Opioids Flashcards
1
Q
Name 6 pure agonist of opioid receptor
A
- codeine
- methadone
- etorphine
- morphine
- fentanyl
- pethidine
-> all high affinity for mu receptors
-> varying affinity for delta and kappa receptors
2
Q
Name 3 partial agonist/ mixed agonist-antagonist
A
- buprenorphine - high mu affinity but partial agonist
- nalorphine - mu antagonist
- pentazocine - mu antagonist
-> diminish analgesia by full agonist
-> k agonist: dysphoria
-> reduce side effects
-> can be used to control mild pain as k agonist (latter two)
3
Q
Name 2 opioid antagonist and their effects
A
- naloxone
- naltrexone
-> block effect of opioids
-> precipitate severe abstinence syndrome in addicts
4
Q
Overall MOA of opioids
A
- reduce presynaptic release
- hyperpolarization of postsynaptic neurons
5
Q
MOA in spinal cord dorsal horn
A
- presynaptic neuron terminal: mu, delta, kappa receptors -> lower Ca2+ influx -> less presynaptic neurotransmitter release
- postsynaptic neuron: mu receptor -> K+ efflux -> hyperpolarizaton
6
Q
MOA in brainstem
A
- GABA inhibitory interneuron/ terminal:
- bind mu receptor on it -> removes its inhibition on the downstream pain inhibitory neuron -> activation of the pain inhibitory neuron
- the pain inhibitory neuron goes from PAG to nucleus raphe magnus -> release 5-HT and enkephalin at dorsal horn
7
Q
Functional effect of opioids receptor with elaboration
A
- euphoria
- dysphoria
- sedation and drowsiness
- respiratory depression
- cough supression
- nauseant and emetic effect
- miosis
- tolerance, addiction, dependence
- GI effects: increase resting tone but decrease motility
- histamine release
- CV effects: vasodilation & bradycardia
8
Q
State 11 functional effects of opioid receptors
A
- euphoria
- dysphoria
- sedation and drowsiness
- respiratory depression
-> direct effect on brainstem resp centre
=> usual cause of death from morphine - cough suppression
-> direct effect on cough centre in medulla - nauseant and emetic
-> direct stimulation of chemoreceptor trigger zone in area postrema of medulla - miosis
-> pinpoint pupil - characteristic of opioid use
-> removal of cortical inhibitory action on Cn3 -> increased parasym. tone - tolerance, dependance, addiction
- GI effects: increase m. resting tone but decrease motility -> delay gastric emptying -> constipation
-> biliary colic (increase intraluminal pressure) - histamine release
- cardiovascular effects:
- vasodilation
- impair sym. vascular reflex: veno and arteriolar dilation
- stimulate vagal center: bradycardia
9
Q
State morphine metabolism and hence contraindicated use in what person
A
- glucuronic conjugation in liver (p450) -> urinary excretion
-> morphine 6 glucuronide - more active analgesia - neonates: low level of conjugating enzyme
-> avoid morphine cogeners in neonates and childbirth
10
Q
State acute and chronic adverse effects
A
acute:
1. resp depression
2. nausea and vomitting
3. constipation
4. sedation and mental clouding
5. itching
chronic:
1. tolerance
2. dependance
11
Q
Pharmacological effects with minimal tolerance
A
- miosis
- constipation
12
Q
Mechanism of tolerance
A
- prolonged agonist stimulation
- endocytosis of receptors (GPCR internalization)
-> loss of receptors on cell surface
-> desensitization and dev of tolerance
13
Q
Physical symptoms of abstinence syndrome due to dependence
A
- sweating, fever
- piloerection
- yawning
- pupillary dilation
- nausea/ diarrhoea
- insomnia
14
Q
Symptoms of acute opioid poisoning and treatment
A
Symptoms:
1. unconsciousness
2. pupillary constriction
3. resp depression
Treatment:
- intravenous naloxone injection
-> acute withdrawal syndrome in addicts
15
Q
Heroin/ diamorphine
A
- rapidly convert to morphine and 6 monoacetylmorphine
- strong agonist
- more lipid soluble than morphine -> enter CNS rapidly
16
Q
Etorphine
A
- very strong agonist (x100 than morphine)
- immobilize wild animals
- injectable naloxone must be avavilable (in case potential human exposure)
17
Q
codeine
A
- weak agonist for mild pain
- marked antitussive action
- often pair with paracetamol
- metabolize to morphine in liver by 2D6
18
Q
pethidine / meperidine
A
- strong agonist
- anti muscarinic: confusion
- useful in labour: rapid clearance, not delay labour
- n-demethylation -> norpethidine => hallucinogenic and convulsant
- block neuronal uptake of serotonin
19
Q
fentanyl
A
- strong agonist
- short duration of action
- transdermal patch: high abuse potential and risk of overdose
20
Q
methadone
A
- strong agonist
- longer duration of action: extensive plasma protein binding
- clinically used to treat opioid addiction
-> due to more prolonged & smooth effect but slower onset
-> less severe physical abstinence syndrome
21
Q
tramadol
A
- opioid substitute
- weak mu receptor agonist and potency
- inhibitor of 5HT and NA reuptake -> the main mechanism for its analgesia
- weakly antagonised by naloxone
22
Q
buprenorphine
A
- partial mu receptor agonist
- strong binding to receptor
-> more resistant to naloxone reversal
-> displace morphine/ stronger opioids fro receptors
=> withdrawal syndrome in opioid addicts - very lipid soluble (sublingual and transdermal)
23
Q
pentazocine
A
- mixed agonist antagonist (mu receptor antagonist)
-> reduce analgesia if concurrent with morphine
-> withdrawal syndrome in heroin addict
24
Q
Drug interaction
A
- sedative-hypnotics: increase CNS and resp depression
- antipsychotics tranquilizers: compete for conjugating enzyme -> increased CNS depression
- monoamine oxidase inhibitor
-> contraindication to all opioids analgesics
-> intensity toxicity due to CYP450 inhibition by MAOI
-> serotonin syndrome when pethidine used with MAOI
25
Q
Contraindication in what people
A
- pulmonary failure and asthma
- severe hepatic and renal disease
- cranial trauma, increased intracranial pressure
26
Q
Name 6 non-opioid drugs for pain relief
A
- paracetamol
NSAIDs: - aspirin
- ibuprofen
- indomethacin -> most likely to cause adverse GI effect
- diclofenac
26
Q
Name 6 non-opioid drugs for pain relief
A
- paracetamol
NSAIDs: - aspirin
- ibuprofen
- indomethacin -> most likely to cause adverse GI effect
- diclofenac
