Opiods

Question 1

Transmitter chemicals on presynaptic neurons that transmit pain

Answer 1

Glutamate
Substance P
CGRP

Question 2

Glutamate activates these post synaptic receptors

Answer 2

NMDA - Ca

AMPA - Na

Question 3

Binds to neurokinin NK-1 receptor that leads to activation of arachidonic pathways, nitric oxide synthesis and activation of NMDA receptors

Answer 3

Substance P

NMDA -> PKC -> Mg removed that blocks NMDA and allows glutamate to attach to NMDA receptor and permit inflow of Ca ions causing increased pain signals

Question 4

CGRP binding promotes

Answer 4

Central sensitization lowered threshold for evoking action potential

Question 5

3 major families of endogenous opiods

Answer 5

Enkaphalin
Dynorphin
Endorphin

Bind to opiod receptors in CNS and spinal cord

Question 6

Major types of opiod receptors

7 transmembrane proteins coupled with G proteins in dorsal horn of spinal cord

Answer 6

Mu
Delta
Kappa

Question 7

Activation of opiod receptor agonists such as mu opiod peptide endorphin causes

Answer 7

Closure of voltage gated Ca channel on pre synaptic nerve terminals and causes decreased release of glutamate, substance P and CGRP

Opening of K channels allowing efflux of K channel leading to hyperpolarization rendering neurons less excited to sensory inputs

Question 8

Majority of opiod analgesics act ptimarily at

Answer 8

mu opiod mimicking effect of endogenous peptides

Question 9

Example of synthetic opiod agonists

Answer 9

Fentanyl
Hydrocodone
Hydromorphone
Methadone
Meperidine
Oxycodone
Oxymorphone

Question 10

Potent mu receptor agonist
Potent antagonist of NMDA
SSRI and SSRI

hence can be used in treatment of nociceptive and neuropathic pain

Answer 10

Methadone

Question 11

Opiod activation SE

Answer 11

Nausea from direct stimulation of CTZ

Dose dependent respiratory depression by reducing brainstem responsiveness to CO2 and pons and medulla (rhythmicity)

Antitussive effect (depressing cough center of medulla)

Supresses immune system

Question 12

Provokes release of histamine and plays major role in producing hypotension

Also causes dilation of cutaneous bv (flushing of skin, neck, thorax)

Answer 12

Morphine

Meperidine

Question 13

Produces tachycardia due to structural similarity with atropine

Answer 13

Meperidine

Question 14

Opiods SE

Answer 14

Dose dependent bradycardia by increasing vagal stimulation

Itching by central action on prurioceptive circuit

Decreases gastric motility and emptying time (constipation)

Depresses renal function and anti diuretic effects

Decreases sphincter tone and cause urinary retention

Physical and psychological dependence

Question 15

Euphoric effect of opiod involves the

Answer 15

GABA inhibitory interneurons of ventro tegmental area of brain

Normally, GABA Decreases dopamine from nucleus accumbens which is part of pleasure and reward system

Attachment of opiod to mu receptor leads to GABA supression and increased Dopamine activity and pleasure

Question 16

Prolonged regular use of opiods leads to

Answer 16

Dec Receptor sensitivity signalling

Lack of receptor causes withdrawal (diarrhea, inc BP, dysphoria and anxiety)

Question 17

Partial mu receptor agonist
Binds to receptor and activates with smaller change or partial receptor respons until they reach plateau

Causes respiratory depression and euphoria with less effects and lower abuse, addiction

Antagonist at delta and kappa receptor

Mixed agonist-antagonist

Answer 17

Bupenorphine

Question 18

Opiod antagonist blocking the effect of opiod drugs

Knocks off opiod on receptors on brain

Stronger affinity for opiod receptors by competitive binding

Answer 18

Naloxone