Medications for pain (nociceptive pain)

Class Examples Mechanism Side effects Additional info

CV
Opioids Morphine Mu-R agonist  Bradycardia
Opioid analgesic of choice
 Postural hypotension Effective against:

Stimulating g protein coupled receptor Derm
Vasodilation
 Ischaemic pain
 Inhibits adenylate cyclase leading to  Sweating  Visceral pain
 Flushing
decreased cAMP -> hyperpolarize  Urticaria  Palliative care
membrane potential through K+ efflux  Pruritis  Neuropathic
Neurological
(conductance)  Confusion Additional examples
 Reduce the number of voltage gated  Dizziness
 Delirium
calcium channels  Sedation
Opthalmological
 Miosis
GI
 Constipation
 Anorexia
 N&V
MSK
 Chest wall rigidity
 Myoclonus
Neuroendocrine
 Hypothalamic
 Decreased
testosterone
 Cortisol
 Increased prolactin
 Increased ADH
 Hepatic insufficiency
Respiratory
 Bronchospasm
 Resp depression
(complicated raised
IP)
 Urinary retention
 Tolerance
NSAIDS COX 1 and/or COX 2 inhibitors Aspirin
Block prostaglandin synthesis to:  Acetylates the enzymes
 Decrease peripheral sensitisation leading to irreversible long
 Decrease vascular permeability lasting effect
(inflammation) Ibuprofen
  Direct spinal action: reducing sensitivity  Non selective for cox 1 and 2
induced by EAA (glutamate) and  Reversible
substance P activity Celecoxib
Paracetamol  Cox 2 selective
 Little anti-inflammatory action
 Analgesic foundation, with additional
agent when necessary layered on top
 Various proposed sites of action:
 Supraspinal: inhibition of hypothalamic
PG synthetase
 Spinal: prevention of PG release
 Prevents release of PG
 Interferes with cox1 and cox2 activity via
peroxidase inhibition
 Metabolite is hepatotoxic

WHO Analgesia ladder

 Medications for pain (neuropathic)

Class Examples Mechanism Side effects Additional info

Antidepressants (eg. Tricyclic) Amitriptyline 5-HT and Nad reuptake inhibitors (dorsal horn  Sedation Use low dose
or descending pathway)  Antimuscarinic
 Weak NMDA antagonism and sodium (dry mouth, Used in diabetic neuropathy
channel blockers dizzy, tachy, and post herpetic neuralgia
urinary
retention Less effective in chronic pain
 Arrythmias states (eg. Lower back pain)
 QT
prolongation
interval
Anticonvulsants Sodium Sodium valproate Carbamazapine Blood and liver monitoring
(mood/membrane stabilisers) valproate  T type calcium channel blocker  SIADH are often important and
Carbamazepine  Use dependant Na channel blocker  Sedation required
Pregablin  Increases central GABA  Ataxia
 Rash Effective for
Carbamazepine  Mood changes ‘shooting/burning’ pain
 Use dependant Na channel blocker (IMPORTANT)
(holds channel in closed state) Pregabalin Carbamazepine
Pregabalin  Dizzy Potent hepatic enzyme
 Gabapentanoid  Drowsiness inducer – dose titration
 Block voltage gated calcium channels  Dry mouth required, drug interactions
(alpha-2-delta subunit)
 Decreases neuronal excitability, Pregabalin useful for
substance P release  Diabetic neuropathy
 Fibromyalgia
 Trigeminal neuralgia
 Post-operative pain
Capsaicin Capsaicin  Vanniloid receptor agonist, which allows Burning Prolonged agonist action on
Ca2+ entry into neurone Itching TRPV causes desensitisation,
 Excess Ca2+ influx induced nerve Redness and this is useful for
terminal degeneration mediating analgesic affect
 Depletes by releasing substance P since there are less TRPV
 Inactivates SP containing fibres transporter which help
 Initial activation leads to irritation mediate pain response
Local anaesthetics Eg. Lignociane  Prevent transmission
Benzocaine  Prevent impulse (AP) conduction along
sensory nerves by blocking voltage
sensitive Na+ channels
 Act by either penetrating cell and then
blocking channel from inside, or by
diffusing within plasma membrane to
binding to their binding site on the
channel
 Rely on lipophilicity to penetrate plasma
membrane
Furthermore
 Decreased pH of inflammatory soup may
cause lower efficacy (local anaesthetics
tend to be basic compounds)
 Usually use dependant: binding site
accessible only when channel is open
 Non selective: other sensory modalities
can also be blocked so local paralysis can
occur which is a serious side effect