Non-Opioid analgesics (Non-narcotic analgesics- antipyretics)

Question 1

How are non-opioid analgesics classified?

Answer 1

1. Para-aminophenol derivatives
   ◦ Paracetamol
2. Pyrazolone derivatives
   ◦ Metamizole (Analgin)

Question 2

What are the PK, main effects, and probable mechanism of Paracetamol?

Answer 2

PK
◦ Oral and rectal administration
◦ Metabolism:
◦ Conjugation with glucuronic acid and sulfate (non-toxic metabolites)
◦ Oxidation (CYP) to N-acetyl-p-benzoquinoneimine (NAPBI) – toxic!

Main effects

• Analgesic effect:
• Headache, toothache, migraine,
• Pains of neuromuscular origin,
• Cancer pain (the lowest step),
• Postoperative and post-traumatic pain

• Antipyretic effect

Analgesic-antipyretic of choice in children and pregnant women

Probable mechanism – COX inhibition in the brain

Question 3

What are the toxic effects of paracetamol?

Answer 3

Serious liver toxicity – toxic
metabolite N-acetyl-pbenzoquinoneimine, which
reacts with cellular proteins
and kills the cell.

Drugs that increase glutathione
(acetylcysteine i.v., within 10
hours of paracetamol
ingestion) can prevent damage

Analgesic nephropathy with
long-term use

Question 4

What are the main effects, clinical uses, and adverse reactions of metamizole?

Answer 4

Main effects
◦ Analgesic – pains of different origins, including visceral pain
◦ Antipyretic
◦ Spasmolytic

Clinical use
◦ As antipyretic
◦ As analgesic in different types of pain:
◦ Headache, toothache, migraine,
◦ Pains of neuromuscular origin,
◦ Cancer pain (the lowest step),
◦ Postoperative and post-traumatic pain
◦ Visceral pains (alone or in combination with spasmolytics)

ADR:
◦ Hypersensitivity reactions – relatively common
◦ Bone marrow toxicity – extremely rare, potentially fatal (aplastic anemia,
agranulocytosis)