Overview of analgesic drugs and their mechanisms of action

Question 1

What is the difference between an opiate and opioid?

Answer 1

Opiates are natural, and drugs with a morphine like structure
Opioids are drugs with a morphine like action (but may have a significantly different structure)

Question 2

Give examples of the morphine analogues

Answer 2

Morphine, codeine, diamorphine (heroin), naxolone (antagonist)

Question 3

Give examples of synthetic opioids; not derived from morphine structure

Answer 3

Pethidine, fentanyl, methadone, pentazocine

Question 4

What are the three types of opioid receptor and what class of receptor do they belong to?

Answer 4

G-protein coupled receptor

1. μ (mu, MOP)
2. k (kappa, KOP)
3. δ (delta, DOP)

Question 5

Where do each opioid receptor have analgesic effect?

Answer 5

μ receptors in periphery, spinal cord and brain
δ mainly peripheral (increased expression in inflammation)
k mainly spinal

Question 6

What happens when an opioid drug stimulates a receptor ?

Answer 6

All primarily coupled to Gi proteins

• inhibit adenylyl cyclase / reduce cAMP levels
• open K+ channels
• close Ca2+ channels (less glutamate release)
• cause hyperpolarisation of neurons and reduce transmitter release

Question 7

Where are opioid receptors expressed?

Answer 7

Mostly on neurons

Question 8

How are opioids effective analgesics?

Answer 8

Effective in acute and chronic pain

Anti-nociceptive and reduce the affective component of pain (physcologial awareness)

Question 9

How do opioids cause euphoria? Does anything counteract this?

Answer 9

Feelings of well being and reduced anxiety mainly μ mediated (possible off set by k mediated dysphoria)

Question 10

How to opioids cause respiratory depression?

Answer 10

Decreased sensitivity of respiratory centre (medulla) to pCO2

Question 11

What opioids are used as anti-tussives and when?

Answer 11

Codeine can be used at sub-analgesic doses as a cough supressant in treatment for terminally ill patients

Question 12

What can happen to the pupils of patients taking opioids?

Answer 12

Pupillary constriction that is centrally mediated

Question 13

What is one of the most common opioid side effect and where is the action of this?

Answer 13

Nausea and vomitting in 40% of patients
Action in area postrema (brain)
Often transient

Question 14

How is constipation caused by opioids and how can this affect the ADME of the drug?

Answer 14

Inhibition of GI tone and motility

This slows drug absorption (caution if taking other drugs)

Question 15

What causes urticaria / itch, possibly bronchoconstrction and hypotension in opioid use?

Answer 15

Opioid receptor dependent

Causes release of histamine from mast cells

Question 16

What are endorphins, where are they distributed and how do they work?

Answer 16

Endogenous opioid peptides distributed in the brain that work on μ receptors as agonists

Question 17

What are enkephalins, where are they distributed and how do they work?

Answer 17

Endogenous opioid peptides distributed in the CNS and in immune cells
μ and δ receptor agonists

Question 18

What are dynorphins, where are they distributed and how do they work?

Answer 18

Endogenous opioid peptides distributed in the CNS and act through K receptors

Question 19

What are endomorphins, where are they distributed, where do they work and what makes them different to other endogenous peptides?

Answer 19

μ receptor agonist, more potent than other endogenous opioids

Question 20

What are the three roles of NSAIDs?

Answer 20

Anti-inflammatory
Analgesic
Antipyretic

Question 21

What is the molecular mechanism of NSAIDs?

Answer 21

Inhibiting cycloxygenases thereby preventing prostaglandin and thromboxane formation from arachidonic acid

Question 22

What is COX-1 responsible for?

Answer 22

Housekeeping, products involved in homeostasis and signalling

Question 23

What is COX-2 responsible for?

Answer 23

Induced as part of the inflammatory response

Question 24

What pathway leads to prostaglandin release?

Answer 24

Arachidonic acid transformed to PGH2 by COX enzymes

PG synthases then transform into 5 primary prostaglandins (including TxA2 thromboxane)

Question 25

What is the role of prostanoid action in our feeling pain?

Answer 25

PGE2 produced in abundance in inflammation
EP receptors cause sensitisation of afferents
PGs (produced from PGE2) enhance the function of bradykinin receptors, TRPV1 channels, P2X receptors etc

Question 26

Cautions and contraindications with NSAIDs

Answer 26

Gastric ulceration 
Aspirin induced asthma 
Kidney impairment 
Ischemic heart disease 
Cardiac failure 
Coagulation defects 
Peripheral artery disease

Question 27

What are the most common GIT disturbances associated with NSAIDs and why are they caused?

Answer 27

Dyspepsia, diarrhoea, gastric bleeding

Result of inhibition of prostanoids that are responsible for promoting clotting and protective gastric mucosa

Question 28

Where do opioids work in the nociceptive pathway?

Answer 28

Work on increasing the descending inhibitory pathways.
PAG –> NRM–> (opioid peptides, 5H-T, NA increased).
This reduces the excitation of the transmission neuron.

They also work by reducing neuropeptide release

Question 29

How do NSAIDs reduce inflammation?

Answer 29

Reduce mediator release such as BK, 5-HT, PGs etc