- Paraquat is a herbicide that causes toxicity through generation of reactive oxygen species, leading to lung and other organ damage. - It is absorbed through the gastrointestinal tract and lungs, and accumulates primarily in the lungs. Clinical features range from mild gastrointestinal symptoms to multi-organ failure and death. - Treatment involves gut decontamination, supportive care, antioxidants, and in some cases extracorporeal removal techniques. C-reactive protein levels may help predict prognosis.

1. PARAQUAT POISONING
PRECEPTOR
ASST. PROF DR. DIPTIRANJAN DARJEE
DR. SUNIL KUMAR BIHARI
PG 1ST YEAR RESIDENT
DEPT. GENERAL MEDICINE

2. INTRODUCTION
 Paraquat is a contact herbicide and dessicant which was
introduced in 1933 as methyl viologen.
 It is a bipyridyl compound (1,1’-dimethyl 4,4’ bipyridylium). It is a
bisquaternary ammonium compound which is synthesized as
dichloride salt.It is a colourless hygroscopic solid nonvolatile
compound, freely soluble in water.
 Diquat- it’s a paraquat analog (1,1’-ethylene 2,2’ dipyridylium
dibromide).it has similar property but different toxic effects.

3. Chemical structure Available paraquat
compounds in market-
• Gramoxone
• Gramoheal
• Paroxone
• Agazone
• Gramogel

4. MECHANISM OF ACTION

5. • NADPH depletion and lipid peroxidation have been proposed as mechanism of
paraquat toxicity.
• Flavoenzymes such as NADPH cyt p450 reductase,xanthine oxidase initiate the
single electron reduction of paraquat to free paraquat radical.
• This paraquat radical is extremely unstable which transfers an electron to oxygen
to form superoxide anion radical, which cause systemic toxicity.
• Superoxide anion radicals react with each other to produce hydrogen peroxide
and molecular oxygen via the enzyme superoxide dismutase. Under the normal
circumstances hydrogen peroxide is detoxified by catalase and glutathione
peroxidase but when these protective mechanisms prove inadequate it can cause
devastating effects on the cell.

6. • Experimentally it has been shown that paraquat toxicity
has been enhanced by administration of oxygen.
• Lung is the primary target organ because of selective
uptake and accumulation of paraquat by type1 type 2
alveolar epithelial cells.
• Selective uptake is due to structural similarity of paraquat
with naturally occurring polyamines taken up alveolar cell.

7. PULMONARY UPTAKE WITHIN 6 HOURS
ACUTE ALVEOLITIS
D3- PROFIBROBLAST MIGRATES INTO ALVEOLAR SPACE
D7- PULMONARY FIBROSIS(ALVEOLI FILLED
WITH PROLIFERATIVE FIBROBLAST)

8. PHARMACOKINETICS
• Paraquat( 5-10% of oral dose) is absorbed through small intestine
plasma concentration reach their peak by 0.5-2 hour.
• It distributes in most organs of body, highest concentration in
kidney followed by lung and liver .Lung and liver act as reservoir
and it slowly releases into body.
• Major organ of elimination – kidney . There is minimal biliary
excretion.
• Before renal failure paraquat clearance is more than creatinine
clearance because of tubular secretion.
• It is detected in urine after 1 hour of ingestion and detectable upto
14-31 days.

9. ROUTES OF EXPOSURE
• SKIN-Epithelial cells act as a barrier to paraquat.
• Local effects- irritation,erythema, blister formation.
• INHALATION-Paraquat is not volatile but liquid Syngenta
paraquat formulations contain an unpleasant 'stenching
agent' which may occasionally cause feelings of nausea or
headaches.
• INGESTION-It is the most toxic route of exposure.

10. CLINICAL FEATURES
• Mild or subacute poisoning: <20 – 30 mg paraquat ion/kg body
weight.
• Asymptomatic or mild gastrointestinal symptoms.
• Renal and hepatic lesions are minimal or absent.
• An initial decrease of the pulmonary diffusion capacity may be
present.
• Complete recovery would be expected.

11. • Moderate to severe acute poisoning: >20–30 but <40–50 mg
paraquat ion/kg body weight.
• Immediate: vomiting.
• Hours: diarrhoea, abdominal pain, mouth and throat ulceration.
• One to four days: renal failure, hepatic impairment, hypotension
and tachycardia.
• One to two weeks: cough, haemoptysis, pleural effusion,
pulmonary fibrosis with deteriorating lung function.
• Survival is possible, but in the majority of cases death occurs
within 2–3 weeks from pulmonary failure

12. • Fulminant or hyperacute poisoning: >40 – 55 mg paraquat ion/kg
body weight.
• Immediate: vomiting
• Hours to days: diarrhoea, abdominal pain, renal and hepatic
failure, gastrointestinal ulceration, pancreatitis, toxic myocarditis,
refractory hypotension, coma.
• Death from cardiogenic shock and multi-organ failure occurs
within 1-4 days.

