Paracetamol

Paracetamol REF: Goodman and Gillman’s 11^th edition, page 1000, CURRENT Medical Diagnosis and treatment Chapter 26. Endocrine Disorders

Indirect repeat from December 2009 ANTITHYROID COMPOUNDS

Metabolic acidosis REF: Harrison 17^th ed chapter 48 Paracetamol poisoning can cause metabolic acidosis

An adverse cutaneous reaction to an ingested drug with characteristic clinical features is fixed drug eruption.

Presentation with a solitary lesion in the genital skin that heals with hyperpigmentation.

Soon after ingestion of paracetamol, one of the most commonly implicated agents for FDE, leads to the diagnosis of FDE.

Ref: Anthony Du Vivier, Phillip H. McKee, Chapter 17, “Reactive Disorder of The Skin and Drug Eruptions”, In the book, “Atlas of Clinical Dermatology”, Elsivier Publication, 2002, 3rd Edition, Spain, Page 367

D i.e. Acetyl cysteine

In cases of moderate to severe poisoning of paracetamol, N‑

acetyl cysteine (mucomyst) should be givenQ orally within 24 hours of overdose to prevent hepatic damage.

Treatment of Paracetamol poisoning

1.     Gastric lavage – useful in < 4 hours.

2.     < 2.5 lit fluid daily, as pcm 1/t fluid retention

3.     N-acetyl cysteineQ (Treatment of choice)

4.   Hemodialysis for ARF

Ans. is ‘b’ i.e., Paracetamol

o It does not possess anti-inflammatory activity because it is ineffective in the presence of peroxides generated at the site of inflammation.

Ans. is ‘c’ i.e., Paracetamol

o Paracetamol is one of the safest NSAIDs.

• It produces very little GI toxicity and can be administered in patients intolerant to other NSAIDs.

Ans. is ‘b’ i.e., N-acetyl cysteine

• N-acetyl cysteine is used as an antidote in paracetamol poisoning (acetominaphan).

C ie Fixed drug eruption 

Fixed Drug Eruption

– Adverse cutaneous drug reaction appearing soon after ingestions (from 30 min to 8-16 hours) of offending agent in previously sensitized individuals

– Numerous drugs, including anti-inflammatory agents (eg salicylates, NSAID’s including paracetamol), phenylhutazone, phenacetin and dapsone, sulfonamides, tetracycline & mefenamic acid may be responsible

– Genital & perianal skin is the most commonly involved siteQ. Nevertheless any site may be involved.

– Most commonly lesions are solitaryQ but they may be multiple

– Lesions evolve from macules to papules to vesicles & bullae and then erode.

– Lesions heal by residual hyper-pigmentation Q

– Usually asymptomaticQ but may be pruritic, painful, or burning (when eroded)

– Lesions persist if drug is continued and resolve days to weeks after drug is discontinued

– FDE occurs repeatedly at the same (ie fixed) site within hours, every time drug is taken and heal by residual grayish or slate colored hyperpigmentationQ. On rechallange, not only do the lesions recur in the same location, but also new lesions often reappears Challenge or provocation/Patch test can ascertain etiology

• Herpes genitalis

– Multiple, painful, bleeding non-indurated vesicles or ulcer with painful lymph­adenopathyQ

• Pemphigus vulgaris

Flaccid intraepidermal bullaeQ on upper part of body in 40 – 60 years adult with mucosal involvement.

Nikolsky sign positive, row of tomb stone & accantholysis presentQ

• Bechet’s syndrome

Multisystemic disorder with recurrent oral & genital ulcerations with ocular involvement

– Recurrent apthous ulcerations are sine qua non for diagnosis

Ulcers heal without leaving scars

– Genital ulcers are less common and do not involve glans and urethra

Ans. is ‘c’ i.e., Paracetamol 

o Sub-center kit A contains :- (i) Iron (Ferrous sulphate) & folic acid; (ii) Zinc sulphate; ii) Cotrimoxazole; (iv) Vitamin A; (v) ORS; and (vi) Gentian violet crystals.

o Sub-center kit B contains :- (i) Paracetamol; (ii) Dicyclomine hydrochloride; (iii)Albendazole; (iv) Methylergometrine; (v) Povidone iodine ointment; (vi) Chloramphenicol eye ointment; (vii) Rolled bandage; and (viii) Absorbent cotton wool.

