PHARM - Drugs for Pain Management - Week 9

Question 1

Define pain.

Answer 1

Unpleasant sensory and emotional experience associated with actual or potential tissue damage

Question 2

What is the vital purpose of pain?

Answer 2

Serves as a defence function

Question 3

Is pain objective or subjective?

Answer 3

It is a uniquely individual and subjective exerience

Question 4

List the two kinds of acute pain and list two properties for each.

Answer 4

Somatic

• sharp
• well localised

Visceral

• dull
• poorly localised

Question 5

Do a significant number of individuals live with constant chronic pain or is it rare?

Answer 5

Common - 1 in 5 for Australia

Question 6

Are current evidence-based treatments of chronic pain under- or over-utilised? Explain.

Answer 6

Under-utilised.

<10% of people with chronic non-cancer pain gain access to care that could allow up to 80% to be treated effectively.

Question 7

What period of time is chronic persistent pain considered to be?

Answer 7

> 3 months

Question 8

List the three broad groups of chronic persistent pain and give an example of each.

Answer 8

Defined nociceptive basis
-cancer
Well-defined neuropathological basis
-peripheral neuropathy
Idiopathic
-chronic musculoskeletal pain

Question 9

Describe the kind of pain felt by the following classifications:
Superficial somatic (3)
Deep somatic (2)
Visceral (2)
Neuropathic (5)

Answer 9

Superficial somatic - hot, burning, stinging
Deep somatic - dull, aching
Visceral - dull, deep
Neuropathic - pins/needles, tingling, burning, shooting, phantom pain

Question 10

Briefly describe, in 5 steps, the nociceptive curcuit for pain.

Answer 10

Activation of the peripheral terminal by a noxious stimulus
It is conducted to the dorsal horn of the spinal cord
Dorsal horn relays the signal to the CNS
Signal passes through brainstem areas, the thalamus, to the cortex of the brain
Signal descends along a modulatory control pathway

Question 11

What are the three kinds of sensory events that can activate a nociceptive neuron? Can all the receptors be activated by a single event or are there specific receptors for specific events?

Answer 11

Thermal, chemical, and mechanical

Each one activates a specific peripheral receptor

Question 12

What three pieces of information can frequency and duration of an action potential by a nociceptor transfer to the CNS?

Answer 12

Onset
Intensity
Duration

Question 13

Describe the two inhibitory regulations that can occur to the spinal cord.

Answer 13

Local inhibitory interneurons

Projections that descend from the brainstem to the dorsal horn

Question 14

Name 5 major inhibitory neurotransmitters in the dorsal horn.

Answer 14

Opioid peptides
Noradrenaline
5-HT
Glycine
GABA

Question 15

Consider acute pain severity. Describe the pharmacological treatment for mild (1), moderate (3), and severe (4) score ratings.

Answer 15

Mild - paracetamol
Moderate - paracetamol ± an NSAID ± oral opioid
Severe - as in moderate with an increased dose of oral opioid ± i.v./s.c. opioid or fentanyl patch

Question 16

What are opiate substances derived from?

Answer 16

Opium poppy

Question 17

What are the two naturally occuring opioid compounds in opium poppy?

Answer 17

Morphine and codeine

Question 18

What are endogenous opioid peptides called?

Answer 18

Endorphins

Question 19

What are endorphins, where are they made, and what molecule does it have similar activity to?

Answer 19

Neurotransmitter and hormone peptides made in the brain that acts similar to morphine

Question 20

Aside from the brain, where else are endorphins made and released?

Answer 20

Gastrointestinal tract

Question 21

List two roles of endorphins.

Answer 21

Analgaesia - inhibit pain neurotransmission/perception of pain
Regulation of intestinal motility

Question 22

Can endorphins be absorbed from the gut? What happens to them? Do they pass the blood-brain barrier? Are they useful therapeutic agents?

Answer 22

Not absorbed by the gut.
Rapidly metabolised and cannot pass the blood-brain barrier.
Not useful as therapeutic agents.

