Opioids Flashcards
Define an opioid (1)
any drug that mimics endogenous opioid peptides by causing prolonged activation of opioids receptors
Define an opiate (1)
any synthetic morphine-like drug without a peptide structure
Endogenous opioids are derived from 3 different peptides (3)
B-endorphins, Encephalins, Dynorphins
Describe opioid receptor activation (3)
G-protein coupled
opens K+ channels and closes Ca++ channels
causes hyperpolarisation and inhibits NT release
What is the variation between Diamorphine and Morphine (1)
Diamorphine is more lipid soluble so has a more rapid onset of action when given IV
Which opioid can be given transdermally for pain? (1)
Fentanyl
Describe the specific use of Pethidine and why (2)
what are the downsides (1)
Used for childbirth pain
does not inhibit contractions, rapid onset + shorter duration of action
neonate may need nalaxone to treat respiratory depression
Describe the variations of buprenorphine from other opioids (1)
Which receptor does it act upon and how (1)
Has a longer duration and a slower onset and can therefore cause prolonged vomiting
partial agonist of Mu receptors
Can weak opioids cause tolerance? (1)
Yes but to a lesser extent
What are the effects of opioids use? (4)
Euphoria
sedation
analgesia
respiratory depression
Name the opioid receptors and state what activates them (8)
Mu - acted on by B-endorphins
Delta - acted on by B-endorphins and enkephalins
Kappa - acted on by dynorphins
ORL1 - non classical receptor acted on by nociceptin/OFW
has shared homology and also uses Gi/Go and has an endogenous ligand
What are B-endorphins made from? (1)
Propriomelanocortin
What are enkephalins made from? (1)
Proenkephalin
What are dynorphins made from? (1)
Prodynorphin
What is nociceptin made from? (1)
Pronociceptin
Where are Mu receptors located? (4)
Rostral and caudal cortex and motor regions eg caudate
Limbic structures eg amygdala and stria terminalis
Reward areas eg accumbens
Pain Processing areas eg Thalamus and colliculi
Where are the Delta receptors located? (3)
Limbic structures eg amygdala and stria terminalis
Reward areas eg accumbens
Pain Processing areas eg Thalamus and colliculi
Where are the Kappa receptors located? (3)
Limbic areas
Sensory and Motor Structures
Some expression in endocrine areas such as the hypothalamus - KEY
Effects of opioids and their mechanisms (8)
Analgesia (tissue injury and tumour growth) no as effective at neuropathic pain as it effects the limbic system
Euphoria - strong contentment and decreased anxiety from pain
Resp Depression - less sensitivity to CO2 centre via Mu receptors - most damaging
Cough Reflex - reduces, unknown mechanism (low doses pre analgesia)
N&V - action in area postrema by delta and area prostrema by Mu
Pupil constriction - pinpoint pupils sign of poisoning
GI Tract - increase tone and low motility cause constipation
Itching - morphine release histamine from mast cells
Opioid Tolerance (2)
develops rapidly and needs to be increased reapidly
less for GI symptoms
Physical opioid dependence symptoms and facts (3)
irritable, weight loss,, shakes, writhing, jumping and aggression
less intense with gradual withdrawal
rarely progresses to addiction
Gi/Go receptor activation (4)
increase K+ channel opening causing hypoerpolarisation
decrease opening of VGCC
inhibition of AC, decrease in Ca++ and PKA
opioids decrease excitation in dorsal spinal cord from peripheral neurons
Descending control system of opioids (4)
opioids excite PAG neurons and neurons of nucleus reticularis paragigantocellularis (NRPG)
stimulates neurons in nucleus raphe magnus (NRM)
5-HT and enkephalin neurons of NRM run to dorsal horn and inhibit transmission
opioids act directly on dorsal horn also on peripheral terminals
Receptor and effects of Diamorphine (2)
MOP
pain relief for tissue injury and tumour growth
Receptor and effects of Pethidine (2)
DOP
analgesia in labour
Receptor and effects of Fentanyl (2)
MOP
rapid onset and shorter action - patient controlled
Effects of Codeine (3)
readily absorbed oral analgesic for mild pain
no euphoria
constipation
Use of Dihydrocodeine and why (2)
useful in 10% resistant to codeine
lack demethylating enzyme that connects codeine to morphine
Receptor effect of Tramadol (2)
opioid agonist
weak NA reuptake inhibitor
Nalaxone effect and unique factor (2)
antagonist
does not cross BBB
Chronic Pain and Addiction to opioids (2)
properly managed short term medical used rarely leads to addiction, just physical dependence
risk increases when used in ways other than prescribed (increase dose, different administration, combine with alcohol, history of psychiatric disorder, genetic polymorphisms, age (adolescents/older)
Morphine in MOP KO mice (4)
demonstrated that MOP is the primary receptor for morphine - Keiffers et Al
mice have a preference to morphine in WT
in KO they no longer self administrate
MOP is a mediator of positive reinforcement
Effect of KOP KO in mice (3)
WT spent 400 seconds longer in non-KOP against the injection chamber
KO mice had none of this suggesting KOP is aversive or dysphoric
KO mice had increased dopamine suggesting KOP decreases dopamine
Mechanism of opioid dependence (4)
homeostatic compensatory neuradaptation - adaptive changes to oppose drug action, withdrawal causes rebound effect
HPA axis is hyporesponsive in heroin and cocaine addicts
CRF increased in amygdala
CRF antagonists block withdrawal in animals
Treatment for dependence symptoms and mechanism (2)
Lafexidine
central a2 agonist that suppresses some withdrawal components
Treatment for opioids by substitution and mechanism (4)
Methadone
long acting drug causes no euphoria to morphine
duration 24-36h
30-40mg stops withdrawal but leaves craving
80-100mg is more effective at lowering opioid use as it lowers craving
Treatment for opioids that aims to prevent Euphoric feelings and mechanism (4)
Naltrexone
opioid agonist that prevent impulsive use by blocking agonist effects
dose is 50mg daily, 100mg every 2 or 150mg every 3
side effects involve hepatotoxicity so LFTs required every 3 months and not currently approved for opioid dependence
Treatment for opioids by substitution and mechanism (4)
Burpenorphine
partial MOP/KOP agonist and KOP antagonist
lower risk of respiratory depression
used with nalaxone
