Opioids (Exam V) Flashcards
What are the three endogenous ligands pertinent to pain signaling?
- Endorphins (1°)
- Enkephalins (pain signaling)
- Dynorphins (pain signaling)
What are hierarchical systems?
- Multiple Neurons linked to one another for signaling.
What specific type of neuron is pertinent to feed-forward & feed-back responses in relay systems?
Interneurons
Explain the mechanism of a feed-back response.
What is the purpose of this system?
- Excitatory neuron depolarizes an inhibitory interneuron which suppresses the initial excitatory neuron.
- Seizure prevention from constant excitatory stimulation.
Explain the mechanism of a feed-forward response.
Neuron A excites an interneuron which then inhibits Neuron B.
Are feed-forward & feed-back systems inhibitory or excitatory?
They can be both.
How does an axoaxonic interaction differ from a feedback or feed-forward neuron interaction?
- Inhibition/excitation occurs at the axon rather than the neuron body.
How do non-specific, diffuse systems differ from relay systems?
- Monoamine Transmitters used (NE, Dop, 5-HT)
- Slower
- Diffuse throughout the CNS. (en-passant synapses used)
Where is serotonin produced?
Raphe Nuclei
Where is dopamine produced?
Substantia Nigra & Ventral Tegmental Area
Which diffuse system area of the brain is associated with NE?
Locus Coeruleus
Which area of the brain is associated with ACh diffusion?
What neurotransmitter does ACh have a similarity to in the CNS?
- Pontine Nuclei
- Serotonin/Melatonin
What CNS effects does ACh have?
- Learning & Memory
- Sleep-wake cycles
- Arousal & sensory information
Tachykinins use _________ __ receptors and have a __________ effect on pain signaling.
Substance P; excitatory
Is most pain signaling hierarchical or diffuse?
Hierarchical
Most pain receptors are _____ ______ endings.
free nerve
What fiber type can suppress fast pain?
Aβ through suppression of Aδ fast pain.
What mediators of pain (discussed in lecture) are released in response to tissue damage?
- Bradykinin
- Prostaglandins
- Glutamate
- Substance P
What are the three pain tracts of the CNS (discussed in lecture)?
- Spinothalamic
- Spinoreticular
- Spinomesencephalic
Which spinal tract is suppressive to painful stimuli?
- Spinomesencephalic through μ(mu) opioid receptors in the periaqueductal gray matter.
What is the primary opioid and endogenous ligand receptor?
What endogenous ligands are used by this receptor?
- μ(mu) opioid receptors
- Endorphins
What are the other opioid receptors aside from μ(mu) opioid receptors?
δ(delta) & κ(kappa) receptors.
Differentiate full agonist, partial agonists, & antagonists of the opioid receptors. Give examples for each.
- Full Agonists (strong to moderate effect) morphine, fentanyl, etc.
- Partial Agonists (moderate to mild effect) codeine, oxycodone, etc.
- Antagonists (Reversal) Naloxone
What mediator is utilized with κ(kappa) receptors?
- Dynorphins
What type of receptor are opioid receptors?
Gᵢ GPCRs
Where are mu opioid receptors located on neurons?
- Pre-synaptic & post-synaptic neurons
How do μ(mu) opioid receptors suppress pain?
Gᵢ = ↓AC → ↓cAMP = ↑pK⁺, ↓pCa⁺⁺ = Hyperpolarized neuron.
What opioid pathway leads to decreased effect & opioid tolerance?
G-protein independent pathway with ERK, JNK & β-arrestin.
(ERK = E receptor Kinase, JNK = Janus Kinase)
Which opioid receptors are responsible for analgesia?
Which opioid receptor is responsible for CNS respiratory depression & dependence/addiction?
- Mu, delta, & kappa.
- Mu
What symptom of opioid organ system effects is always present with opioid use & no tolerance develops to it?
Miosis (pupillary constriction)
What effects may opioids have on the cardiovascular system?
What is the exception?
- Indirect CNS bradycardia
- Meperidine (Demerol) has antimuscarinic traits = ↑HR.
Is tolerance developed to the constipatory effects of opioids?
No
What does Loperamide do? Why?
- Antidiarrheal opioid with no CNS effects due to GI ABCB1 clearance.
What drug can cause respiratory depression when given with loperamide?
Why?
- Quinidine
- Blocks ABCB1 so loperamide accumulates and affects CNS.
What is the treatment for Acute Coronary Syndrome?
- Morphine
- Oxygen
- Nitroglycerin
- Aspirin
Why is morphine used in Acute Coronary syndrome?
- ↓ anxiety
- ↓ HR (and thus metabolic demand)
- ↓ pain
What drug is indicated for post-operative shivering?
Demerol (meperidine)
How quickly does opioid tolerance build?
What is the probable mechanism for this?
- Rapidly
- β-arrestin pathway
What mild symptoms might be seen from opioid withdrawal?
- Piloerection
- Hyperventilation
- Lacrimation
- Rhinorrhea
- Yawning
What symptoms would be seen in severe opioid withdrawal?
- Mydriasis
- Hyperthermia
- N/V/D
- Anxiety/Hostility
What is opioid induced hyperalgesia?
How many patients will experience this?
- Increased pain response secondary to chronic use
- 30% of chronic users develop this
What is the mechanism for opioid induced hyperalgesia?
- Sensitization of MuOR-1K variant & ↑cAMP
What is the treatment for opioid induced hyperalgesia?
- Wean opioid
- GABA analogs
Why are opioids partially contraindicated in head injuries?
↑ Resp depression
What can occur when opioids are given to a pregnant mother?
- Fetal Dependence
What structure is indicated in the figure below?
What strength is typically seen with these opioids?
- Phenanthrene
- Very strong (morphine, hydromorphone, heroine)
What structure is indicated in the figure below?
What opioids are seen with this structure?
- Phenylheptylamine
- Very strong (Methadone)
What structure is indicated in the figure below?
What types of opioids are associated with this structure?
- Phenylpiperidine
- Fentanyl & Meperidine
What is heroin used for in the UK?
Palliative Care
What is methadone’s usefulness?
Why is this?
- Suppression of opioid withdrawal symptoms (and chronic pain)
- Long Half-Life = 25-50 hours
What is the primary use of Meperidine?
What cardiac effects are seen with it?
- Post-op shivering
- neg inotrope, + chronotrope
What is the most potent fentanyl derivative?
Carfentanil (10,000:1 morphine ratio)
How much can shivering increase O₂ consumption?
By what mechanism does meperidine treat shivering?
- 500%
- ↑ kappa receptor agonism & serotonergic effects.
Which phenanthrenes are moderate agonists & more useful with acetaminophen or aspirin?
- Oxycodone & codeine
What is Dextromethorphan’s use?
- Anti-tussive
What is Buprenorphine used for?
- Opioid abuse (partial agonist)
What are the two opioid antagonists? What are their uses?
- Naloxone - Overdose antidote (short duration, supportive therapy still needed)
- Naltrexone - EtOH abuse.
