Pharmacological

Treatment of Acute
pain
Dr. T.M. Mwiti
Introduction
• Pain:
• Common complaint
• Common component of diagnostic and
therapeutic procedures
• Pain generally poorly managed
• Analgesia part of the triad anaesthesia
Definitions
• Pain:
“An unpleasant sensory and emotional experience
associated with actual or potential tissue damage, or
described in terms of such damage”. [IASP]
• Acute pain
Pain temporarily related to injury and that resolves during
the appropriate healing period
• Chronic pain
Pain lasting more than 3 months
Definitions
• Nociceptive pain
• Pain arising from actual or threatened damage to non-
neural tissue
• Is due to the activation of nociceptors.
• Induces immobilisation for appropriate tissue/organ
healing
• May be somatic or visceral

• Neuropathic pain
• Pain caused by a lesion or disease of the somatosensory
nervous system
Causes of acute pain
• Trauma
• Burns
• Surgery
• Other therapeutic and diagnostic procedures
• Inflammatory conditions
• Infective processes
• Colic, kidney stones
• Sickle cell crises
Physiology of pain
Clinical presentation of
acute pain
• Background pain
• Breakthrough pain
• Procedural pain
• Post-procedural pain
• Psychologic/anticipatory pain
Acute Pain Treatment
• Acute pain intensity worst in the first few days
• Pharmacologic and non-pharmacologic approaches
• Goals:
• Adequate analgesia
• Physical rehabilitation
• Prevention of acute complications of pain and its
management
• Prevention of chronification of pain
Acute Pain Treatment
• Strategy
• Treatment of underlying disease process
• Round-the-clock interventions for background pain
• On-demand medication for breakthrough (incidental
and procedural) pain
• Pre-emptive management of some adverse effects of
therapies
• Re-evaluation
 Opioids
• Cornerstone

• Effective for severe acute pain

• A variety with different ranges of potency and DoA

• Different routes of administration

• Titrated to effect
Opioids
• Pure agonists
• Morphine, fentanyl, oxycodone, remifentanil, pethidine,
methadone
• Partial agonists
• Buprenorphine
• Agonist-antagonists
• Nalbuphine, pentazocine, nalorphine
• Pure antagonists
• Naloxone, naltrexone
 Opioids
• Mechanism of action
• Activation of opioid receptors (MOP, KOP, DOP, NOP)
• Receptors coupled with inhibitory G proteins
• Close voltage sensitive Ca2+ channels
• Stimulation of K+ efflux → hyperpolarization
• ↓ cyclic AMP production
• Overall effect: ↓ neuronal excitability → ↓transmission
of nociceptive impulses
Opioids
• Effects:
• Analgesia
• Sedation
• Euphoria and dysphoria
• Respiratory depression
• Nausea and vomiting,
• Pruritus and histamine release
• Muscle rigidity
• Mild bradycardia
Opioid
• Effects
• Peripheral vasodilatation
• Meiosis
• Cough suppression
• Constipation
• Tolerance
• Physical dependence
• Addiction (psychological dependence)
• Immune suppression {chronic use}
• Inhibition of ACTH, prolactin and gonadotrophic
hormone release {chronic use}
 Paracetamol
• Opioid dose sparing

• Antipyretic

• Excellent risk profile and few contraindications

• Should be used regularly at its maximal dose , tds or

qid, in all patients

Paracetamol
• Probable mechanisms of action
• Inhibition of prostaglandin synthesis (central)
• Serotoninergic pathway activation
• Endocannabinoid enhancement
Paracetamol
• Maximum PO or PR dose for children (acute
administration for 2 to 3 days):
• 60 mg/kg/day in term neonates and infants;
• 90 mg/kg/day in children aged between 6 months and
12 years.
• Maximum doses of IV paracetamol
• 30 mg/kg/day in neonates and infants
• 40 to 60 mg/kg/day in children
• 1g QID in adults
• Maximum adult dose: 4g/day (1g q6h)
 NSAIDs
• Non selective COX inhibitors and Selective COX2
inhibitors

• Effective analgesia, anti-inflammatory and antipyretic

• Synergistic with opioids

• Not recommended for routine use in patients with

↑risk of renal failure, peptic ulceration

• Caution in the elderly

NSAIDs
• Often first line
• Chemically diverse compounds
• Traditional (non specific) NSAIDs
• Selective COX 2 inhibitors (coxibs)

• Most widely prescribed drugs for acute & chronic

pain
Salicylates Aspirin, diflunisal, and salsalate

Propionic acid derivatives or Ibuprofen, dexibuprofen, ketoprofen,

“profens dexketoprofen, naproxen, fenoprofen,
flurbiprofen, oxaprozin, and loxoprofen

