Lecture 16 - Opioids Flashcards
What is the definition of Pain?
An unpleasant sensory and emotional experience associated with or resembling actual or potential tissue damage
What are some endogenous opioids?
B-endorphins
Endomorphins
Dynorphins
Enkephalins
What are the 2 types of pain fibres?
A delta fibres
C fibres
What type of pain do A delta fibres transmit?
Fast sharp pain
What type of pain do C fibres transmit?
Slow burning pain
What sensory pathway transmits pain?
Spinothalamic pathway
Which pain fibres are myelinated and which pain fibres are not myelinated?
A delta fibres = myelinated (fast sharp pain)
C fibre = unmyelinated (slow burning pain)
Where do the primary sensory neurones (A delta fibres or C fibres ) synapse to the second order neurone?
Synapse to second order neurone in the Ipsilateral dorsal horn
What is considered the pain gate?
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
Once the pain fibre has synapsed to the 2nd order neurone on the Ipsilateral cord what happens next?
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)
What is the function of the limbic system in the pain pathway?
Emotional control
What carries the sensory dimension in the pain pathway?
What carries the affective/emotional dimension of pain?
Sensory = 3rd order neurone to cortex
Affective = 2nd order neurone to limbic system
Go to the first slide and label the spinothalamic pain pathway on the left hand side:
What effect does rubbing an area with pain have?
Relieves the pain
How does rubbing a painful area help relieve the pain?
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
What are the neurotransmitters from inhibitory interneurones that synapse onto the 2nd Order sensory neuorne in the dorsal horn?
GABA
Enkephalins
What class of molecule arer enkephalins?
Endorphins
What receptors do endorphins/enkephalins act on?
What do they do?
Mu opioid receptors
Inhibit pain transmission
What neurotransmitters are produced by descending fibres that inhibit the activation of the 2nd order sensory neurone prevntinig pain?
Noradrenaline
5-HT (serotonin)
Go to the first slide and label the right side pain pathway:
What part of the CNS have high levels of Mu opioid receptors so are important in pain?
High. Levels in Brain
Periqueductal grey matter in midbrain
Reticular formation (grey matter in medulla)
What is the pathway for altering pain threshold during stress?
Amygdala to periaqueductal grey matter then travels to reticular formation in medulla then to the dorsal horn in the cord
What is the pathway for altering pain threshold during the menstrual cycle?
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
What is the thought process behind the cause of opioid drug addiction?
Activation of Mu opioid receptors in the midbrain can lead to the substantia nigra releasing lots of dopamine which leads to addiction q
What are opiates?
What are some examples?
The natural substances of opioids
Codeine
Morphine
Diacetyl morphine (heroin)
What are some synthetic opioids?
Methadone
Fentanyl
What does codeine get metabolised into?
What does this metabolism?
Morphine
CYP2D6
What is the simple way by which opioids cause pain relief?
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
What are therapeutic opioids used for?
Analgesia (euphoria)
Antitussive (cough suppression)
Dyspnoea
Anaesthetic
Anti diarrhoeal (since side effect is constipation)
Palliation (symptom relief not underlying cause treatment)
What are some examples of therapeutic opioids?
Codeine
Morphine
Fentanyl
Buprenorphine
Tramadol
What is the lipid solubility, onset time and duration time of morphine?
Lower lipid solubility
Slower onset
Relatively long duration
What is the lipid solubility, onset time and duration time of fentanyl?
Highly lipid soluble
Fast onset
Short duration of action
100x POTENCY OF MORPHINE
What type of drug is codeine?
Prodrug converted to morphine (secondary metabolite) by CYP2D6
How is codeine administerd?
Oral
Subcutaneous
How is morphine adminstered?
Oral
IV
IM
Subcutaneous (SC)
rectally
How is fentanyl administered?
Transdermal
Intra nasal
IV
Epidural
Go to slide 2 and label the pain altering pathways:
What drugs are given for mild pain?
Paracetamol
Ibuprofen
What drug is given for mild to moderate pain?
Codeine
What drug is given for moderate to severe pain?
Morphine
Fentanyl
Label slide 6
What is the problem with compound analgesics like co-codamol?
Cant change dose of one of the drugs in the preparation very well
What are some adverse drug reactions of Opioids?
Constipation
Drowsiness
Dysphoria
Euphoria
Flushing
Headache
MIOSIS (pupillary constriction)
Respiratory depression
Itching
Why do you get itching with opioids?
Leads to histamine release
What are the contraindications to opioids?
Comatosed patients
Head injuries or raised ICP
Resp depression
Paralytic ilium
Asthmatics (histamine)
Pregnancy
What ae some drug drug interactions with opioids?
CNS depressants (antiepilieptics and benzodiazepines)
Opioids
Drugs reducing gut motility
CYP450 inducing or inhibiting enzymes
What is buprenorphine?
What is it used for?
Partial opioid receptor agonist with long action
Can be given to addicts to provide small high and not got resp depression
What is Naloxone?
What is it used for?
Mu opioid receptor competitive antagonist
Used in overdose as it rapidly distributes and doses not last long
What is methadone?
Very lipophilic opioid (more lipophilic than morphine nad has. A longer duration of action
Why may Naloxone be amidnstered multiple times in respiratory depression?
It may wear off then the opioid can cause respiratory depression
Go to slide 10 and match the analgesic repsonse graph tot the opioid agonist or antagonist:
What is the idea that leads to development of tolerance with opioid use?
More cAMP is made so base levels are higher since body is anticipating th opioid to reduce the cAMP levels
Receptor internalising and uncoupllling
What causes the withdrawal symptoms of opioid use?
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
What are some symptoms of opioid withdrawal?
Insomnia
Anxiety
Excessive sweating
Enlarged pupils
Tachycardia
Tachypnoae
Diarrhoea
What are the 3 classes of controlled drug?
Class A
Class B
Class C
How are controlled drugs assigned to a class?
A is the most harmful when misused
What are some Class A drugs?
LSD
Fentanyl
Hat are some Class B drugs?
Codeine
Ketamine
What is a Class C drug?
Anabolic steroid
