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Analgesics
Drugs which relieve pain without causing unconsciousness. Opioids NSAIDs
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Pain
Definition: Unpleasant sensory and emotional experience associated with actual or potential tissue damage. The perception of noxious stimuli is termed nociception. Opioids can change both the sensation and the affective response.
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Pain
The sensation of pain arises from the activation of the peripheral terminals of C-fibres and Adfibres in response to mechanical and thermal stimuli. At their central terminals in the spinal cord C-fibres release peptides such as Substance P which activate spinal cord neurones.
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Endogenous Opioids
Derived from 3 precursor molecules: Proopiomelanocortin [POMC], pro-enkephalin and pro-dynorphan
Endogenous Opioids
Analgesia Motivation and reward Feeding Locomotor activity Thermoregulation Stress and anxiety
Receptor classes
Mu () - analgesia, respiration, cardio, intestinal transit, feeding, mood, thermoregulation, hormone secretion and immune function Kappa () - analgesia, diuresis, feeding, hormone secretion, immune function. Delta () - analgesia, mood, cardioregulation, immune function.
Cellular actions
Inhibit adenylate cyclase thereby reducing intracellular cAMP Facilitate the opening of K+ channels Inhibit the opening of Ca2+ channels
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Weak
Codeine
Moderate
Oxycodone Tramadol
Strong
Morphine Pethidine Methadone Buprenorphine Fentanyl
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Codeine
Well absorbed orally Metabolised in liver to morphine and codeine-6 glucoronide, excreted in urine Indication: mild to moderate pain, diarrhoea, cough half life: 4 - 6 hrs
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Oxycodone
10 x potency of codeine Indication: mild to moderate pain, antitussive Half life: 2-3 hrs
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Morphine
Bioavailability 25% Metabolised in liver to M3G and M6G, excreted in urine Indication: Moderate and severe pain, cancer-related pain, post operative pain. Half life: 2 - 4 hrs
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Pethidine [Mepiridine]
1/10 potency of morphine Bioavilability 40 to 60% Metabolised in liver to norpethidine, excreted in urine. Indications: moderate to severe pain. Half life: 3 - 4 hrs Not recommended for long term use
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Methadone
Bioavailability > 85% Metabolised in liver, mainly excreted in urine Indication: moderate to severe pain, opioid maintenance programs (decreases rapid lows and highs seen with heroin) Half life: 13 - 58 hrs
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Buprenorphine
Bioavailability 16% Metabolised in liver, excreted in bile and urine Indication: moderate pain Partial agonist; may be used for opioid withdrawal or maintenance Half life: 6 - 9 hrs
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Fentanyl
50 100 X potency of morphine Metabolised in liver, excreted in urine Indication: moderate to severe pain, child birth, anaesthetic/analgesic Half life: 1hr (high lipid solubility)
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Tramadol
Low affinity for opioid receptors Non-opioid actions; inhibits noradrenaline and serotonin reuptake Indication: moderate to severe pain including post-operative pain and neuropathic pain Half life: 5 hrs
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Which opioid?
Consider: Severity and duration of pain Previous experience with opioids Co-morbidity Age Biological variability in response Pharmacological e.g. potency, half-life, active or toxic metabolites Available formulations
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Route of administration
Use the least invasive route possible
Oral; least invasive; consider bioavailability, slow absorption Intramuscular; injections painful, absorption may be erratic, not recommended Subcutaneous; less painful than i.m., similar onset of pain relief Intravenous; rapid onset
Steady state concentrations approached in 4 half-lives unless loading dose is used
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Administration
On demand - a) on recurrence of pain - b) fixed intervals Patient controlled Analgesia (PCA) infusion systems -pre determined: intermittent injection dose, lockout interval, drug over time limits
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Pain Control
Morphine 10 mg oral, s.c. or i.m. will control pain in 70% of patients with mild - moderate pain. Severe pain may require i.v. morphine via intermittent or continuous infusion. May also use PCA.
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Respiratory depression
Opioids decrease the sensitivity of chemoreceptors to CO2 Usually little respiratory decline at therapeutic doses Can be assessed by the degree of sedation Caution:
Patients with decreased respiratory reserve; e.g. chronic airway limitation, morbid obesity Head trauma; increased CO2 tension in blood and cerebrospinal fluid increased intracranial pressure
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Acute Toxicity
Opioid overdose leads to coma with hypotension and marked respiratory depression, may be fatal.
Addiction; multiple drug use; drug purity
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