Pharmacology of pain

Question 1

Where does opium come from?

Answer 1

Opium poppies

Question 2

What are opiates?
What are opioids?
What are semi synthetic opiates?

Answer 2

Derived from opium
Drugs with opiate like effects
Derivates of natural opiates e.g heroin/diamorphine

Question 3

What are some of the undesired effects from morphine?

Answer 3

respiratory depression
nausea vomiting
dependency, withdrawl, tolerance
reduced GI motility

Question 4

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?

Answer 4

morphine-6-gluconoride
6-monoacetyl morphine
- 6
- 3

Question 5

What is kdiss?

Answer 5

The concentration of ligand when 50% of the receptors are occupied

Question 6

What is nalorphine?

How is it used clinically?

Answer 6

Morphine antagonist

Can be used as an anidote but at high doses it exhibits similar adverse effects as morphine

Question 7

When is naloxone used as an antidote?

Answer 7

morphine = natural opiate
heroin = semi synthetic opiate
naloxone = potent antagonist at  μ receptors

Question 8

What do endogenous peptides show?

Answer 8

Physiological role of opiate receptors =

Question 9

What modalities does the spinothalamic tract carry? ( ascending tract)

Answer 9

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

Question 10

Where do a delta fibres synapse with 2ndON ?

Where do C fibres synapse with 2nd ON?

Answer 10

Laminae I + V

Laminae I + II( substantia gelatinosa)

Question 11

Which tract carries A delta fibres?

Which tract carries C fibres?

Answer 11

Neo spinothalamic = lateral

Paleo spino thalamic = anterior

Question 12

What are the 2 divisions of the spina thalamic tract ( antero lateral system ) and what fibres do they carry?

Answer 12

Neospinothalamic ( lateral) - A delta fibres

Paleospinothalamic ( anterior) - C fibres

Question 13

How is pain modulated?

Answer 13

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

Question 14

What are the 3 main morphine/opiate receptors and what class are they?

Answer 14

μ, κ, δ ( mu, kappa + delta)
GPCRS
Signal via Galpha Gi/o signalling

Question 15

How do GPCRS work?

Answer 15

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

Question 16

What does Galpha i/o signalling lead to ?

Answer 16

decreases adenylate cyclase
decreases cAMP
decreases Ca2+ channel opening + Ca2+ influx

Question 17

What does GBy signalling lead to?

Answer 17

decreased Ca2+ channel opening 
Activates PLA2 + GIRK
Increased K+ conductance
hyperpolarisation 
less likely AP

Question 18

Why do opiates cause reduced gut motility?

Answer 18

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

Question 19

What is the function of loperamide?

Answer 19

Anti diarrhoea medication
= μ receptor agonist
Only acts in the periphery
P glycoprotein in BBB kicks out drugs from brain so low conc

Question 20

How does methlnaltrexone work ?

Answer 20

Antagonist of μ receptor
Has methyl group so cannot cross BBB
Reduces constipation