39. Drug Action as Opioids Flashcards
Describe pain.
Distressing feeling often caused by intense or damaging stimuli
* can be a symptom of an underlying condition
Explain a pain scale.
A tool that doctos use to help assess a person’s pain.
Describe the differences between acute and chronic pain.
Acute pain
cause: generally known
duration: short (hours-days)
mood: anxiety and fear
treatment: primary analgesics
respond to medicine: well
Chronic pain
cause: often unknown
duration: long (months-years)
mood: depression
treatment: multimodal required
respond to medicine: not well
Explain the difference between pain from tissue and pain from nerve damage.
Tissue damage: bone, soft tissues, organs
* cancer
* physical injury (cut or broken bone)
Nerve damage: CNS, PNS
* diabetes
* trauma
* chemotherapy drugs
* stroke
* HIV infection
Describe pain management by opioid drugs.
- opioids are a class of drugs including opiates primarily used for pain relief, including anesthesia
- opiates are natural drugs derived from opium poppy, including morphine, codeine, and heroin
- among the oldest known drugs
Explain the 4 types of opioids.
endogenous
* endorphins, enkephalins, dynorphins
nature opiates
* morphine, codeine, heroin
semisynthetic
* hydromorphone, oxymorphone, hydrocodone, oxycodone
synthetic
* fentanyl, meperidine, methadone, tapentadol, tramadol
Endogenous opioids are neuropeptides. Explain these neuropeptides.
All have tyrosine as the first amino acid, with other amino acids coupled (form peptide - not small molecule)
- tyrosine (also used for biosynthesis of other neurotransmitters)
- endorphin (Tyr-Gly-Gly-)
- enkephalin (Tyr-Gly-Gly-)
- dynorphin (Tyr-Gly-Gly-)
Describe the structure activity relationship of opioids.
- tyrosine, morphine, fentanyl
- red is shared
- positions at 3, 6, 14, and 17 are most important
- morphine and fentanyl bind to opioid receptors
Structure of nature opiate drugs.
Structure of semisynthetic opioid drugs.
Structure of synthetic opioid drugs.
Explain the potency of opioids to their receptors (in comparison to morphine)
ex. fentanyl is 100x as potent as morphine
- can react faster
Explain this graph of opioid drug duration of action.
- lipid solubility of opioid drugs determines rate of onset and duration of action
- solubility of fentanyl is greater than morphine
- fentanyl is highly lipid-soluble (rapid time to peak effect but short duration of action)
- morphine is not very lipid-soluble (slower time to peak effect but long duration of action)
Explain the duration of action of opioid drugs.
- morphine is 4-5 hours
- fentanyl is 1-2 hours (short duration)
- alfentanil is the shortest in duration of minutes
duration is used to decide treatment for pain (longer vs. shorter time)
Describe the mechanism of pain relief by opioid drugs.
- Opioids trigger release of chemicals from the brain’s reward system.
- calm emotions –> pleasure
- Slow down automatic functions
- interact with opioid receptors on nerve cells in the body and brain to regulate functions (pain, pleasure, breathing, digestion)
Name the 4 major subtypes of opioid receptors.
- u-receptor
- d-receptor
- k-receptor
- nociceptin/orphanin receptor
Describe opioid receptors as GPCRs.
group of inhibitory Gai/o protein-coupled receptors with opioids as ligands
* inhibiting adenylate cyclase activity
* lowering cAMP levels
Explain the inhibition of neuron communication by opioids.
can inhibit both presynaptic and postsynaptic signals
* The presynaptic neuron releases excitatory neurotransmitters (ex. glutamate)
* Depolarization in the postsynaptic neuron –> increases positive charge
* Without opioids - action potential forms in postsynaptic neuron –> signal continues
* With opioids - opioids block action potential from forming –> signal stops
* GABA is an inhibitory neurotransmitter –> neuron signal stops
Describe inhibition of presynaptic activation by opioids.
- opioids bind to opioid receptors –> close Ca2+ channel
- action potential no longer opens Ca2+ channel
- No Ca2+ flow into neuron.
- No neurotransmitter release
Describe inhibition of postsynaptic activation by opioids.
- opioids bind to opioid receptors and disassociate neurotransmitter binding from their receptors at postsynaptic membrane
- opens K+ channels and result in loss of positive charges
- postsynaptic neuron is no longer depolarized
- no formation of action potential
Explain the transmission of pain signals through the ascending pathway.
For transmitting pain signals to the brain for pain perception.
inhibited by opioids
Explain the transmission of pain signals through the descending pathway.
For blocking the ascending pathway to stop pain perception.
* constantly inhibited by GABA-releasing inhibitory interneuron
Activated by opioids
Explain where opioid drugs bind!
- At the brainstem –> stops inhibition of descending pathway neurons + blocks the ascending pathway and pain transmission
- At the spinal cord –> stops pain transmission
C. codeine
A. fentanyl
C. potassium efflux postsynaptically
D. Opioids inhibit descending pathway of pain signals
D. hypertension
