Pharmacology of pain Flashcards
Where does opium come from?
Opium poppies
What are opiates?
What are opioids?
What are semi synthetic opiates?
Derived from opium
Drugs with opiate like effects
Derivates of natural opiates e.g heroin/diamorphine
What are some of the undesired effects from morphine?
respiratory depression
nausea vomiting
dependency, withdrawl, tolerance
reduced GI motility
What is the main active ingredient of morphine?
What is the active form of heroin?
At what positions are opiates most active?
At what positions are opiates generally inactive?
morphine-6-gluconoride
6-monoacetyl morphine
- 6
- 3
What is kdiss?
The concentration of ligand when 50% of the receptors are occupied
What is nalorphine?
How is it used clinically?
Morphine antagonist
Can be used as an anidote but at high doses it exhibits similar adverse effects as morphine
When is naloxone used as an antidote?
morphine = natural opiate heroin = semi synthetic opiate naloxone = potent antagonist at μ receptors
What do endogenous peptides show?
Physiological role of opiate receptors =
What modalities does the spinothalamic tract carry? ( ascending tract)
Pain, temperature, crude tough
= anterolateral system
Fibres will dessucate in the spinal cord
- 1st oder Neurone has cell body in DRG enters the dorsal horn of the spinal cord + synapses with a second order neurone
- 2nd ON dessucates in the spinal cord to form an anterior + lateral system
- 2nd order neurone ascends through the PONS-> medulla -> thalamus
- Synapses with a 3rd ON in the thalamus
- 3rd ON relays information to the cingulate cortex, limbic cortex and sensory cortex
Where do a delta fibres synapse with 2ndON ?
Where do C fibres synapse with 2nd ON?
Laminae I + V
Laminae I + II( substantia gelatinosa)
Which tract carries A delta fibres?
Which tract carries C fibres?
Neo spinothalamic = lateral
Paleo spino thalamic = anterior
What are the 2 divisions of the spina thalamic tract ( antero lateral system ) and what fibres do they carry?
Neospinothalamic ( lateral) - A delta fibres
Paleospinothalamic ( anterior) - C fibres
How is pain modulated?
Descending pathways
Gate control: Non noxious stimuli decrease transmission up the spinal cord, interneurones in substantial gelatinosa, branches of A delta + C fibres will regulate the gate
What are the 3 main morphine/opiate receptors and what class are they?
μ, κ, δ ( mu, kappa + delta)
GPCRS
Signal via Galpha Gi/o signalling
How do GPCRS work?
GPCRS = hetertrimeric protein made of Galpha + Gbetagamma subunits
- At rest GDP is bound to the Galpha subunit
- Agonist binds to receptor
- GDP -> GTP
- Subunits and receptor dissociate
- Subunits interact with proteins for signalling cascade
- Galpha subunit has intrinsic GTPASE activity so GTP -> GDP
- Signalling pathway terminates
What does Galpha i/o signalling lead to ?
decreases adenylate cyclase
decreases cAMP
decreases Ca2+ channel opening + Ca2+ influx
What does GBy signalling lead to?
decreased Ca2+ channel opening Activates PLA2 + GIRK Increased K+ conductance hyperpolarisation less likely AP
Why do opiates cause reduced gut motility?
There are μ receptors on post sympathetic fibres in the gut
opiates bind and activate Galpha i/o signalling -> less Ca2+ influx -> less NT released
What is the function of loperamide?
Anti diarrhoea medication
= μ receptor agonist
Only acts in the periphery
P glycoprotein in BBB kicks out drugs from brain so low conc
How does methlnaltrexone work ?
Antagonist of μ receptor
Has methyl group so cannot cross BBB
Reduces constipation
