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Principles of Pharmacology - Week 9 Seminar Notes

Topic = Drugs Used to Relieve Pain and Inflammation

Overview of Key Topics

  • Classification of Pain

  • Nociception

  • Physiology of Pain

  • Drugs to Relieve Pain:

    • Opioid Analgesics

    • Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

    • Non-opioid Analgesics

  • Treating Pain

Pain Definitions and Categories

  • Definition of Pain:

    • "An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage" (International Association for the Study of Pain, 2011).

Types of Pain

  • Compare and Contrast:

    • Acute Pain:

    • Sudden onset.

    • Site is readily identifiable.

    • Typical set of clinical manifestations.

    • Self-limiting.

    • Readily corrected.

    • Chronic Pain:

    • Persists for three or more months.

    • Difficult to evaluate.

    • Treatment rarely brings complete relief.

    • Often accompanied by depression and a sense of hopelessness.

    • Can be primary (not due to another disease) or secondary (caused by an underlying condition).

Nociceptive Pain vs Neuropathic Pain

  • Somatic Pain:

    • From skin, muscles, bones, joints, or connective tissue.

    • Usually acute and well localized, can be chronic.

  • Visceral Pain:

    • Originates from internal organs like the heart, lungs, or GI tract.

    • Usually a diffuse, deep or aching pain.

    • Responds better to opioid medication.

  • Nociceptive Pain:

    • Arises from activation of nociceptors in response to actual tissue damage.

  • Neuropathic Pain:

    • Results from damage or dysfunction in the somatosensory nervous system.

Pain Pathways

  • Pain Transmission Pathway:

    • Pain receptors (nociceptors) activate due to noxious stimuli (heat, chemical, mechanical).

    • Transduction: Nociceptors convert stimuli to electrical signals, transmitted to CNS.

    • Transmission: Impulses are transmitted along nociceptive afferents (primary afferents) to the spinal cord.

    • Synapse in the substantia gelatinosa of the dorsal grey matter.

    • Secondary Afferents: Transmit information via ascending pathways, notably the spinothalamic tract, to the thalamus.

    • Perception: Thalamus sorts the information and relays it to the cortex for localization and full pain perception.

    • Modulation: Signals are modulated or inhibited at various levels via descending pathways from the brain and spinal cord.

Neurotransmitters in Pain Pathways

  • Nociceptive pathways utilize several neurotransmitters:

    • Endogenous Opioids

    • Noradrenaline

    • GABA

    • Serotonin

    • Substance P

    • These neurotransmitters are crucial for perception, processing, and modulation of pain, identifying potential sites for intervention.

Comparison of Pain and Nociception

  • Pain vs Nociception:

    • Pain involves the emotional and sensory experience of discomfort, while nociception refers purely to the physiological detection of harmful stimuli.

Drugs Used to Relieve Pain

  • Analgesic Drugs: Medications specifically meant to provide pain relief by blocking pain signals or altering the perception of pain.

  • Anti-inflammatory Drugs: Reduce inflammation, thereby indirectly relieving pain caused by inflammation.

    • Analgesics: Provide direct pain relief.

    • Anti-inflammatories: Address the underlying cause (inflammation) leading to pain relief.

Therapeutic Options for Treating Pain and Inflammation

  • Drug Classes:

    • Opioid Analgesics:

    • Examples: Morphine, Codeine, Fentanyl.

    • Non-Opioid Analgesics:

    • Example: Paracetamol.

    • NSAIDs:

    • Examples: Ibuprofen, Naproxen, Diclofenac.

    • Corticosteroids:

    • Drugs for Neuropathic Pain:

    • Examples: Antiepileptics, Antidepressants.

    • Muscle Relaxants and Local Anesthetics:

  • Understanding Pain Mechanisms:

    • Acknowledge nociceptor activation, inflammation, and the immune system's role in pain perception.

Opioid Analgesia

Actions of Opioids

  • Opioids interact with opioid receptors affecting several physiological effects:

    • Types of Receptors:

    • Mu (μ)

    • Delta (δ)

    • Kappa (κ)

  • Mechanism of Action:

    • Opioids bind to opioid receptors, primarily μ receptors, modulating pain perception and transmission, leading to analgesia.

