Lecture 20 - Gentile - Opioids Flashcards
What 4 areas of the brain are activated in acute pain?
Insula, Anterior Cingulate, Thalamus, and Basal Ganglia
Which regions are involved in anticipating and perceiving pain?
Brain stem and descending pain modulatory system
Chronic pain leads to increasing activation of which brain region?
Pre-frontal cortex
Define excitatory neurotransmitters and name 2 of them
They are inflammatory chemicals that are released after tissue is damaged
Histamine and Bradykinin
What does Bradykinin do?
Stimulates release of prostaglandins and substance P, a potent neurotransmitter that enhances movement of impulses
Most opioids act on the ___
Synapse
What cortex identifies the location and intensity of pain?
Somatosensory cortex
What cortex determines how an individual interprets the meaning of pain?
Associated Cortex
Acute vs Chronic Pain
Acute pain is a normal response that can be beneficial (signal damage or warn of harm) and will disappear once the cause is treated
Chronic pain persists and is no longer beneficial
How do you manage pain for acute vs chronic?
Acute - reduce the pain by treating the cause
Chronic - can only reduce pain
The most successful way to treat pain is ____
Opioids!
What are the 4 types of opioid receptors?
Delta, Kappa, Mu, and Nociceptin receptor
Where is the Mu receptor found?
Brain, Spinal Cord, and Intestinal Tract
What are the functions of the delta receptor?
Analgesia, antidepressant, and physical dependence
Define Analgesia
Absence of pain without loss of consciousness
What does physical dependence refer to?
Chronic use of drug has produced tolerance
What are the functions of the kappa receptor?
Spinal analgesia, sedation, miosis, inhibition of ADH release, dysphoria
What is miosis?
Constriction of the pupil to less to 2 mm
What is dysphoria
The opposite of euphoria
What are 2 methods to reduce the amount of action potentials generated pre-synaptically?
Reduce the amount of neurotransmitter released (inhibit ca entry via ca channels) or hyperpolarize membrane via stimulating k channel and inc k+
How would you shut down neurotransmission post-synaptically
K+ channel stimulation
IPSP
What opioid receptors are seen pre-synaptically? post-synaptically?
pre-synaptically = mu, kappa, and delta
post-synaptically = mu
How do opiates work?
Inhibit LC neurons via activating K+ channels and inhibiting Na+ dependent inward current (thru inhibition of cAMP via G protein)
What is the most important side effect of opioids?
Respiratory Depression
KNOW THIS!
What are the 3 strong drugs used for pain management?
Morphine, Methadone, and Meperidine
What are the 2 moderately strong drugs used for pain management?
Codeine and Oxycodone
What antagonist is used for pain management?
Naloxone
What are the 2 receptor agonist-antagonists used for pain management?
Pentazocine and Buprenorphine
Morphine: Indications
Pain from MI, sickle cell crisis, surgery, trauma, chronic pain or severe pain
Morphine: Side effects
Contsipation!
As well as addiction and tolerance
Meperidine: MOA
Binds kappa receptor, K+ channels, muscarinic receptor, dopamine transporter
Meperidine: Indications
Moderate/severe pain from biliary spasm or renal colic
Meperidine: Side effects
*Are mainly from it’s metabolite (norpethidine)
Serotonin syndrome, seizure, dysphoria, temror, respiratory depression
Hydrocodone acts at what receptors?
Mu receptor (agonist)
Delta receptor (agonist)
Hydrocodone: Indications
Cough during operations, dry cough from bronchitis
*hydrocodone is an anti-tussive (“anti-cough”)
Hydrocodone: Side Effects
Constipation
*taken recreationally for mental numbness and euphoria
Hydrocodone: OD
Pupil widening, loss of consciousness, muscle seizures
Describe the mechanism of Euphoria
There are 2 presynaptic neurons (one has GABA receptor and other has Mu receptor)
Release of GABA activates negative pathway for dopamine release, but when morphine binds mu receptor there’s inhibited release of GABA so dopamine can be released
*Basically…morphine inhbitits the inhibitor of dopamine secretion (GABA)
Codeine: Indications
Cough, diarrhea, IBS, narcolepsy
Codeine: Side Effects
Euphoria, itching, urinary retention, depression, constipation, increased complications in erectile dysfunction
Pentazocine binds which receptors?
Mu (antagonist)
Delta (agonist)
Kappa (agonist)
Pentazocine: Indications
Dental extraction
Pentazocine: Side Effects
Weakly antagonizes the analgesic effects of morphine and meperidine (know)
Hallucinations
Psychomimetic effects
CV effects
Naloxone binds which receptors?
Mu, delta, and kappa
*is an antagonist for all 3
Naloxone: Indications
Reverse effects of OD (respiratory depression, sedation, and hypotension)
Naloxone cannot be used to counter which drug?
Meperidine
Naloxone: Side Effects
Change in mood
Trembling
Change in heart rhythm
Block the action of pain-lowering endorphins
Signs of OD
1st = blue lips
Unresponsive to pain stimuli
Methadone binds which receptors?
Mu - (agonist)
Delta - (agonist)
Glutamate [NMDA] - (antagonist)
Neuronal ACh - (antagonist)
What is methadone and why is it used?
It is an opioid that lasts longer and is cheaper than morphine
Is used to control intractable cough associated with terminal lung cancer and is also another way to reverse opioid effect
Why is methadone used in the treatment of opioid dependance?
Methadone binds opioid receptor and stays there much longer… so now the agonist can’t interact with the receptor
Remember: Slide 45 of the lecture has a summary table for our reference as well
Remember: Slide 45 of the lecture has a summary table for our reference as well
