasionally observed in
Organophosphate agent poisoning. It is unclear whether
these cardiac effects are due to direct toxicity or secondary
hypoxemia.
•case reports and case series suggest that up to 1/3rd of
patients with severe OP poisoning manifest signs of
myocardial ischemia such as elevated troponin or changes
in ECG.

51. RESPIARTORY ISSUES
•Fatalities from Organophosphorus agents poisoning
generally result from respiratory failure due to
combination of depression of CNS respiratory center,
neuromuscular weakness, excessive respiratory
secretions and bronchoconstriction.

52. ADDITIONAL EFFECTS
•several case reports describe acute kidney injury AKI
requiring renal replacement therapy in setting of
severe Organophosphate poisoning .
•It remains unclear whether the AKI is due to direct
toxicity or general effects of critical illness, but in
severe OP poisoning it is prudent to monitor renal
function. Acute pancreatitis may complicate poisoning
caused by organophosphates.

56. DIAGNOSIS
•CLINICAL FINDINGS clinical features of cholinergic
excess should indicate the possibility of
organophosphate poisoning. If doubt exists weather
an OP agent or carbamate has been ingested a trial of
1mg atropine in adults is employed. The absence of
signs and symptoms of anticholinergic effects
following atropine challenge strongly support
poisoning with acetylcholine esterase inhibitor.

57. CHOLINE ESTERASE LEVEL
•Choline esterase level (plasma butryl ChE or RBC ChE )
are only useful biochemical tools to confirm exposure to
OP but are a poor guide to management & prognosis.
•Clinical severity graded on the basis of pseudo choline
esterase level
MILD 20-25 % of enzyme activity
MODERATE 10-20% of enzyme activity
SEVERE <10% of enzyme activity

59. PRINCIPLES OF MANAGEMENT
•Maintain Airway, Breathing, Circulation
•Resuscitation, Decontamination, Stabilization
•Gastric Decontamination, Fluids
•Muscarinic inhibitors (Atropine),
• Acetylcholine esterase reactivators (Pralidoxime)

61. DECONTAMINATION
• Preventing further exposure ,contaminated clothing
all the belongings should be removed, and discard in
ventilated area, thorough irrigation with water.
•Wash Skin with soap and water.
•Ocular decontamination with water only.
•Gastric lavage or activated charcoal may be
considered if patient presents within one hour of
ingestion

62. GASTRIC LAVAGE
• It does not decrease morbidity or mortality, however it
may b performed if the patient presents within one hour of
ingestion of organophosphate agent after initiating therapy
with atropine and oxime.
• Gastric lavage involves substantial risk of aspiration in
patients with increase secretions and decrease mental
status.
•Following initial resuscitation and treatment activated
charcoal can be given to patient presenting within one hour
of ingestion. Standard dose is 1g/kg (max dose 50 g).

63. CHOLINERGIC TOXICITY
• Patients with cholinergic toxicity with OP poisoning are
treated with ATROPINE & OXIME therapy.
•ATROPINE competes with acetylcholine at muscarinic
receptors and prevent cholinergic activation. If used early in
sufficient doses atropine is potentially life saving in severe
toxicity.
•OXIME , since atropine does not bind to nicotinic receptors
it is ineffective in treating neuromuscular dysfunction.
Pralidoxime and other oxime are cholinesterase reactivating
agents that are effective in treating both muscarinic and
nicotinic symptoms.

64. DOSING
• In OP poisoning Atropine should be administered at a
dose of 2 mg IV and if there is no response after 5
minutes give repeated boluses in rapidly escalating doses
(eg, doubling the dose each time) as needed to dry
bronchial secretions and decrease wheezing; as much as
several hundred milligrams of atropine have been given to
treat severe poisoning.
•Atropine dosing should be titrated to the Theraptic end
point of clearing respiratory secretions and cessation of
bronchoconstriction.

65. •patients who do not respond adequately to high
dose atropine therapy may require treatment with
epinephrine. Initiate epinephrine therapy for
patients whose heart rate is below 80 or who are
hypotensive with adequate heart rate 80-10
despite receiving high dose atropine therapy.

68. OXIMES
•Oxime therapy should be given to all patients with
evidence of cholinergic toxicity, and in patients with
neuromuscular dysfunction. Treatment with oximes
should b started as early as possible as there is no role if
started after 48 hrs. (aging).
•Pralidoxime and other oxime are cholinesterase
reactivating agents. Pralidoxime should not be
administered without concurrent atropine in order to
prevent worsening symptoms due to transient oxime-
induced acetyl choline esterase inhibition.

69. • PRALIDOXIME__1-2 g IV as a loading dose and begin as a
continuous infusion (200-500 mg/hour; titrated to clinical
response) over 15 to 30 mints, repeat in one hour if necessary,
if still muscle weakness has not relieved may repeat 10-12
hourly.
•Continue to give Pralidoxime as long as there is evidence of
acetylcholine excess.
•Oximes work by reactivating acetylcholine esterase that has
not undergone aging and are therefore less effective with
dimethyl compounds and nerve agents specially Soman.

70. Theraptic effectiveness of OXIME depend upon
;
•Concentration of poison consumed.
•Time lapse between poisoning and administration.
•Type of Organophosphate compound (more effective
on diethyl than dimethyl organophosphate
compounds) Dimethyl reactivate and age at slower
rate.
•lipid solubility of OP compounds.
•concentration of oxime in blood.

71. INTERMEDIATE SYNDROME
•IMS generally develops rapidly between 1-4 days
after exposure, often after resolution of acute
cholinergic syndrome and may last 2-3 weeks.
•There is no specific treatment but supportive care
including maintenance of airway, and ventilation
should be provided if necessary.

72. ORGANO OHOSPHATE INDUCED DELAYED
POLYNEUROPATHY
•It is a rare complication that usually occurs 2 to 3
weeks after acute exposure.
•There is no specific therapy for OPIDN. Regular
physiotherapy may limit deformity caused by muscle
wasting. Recovery is often incomplete, although
substantial functional recovery after 1-2 years may
occur, especially in younger patients.

74. •Benzodiazepines may be used to control agitations
and it is first line therapy in OP poisoning to control
seizures. Diazepam (e.g. 10 mg IV) can decrease
neurocognitive dysfunction in patients with OPP.
•Forced emesis is contraindicated due to risk of
aspiration.
•urinary alkalization has been suggested but there is
no clear evidence that this intervention improves
outcome.

75. PREVENTION
• Prevention efforts include banning the easy availability
of every toxic type of OP over the counters in community.
•Those who work with pesticides should use protective
clothing, and showering before going home is also useful.
•Health care workers must take precautions to avoid
accidental exposure, including providing treatment in a
well ventilated area.

76. •keep these products at a secure place and mark them
clearly.
•Stay indoor with windows closed if spray is occurring
nearby.
•Wash all fruits and vegetables before use.