Question 23

What are the receptors for opioids, what effect do they elicit, and in what two areas of the body are they dense?
Can they be found in peripheral tissues or na?

Answer 23

μ Opioid Gi-coupled GPCRs
They elicit analgaesia
Dense in the brain and spinal cord
Can also be found in peripheral tissues

Question 24

Consider peripheral nerve transmission for pain. Keeping whether opioid receptors are present peripherally or not, describe the effect μ-opioid agonists would have on this transmission.

Answer 24

Opioid receptors are found peripherally, and so agonists to these receptors would inhibit peripheral pain transmission.

Question 25

Consider a peripheral pain signal being conducted to the dorsal horn of the spinal cord. What effect would a μ-opioid receptor agonist have on this process?

Answer 25

No effect.

Question 26

Consider a pain signal at the dorsal horn. What effect would a μ-opioid receptor agonist have here?

Answer 26

An agonist would inhibit the activity of relay neurons.

Question 27

Consider a pain signal passing through brainstem areas, the thalamus, and to the cortex of the brain. What effect would a μ-opioid receptor agonist have here?

Answer 27

No effect.

Question 28

Consider the descending modulatory control pathway. What effect would a μ-opioid receptor agonist have here?

Answer 28

They enhance descending inhibition

Question 29

Describe the pre-synaptic mechanism of action of a μ-opioid receptor agonist (2).

Answer 29

Inhibits Ca2+ influx | -decreases neurotransmitter release

Question 30

Describe the post-synaptic mechanism of action of a μ-opioid receptor agonist (3).

Answer 30

Increases K+ conductance, leading to hyperpolarisation, and decreased post-synaptic response to excitatory neurotransmission

Question 31

Name three effects of morphine.

Answer 31

Analgaesia Euphoria Less emotional response to pain

Question 32

List 8 adverse effects of morphine in the CNS.

Answer 32

``` Sedation Respiratory depression Nausea/vomiting Miosis Antitussive Constipation Urinary retention Orthostatic hypertension Histamine release from mast cells ```

Question 33

What is miosis an important diagnostic feature of regarding morphine?

Answer 33

Overdose

Question 34

What may morphine administration trigger?

Answer 34

Athsma

Question 35

How is morphine usually administered (3)?

Answer 35

IV, intramuscularly, or subcutaneously

Question 36

Can morphine be administered orally?

Answer 36

Yes but absorption is variable

Question 37

Where is morphine mostly metabolised?

Answer 37

Liver

Question 38

What is the duration of action for morphine?

Answer 38

Plasma half life is 3-6h

Question 39

Does tolerance occur for morphine? Explain.

Answer 39

Yes, an increased dose is needed for the equivalent effect due to gradual loss of effectiveness

Question 40

What does the level of tolerance typically depend on (2)?

Answer 40

Potency of the agonist | Route/frequency of administration

Question 41

What is typically done when tolerance levels increase (3)?

Answer 41

A change of analgaesic drug Higher dose Higher frequency

Question 42

Name 6 effects of tolerance to morphine.

Answer 42

``` Analgaesia Euphoria Sedation Respiratory depression Nausea Emesis ```

Question 43

Do constipation and miosis occur as a result of morphine tolerance?

Answer 43

No

Question 44

Describe physical and psychological dependence on morphine.

Answer 44

Physical - withdrawal symptoms that occur when morphine use stops Psychological - craving for morphine

Question 45

How long can psychological dependence on morphine last?

Answer 45

Months or years

Question 46

How long can physical dependence on morphine last?

Answer 46

Days

Question 47

What is the physical dependence reaction to morphine proportional to?

Answer 47

The level of tolerance

Question 48

What kind of drug is heroin (aside from being an opiate)?

Answer 48

A prodrug

Question 49

Is heroin highly lipid or water soluble?

Answer 49

Lipid

Question 50

Which gains more rapid entry to the CNS, heroin or morphine?

Answer 50

Heroin

Question 51

What happens to morphine in the brain?

