**3.1 Mechanism of action**

*Pain Management - Practices, Novel Therapies and Bioactives*

General Acute generalised exanthematous pustulosis Malaise Skin reactions

Specific With iv use, flushing and tachycardia

**Side effects Rare Frequency not known**

• Steven-Johnson syndrome • Toxic epidermal necrolysis

decrease in glutathione.

**2.2 Interactions**

**Table 1.**

*Paracetamol side effects.*

are prescribed (**Table 1**) [2, 4].

Paracetamol is metabolised in the liver primarily through conjugation to sulphate or glucuronides [2]. A minor pathway for the oxidative metabolism of paracetamol produces the toxic metabolite N-acetyl-P-benzoquinone (NAPQI) [2]. NAPQI requires glutathione for detoxification and elimination. Hepatic toxicity can occur when glutathione pathways are overwhelmed by an increase in NAPQI or

Paracetamol is generally well tolerated with rare side effects when the right doses

Blood disorders: leucopoenia neutropenia, thrombocytopenia as is bone marrow suppression

With iv use, hypotension

It is associated with several important drug interactions. Many anticonvulsants, including phenytoin, barbiturates and carbamazepine induces hepatic microsomal enzymes. Increased conversion of paracetamol to its toxic metabolite may occur in patients who are taking anticonvulsants, but this rarely leads to concerning conse-

Although uncommon, drug interaction resulting in an increased INR is reported for patients taking both paracetamol and warfarin, particularly among patients taking high doses of paracetamol (> 9 g/week) [2, 12, 13]. Long term use of paracetamol should be avoided in patients with hepatic or renal impairment. Patients with a history of salicylate hypersensitivity characterised by urticaria have a 11% cross-reactivity to paracetamol, and the agent should be used with caution in this group [2, 7].

The NSAIDs share several properties with aspirin and may be considered together. NSAIDs are particularly used for the treatment of patients with chronic disease

Some of them are also used for acute pain management and in the short-term treatment of mild to moderate pain including transient musculoskeletal pain. They are also suitable for the pain control in dysmenorrhoea and to release pain caused by secondary bone tumours, many of which produce lysis of bone and increase prostaglandins synthesis. Many of the NSAIDs are also used for postoperative analgesia as part of the multimodal analgesia strategy. Selective inhibitors of COX2 may be used in preference to non-selective NSAIDs for patients at high risk of developing serious

There are some limited and low quality evidences against the use of NSAIDs in bone pathology, suggesting that prostaglandins promote bone formation and that NSAID might impair this process [14, 15], theory not proven through properly

quences in the context of the usual doses for pain management [2, 6].

**3. Nonsteroidal anti-inflammatory drugs**

accompanied by pain and inflammation.

gastro-intestinal side-effects.

**238**