Acetic acid derivatives Indomethacin, diclofenac, nabumetone,

tolmetin, sulindac, etodolac, and ketorolac
Enolic acid derivatives or Piroxicam, isoxicam, meloxicam, tenoxicam,
oxicams droxicam, and lornoxicam

Fenamic acid derivatives or Mefenamic acid, flufenamic acid, tolfenamic

fenamates acid, and meclofenamic acid

Phenylpyrazolones Phenylbutazone, oxyphenbutazone

COX-2 selective inhibitors Celecoxib, rofecoxib, and valdecoxib

NSAIDs
• Action
• Inhibition of cyclooxygenase (1 &2) : PG synthesis
• Anti-inflammatory and analgesic

• Analgesic equipotency, analgesic ceiling

• Switching to a different NSAID may be considered if

the first is ineffective
Adverse effects of NSAIDs

• GI adverse effects
• More with nonselective NSAIDs
• Cause for concern
• Increased risk of GI ulcers on endoscopy
• Serious upper GI complications: GI
haemorrhage, perforation and obstruction
Adverse effects of NSAIDs
• GI adverse effects
• Risk factors
• patients over the age of 65,
• patients with a history of previous peptic ulcer
disease,
• patients taking corticosteroids,
• patients taking anticoagulants,
• patients taking aspirin
Adverse effects of NSAIDs

• Therapeutic approaches to reduce GI toxicity

• Co-administration of proton pump inhibitors
with traditional NSAIDs
• COX-2 inhibitors
Adverse effects of NSAIDs
• Cardiovascular risk of NSAIDs
• A class effect of all NSAIDs
• Includes
• Thrombotic events
• New onset of hypertension
• Worsening pre-existing hypertension

• Respiratory
• Bronchospasm in susceptible asthmatics (traditional
NSAIDs)
Adverse effects of NSAIDs
• Renal toxicity
• Transient decrease in renal function.
• Occur more often in patients with underlying
renal disease.
• May alter responses to thiazides or loop
diuretics.
• Fluid retention & oedema in some patients
Adjuvants
• Ketamine
• Powerful analgesic at subanaesthetic doses
(0.25-0.5mg/kg IV
• Postop infusion for up to 48hrs
• Opioid sparing

• Anticonvulsants and antidepressants

• Gabapentin, pregabalin, amitriptyline, nortriptyline
• Neuropathic pain
• Burn itch
Pharmacological:
Adjuvants
• α2- adrenergic blockers: clonidine, dexmedetomidine

• IV lignocaine infusion
 Regional analgesic
techniques
• Wound infiltration
• Epidural analgesia
• ‘conventional’
• Patient controlled epidural analgesia
• LAs, opioids
• Neural blocks
• Peripheral nerves
• Plexus blocks
• Other truncal blocks: transversus abdominis plain block,
paravertebral block
Patient Controlled
analgesia
• Allows the patient to administer preset doses of an
analgesic, on demand
• Gives patients a sense of control over their pain.
• Types
• IV patient controlled analgesia (IV PCA)
• Patient controlled epidural analgesia (PCEA)
• Transdermal – on trials
MULTIMODAL ANALGESIA

• Use of several different analgesics and routes of

administration, which then act in synergy
• Improves the effectiveness of pain relief
• Reduces the maximal dosage and adverse effects
• Procedure-specific
Treatment options in relation to magnitude of
postoperative pain expected following
different types of surgery
Mild intensity pain Moderate intensity Severe intensity pain
e.g. inguinal hernia, pain e.g. thoracotomy, upper abdominal
varices, laparoscopy e.g. hip replacement, surgery, aortic surgery, knee
hysterectomy, jaw surgery replacement

1. Paracetamol and wound infiltration

with local anaesthetic
2. NSAIDs (unless contraindicated)
3. Epidural local analgesia or major
peripheral nerve or plexus lock or
opioid injection (IV PCA)

1. Paracetamol and wound infiltration with local anaesthetic

2. NSAIDs (unless contraindicated)
3. Regional block anaesthesia (single shot or continuous infusion)
or opioid injection (IV PCA)

1. Paracetamol and wound infiltration with local anaesthetic agents

2. NSAIDs (unless contraindicated)
3. Regional block anaesthesia
Add weak opioid or rescue analgesia with small increments of strong opioid if necessary
 Non-pharmacological

•
methods
Psychological techniques:
• Relaxation techniques, cognitive behavioural therapy

• Distraction
• Music therapy, virtual reality, bubble blowing, play therapy
Conclusion
• Pain is a subjective experience
• Acute pain is a common presenting symptom
• Opioids are useful but should be used appropriately
• Paracetamol has few contraindications
• NSAIDs are useful but can cause serious adverse
effects
• Consider regional analgesia
• Best approach: Multimodal analgesia
Further Reading
Macinyre, P.E and Schug, S.A. Acute Pain
Management: A Practical Guide. 4th Edition.