Pharmacology of Pain Flashcards
Opioids
Diversity of opioid peptides- Enkephalins, dynorphins, beta-endorphin
Peptides derived from large molecular weight precursors
–> enkephalins from proenkephalin
Peptides are targets for peptidases
Endogenous opioid systems
Proopiomelanocortin-derived
Proenkephalin-derived
Prodynorphin-derived
Opioid receptors
Mu- 1,2,3 Delta- 1,2 Kappa- 1,2,3 Nociceptin/orphanin Opioid receptors are widespread
Morphine MOA
Attaches to receptor in cell
Activation of potassium conductance and decreased calcium conductance
Ca2+ entry blocked
–> decreased excitability + decreased release of neurotransmitters
Effects mediated by main opioid receptors
Analgesia Resp. depression Pupillary constriction Reduced GI motility Sedation Euphoria Dysphoria Dependence
Types of opioid
Codeine Methadone Morphine Oxycodone Tramadol
Effects of opioids- CNS
Analgesia Resp. depression Drowsiness Euphoria Miosis Nausea + vomiting
Effects of opioids- CV system
Hypotension
Effects of opioids- GI
Delayed gastric emptying
Decreased biliary and pancreatic secretions
Other Effects of opioids
Urinary urgency
Itching
Morphine
M6G active metabolite
Heroin
High solubility compared to morphine
Dextromoramide
Active sublingually
Meptazinol
Less resp. depression
Mu 1 receptor agonist
Warnings of opioid use
Resp. depression
Toxicity
Accumulation of methadone
Accumulation of M6G if renal function impaired
Opioid tolerance
Depends on genetic background + ethnicity
Can switch opioids when patients become tolerant to particular opioid drug
Analgesic ladder
1= non-opioids + adjuvant drugs 2= moderate efficacy opioids, non-opioids and adjuvant drugs 3= high-efficacy opioids, non-opioids and adjuvant drugs
Paracetamol
Reduced active oxidised form of COX2 Modulates endogenous cannabinoid system Analgesic Antipyretic Little anti-inflammatory
Aspirin
COX1 and COX2 inhibitor
Analgesic
Antipyretic
Anti-inflammatory
Ibuprofen, diclofenac, ketoprofen
COX1 and COX2 inhibition
Analgesic and anti-inflammatory
Rofecoxib
Selective COX2 inhibitor
NSAID indications
RA OA Dysmenorrhea Gout Muscle spasm
NSAID SE
Nausea
GI bleeding
NSAID Combinations
Codeine/paracetamol
Dihydrocodeine/paracetamol
Anticonvulsants
Cabamazepine, sodium valproate, pregabalin
Neuropathic pain
Trigeminal neuralgia
Carbamazepine MOA
Acts on Na channels
Na Valproate MOA
Acts on Na channels
Pregabalin
Acts on alpha 2 delta subunit on Ca channels
Tricyclic antidepressants
Inhibit reuptake of amines Block Na and Ca channels Amitriptyline Neuropathic pain Cancer pain
Migraine pain
Triptans
Ergotamine derivatives
Antidepressants
TCA
SSRI
Anticonvulsants
Na channels
Calcium channel ligands
Gabapentin
Pregabalin
Verapamil
Vanilloid receptors
TRPV family ligands
Capsaicin
NMDA glutamate receptors
Ketamine
Dextromethorphan
GABA receptor agonists
Baclofen
Local anaesthetics
Lignocaine, bupivacaine, prilocaine
Block Na channels
Surface, infiltration, epidural
Risk of systemic toxicity - hypotension, resp. depression, bradycardia
Inhalational general anaesthetics
Halothane NO Xenon Isoflurane Enflurane
IV general anaesthetics
Propofol
Thiopental
Ketamine
Trigeminal neuralgia
Most common facial pain syndrome Tic douloureux Sudden, paroxysmal attacks of pain Commonly unilateral Cheekbone, nose, upper lip + teeth
Trigeminal neuralgia cause
Compression
Distortion
Stretching of V nerve root fibres by branch of AICA or PICA
Trigeminal neuralgia treatment
Carbamazepine
Baclofen
Valproate
Clonazepam