creation date: 2026-02-02 17:58
tags: Pharmacology
Analgesics
Background
Analgesics are medications used in pain management. This page specifically discusses pharmacological options.
WHO Analgesic Ladder
The WHO is a ladder which recommends categories of analgesic based on the severity of symptoms. Inadequate pain control warrants escalation up a step.
| Step | Severity | Non-opioids | Mild opioids | Strong opioids |
|---|---|---|---|---|
| 1 | Mild | Include | Avoid | Avoid |
| 2 | Moderate | Include | Consider | Avoid |
| 3 | Severe | Include | Consider | Consider |
| If required, adjuvant drugs can be added to the choice of analgesic above. |
Non-Opioid
Acetaminophen
Mechanism of Action
- Inhibits peroxidase activity of cyclooxygenase enzyme (especially COX-2) which reduce prostaglandin synthesis (prostaglandins sensitize nociceptors)
Contraindications / Considerations
- Contraindicated in liver failure or active hepatic disease
Examples
- Acetaminophen 325-1000 mg PO q4-6h prn (max dose: 4000 mg/day)
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Mechanism of Action
- Non-selective inhibition of COX-1 and COX-2 enzymes
- Blocks arachidonic acid conversation to prostaglandins which sensitize nociceptors and cause inflammation
- Reduces pain transmission and activates descending inhibitory pathways in brainstem
Contraindications / Considerations
Contraindications:
- Recent MI (except aspirin)
- Perioperative period of CABG
Relative contraindications/avoid: - Bleeding disorders
- Prior to surgery or invasive procedure
- Peptic ulcer disease
- Renal disease
Examples
- Ibuprofen (first-line)
- Naproxen (first-line)
- Diclofenac (oral, parenteral, or topical)
- Indomethacin
- Meloxicam
- Aspirin
Selective COX-2 Inhibitor
Mechanism of Action
- Selective inhibition of COX-2 reducing prostaglandin production
- COX-1 sparing reduces gastrointestinal risks
Contraindications / Considerations
- Preferred second line for mild-to-moderate
- Alternative to NSAIDs in patients with peptic ulcer disease
Caution in use:
- Renal disease
- Cardiovascular disease
Examples
- Celecoxib
Sodium Channel Blocker
Mechanism of Action
- Binds to voltage-gated sodium channels in nociceptive neurons, stabilizing the membrane and preventing action potential propagation
Contraindications / Considerations
- Take first dose on empty stomach
Avoid use in:
- Severe hepatic impairment
Examples
- Suzetrigine
Opioids
Mechanism of Action
- Binds to mu, kappa, and delta receptors presynaptically to inhibit Ca channels and neurotransmitter release responsible for pain conduction
Indications
For chronic non-cancer pain, a trial of opioids is indicated if:
- Nonopioid pharmacotherapy and nonpharmacological therapy has been optimized
- Patient does not have current or past substance use disorder, psychiatric disorders, past history of opioid overdose, and other therapy has been optimized
A trial of opioids may be considered in patients with history of substance use disorder but shared decision-making should be used.
In patients with a history of mental illness or active mental health disorder, a trial of opioids is not recommended.
Contraindications / Considerations
- Monitor for respiratory depression in first 72 hours after initiating or after increase of dose
- Oxycodone: not recommended for perioperative/postoperative in opioid-naive patients
- Tramadol: not recommended with epilepsy
Contraindications:
- Asthma
- Bowel obstruction
- Biliary colic
- Head injury
Prescribing Practices
Dosing
- Daily dose should ideally be ≤80 mg morphine equivalents daily
- Daily dose should seldom if ever exceed 150 mg morphine equivalents daily
- The lowest effective dose should be used
Intervals
- Tapering should be offered to the patient every 6-12 months once main management is stable
Opioid contract
- A contract can be used as an educational tool (not required by CPSO nor recommended by guideline)
- Outlines expectations for prescribing opioids; components include:
- Only obtaining prescription from one physician
- Purpose of the opioids and the expectations of its benefits
- Taking medication as prescribed including dosing and frequency
- Understanding risks (eg. driving risk, complications, side effects)
- Safe storage
Urine toxicology screen
- Can be used to identify opioid misuse
Examples
- Oxycodone
- Hydromorphone
- Tramadol
Adjuvant
Anticonvulsants
Mechanism of Action
- Stabilizes neuronal membranes by blocking voltage-gated sodium or calcium channels, suppressing ectopic firing and hyperexcitability
- Gabapentinoids bind to a2g subunits which inhibit calcium influx and excitatory transmitter release
Contraindications / Considerations
Examples
- Gabapentin
- Pregabalin
- Carbamazepine
Muscle Relaxants
Mechanism of Action
- Inhibits neurotransmitter release and postsynaptic activity in the spinal cord to reduce muscle tone and spasm-related pain
Contraindications / Considerations
Examples
- Cyclobenzaprine
- Metehocarbamol
- Baclofen
Antidepressants
Mechanism of Action
- Inhibits serotonin or norepinephrine which boost descending inhibitory pathways
- Activates a2-adrenergic receptors to suppress ascending pain signals
Contraindications / Considerations
Examples
Tricyclic antidepressants
- Amitriptyline
- Doxepin
- Clomipramine
SNRIs - Duloxetine
- Venlafaxine