toxicolgy principles of toxicology paracetamol toxicity samer

1. Laboratory principles
of Toxicological screening
Samer Shukur

13. Analytical tests
Biochemical tests
• Blood glucose:
• Hypoglycemia Ethanol, Iron salt, Paracetamol, Salicylate toxicity
• Hyperglycemia Salmutamol, Theophylline toxicity
• Plasma Enzymes:
LDH, AST, ALT enzymes shock, coma, convulsion
serum Aldolase, CK Rhabdomyolysis
Plasma K , Uric acid, Phosphate Acute renal failure
GGT activity Chronic alcoholism

14. Analytical tests
Hematological tests
• Blood clotting:
• PTT abnormal in some snake bites, rodenticides containing anti coagulant
• Hematocrit :
• Iron salts, NSAIDs, Salicylate cause GI bleeding Anemia
• Chronic exposure to Arsenic & Lead Anemia
• Chloramphenicol , Chloroquine, Nitrofurantoin, Primaquine
G6PD Anemia
• WBC count:
• Leukocytosis from ingestion of Ethylene Glycol & Methanol

15. Analytical tests
Qualitative tests
A. Color Test:
1. Trinder ‘s test
Sample: Urine
For indication of Salicylate Violet or Purple
2. Ferric Chloride test
Sample : Urine
Indication of Phenol, Phenylbutazone , Oxyphenbutazone, Salicylate Purple color
3. FPN Test (Ferric chloride, Perchloric acid, Nitric acid)
Sample : Urine
Indication of Phenothiazine color range from pink to blue
4. O-Cresol test
Sample :urine
Paracetamol or Phenacetine Blue- Bluish black color

16. Analytical tests
Qualitative tests
5. Dichromate test
Ethanol Green color
6. Marquis test
Opium Purple turn into blue color
7. Lee-Jones test
Cynide Greenish- blue
Salicylate Purple
8. Reinsch test
Mercury Silvery deposit
Arsenic or bismuth purplish black
9. Meixner Test
Sample: stool, gastric fluid
Amatoxin (toxic mushroom) Blue color

20. Analytical tests
Quantitative tests

23. 3. High Performance Liquid Chromatography
Similar to GC (for Organic poisons)
The stationary phase is a column packed with solid particles and the mobile phase is a
liquid solvent.
B. Immunoassay methods
1. Enzyme mediated Immunoassay Technique
Fast, expensive, accurate, in emergency situation (Why?) (in urine)
2. Radio Immunoassay
Slow, expensive, highly accurate, in blood
3. Atomic Absorption Spectrophotometry
inorganic Elements, need large sample of blood
4. Neutron Activation Analysis (NAA)
sophisticated , expensive, for very small samples

24. Paracetamol Toxicity

26. 90%
Inactive metabolites
10%
Inactive metabolites

28. • Fatal dose: 20-25 grams
• 10 grams may cause hepatotoxicity
• Children under 10 years are more resistant to toxicity for unclear reasons.
• Risk factors
1. Dose ingested.
2. Excessive cytochrome P450 activity due to induction by chronic
alcohol or other drug use e.g. carbamazipine, phenytoin,
barbiturates.
3. Decrease capacity for glucuronidation.
4. Depletion of glutathione stores due to malnutrition
5. The concomitant use of the CYP2E1 inhibitor isoniazide increases
the risk of hepatotoxicity.

29. Clinical features of Acute poisoning
•stage I (first 24 hours)
anorexia, nausea, and vomiting
•stage II (24-48 hours)
the patient may show improvement in their clinical symptoms. The
liver enzymes may begin to elevate (AST, ALT).
•Stage III (72-96 hours)
called the hepatic stage. The patient may have vomiting, jaundice,
abdominal pain, bleeding, confusion, lethargy, encephalopathy,
jaundice, or even be in a coma and death due renal failure and
myocardial damage.
• stage IV (4 days- 2 weeks)
Called recovery phase

30. Diagnosis
The serum acetaminophen concentration is the basis for
diagnosis and treatment, even in the absence of symptoms,
because of the delay in onset of clinical manifestations of
toxicity (Rumack- Matthew nomogram).
Recommended serum studies are follows:
• Liver function tests (alanine aminotransferase [ALT], aspartate
aminotransferase [AST], bilirubin) all increase
• Prothrombin time (PT) with international normalized ratio
(INR)
• Glucose (hypoglycemia)
• ECG (Myocardial damage)
• Renal function studies (Proteinuria, phosphaturia)
• Lipase and amylase (in patients with abdominal pain)

31. Management
1. Gastric Lavage (within 1st hour)
2. Activated Charcoal within 4 hours of ingestion
May reduce absorption by 50 to 90 percent
it Inhibits absorption of oral methionine and NAC
3. Supportive treatment

32. 4. Antidotes
• Methionine: within 8-10 hours , given orally
• N-acetylcysteine (NAC)
• Within 10 hours
• Given orally or IV