Opioids (Exam V) Flashcards
What is a Hierarchical System in the CNS?
NT Examples
A chain of neurons that activates the next subsequent neurons. They are referred to as relay neurons, a multi-neuron web in the nervous system.
Glutamate (Excitatory NT)
GABA, Glycine (Inhibitory NTs)
What is the Nonspecific (Diffuse) System in the CNS?
NT Examples
NT diffused slowly through the nervous system either through the CSF, small unmyelinated fibers, or en-passant synapses. Slower conduction. Non-hierarchical, no-relay.
Monoamines, Dopamine, NE, 5-HT.
The diffuse system means that these NT can activate wide stretches of the CNS all at once.
Name 4 diffuse systems mentioned in lecture.
- Raphe Nuclei - 5HT
- Substantia Nigra/Ventral Tegmental Area- Dopamine
- Locus Coeruleus - NE
- Pontine Nuclei - ACh
What are Aβ fibers associated with?
What are Aδ fibers associated with?
What are C fibers associated with?
Aβ fibers are myelinated fibers involved with touch and non-noxious mechanical stimuli.
Aδ fibers are fast myelinated fibers involved with noxious heat, mechanical stimuli, sharp pain, produces initial reflex response.
C fibers are slow thin non-myelinated fibers involved with noxious chemical, heat, mechanical stimuli. Slow burning pain. Also has a prolonged response.
What is the Gate Control Theory of Pain?
What can be used to suppress pain?
There are “gates” in the spinal cord that allow pain signals through. These gates can be adjusted to increase/decrease pain sensation.
Opioids (blocks signaling) and anti-inflammatory agents (suppress nociceptor signaling)
How will Aβ fibers suppress pain signaling (close gate).
What would this be an example of activating Aβ fibers to suppress pain signaling.
Aβ fibers will activate the inhibitory neuron which will close the pain signaling of the interneuron.
Rubbing you arm knee after falling (Peter Griffin).
What will activate bradykinin release?
What two receptors does bradykinin bind to?
What do these receptors do?
Tissue damage
B1 receptors (inflammatory)
B2 receptors (constitutive)
Both receptors will activate PKA and PKC, which will send an action potential in the free nerve ending to release glutamate and substance P.
What three tracts are involved with pain transmission in the CNS?
Spinothalmic Tract (Affective Sensation)
Spinoreticular Tracts (Affective Sensation)
Spinomesencephalic Tract
Where is the signal sent in the spinomesencephalic tract?
What kind of receptors are at this location?
Periaqueductal gray matter (PAG).
Lots of opioid (mu) receptors that will suppress the spinothalmic and spinoreticular signaling.
The spinothalmic and spinoreticular tract will also send signals to the PAG to release more endogenous opioids.
Differentiate full agonist, partial agonists, & antagonists of the opioid receptors. Give examples for each.
- Full Agonists (strong to moderate effect) morphine, fentanyl
- Partial Agonists (moderate to mild effect) codeine, oxycodone, etc.
- Antagonists (Reversal) Naloxone
Name the 3 opioid receptors, which one is the the primary receptor?
Mu Receptor (Primary Opioid Receptor) - most responsive to endorphins/endogenous ligand
Delta Receptor- Analgesia
Kappa Receptor- Analgesia (May have negative analgesia effects mediated by dynorphins)
Pharmacokinetics of Opioids:
Absorption:
Distribution:
Metabolism: Morphine, Heroin, Other.
Elimination:
Pharmacokinetics of Opioids:
A: Well absorbed (IM, SQ, Oral- only with demerol or codeine)
D: Opioids can accumulate in the tissues
M: Morphine - metabolized by Phase II
M: Heroin - metabolized by tissue esterases to morphine
M: Other: Phase 1 (CYP3A4, CYP2D6)
E: Urine
Opioids will bind to the receptors in the brain and spinal cord. What type of receptor are opioid receptors?
