Treatment of pain 1- simple analgesics and opioids Flashcards
Learning outcomes
• Describe the ways in which different analgesics target the neural pain mechanism
•Apply the analgesic ladder in hypothetical clinical scenarios of uncontrolled pain
-Contrast the different uses and adverse effects of common simple analgesics and opioid drug
-Describe how combinations of analgesic drugs can work synergistically to effectively and potentially more safely relieve pain
Pain assessment
- Pain can be very hard to describe, clinicians often underestimate pain
- Must hear what the patient is saying and how they are saying it
- Characterize the pains
- Identify their mechanisms and causes
- Assess their impact on the patient’s functioning and QOLNB: When pain does not respond to usual therapy, re-evaluate the patient for causes that may have been missed.
Use a pain scale (e.g 0-10)
Pain classification
- Nociceptive pain
- tissue damage (two types)
- Somatic • e.g. metastatic bone pain
- Visceral • e.g. liver capsule pain
- e.g. colic from malignant bowel obstruction
- Neuropathic
- nerve damage
- Peripheral or central
- Dysaesthetic (burning)
- Lancinating
Analgesics examples
mild > severe Paracetamol(NSAIDs)> Codeine> Dihydrocodeine> Tramadol> Morphine> Diamorphine
Paracetamol
Classification:analgesic, antipyretic, misc. NOT an NSAID
Mechanism of action: Despite 100 years , MOA remains unclear- inhibits prostaglandin synthesis via CNS inhibition of COX3 (or COX1 variant, not peripheral COX); peripherally blocks generation of pain impulses, inhibits hypothalamic heat-regulation centerIndications:
Mild to moderate pain without inflammation
Adverse effects: Rare at normal dosage
Caution in liver impairment/low body weight
Liver/renal toxicity in over dosage
Phase 1- redox hydrolytic of cP450, more reactive and ready to bind and be eliminated by liver or bile
Conjugation with glucothione (mercapturic acid> non toxic)
Without glucothione can cause hepatorenal damage
Or conjugation to sulphate or gluconoride metabolites (non toxic)
Opioid terminology
- “opium” is a Greek word meaning “juice,” or the exudate from the poppy
- “opiate” is a drug extracted from the exudate of the poppy (morphine and codeine mainly)
- “opioid” is a natural or synthetic drug that binds to opioid receptors producing agonist effects
Pharmacological effects
- Sedation and anxiolytic
- Drowsiness and lethargy
- Apathy
- Cognitive impairment
- Sense of tranquility
- Depression of respiration
- Main cause of death from opioid overdose
- Combination of opioids and alcohol is especially dangerous
- Cough suppression
- Opioids suppress the “cough center” in the brain
- Pupillary constriction•pupillary constriction in the presence of analgesics is characteristic of opioid use
Pharmacological efffects- continued
•Nausea and vomiting•Stimulation of receptors in an area of the medulla called the chemoreceptor trigger zone causes nausea and vomiting•Unpleasant side effect, but not life threatening
- Gastrointestinal symptoms•Opioids relieve diarrhoea as a result of their direct actions on the intestines
- Other effects•Opioids can release histamines causing itching or more severe allergic reactions including bronchoconstriction•Opioids can affect white blood cell function and immune function
Opioid mechanism of action
•Activation of peripheral nociceptive fibers causes release of substance P and other pain-signaling neurotransmitters from nerve terminals in the dorsal horn of the spinal cord
•Release of pain-signaling neurotransmitters is regulated by endogenous endorphins or by exogenous opioid agonists by acting presynaptically to inhibit substance P release, causing analgesia
-
3 types of opioid receptor
Mu
Mu-1• Responsible for central interpretation of pain
Mu-2• Responsible for respiratory depression, spinal analgesia, physical dependence, and euphoria
- Kappa
- Only modest analgesia
- Little or no respiratory depression
- Little or no dependence
- Dysphoric effects
- Delta
- It is unclear what delta’s responsible for
- Delta agonists show poor analgesia and little addictive potential
- May regulate mu receptor activity
Prescribing opioids
Weak opioids:• Codeine limited by presence of paracetamol and constipation
• Tramadol (caution in elderly and with SSRIs)
- Strong opioids• Morphine, oxycodone, diamorphine, fentanyl, hydromorphone, methadone, buprenorphine
- Do NOT use: • Pethidine
There exists wide inter- and intra-individual variability in responses (both analgesic and adverse effecs) to various opioids
Principles of opioid anagelsia
The right dose of opioid is the one that achieves the best analgesia with the fewest side effects:
• By the cause of the pain(s)• By the clock• By the ladder• By the mouth• For breakthrough pain• For the individual• Adjuvant therapies as needed• Prevent side effects
Opioid formulations: Short-acting formulations for •Opioid-naïve patients •Pain crises Long-acting formulations •Reserve for stable situations •Add short-acting opioids for breakthrough pain
Pharmacokinetics of opioids
- Onset of pain relief
- Oral opioids 15 - 30 min
- SC opioids5 - 10 min
- IV opioids3 - 5 min
- Duration of pain relief
- Short-acting oral opioids 3 - 5 hours
- Long-acting oral opioids 8 - 12 hours
- Fentanyl patches 48 - 72 hours
- IV or SC opioids 2 - 4 hours
- IV/SC fentanyl 40 minutes
- Half-life of transdermal fentanyl• 12 to 24 hours
Breakthrough dose
The breakthrough dose should be equivalent to a 4 hourly dose (i.e. 1/6th of the daily dose)
• May need to titrate dose according to patient needs: 5% to 25% of total daily opioid dose
• Generally use the same opioid as being used for regular regimen
Contraindications
- Patients with impaired pulmonary function
- Patients with impaired hepatic and/or renal function
- Patients with hypothyroidism
- Patients with recent head injury
