2018A05 List the desired and adverse effects of opioids and the corresponding
anatomical location of the receptors being acted upon.

 

List:

·      Intro: opioids and receptors

·      CNS effects

·      CVS effects

·      Resp effects

·      Other effects

 

Intro: opioids

Definitions

·  Opioid: a drug acting via opioid receptors

(cf. opiate: a naturally occurring derivative of the opium poppy (papaver somniferum)

Opioid receptor

·  G-inhibitory protein-coupled receptor

·  ↓cAMP, ↓VDCC activation, ↓K+ efflux

·  ↓Action potential formation

Opioid receptor subtypes

·  M 1, 2: most opioid effects

·  K 1, 2, 3: spinal analgesia, sedation, miosis

·  D 1,2: spinal analgesia, respiratory depression

·  NOP: role unclear

 

Central nervous system:

Effect

Receptor

Location / (drug)

Supraspinal analgesia

M

·  Peri-aqueductal gray area

·  Nucleus raphe magnus

·  Rostral ventromedial medulla

·  Cerebral cortex

Spinal analgesia

M, K, D

·  Layers 1,2 of dorsal horn

·  Pre-synaptic terminal of nociceptors

Peripheral analgesia

M

·  Peripheral sensory neurons

·  Function unclear

Hyperalgaesia

TLR4

·  WBCs

·  (Remifentanil’s carboxylic acid metabolite)

Anti-hyperalgaesia

NMDA

·  Post-synaptic, dorsal horn

·  Short term: ↓excitability = ↓wind up

·  Long term: ↓synaptic reinforcement, ↓long term potentiation

·  (Methadone, tramadol)

Descending inhibition

Monoamine transporters

·  5-HT and NAd reuptake inhibition

·  ↑Descending modulation of dorsal horn

·  Especially layers 2, pre-synaptic inhibition

·  (Tramadol, tapentadol, methadone)

Local anaesthetic

VdNaC

·  Sensory neurons

·  (Pethidine)

Sedation

M, K

·  Ascending reticular activating system

·  ↓Release of glutamate, NAd, ACh, 5HT etc

Miosis

M, K

·  Nucleus of Edinger-Westphal of CNIII

Euphoria, dysphoria, addiction

M, K

·  Limbus, nucleus accumbens

Hallucinations

M

?

Tolerance

M

·  Receptor, intracellular

Anxiety, depression

NOP

·  ? Limbic system

Appetite modulation

NOP

·  ? Hypothalamus

Seizures

Monoamine transporters

·  (Tramadol, norpethidine): ↓5-HT reuptake

·  (Morphine-3-glucuronide): ? mechanism

Cognitive dysfunction

?

·  (Norpethidine)

·  (Morphine-3-glucuronide)

Nausea, vomiting

M

5-HT

·  Chemoreceptor trigger zone

·  (serotonin: pethidine, tramadol)

Serotonin syndrome

N/A

·  (Tramadol, norpethidine, methadone 5HT reuptake)

 

Cardiovascular:

Effect

Subtype

Location / (drug)

↓SNS outflow: ↓HR, ↓SVR, postural ↓mAP

M

·  SNS: rostral ventrolateral medulla

·   

↑Vagal: ↓HR

M

·  PSNS: dorsal motor nucleus, nucleus ambiguus

·  Morphine more than others

↑HR

mAChR

·  Post-ganglionic neuron in cardiac plexus

·  (Pethidine – antagonist)

 

Respiratory:

Effect

Receptor

Location / (drug)

↓RR > ↓VT

↓MV response to ↑PaCO2 (R shift, ↓slope)

↓MV response to ↓PaO2 (less affected)

M, D

M

·  Medulla respiratory centre

·  Peripheral and central chemoreceptors

↓Airway reflexes, anti-tussive, ETT tolerance

?

·  Medulla

Chest wall rigidity

M

·  GABA-ergic neurons in basal ganglia

↓Cilia activity

?

·  Respiratory epitheilum

 

Other:

Effect

Receptor

Location / (drug)

↓GIT motility

↓GIT sphincter tone

M

·  GIT, medulla

Urinary retention

?

·  Spinal cord

Pituitary dysfunction

↓ADH/ACTH/PRL/FSH/LH

Hypogonadism

Osteoporosis

?

·  Hypothalamus, pituitary

Immune suppression

?

·  WBCs

Histamine release

?

·  Mast cells

·  (Morphine)

 

 

 

Feedback welcome at ketaminenightmares@gmail.com