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