8 Analgesics Flashcards
Following this lecture you should be able to …
Demonstrate an understanding of the physiological basis for pain detection and transmission and describe the key aspects of pain sensing in the central nervous system.
Demonstrate an understanding of the applied pharmacology for pain management with specific reference to:- Opioids Antidepressants Antiepileptics Local Anaesthetics
Identified Applied Pharmacology
Corticosteroids in analgesia (e.g. methylprednisolone, dexamethasome)
NSAIDs and paracetamol in analgesia
Opioids in analgesia
Anti-epileptic medications in analgesia (e.g. carbamzepine, gabapentin)
Anti-depressants in analgesia
- Selective serotonin Re-uptake Inhibitors (SSRI’s) (e.g. paroxetine, citalopram)
- Serotonin and Noradrenaline Re-uptake Inhibitors (SNRI) (e.g. venlafaxine)
Anaesthetics in analgesia (e.g. lidocaine)
Drugs - Analgesics
NSAIDS & Paracetamol Anti-inflammatory actions of the steroids Opioids Antidepressants Antiepileptics Local Anaesthetics
General Statements
Pain control is a high therapeutic priority
Classic analgesics: opiates & NSAIDs used for centuries
Original compounds e.g. morphine & aspirin, are in widespread use, but new analogues acting in the same way have been developed.
Several alternate classes of drugs e.g. antidepressants, antiepileptics drugs, are now widely used to treat certain types of pain.
Future? understanding the neural mechanisms underlying pain will lead to new drug targets and thereapies..
Pain – General Definitions
Acute / Nociceptive; short-term pain, with an easily identifiable cause. A warning of present damage to tissue or disease which responds well to medication.
Chronic / Neuropathic; pain which persists. Is constant or intermittent and has “outlived its purpose” since it no longer help the body to prevent further injury.
Allodynia – pain from a stimulus that does not normally cause pain
Parasthesis – painful feelings (e.g. pins & needles) with no apparent stimulus
Unpleasant sensation; varying degrees of severity; consequence of injury, disease, or emotional disturbance
Pain Management – General Considerations
Assessments Type of pain (nociceptive versus neuropathic) Form of pain (acute versus chronic) Severity of pain Route of administration
Objectives
Best analgesic for the individual
Lowest effective dose
Least invasive route - topical, oral, sublingual, i.v., i.m., i.p., i.t., epidural
Analgesics – Broad Overview
Opioids
Modify the transmission of pain signals and the subjective perception of pain
Antidepressants
Antiepileptics
Trigeminal neuralgia
Neuropathic pain (which is resistant to opioids)
Local Anaesthetics
Particularly effective for severe intractable or crescendo neuropathic pain: emergency medicine
Opioids – Therapy
Advantages Variety of routes Range of durations of effects Highly effective Disadvantages Interactions Cautions / Contraindications Side effects
Dose-related; from nausea, vomiting, constipation, drowsiness, to respiratory depression, hypotension, sedation, dependency
Acute respiratory depression, acute alcoholism, head injury
alcohol - inc. hypotensive and sedative effects
MAOI - inc. CNS excitation/inhibition
SSRI / TCA - inc. sedation
carbamazepine gi plasma conc. of methadone
cimetidine (ulcer healing) - inhibit opioids metabolism
Opioids
Neuropharmacology
Mimic Our Endogenous Ligands “enkephalins”
β-Endorphin; Leu-enkephalin;
Met-enkephalin; dynorphin
Act as Agonists at Opioid Receptors
Three types of receptors: m, k, d
Six sub-types: m, k1,2,3: d1,2
Signal Transduction
G-protein coupled receptors
Integrated Physiology
“act as suppressors..”
Opioid Receptors & Opioids
CNS & Peripheral Sensory Neurons
May contribute to analgesia
CNS, Spinal Cord, Peripheral Sensory Neurons
Sedation & dysphoria, but few side effects
Does not contribute to dependence
CNS, Spinal Cord,
Peripheral Sensory Neurons, GI Tract
Responsible for most of the analgesic effects
Responsible for side effects
Most analgesic opioids are μ-receptor agonists
Opioids Pharmacodynamics
Pure Agonists
Typified by morphine-like drugs
Have high affinity for μ-receptors; low affinity for δ & κ
Partial agonists & Mixed Agonist-Antagonists
e. g. nalorphine: mixed effects on μ-receptors e. g. pentazocine & cyclazocine: (-) at μ-, but partial (+) on δ- & κ-
Antagonists
Block the actions of opiates
e.g. naloxone and naltrexone; treatment of heroin/morphine overdose
Most analgesic opioids are μ-receptor agonists
Antidepressants & Analgesia; Mechanism of Action
Serotonin and noradrenaline mediate descending inhibition of ascending pain pathways in the brain and spinal cord
SNRI - Serotonin and Noradrenaline Reuptake Inhibitors (SNRI)
Highly effective for neuropathic pain, but not in all patients
Actions are independent of their antidepressant effects
SNRI - Venlafaxine (Effexor, Efexor)
Duloxetine (Cymbalta, Ariclaim, Xeristar, Yentreve, Duzela)
SSRI - Selective serotonin reuptake inhibitors (SSRI)
Not particularly effective analgesics
Appear to work well in the disease environment, e.g. diabetic- or HIV-related neuropathy e.g. paroxetine, citalopram
SSRI - Paroxetine (Aropax, Paxil, Pexeva, Seroxat, Sereupin)
Citalopram (Celexa,Cipramil)
SNRI/SSRI Mode of Action
Prevent the recycling of neurotransmitters & enhance the signal..
SNRI Antidepressants & Analgesia
Duloxetine
Prescribed for peripheral neuropathy, particularity diabetic neuropathy.
Side-effects include nausea, somnolence, insomnia, dizziness
Venlafaxine (Effexor, Efexor)
Prescribed for diabetic neuropathy
Side-effects include nausea, sedation, headache and dizziness.
Cautions / Contraindications:
Epilepsy, cardiac disease, diabetes, angle closure glaucoma, pregnancy / breast feeding
Interactions:
Alcohol g h sedation
NSAIDS / aspirin g h risk of bleeding
Tramadol g h risk of CNS toxicity
Increase in sedative effectiveness when given with opioid analgesics
SSRI’s antagonise anticonvulsant effect of antiepileptics
Antiepileptic Agents – Mechanism of Action
Inhibit of voltage gated Na+ channels
Inhibit of voltage gated Ca2+ channels
Inhibit Glutamate, g-Aminobutyric Acid (GABA) & Glycine receptors
Inhibit action potential firing
g prevent impulse transmission
limit neuronal excitation
g enhance neuronal inhibition
