How many transmembrane domains do opioid receptors generally have?
How many major classes of receptors are there and home similar are they to each other?
3 major classes with 90% of amino acids identical. They are:
µ (mu for morphine)
k (kappa bound a little bit by 1 substance)
Which opioid receptor is most often used for medication?
Where are opioid receptors located?
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)
Why can heroin cause people to stop breathing?
The opioid receptor is located near the respiratory center of the medulla
Why are opioids sometimes given epidurally?
They can provide pain relief due to receptors in the spinal cord.
What is the most relevant effect of mu receptor binding by opioid receptors?
Myosis (very small irises)
Why are kappa agonists not used?
They have not been found to be effective or they had too many side effects
What are the adverse effects of opioids?
Respiratory depression, nausea, and vomiting as well as constipation (Sites in the brainstem near the opioid receptors include the respiratory and nausea/vomiting center.)
Physical dependence and tolerance
What substances are administered for treating morphine overdoses?
Naloxone (commonly used)
What causes tolerance to opioids?
Physiological adaptation to the chronic effects of opioids. Necessitates increase in dose and/or frequency to achieve same effect as initially.
How can physical dependence on opioids be stopped?
Tapering opioid use gradually.
What is addiction?
Compulsive use of a substance despite physical harm
Tolerance and physical dependence with opioids are not indicative of addiction.
Iatrogenic opioid addiction can occur
What has happened to prescription opioid related deaths in the past 20 years?
It has risen dramatically
Should opioids be used in all patients?
No, opioids are useful in some patients but chronic pain shouldn’t be treated with opioids.
When should opioids be prescribed?
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.
When should opioids not be prescribed?
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.
How should opioids be used?
Opioids should be used only as part of a pain management approach and not the only way to manage pain.
How is an opioid administration trial considered successful vs unsuccessful?
Lack of functional improvement
Lack of analgesia
Repeated requests for increased dose
Why is codeine such a problem?
It was over the counter and it is metabolised into morphine.
How is codeine converted into morphine?
Cytochrome p456 converts codeine to morphine via demethylation.
10% of the population lack the enzyme.
Where does tramadol action take place?
It is centrally acting and acts on kappa receptors without much action on mu receptors.
Where should tramadol be used?
In situations where one wants to avoid or reduce opioid adverse effects.
Problems with serotonergic effects (such as nausea, confusion, vomiting)
What are the advantages of using tramadol over other opioids?
No respiratory depression
No risk of abuse
Causes sedation/confusion which makes it undesirable
What drug is used instead of tramadol to avoid serotonin excess?
How is tapentadol’s pain relieving properties relative to addictive properties?
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.
What is the benefit of using of tapentadol over strong opioids?
Better quality of life
Lower risk of respiratory depression
Lower risk of addiction
Lower risk of abuse and diversion
What is the gold standard for strong opioids?
Morphine remains gold standard.
What are the strongest opioids?
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)
Conclusion on Opioids:
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!