13. Systemic involvement
• Gastrointestinal system- vomiting diarrhea, pain abdomen , oral
ulceration ,esophageal ulceration and perforation.
• Abdominal pain due to pancreatitis.
• Jaundice ,liver toxicity due to centrilobular hepatic necrosis and
cholestasis.
• CVS- myocarditis (rare)
• CNS- cerebral edema

14. •Kidney- oligouric or non-oligouric renal failure due to
acute tubular necrosis which becomes evident after 24 hr.
•In rat study it is shown swollen glomeruli and mild
hemorrhages after 24hr and after 48hr hemorrhages with
abnormal erythrocytes and leucocytes are seen.
•Endocrine-adrenal cortical necrosis

15. • Lung-Acute study lung showed an increased thickness of
septa and collapsed alveoli ,hyperplasia of epithelial cells
focal area of inflammatory cells ,fibrous tissue
proliferations.
• Patients who survive after paraquat poisoning have
restrictive type of lung disease due to pulmonary fibrosis.

16. DIAGNOSIS
• Diagnosis can be done by proper history taking .
• Qualitative urine test-
• Urine or gastric aspirate can be tested for paraquat using the
method based on reduction of the paraquat cation to a blue radical
ion in the presence of alkali and sodium dithionite.
• Add alkali, such as sodium hydroxide, to 10 ml of urine or gastric
aspirate until the pH is above 9 (approximately half to one teaspoon
of sodium bicarbonate can be used as an alternative).
• Add a spatula blade full of sodium dithionite to the alkaline urine or
gastric aspirate and mix gently.
• Blue or green colour indicates paraquat poisoning.

17. Quantitative test-
• Spectrophotometry
• Ion exchange
chromatography
• Gas chromatography

18. TREATMENT
• Early management
• I.V. fluids – the kidney is the major route of excretion of paraquat and renal
function must therefore be closely monitored and optimum function
maintained.
• Analgesics – aggressive analgesia (e.g. opiates) may be required since
patients can have severe pain from oral, oesophageal or abdominal
corrosive injury.
• Mouth care for ulceration and inflammation.
• Patients should be kept nil by mouth if there is a suspicion of oropharyngeal
or esophageal injury. Early insertion of a nasogastric feeding tube should be
considered taking care to avoid additional mucosal damage.
• Avoid supplemental oxygen unless significant hypoxia exists (oxygen
enhances paraquat toxicity).

19. • 0ral absorbent- If the patient is conscious cooperative administer
activated charcoal 50-100g for adults and 0.5-1g /kg wt for children.
• Alternative –fuller’s earth (15% suspension),bentonite(7.5%
suspension).
• Use of gastric lavage without administration of any absorbent has
not shown any clinical benefit.
• Rehydrate the patient to optimise renal clearance and to replenish
gastrointestinal loss.
• Urine spot test should be done as soon as possible,if negative repeat
after 6hour.Quantitative plasma test should be done after 4 hour of
ingestion.

21. ANTIOXIDANTS
• N-acetyl cysteine
• Vitamin E
• Ascorbic acid
• Desferrioxamine -100mg/kg over 24 hr .It is used to chelate iron
• Salicylic acid-It can scavange hydroxyl radical
• Glutathione

22. EXTRACORPORAL REMOVAL TECHNIQUES
• Peritoneal dialysis is a poor means of removing paraquat. Hemodialysis
achieves good clearance when paraquat plasma concentrations are high (>10
mg/L) and can reach 150 mL/min. 160-162 Clearance decreases significantly,
however, when the plasma concentration is less than 1 mg/L.
• Hemoperfusion is the most effective means of achieving extracorporeal
elimination of paraquat. Clearance is greater than 50 mL/min even when the
plasma paraquat concentration is less than 0.2 mg/L and can be increased
further by using hemodialysis and hemoperfusion in series, Platelet counts
should be measured during hemoperfusion.

23. CYCLOPHOSPHAMIDE AND STEROID THERAPY
• A number of studies have reported that a beneficial effect of a
combination therapy of cyclophosphamide and steroid.
• Cyclophosphamide 1gram per day for 2 days and
methylprednisolone 1gram per day for 3 days.

24. CRP AS PROGNOSTIC INDICATOR
REFERENCE-ASIAN PACIFIC JOURNAL OF
TROPICAL BIOMEDICINE

25. •In the study 162 patients were enrolled.
•Out of them 75 died and 87 survived.
•They found that plasma CRP levels were significantly
increased in non survival group compared to survival
group(p<0.05).

26. THANK YOU…