Answer 51

Rapidly metabolised into morphine

Question 52

What is the result of taking heroin (2)?

Answer 52

Results in a fast, strong activation of the pleasure centre and euphoria

Question 53

Briefly explain what diamorphine was used for and whether it is common practice to use it.

Answer 53

Typically prescribed for opiate addicts as well as some general medical conditions like paliative or post-op care. Generally only used in the UK, not well understood outside the UK, and specifically prohibited in most countries.

Question 54

Can methadone be taken orally? What is its onset like? Does it have a quick or long half-life?

Answer 54

Orally active Slow onset Long half life >24h

Question 55

Compare the withdrawal reaction of methadone to other opiates like morphine.

Answer 55

Reaction is less intense but prolonged

Question 56

What may occur due to methadones half-life?

Answer 56

Accumulation

Question 57

What can methadone be used to treat aside from pain management?

Answer 57

Opioid dependence

Question 58

What is the mechanism of action for naloxone? Does it have an affinity for all opioid receptors?

Answer 58

Opioid receptor antagonist | Affinity for all opioid receptors

Question 59

What kind of metabolism does naloxone undergo and how is it normally administered?

Answer 59

Rapid hepatic metabolism, sousually given i.v.

Question 60

What is the normal effect of naloxone and what does it induce in an opioid-tolerant patient? What is it used to treat? What two symptoms does it reverse?

Answer 60

Normally has no effect In opioid-tolerant patients, it will induce withdrawal Used to treat opioid overdose Can be used to reverse sedation and respiratory depression

Question 61

What is more potent, codeine or morphine?

Answer 61

Morphine

Question 62

Is codeine orally active?

Answer 62

Yesd

Question 63

In what population (percentage) can codeine cause no analgaesia and why?

Answer 63

In 10% of caucasians, they lack the metabolising enzyme for codeine to morphine (hepatic) so no analgaesia

Question 64

``` Which of the following are induced by codeine (4): Euphoria Respiratory depression Constipation Antitussive ```

Answer 64

Little to no euphoria Little respiratory depression Causes constipation Antitussive only at sub-analgaesic doses

Question 65

What is fetanyl?

Answer 65

Short acting synthetic opioid

Question 66

What is more potent, fetanyl or morphine?

Answer 66

Fetanyl, 75-100x more than morphine

Question 67

Is fetanyl highly lipid- or water-soluble?

Answer 67

Lipid

Question 68

Does fetanyl have a long or short half-life?

Answer 68

Short

Question 69

What is fetanyl suitable for given its half-life (2)?

Answer 69

Incident or procedure-related pain

Question 70

What is the analgaesic effect of fetanyl limited by?

Answer 70

Redistribution to inactive tissue stores

Question 71

Does fetanyl have active metabolites?

Answer 71

Noh

Question 72

What is the least constipating opioid?

Answer 72

Fetanyl

Question 73

Which has more CNS adverse effects, fetanyl or morphine?

Answer 73

Morphine

Question 74

What does the high lipophilicity of fetanyl allow for?

Answer 74

Bioavailability via various routes, including oral

Question 75

What is fetanyl typically used for and how? Why is it administered this way? How often is it readministered?

Answer 75

Used for ongoing severe pain as a transdermal patch Changed every three days This releases the drug slowly for long acting systemic analgaesia

Question 76

Consider the administration of fetanyl. What is the half-life like after one administration cycle and why?

Answer 76

Half-life is 15-20h | This is due to the redistribution of fetanyl out of inactive stores to active sites

Question 77

What is the first choice opiate for chronic pain (like cancer)?

Answer 77

Morphine

Question 78

What is the first choice opiate for myocardial infarction?

Answer 78

Morphine

Question 79

What two drugs can be used as anaesthesia and how is it administered (3)? What is the benefit of doing it this way?

Answer 79

Fetanyl - epidural or transdermal patch Morphine - epidural Decreases the need for IV/inhaled anaesthetics, less circulatory depression