Lecture 16 - Opioids

Question 1

What is the definition of Pain?

Answer 1

An unpleasant sensory and emotional experience associated with or resembling actual or potential tissue damage

Question 2

What are some endogenous opioids?

Answer 2

B-endorphins
Endomorphins
Dynorphins
Enkephalins

Question 3

What are the 2 types of pain fibres?

Answer 3

A delta fibres
C fibres

Question 4

What type of pain do A delta fibres transmit?

Answer 4

Fast sharp pain

Question 5

What type of pain do C fibres transmit?

Answer 5

Slow burning pain

Question 6

What sensory pathway transmits pain?

Answer 6

Spinothalamic pathway

Question 7

Which pain fibres are myelinated and which pain fibres are not myelinated?

Answer 7

A delta fibres = myelinated (fast sharp pain)

C fibre = unmyelinated (slow burning pain)

Question 8

Where do the primary sensory neurones (A delta fibres or C fibres ) synapse to the second order neurone?

Answer 8

Synapse to second order neurone in the Ipsilateral dorsal horn

Question 9

What is considered the pain gate?

Answer 9

The point where the primary sensory pain neurones (A delta and C fibres) synapse to the 2nd order neurone in the dorsal horn on the Ipsilateral side of the cord

Question 10

Once the pain fibre has synapsed to the 2nd order neurone on the Ipsilateral cord what happens next?

Answer 10

2nd order neurone decussates and ascends to the thalamus where it synapses to a 3rd order neurone going to the cortex
A 2nd order neurone also goes to the limbic system (emotional response to pain)

Question 11

What is the function of the limbic system in the pain pathway?

Answer 11

Emotional control

Question 12

What carries the sensory dimension in the pain pathway?

What carries the affective/emotional dimension of pain?

Answer 12

Sensory = 3rd order neurone to cortex

Affective = 2nd order neurone to limbic system

Question 13

Go to the first slide and label the spinothalamic pain pathway on the left hand side:

Question 14

What effect does rubbing an area with pain have?

Answer 14

Relieves the pain

Question 15

How does rubbing a painful area help relieve the pain?

Answer 15

Stimulating mechanoreceptors leads to their primary sensory neurone Stimualting inhibitory encephinergic neurones that lead to the secondary sensory neurone in the dorsal horn prevention pain reaching the cortex

Question 16

What are the neurotransmitters from inhibitory interneurones that synapse onto the 2nd Order sensory neuorne in the dorsal horn?

Answer 16

GABA
Enkephalins

Question 17

What class of molecule arer enkephalins?

Answer 17

Endorphins

Question 18

What receptors do endorphins/enkephalins act on?

What do they do?

Answer 18

Mu opioid receptors

Inhibit pain transmission

Question 19

What neurotransmitters are produced by descending fibres that inhibit the activation of the 2nd order sensory neurone prevntinig pain?

Answer 19

Noradrenaline
5-HT (serotonin)

Question 20

Go to the first slide and label the right side pain pathway:

Question 21

What part of the CNS have high levels of Mu opioid receptors so are important in pain?

Answer 21

High. Levels in Brain
Periqueductal grey matter in midbrain
Reticular formation (grey matter in medulla)

Question 22

What is the pathway for altering pain threshold during stress?

Answer 22

Amygdala to periaqueductal grey matter then travels to reticular formation in medulla then to the dorsal horn in the cord

Question 23

What is the pathway for altering pain threshold during the menstrual cycle?

Answer 23

Hypothalamus sends axons to periaqueductal grey matter in the midbrain
Then axons sent from here to the reticular formation in the in the medulla
Then axons sent from here to the spinal cord

Question 24

What is the thought process behind the cause of opioid drug addiction?

Answer 24

Activation of Mu opioid receptors in the midbrain can lead to the substantia nigra releasing lots of dopamine which leads to addiction q

Question 25

What are opiates? What are some examples?

Answer 25

The natural substances of opioids Codeine Morphine Diacetyl morphine (heroin)

Question 26

What are some synthetic opioids?

Answer 26

Methadone Fentanyl

Question 27

What does codeine get metabolised into? What does this metabolism?

Answer 27

Morphine CYP2D6

Question 28

What is the simple way by which opioids cause pain relief?

