Opioid analgesics

Question 1

How many transmembrane domains do opioid receptors generally have?

Answer 1

7

Question 2

How many major classes of receptors are there and home similar are they to each other?

Answer 2

3 major classes with 90% of amino acids identical. They are:

µ (mu for morphine)

k (kappa bound a little bit by 1 substance)

d (delta)

Question 3

Which opioid receptor is most often used for medication?

Answer 3

morphine

Question 4

Where are opioid receptors located?

Answer 4

In the brain stem (same place as the chemoreceptor trigger zone)

Dorsal horn of the spinal cord (used for epidural anaesthesia)

Periphery (on nociceptive fibers for pain relief after injury)

Question 5

Why can heroin cause people to stop breathing?

Answer 5

The opioid receptor is located near the respiratory center of the medulla

Question 6

Why are opioids sometimes given epidurally?

Answer 6

They can provide pain relief due to receptors in the spinal cord.

Question 7

What is the most relevant effect of mu receptor binding by opioid receptors?

Answer 7

Supraspinal analgesia

Myosis (very small irises)

Respiratory depression

Question 8

Why are kappa agonists not used?

Answer 8

They have not been found to be effective or they had too many side effects

Question 9

What are the adverse effects of opioids?

Answer 9

Respiratory depression, nausea, and vomiting as well as constipation (Sites in the brainstem near the opioid receptors include the respiratory and nausea/vomiting center.)

Sedation

Hallucinations, confusion

Physical dependence and tolerance

Psychological dependence/abuse

Question 10

What substances are administered for treating morphine overdoses?

Answer 10

Naloxone (commonly used)

Naltrexone

Question 11

What causes tolerance to opioids?

Answer 11

Physiological adaptation to the chronic effects of opioids. Necessitates increase in dose and/or frequency to achieve same effect as initially.

Question 12

How can physical dependence on opioids be stopped?

Answer 12

Tapering opioid use gradually.

Question 13

What is addiction?

Answer 13

Compulsive use of a substance despite physical harm

Tolerance and physical dependence with opioids are not indicative of addiction.

Iatrogenic opioid addiction can occur

Question 14

What has happened to prescription opioid related deaths in the past 20 years?

Answer 14

It has risen dramatically

Question 15

Should opioids be used in all patients?

Answer 15

No, opioids are useful in some patients but chronic pain shouldn’t be treated with opioids.

Question 16

When should opioids be prescribed?

Answer 16

After full assessment process which includes pain diagnosis. Excluded people include people with mental health problems, alcohol abuse problems, and other drug abuse problems.

Pain diagnosis works for defined nociceptive or neuropathic pain.

Question 17

When should opioids not be prescribed?

Answer 17

People with history of mental health issues or alcohol/drug abuse problems.

Should not be used to treat headaches, migraines, or not pain states such as fibromyalgia, chronic visceral pain, or non-specific lower back pain.

Question 18

How should opioids be used?

Answer 18

Opioids should be used only as part of a pain management approach and not the only way to manage pain.

Question 19

How is an opioid administration trial considered successful vs unsuccessful?

Answer 19

Unsuccessful if:

Lack of functional improvement

Lack of analgesia

side effects

Repeated requests for increased dose

Question 20

Why is codeine such a problem?

Answer 20

It was over the counter and it is metabolised into morphine.

Question 21

How is codeine converted into morphine?

Answer 21

Cytochrome p456 converts codeine to morphine via demethylation.

10% of the population lack the enzyme.

Question 22

Where does tramadol action take place?

Answer 22

It is centrally acting and acts on kappa receptors without much action on mu receptors.

Question 23

Where should tramadol be used?

Answer 23

In situations where one wants to avoid or reduce opioid adverse effects.

Neuropathic pain

Problems with serotonergic effects (such as nausea, confusion, vomiting)

Question 24

What are the advantages of using tramadol over other opioids?

Answer 24

No respiratory depression

No constipation

No risk of abuse

Causes sedation/confusion which makes it undesirable

Question 25

What drug is used instead of tramadol to avoid serotonin excess?

Answer 25

Tapentadol

Question 26

How is tapentadol’s pain relieving properties relative to addictive properties?

Answer 26

1 mg of morphine can be made from 2.5/3 mg which isn’t mu active but oxycodone needs 5mg and is much more opioid like.

Question 27

What is the benefit of using of tapentadol over strong opioids?

Answer 27

Less constipation

Less nausea

Less vomiting

Better quality of life

Lower risk of respiratory depression

Lower risk of addiction

Lower risk of abuse and diversion

Question 28

What is the gold standard for strong opioids?

Answer 28

Morphine remains gold standard.

Question 29

What are the strongest opioids?

Answer 29

Morphine (gold standard)

Oxycodone (no active metabolites but additional kappa effect)

Methadone (good alternative to morphine and oxycodone)

Fentanyl (good parenteral and transdermal alternative)

Pethidine (must be avoided.due to being highly addictive)

Question 30

Conclusion on Opioids:

Answer 30

Weak opioids are not much more than an

Educational substitute for morphine

Tramadol and tapentadol as atypical centrally acting analgesics can fill a therapeutic gap

Strong opioids remain the mainstay of treatment of severe pain

The use of opioids in chronic pain has limited
benefits and needs cautious prescribing!