How do μ(mu) opioid receptors suppress pain?
Where are three locations in the neuron where Mu receptors can suppress pain signaling?
Gᵢ GPCRs
Gᵢ = ↓AC → ↓cAMP = ↑pK⁺, ↓pCa⁺⁺ = Hyperpolarized neuron. This will reduce NT release: glutamate, ACh, NE, serotonin, Substance P.
Mu receptors are located in the:
1. Free nerve endings
2. Presynaptic Neuron
3. Postsynaptic Neuron
What are the CNS effects of opioids (9 items).
- Cough Suppression
- Hyperthermia (mu receptors)/ Hypothermia (kappa receptors)
- Analgesia- sensory/emotional
- Increase muscle tone (trunk)
- Respiratory Depression (brainstem)
- Miosis (always a marker, pinpoint)
- Euphoria (Dysphoria sometimes)
- N/V
- Sedation
CHAIRMENS
People who take opioids will develop a tolerance to what factors (8)?
Cough Suppression
Analgesia
Mental clouding
Euphoria/Dysphoria
Respiratory Depression
Antidiuresis
Sedation
N/V
CAMERAS N
People who take opioids do not develop a tolerance to what factors (4)?
- Miosis
- Constipation
- Convulsions
- Antagonist actions
Why would opioids be used for acute pulmonary edema?
What is a better alternative?
Reduce Anxiety
Reduce Preload (Decreasing Venous Tone)
Reduce Afterload (Decrease SVR)
Better alternative to treat acute pulmonary edema would be loop diuretics.
Name Opioid Toxicities (8 items)
Increase ICP
Constipation
Urinary Retention
Postural hypotension (worsens with hypovolemia)
Itchy nose, urticaria
Dysphoric Reactions: Restlessness, hyperactivity
Respiratory Depression
N/V
I CUPID RN
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 (6)?
Piloerection (goosebumps)
Rhinorrhea
Lacrimation (tears)
Yawning
Chills
Hyperventilation
PR LYCH
What symptoms would be seen in severe opioid withdrawal (6)?
Hyperthermia
Mydriasis
Muscle aches
N/V/D
Anxiety
Hostility
HMM NAH
What is given to reverse opioid overdose?
Why are opioids partially contraindicated in head injuries?
What can occur when opioids are given to a pregnant mother?
Narcan (short half-life)
↑ Resp depression
Fetal dependence
Name 3 main structures of strong opioid agonist and examples for each.
- Phenanthrenes (Morphine, Dilaudid, Heroin) basket of morphine, 3 rings
- Phenylheptylamines (Methadone) 7 carbon chain with an amine group at the end
- Phenylpiperadine (Fentanyl, Demerol) Has a N inside the ring
What is heroin used for in the UK?
Palliative Care/ Terminal 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?
People who are prone to _________ should not receive demerol.
Post-op shivering
neg inotrope, + chronotrope (antimuscarinic effect)
Seizures
What is the most potent fentanyl derivative?
Carfentanil (10,000:1 morphine ratio)
Give examples of moderate agonist in each structural class
Phenanthrenes:
Phenylheptylamines:
Phenylpiperadine:
Moderate agonist
Phenanthrenes: Codeine, Oxycodone
Phenylheptylamines: Propoxyphene (Darvon) decreasing
Phenylpiperadine: Loperamide (Imodium) diarrhea
What combination makes Percocet?
What combination makes Percodan?
Percocet = Oxycodone + Acetaminophen
Percodan =Oxycodone + ASA
What is Codeine converted to in the body?
Morphine
What opioid antagonists are a derivative of morphine (2)?
- Naloxone (Narcan) - Overdose antidote (short duration, supportive therapy still needed)
- Naltrexone (longer acting)- EtOH abuse.
How long does it take Narcan to take effect?
What do you need to take into consideration with Narcan’s short duration?
1 to 3 minutes.
Short duration means that the effects may return there is a longer acting opioid in the system.
