Discuss the pharmacological factors to be considered when choosing an analgesic drug. Illustrate your answer with relevant examples.

Outline:

·        Clinical efficacy.

·        Mechanism of action & side effects.

·        Onset of pain relief and duration of action.

Suggested answer:

An analgesic drug is a drug that relieves pain due to multiple causes. Analgesics are classed as opioid and non-opioid. Opioids act on opioid receptors in the CNS, producing analgesia by altering the emotional response to pain. Non-opioid analgesics, which are chiefly NSAIDs, act peripherally by inhibiting cyclooxygenase and thus prostagladin synthesis. Prostaglandins are mediators of inflammation and they also sensitize nerve endings, lowering their threshold of response to stimuli, mechanical and chemical, and allowing the other mediators of inflammation, e.g. histamine, serotonin, to intensify the activation of the sensory endings.

The choice of an analgesic is determined chiefly by its clinical efficacy and the degree of pain that needs to be relieved. For mild pain such as headache, musculoskeletal pain, NSAIDs, e.g. aspirin, ibuprofen and paracetamol are used. When these fail after using the full dose range, low-efficacy opioids, e.g. codeine, pentazocine, are employed. In severe pain due to cancer, high-efficacy opioids, e.g. morphine, pethidine, buprenorphine, are used. An added NSAID is useful if there is a substantial tissue injury component, e.g. gout, bone metastasis.

The therapeutic index and properties of the NSAID, e.g. anti-inflammatory are important pharmacological factors in their clinical usage. As all NSAIDs cause gastric intolerance and renal toxicity to varying degrees, they should be avoided in patients with a history of peptic ulcer disease or renal failure. Mefenamic acid is relatively safe and is used commonly to relieve mild musculoskeletal pain and heavily promoted for dysmenorrhoea. However, it may cause severe diarrhea with chronic usage and therefore should not be used for more than 1 week and never in children. Indomethacin is a potent anti-inflammatory anti-pyretic analgesic and is indicated in rheumatic arthritis, ankylosing spondylitis, osteoarthritis and acute gout.

In control of chronic intractable pain in a palliative care setting, analgesics should be given regularly, adjusted to the patient’s need to prevent pain and not only to suppress it. Oral use preserves patients’ independence as well as reducing the unpleasantness of frequent injections. Morphine is commonly used to control severe pain in palliative care as it can be administered orally either as a simple aqueous solution or as sustained-release tablets.

The rapid onset of pain relief is valued in the management of acute pain, e.g. myocardial infarction and chronic pain. Diamorphine is generally preferred over morphine for acute pain. It provides a more rapid onset of pain relief than morphine because it is more soluble and enters the brain more readily, and its duration of action is about the same. Diamorphine is more soluble than morphine to a useful degree. This, together with its greater potency makes diamorphine suitable to deliver by s.c. infusion through a syringe driver when continuous pain control is required in palliative care and can no longer be achieved by enteral morphine.