Answer 28

Activating Mu opioid receptors inhibit Ca2+ influx into neurones decreasing the release of excitatory neurotransmitters (GLUTAMATE) to the second order neurone so inhibts pain signal transmission

Question 29

What are therapeutic opioids used for?

Answer 29

Analgesia (euphoria) Antitussive (cough suppression) Dyspnoea Anaesthetic Anti diarrhoeal (since side effect is constipation) Palliation (symptom relief not underlying cause treatment)

Question 30

What are some examples of therapeutic opioids?

Answer 30

Codeine Morphine Fentanyl Buprenorphine Tramadol

Question 31

What is the lipid solubility, onset time and duration time of morphine?

Answer 31

Lower lipid solubility Slower onset Relatively long duration

Question 32

What is the lipid solubility, onset time and duration time of fentanyl?

Answer 32

Highly lipid soluble Fast onset Short duration of action 100x POTENCY OF MORPHINE

Question 33

What type of drug is codeine?

Answer 33

Prodrug converted to morphine (secondary metabolite) by CYP2D6

Question 34

How is codeine administerd?

Answer 34

Oral Subcutaneous

Question 35

How is morphine adminstered?

Answer 35

Oral IV IM Subcutaneous (SC) rectally

Question 36

How is fentanyl administered?

Answer 36

Transdermal Intra nasal IV Epidural

Question 37

Go to slide 2 and label the pain altering pathways:

Question 38

What drugs are given for mild pain?

Answer 38

Paracetamol Ibuprofen

Question 39

What drug is given for mild to moderate pain?

Answer 39

Codeine

Question 40

What drug is given for moderate to severe pain?

Answer 40

Morphine Fentanyl

Question 41

Label slide 6

Question 42

What is the problem with compound analgesics like co-codamol?

Answer 42

Cant change dose of one of the drugs in the preparation very well

Question 43

What are some adverse drug reactions of Opioids?

Answer 43

Constipation Drowsiness Dysphoria Euphoria Flushing Headache MIOSIS (pupillary constriction) Respiratory depression Itching

Question 44

Why do you get itching with opioids?

Answer 44

Leads to histamine release

Question 45

What are the contraindications to opioids?

Answer 45

Comatosed patients Head injuries or raised ICP Resp depression Paralytic ilium Asthmatics (histamine) Pregnancy

Question 46

What ae some drug drug interactions with opioids?

Answer 46

CNS depressants (antiepilieptics and benzodiazepines) Opioids Drugs reducing gut motility CYP450 inducing or inhibiting enzymes

Question 47

What is buprenorphine? What is it used for?

Answer 47

Partial opioid receptor agonist with long action Can be given to addicts to provide small high and not got resp depression

Question 48

What is Naloxone? What is it used for?

Answer 48

Mu opioid receptor competitive antagonist Used in overdose as it rapidly distributes and doses not last long

Question 49

What is methadone?

Answer 49

Very lipophilic opioid (more lipophilic than morphine nad has. A longer duration of action

Question 50

Why may Naloxone be amidnstered multiple times in respiratory depression?

Answer 50

It may wear off then the opioid can cause respiratory depression

Question 51

Go to slide 10 and match the analgesic repsonse graph tot the opioid agonist or antagonist:

Question 52

What is the idea that leads to development of tolerance with opioid use?

Answer 52

More cAMP is made so base levels are higher since body is anticipating th opioid to reduce the cAMP levels Receptor internalising and uncoupllling

Question 53

What causes the withdrawal symptoms of opioid use?

Answer 53

The increased base levels of cAMP levels without opioids inhibiting it leads to excess of normal function (tachycaradai, tachypnoea etc..) Opioids inhibit the levels of cAMP when given

Question 54

What are some symptoms of opioid withdrawal?

Answer 54

Insomnia Anxiety Excessive sweating Enlarged pupils Tachycardia Tachypnoae Diarrhoea

Question 55

What are the 3 classes of controlled drug?

Answer 55

Class A Class B Class C

Question 56

How are controlled drugs assigned to a class?

Answer 56

A is the most harmful when misused

Question 57

What are some Class A drugs?

Answer 57

LSD Fentanyl

Question 58

Hat are some Class B drugs?

Answer 58

Codeine Ketamine

Question 59

What is a Class C drug?

Answer 59

Anabolic steroid