Acetaminophen poisoning

Maximum recom daily 4 gm

Single dose 10 gm no toxicity
>250 mg/kg or 12 gm single dose toxicitty

Onset 30 min -2 hours

Peak--4 hours

Food,opiatesand anticholinergics slow gastric emptying

Increasing risk: chronic alcohol ,CYP 2E 1 enzyme system affeccted

Acuute >3000 enzymes and inr raisedd

Chronicn >3000with hypovolemia ,hhypoglycemia and aki

Therapeutic dose level: 10-20 mcg /ml after 4 hrs

Modified RumakMatthew normogram
Eliminatiionhalf life : 2to 4 hours

Metabolism : SULT and UGT ‘

Highly toxic : n acetyl benzo quinoneimine
Usuallyt cysteiine in excess toxic

Affected : mitochondrial ATP synthase alpha subunit

Hepatic centrilobular neccrosis by lipid peroxidaion and membrane injury
Peroxynitrite

Apoptosis inducng factor ,Endo G

Reactive nitrogen and oxygen species
18 std drinks = chronic ]

Factorsinfluencing ;

Dosse
Delay to NAC
C450
Decreased capacity SULT and UGT
Low glutahione

Protecting : acute alcohol

Chronic alcohol : increases toxicity only with repeated dosing not with singleddose

CLD : no increasedrate

Concominant drug s: anti conv ,anti tubercular , zidovudine garlic,St John’s wart

Schisandra plant --protective

Malnutrition :as glucuronidation is dependant on carb reserves so more shunting

Polymorphism : enz and others : Nacetylase,NAT 2,fatty acid amide hydrolase
Age >40 ,tobacco asCYP 1A2inducer-increases oxidativemetabolism

Protective : low phosphate

D/D :
Hepatitis --drug,toxin,alcohol

Usuallu Bil >10 is uncommon in APAP--but high bili can give false+ve serum APAp levels
Aminotransf. <500 in alcoholic hepatitis

Clinical manifestations :
Stage 1 -0-24 hrs

Nausea ,vomiting ,diaphoresis ,CNS depression .high anion gap met acidois--usuaaly due to
Diphenhyd,aspirirn

Stage 2 : 24-72 hrs

Improve clinically while subclinical worsenign of lab enz

PT ,bil high and oliguria

Stage 3 72-96 hrs

Jaundice ,confusion reappear
High hepatic enz .,hyperammonemia ,bleedig diathesis
>10000
Hypoglycemia
High lactate
B >4
10-25 % AKI
MODS

Stage 4 -recovery phase 4 d - 2 weeks

Cytolysis to centrilobular necrosis ::zone III highest cyp 2E1

AKI : recovery in 7 days

Serum monitoring ;after 4 hrs

Possble risk : 150 mcg /ml at 4 hrs
18 at 16 hrs ‘in Rumack Matthew Normogrm

Sustainedd release tab to checkk afte 8 hrs ‘

Indications for NAC :

Liver tenderness
Elevation of aminotransferases’
Supratherapeutic levels : >10

Chronic :test of choice is Aceta STAT: APAP proteinadducts

Management :
Activated chaarcoal 1g /kg upto 4 hrs
NAC in 8 hrs
Load 150 mg/kg then
12.5 mg/kg --4 hrs
6.25 ---16 hrs
Total 300 mg/kg over20-21 hrs

Stop when INR <1.3 In 12 hrs protocol 50 f/b 20 or <100 and not more than twiceadmission value
Or INR <2 in others with clearly decreasing enzymes <1000 three consecutive values or 50% from
baseline
Advantages over 72 hr s oral(140 load f/b 70 for 17 dosages
Anaphylactoid reactions :

Flushing without pruritus and urticaria : continue

Urticaria : IM adrenaline ,diphennhydr.,gucocorticoids and continue
Respi.: to stop and treat with above plus albuterol if wheezing

Serum bicarbonate ,sugar and creatinine if coagulopathy or encephalopathy

Cimetidine ,dialysis has no advatage
If because of AKI dialysis --to increase dose as It removes both