Ans. B: Paracetamol

Pyuria refers to urine which contains pus.

It is defined as the presence of 10 or more neutrophils per high power field of unspun, voided mid-stream urine. Sterile pyuria is urine which contains white blood cells (pus) while appearing sterile by standard culture techniques. Sterile pyuria is listed as a side-effect from some medications such as paracetamol (acetaminophen).

Ans. A: N-acetyl cysteine

In paracetamol poisoning, depletion of hepatic and renal glutathione potentiates the toxicity whereas treatment with sulfhydryl compounds such as cysteamine, 1- methionine and N-acetyl cysteine (NAC) is beneficial

Acetylcysteine/ N-acetylcysteine/ N-acetyl-L-cysteine/ NAC)

• It is used primarily as a mucolytic agent and in the management of paracetamol (acetaminophen) overdose.
• Other uses include sulfate repletion in conditions, such as autism, where cysteine and related sulfur amino acids may be depleted.
• Acetylcysteine is a derivative of cysteine; an acetyl group is attached to the nitrogen atom.
• It is used as a cough medicine because it breaks disulfide bonds in mucus and liquefies it, making it easier to cough up.
• It is also this action of breaking disulfide bonds that makes it useful in thinning the abnormally thick mucus in Cystic Fibrosis patients
• Intravenous acetylcysteine is indicated for the treatment of paracetamol (acetaminophen) overdose.
• When paracetamol is taken in large quantities, a minor metabolite called N-acetyl- p-benzoquinone imine (NAPQI ) accumulates within the body.
• It is normally conjugated by glutathione, but when taken in excess, the body’s glutathione reserves are not sufficient to inactivate the toxic NAPQI.
• This metabolite is then free to react with key hepatic enzymes, therefore damaging hepatocytes.
• This may lead to severe liver damage and even death by fulminant liver failure.
• For this indication, acetylcysteine acts to augment the glutathione reserves in the body and, together with glutathione, directly bind to toxic metabolites.
• These actions serve to protect hepatocytes in the liver from NAPQI toxicity.
• Although both IV and oral acetylcysteine are equally effective for this indication, oral administration is poorly tolerated because high oral doses are required due to low oral bioavailability, because of its very unpleasant taste and odour, and because of adverse effects, particularly nausea and vomiting.
• Inhaled acetylcysteine is indicated for mucolytic (“mucus-dissolving”) therapy as an adjuvant in respiratory conditions with excessive and/or thick mucus production.

Ans. Paracetamol

Ans. Acetylcysteine

Ans:A.)Paracetamol.

In cases of moderate to severe poisoning of paracetamol, N‑acetyl cysteine  should be given orally  to prevent hepatic damage.

Overdose of Paracetamol

• Paracetamol is mainly inactivated by the liver by conjugation leading to two metabolites; glucuronide or sulfate. It is then renally excreted through urine.
• When taken in overdose the liver conjugation becomes inundated, causing paracetamol to be metabolised by an alternative pathway.
• This results in a toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), which is itself inactivated by glutathione, rapidly preventing any harm.
• When glutathione stores are depleted to less than approximately 30%, NAPQI reacts with nucleophilic aspects of the cell, leading to necrosis. Necrosis occurs in the liver and in the kidney tubules.
• Commonly, patients are asymptomatic for the first 24 hours or have nonspecific abdominal symptoms (such as nausea and vomiting).
• Hepatic necrosis begins to develop after 24 hours (elevated transaminases, right upper quadrant pain and jaundice) and can progress to acute liver failure.
• Patients may also develop:Encephalopathy,Oliguria,Hypoglycaemia,Renal failure – usually occurs around day three,Lactic acidosis.
• Treatment of Paracetamol poisoning
  • Gastric lavage – useful in < 4 hours.
  • N-acetyl cysteine (Treatment of choice)
    • NAC is believed to work by a number of protective mechanisms. It acts as a precursor for glutathione, promoting normal conjugation of any remaining paracetamol, and also supplies thiols that function as antioxidants. It is virtually 100% effective in preventing liver damage when given within eight hours of ingestion.
  • Hemodialysis for ARF