Opioid Analgesics

Question 1

Where do opioids exert their effect?

Answer 1

The CNS, but also in the periphery.

Question 2

What is Gate theory?

Answer 2

Opites act as a gate between dorsal root of spinal cord and the thalamus and primary sensory cortex, to prevent the signal from the sesory receptor being noticed

Question 3

What endogenous opioids does the body produce?

Answer 3

Enkephalins
Endorphins
Dynorphins

Question 4

Where do endogenous opioids come from?

Answer 4

Cleaved from precursors - proenkephalin, POMC, and prodynorphin

Question 5

What opioid receptors are present through the body?

Answer 5

M (mu) receptors
Delta receptors
K (kappa) receptors

Question 6

What binds to delta receptors?

Answer 6

Enkephalins in the brain, CNS, and at the NMJ.

Question 7

Where are K receptors found?

Answer 7

The spinal cord

Question 8

Where are M receptors found?

Answer 8

Supraspinally.

Also in lymphocytes which is why opiates long term have an immunosuppressive effect.

Question 9

What kind of receptors are opioid receptors?

Answer 9

GPCRs

Question 10

What is the general effect that activating a opioid receptor has?

Answer 10

Increased efflux of K+ causing decreased excitability

Also decreased Ca2+ influx and cAMP synthesis

Question 11

What effect does decreasing Ca2+ influx have?

Answer 11

Decreased release of neurotransmitter into the synaptic cleft

Question 12

Which receptor are most opiate ADRs associated with?

Answer 12

M receptors

Question 13

What ADRs are associated with M receptors?

Answer 13

N&V
Constipation
Drowsiness
Miosis
Dependance
Tolerance

Question 14

What ADRs are generally associated with all opioid receptors?

Answer 14

Respiratory depression

Hypotension

Question 15

What ADRs are associated with K receptors?

Answer 15

Dysphoria (esp. with pentazocine)

Question 16

How do opiate drugs work?

Answer 16

All fairly differently to each other

Question 17

How does morphine work?

Answer 17

As a receptor agonist

Question 18

How does bupranorphine work?

Answer 18

As a partial agonist

Question 19

How does nalbuphine work?

Answer 19

As an agonist at some receptors, and an antagonist at others

Question 20

How does naloxone work?

Answer 20

As an antagonist - used to reverse respiratory depression.

Question 21

Tell me about morphines pharmacokinetics?

Answer 21

T1/2 ~ 4.5 hours

Oral bioavailability 25% so more effective if given IV.

Question 22

What is the half life of diamorphine?

Answer 22

0.08 hours = about 5 minutes

Question 23

What is methadone used for?

Answer 23

Maintenance in opiate dependancy

Question 24

Tell me about the pharmacokinetics of methadone?

Answer 24

T1/2 = 1.9-3.9 hours

90% oral bioavailability if given as a syrup.

Question 25

What is the t1/2 of bupranorphine?

Answer 25

2-4 hours

Question 26

Tell me about codeine.

Answer 26

T1/2 = 2-4 hours. | 90% oral bioavailability.

Question 27

What is the gold standard opiate?

Answer 27

Morphine!

Question 28

How is morphine metabolised?

Answer 28

Phase 2 glucuronidation in th liver to its also active metabolite which prolongs the effective t1/2.

Question 29

How are the metabolites of morphine excreted? Why is this important?

Answer 29

Via urine. A urine screen can be used to look for morphine use.

Question 30

Compare the structure of morphine and diamorphine.

Answer 30

Morphine is tricyclic with 2 polar groups, so is water soluble. Diamorphine has 2 acetyl groups so is much more lipid soluble.

Question 31

What is good about diamorphine?

Answer 31

It crosses the BBB rapidly and effectively, so gives you a big ol hit of morphine straight to the brain.

Question 32

What is diamorphine metabolised to?

Answer 32

Morphine!

Question 33

What do we use opiates for generally?

Answer 33

Analgesia for moderate to severe pain

Question 34

What are opiates bette for, visceral pain or sharp stabby pains? stabby stabby 🔪

Answer 34

Visceral pain Did i catch you out with that lil ol knife? 🔪 stabby stabby

Question 35

What kind of pain setting is morphine used in often?

Answer 35

Terminal illness and palliative care

Question 36

When is tramadol used?

Answer 36

Analgesia, with slight antidepressant effect

Question 37

What kind of analgesic is codeine?

Answer 37

Mild but metabolises to morphine

Question 38

Why do people respond differently to codeine?

Answer 38

Metabolised to morphine by CYP2D6 which is highly polymorphic.

Question 39

Which population tends to have a less effective CYP2D6 and therefore respond poorly to codeine?

Answer 39

Chinese populations

Question 40

What are fentanyl, afentanil, and remifentanil?

Answer 40

Anaesthetics ~100-1000 times more potent than morphine

Question 41

What is pethidine used for?

Answer 41

IM pain relief if labour

Question 42

Can you give pethidine over and over?

Answer 42

Noop, because its metabolite can cause convulsions.

Question 43

What are the agonist-antagonists?

Answer 43

``` Pentazocine Nalbuphine Butorphanol Buprenorphine Meptazinol ```

Question 44

What are the antagonists to opioid receptors?

Answer 44

Naloxone | Naltrexone

Question 45

What is the medicolegal aspect to opiates?

Answer 45

Some are controlled drugs under the 1971 and 2001 acts.

Question 46

Which are the main controlled opiates?

Answer 46

``` Diamorphine Morphine Remifentanil Pethidine Certain preparations of codeine ```