Pharmacological Management of Pain

*Adjuvants can be simple analgesics, steroids, antihistamine, antidepressants, anticonvulsants etc.

3 Step Ladder for Pain Management - introduced by WHO

Step 1 : Mild Pain

• SImple analgesic such as paracetamol and aspirin or NSAID
• Paracetamol do not have anti-inflammatory action but aspirin does and has antipyretic action.
• Both simple analgesic and NSAID have similar mechanism of action that is,they both inhibit COX-2
• Side effect of aspirin: causes stomach ulcers due to the decrease production of protective mucous (due to inhibition of prostacyclin 2 and 3) and increases gastric acid secretion (due to inhibition of prostacyclin 1)
• Aspirin is hydrolysed and removed by kidney

Diclofenac (voltaren) - NSAID

• accumulates in the synovial fluid

• should not be given to patients who have experienced asthma, urticaria, or other

  allergic-type reactions after taking aspirin or other NSAIDs.

• exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models.

Step 2: Mild to Moderate Pain

Weak opioids such as codeine (fyi, codeine is antitussive= cough supressore)

• Codeine less potent analgesic than morphine
• High oral effectiveness
• Used in combination with aspirin
• Rarely causes dependence

Step 3: Moderate to Severe Pain

Strong opioids such as morphine

• Mechanism of action: cause hyperpolarization of nerve cells, inhibition of nerve firing and presynaptic inhibition of transmitter release and inhibition of excitatory transmitters release from nerve terminals carrying nociceptive stimuli
• Usually given IV, subcutenously or IM because first pass metabolism of morphine occurs in the liver but the absorption of morphine from the GIT is slow
• Relieves pain by raising pain threshold at spinal cord level and altering brain's perception of pain
• Side effects : respiratory depression (acute opioid poisoning), vomiting, dysphoria(opposite of euphoria), sedation, constipation, nausea, urinary retention, potential addiction
• Depressant actions of morphine are enhanced by MAO inhibitors, tricyclic anti depressants
• Morphine is conjugated in the liver to glucuronic acid and excreted primarily in the urine
• Duration of action is 4 to 6 hours if administered systemically
• Fentanyl is used if patient is tolerant to opioids because fentanyl has 100-fold analgesic potency of morphine

*Diagnostically important- morphine causes pupil constriction known as pinpoint pupils but many other cases of coma and respiratory depression will produce dilation of pupils.

Methadone

• Well absorbed when administered orally
• Long lasting because accumulates in tissue and binds to protein which are slowly released from
• can cause constipation due to increase in biliary pressure
• can cause physical dependance but milder
• usually use for drug abuses who experiences withdrawal symptoms