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Therapeutics Neuro Schober
Final Opioids
38
Anthropology
09/21/2010

Additional Anthropology Flashcards

 


 

Cards

Term
Ascending Pathways
Definition

AKA Afferent Neuron

  • The primary (first) afferent neuron is the nociceptor
  • The cell body of the nociceptor is in the dorsal root ganglia (DRG) and the nociceptors synapse with the secondary neuron in the dorsal horn (DH) of the spinal cord
  • The secondary neuron synapses with the tertiary neuron in the thalamus
  • The tertiary neurons go to the cortex where pain perception occurs
  • Pain information is processed in cortex
Term
Descending Pathways
Definition

AKA Efferent

  • Neurons beginning in the cortex make the first synapse in the brainstem
  • The next neuron in the descending pathway makes a synapse with the ascending pathway in the spinal cord
  • The descending neuron input modulates the ascending pain sensory pathway
  • Modulation by the descending pathways results in enhancement or reduction of pain perception
Term
Chemical stimuli activate which receptors?
Definition
  • ASIC
  • P2X
  • P2Y
  • B1
  • B2
Term
Mechanical stimuli activate which receptors?
Definition
Mechanosensitive Ion Channels
Term
Thermal stimuli activate which receptors?
Definition
  • TRPV1
  • TRPV2
Term
Activation of Chemical, Mechanical, and Thermal receptors results in:
Definition
  • Increased Na+ and Ca2+ influx
  • Generator potential (membrane depolarization)
  • Voltage-gated sodium channel threshold is reached
  • ACTION POTENTIAL!
Term
The synapse between the primary and secondary neuron is in the:
Definition
Dorsal Horn of the spinal cord
Term
At the synapse between the primary and secondary neuron, the primary neuron releases:
Definition
  • Glutamate
  • CGRP
  • Substance P

 

Term
At the synapse between the primary and secondary neuron, which receptors mediate the fast response?
Definition
  • Ionotropic receptors
  • NMDA-R, AMPA-R
Term
At the synapse between the primary and secondary neuron, which receptors mediate the slow response?
Definition
  • Metabotropic Receptors
  • mGluR, NK1, CGRP-R
Term
The release of neuropeptides from the primary neuron is associated with what kind of pain?
Definition
High intensity pain
Term
Mu, Kappa, and Delta are all linked to what receptor?
Definition

Gi-Coupled Protein Receptor

 

Term
The result of activating Mu, Kappa, or Delta receptors is:
Definition
  • Decreased cAMP
  • Decreased presynaptic [Ca2+]i --> prevents vesicular exocytosis of neurotransmitters
  • Opening of postsynaptic K+ channels (efflux)

 

Term
Sites of Opioid Analgesic Action in the Ascending Pathway
Definition
  • The site of noxious stimuli in the periphery
  • The synapse between the primary and secondary neuron in the spinal cord
  • The synapse between the secondary and the tertiary neuron in the thalamus
Term
Site of Opioid Analgesic Action in the Descending Pathway
Definition
The site where descending neurons synapse with the primary neuron on the secondary neuron in the dorsal horn of the spinal cord
Term
The Three Mechanisms of Opioid Tolerance are:
Definition
  1. Metabolic
  2. Intracellular Signaling Involving Gi-CPR
  3. NMDA Receptor Signaling
Term
Mechanism of Tolerance: Metabolic
Definition
  • Occurs due to increased metabolic rate of the drug
  • Log plasma concentration falls at faster rate with accelerated metabolism
Term

Mechanism of Tolerance: Intracellular Signaling Involving Gi-CPR

ACUTE

Definition
  • The binding of opioid receptor causes direct inhibition of AC and opening of K+ channels through G-alpha-i-GTP
  • Low AC activity results in decrease cAMP, which in turn results in decreased PKA activity
  • Decreased PKA activity results in closure of Na+ channels
Term