  • They are beneficial for moderate to severe pain management.

Pharmacological Effects of Opioids

  • Activation of opioid receptors leads to:

    • Decreased release of Substance P and Glutamate from primary afferent neurons, reducing secondary afferent activation.

Other Actions of Opioids

  • Respiratory Depression:

    • Diminishes sensitivity in respiratory centers to CO2, risking hypoventilation.

  • Sedation and Euphoria:

    • Induces sedation; may lead to increased risk of respiratory depression.

  • Miosis:

    • Pupil constriction that does not develop tolerance, useful for identifying overdose.

  • Nausea and Vomiting:

    • Direct activation of brain’s vomiting center, manageable with anti-emetics.

  • Gastrointestinal Effects:

    • Reduced motility and secretion; can be used to treat diarrhea.

  • Immunosuppression: Evidence suggests long-term use may immunosuppress.

Tolerance and Dependence

  • Mechanism:

    • Continued exposure leads to less responsive receptors; varying tolerance rates for different effects.

    • Addiction: Involves a compulsion to use opioids due to psychological dependence.

Clinical Effects and Indications for Opioids

  • Pain Relief: Reserved for moderate to severe pain not responsive to other treatments.

    • Acute Indications: Myocardial infarction, bone fractures, pulmonary edema.

    • Chronic Pain: Cancer-related pain and palliative care.

  • Contraindications:

    • Respiratory depression and reduced consciousness.

    • Caution in elderly, patients with respiratory disease, those on sedatives.

Common Opioid Analgesics in Australia

  • Codeine: Used in combination with non-opioids; the gold standard for moderate pain.

  • Oxycodone: Potent synthetic opioid for severe pain, various formulations available.

  • Tramadol: Multi-mechanism with lower respiratory depression risk; still an addiction risk.

  • Pethidine: Limited use due to accumulation and adverse effects.

Penthrox (Methoxyflurane)

  • Analgesic Properties: Through anesthetic action; short-term pain relief primarily in emergency situations.

  • Administration: Self-administered via inhalation.

Cultural Impact: Dopesick

  • Evaluates the opioid crisis in the USA through aggressive marketing and over-prescription of OxyContin by Purdue Pharma.

  • Highlights ethical marketing implications and real-world consequences of drug regulation.

Non-Opioid and Anti-Inflammatory Agents

NSAIDs Definition

  • Medications treating pain and inflammation, including conditions like osteoarthritis and rheumatoid arthritis.

Mechanism of Action of NSAIDs

  • Inhibit COX enzymes (COX-1 and COX-2) that synthesize prostaglandins, thus reducing inflammation and pain.

  • Prostaglandins play critical roles in inflammation and protective functions in healthy tissues.

Adverse Effects of NSAIDs

  • Potential side effects include gastric irritation, ulceration, and renal function impairment.

NSAID Classification

  • Common Categories:

    • Salicylates (e.g., Aspirin)

    • Propionic Acid Derivatives (e.g., Ibuprofen, Naproxen)

    • COX-2 Inhibitors (e.g., Celecoxib)

Paracetamol (Acetaminophen)

  • Definition: A non-opioid analgesic, lacks anti-inflammatory or antiplatelet properties.

  • Mechanism: Weak COX-1 and COX-2 inhibitor in peripheral sites, acting primarily in CNS.

  • Advantages: Fewer gastrointestinal disturbances, suitable for post-surgical pain management.

  • Risks: Overdose can lead to hepatic necrosis.

Assessing Pain Management

  • Assessment Tools:

    • Numerical Rating Scales, Wong-Baker FACES Pain Scale.

  • Type of Pain: Distinction between nociceptive and neuropathic pain, tailored treatment plans based on severity and type.

Non-Pharmacological Treatments

  • Physical: RICE (rest, ice, compression, elevation), surgical interventions, acupuncture.

  • Psychological: Counselling, reassurance, education.

Summary of Action Sites and Effectiveness of Medications

  • Understand the specific effects of various analgesics at different sites (brain, spinal cord, periphery).

Conclusion

  • Emphasizes the significance of proper pain assessment and tailored treatment plans incorporating both pharmacological and non-pharmacological approaches.