Mechanism of Tolerance: Intracellular Signaling Involving Gi-CPR

CHRONIC

Definition
  • After chronic administration of an opioid, CREB becomes activated (phosphorylated) which increases expression of AC above baseline
  • As a result of increased levels of AC, levels of cAMP return toward baseline
  • PKA activity opens Na+ channels
  • K+ channels are not affected
Term
Mechanism of Tolerance: NMDA Receptor Signaling
Definition
  • Activation of NMDA receptor by glutamate induces the activation of NO synthase
  • NO complexes with guanylyl cyclase and activates GC
  • NO also S-nitrosylates proteins, including subunit 1 and subunit 2 of the NMDA receptor
  • NO is converted to peroxynitrate which will nitrate tyrosine residues with proteins
  • All of these actions result in opiate tolerance
Term
Morphine: Metabolism, Receptor Selectivity
Definition

First pass metabolism

Mu receptor selectivity

Term
Codeine: Uses, Metabolism
Definition

Antitussive

 

Demethylated to morphine

Term
Methadone: T1/2, Uses
Definition

Long half-life = withdrawal symptoms less severe

Detoxification for heroin addicts

Term
Meperidine: Potency, Uses, Metabolism, Warnings
Definition

Less analgesic potency than morphine

 

For moderate to severe pain

 

Metabolite (normeperidine) can cause seizures

Monoamine reuptake blocking activity

Warning with MAOI use -- Serotonin Syndrome

Term
Propoxyphene: Potency, Side effects, Uses
Definition

Far less analgesic potency and much less adverse effects  than methadone

 

For mild pain

Term
Fentanyl: Potency, Onset, Side effects, Uses
Definition

Very potent

 

Faster onset and recovery than morphine

 

Similar side effect profile as morphine

 

For moderate to severe pain

Term
Pentazocine: Receptor activity, Uses, Side effects
Definition

Agonist at Kappa, Antagonist at Mu

 

Effective for moderate to severe pain

 

Higher doses increase BP and HR

Term
Butorphanol: Receptor activity, Uses
Definition

Agonist at Kappa, Antagonist at Mu

 

Effective for moderate to severe pain

 

 

Term
Nalbuphine: Receptor activity, Potency, Uses
Definition

Kappa Agonist, Mu Antagonist

 

Similar analgesic potency as morphine

 

Reaches maximal (ceiling) analgesic and respiratory depression effect

 

For moderate to severe pain

Term
Buprenorphine: Receptor Activity, Uses
Definition

Mu Partial Agonist, Kappa Antagonist

Slowly dissociates from Mu receptor

 

Used in opioid addiction management

Term
Naloxone: Receptor Activity, Side effects, Uses
Definition

Reverse (Inverse) Mu Agonist Activity

 

Few effects when administered alone

 

Causes withdrawal

 

Reverses toxicity

 

Used for overdose

Term
Naltrexone: Receptor Activity, Side effects, Uses
Definition

Reverse (Inverse) Mu Agonist Activity

 

Few effects when administered alone

 

Causes withdrawal

 

Reverses toxicity

 

Used for overdose

Term
Nalmefene: Receptor Activity, Side effects, Uses
Definition

Reverse (Inverse) Mu Agonist Activity

 

Few effects when administered alone

 

Causes withdrawal

 

Reverses toxicity

 

Used for overdose

Term
Ziconotide: MOA, Uses
Definition

Non-Opioid

Blocks N-Type Ca2+ Channel -- a type of HVA channel found presynaptically

 

For severe chronic pain

Term
H+ binds to which receptors on the primary afferent?
Definition
ASICs
Term
ADP and Adenosine bind to which receptors on the primary afferent?
Definition

P2X

P2Y

Term
Bradykinin binds to which receptors on the primary afferent?
Definition

B1

B2

Term
Temperature and capsaicin stimulate which receptors on the primary afferent?
Definition
TRPV Receptors