Opioids Flashcards
What neurotransmitters are used in afferent pain signaling?
Aδ fibers signal usng glutamate. C fibers signal using glutamate and substance P.
What neurotransmitters are involved the descending inhibition of pain?
Norepinephrine, Serotonin, and Enkephalin.
What is the precursor molecule to endorphins? With what are they co-released?
Where are dynorphins localized to?
Distinguish between a methionine and leucine enkephalin. What sequence is common to all of these compounds?
Proopiomelanocortin (POMC), co-released with ACTH.
Dynorphins co-localize with vasopressin in the hypothalamus and posterior pituitary (neurohypophysis).
Both enkephalins (and endorphins, dynorphins) contain a Tyr-Gly-Gly-Phe sequence. The enkephalins are followed by the amino acid indicated in their names.
What is the natural ligand for the δ receptor?
What drugs act on it?
What are the effects of its stimulation?
Enkephalins and endorphins.
None that we talk about.
Mild analgesia.
What is the natural ligand for the κ receptor?
What drugs act on it?
What effects does it have?
Dynorphins only.
Nabuphine (and butorphanol, pentazocine)
Dysphoria.
What is the natural ligand for the μ receptor?
What drugs act on it?
What effects does it have?
Enkephalins and endorphins.
Most of the opioids.
Analgesia, sedation, euphoria.
What is the common signal which all opioid receptors activate?
All opioid receptors are GPCRs linked to a heterotrimeric Gi protein. The reduction of cAMP due to AC inactivation increases potassium conductance and decreases calcium conductance (hyperpolarization).
Which opioids are metabolized to an active metabolite?
What factors influence onset and duration?
Codeine and heroin. (to morphine and monoacetyl morphine)
Lipophilicity and elimination rate.
Describe the basis for each of the following opioid effects:
Cough suppression
Constipation
Respiratory depression
Nausea
Miosis
Cough suppression at sites in the brainstem–may not be opioid, as dextromethorphan is efficacious.
μ receptor stimulation in the GI tract.
Decreased sensitivity to carbon dioxide (medullary).
Area postrema trigger zone activation.
EWN stimulation.
To which opioid effects is tolerance quickly achieved?
To which effects is tolerance not achieved?
Nausea and vomiting–much like with cigarettes.
Miosis and constipation.
What are the early and late symptoms of opioid withdrawal?
6-12hrs: Restlessness, lacrimation, sweating, rhinorrhea.
12-24hrs: Irritability, tremor, diminished appetite, goosebumps, mydriasis.
24-72hrs: Depression, nausea/vomiting, cramps, diarrhea, aches, tachycaria, involuntary movements.
Morphine
What receptors does it agonize/antagonize?
What formulation is used?
What is its clinical indication?
What is its duration?
Morphine
Mostly μ, but actually agonizes all.
Oral or parenteral; latter is preferable. Suppository available to reduce nausea.
It is the prototypical opioid analgesic.
4-5hrs.
Heroin
What receptors does it agonize/antagonize?
What formulation is used?
What is its clinical indication?
Compare its structure to morphine.
Heroin
Mostly μ, but actually agonizes all.
Heroin is typically injected or snorted.
None–heroin is purely a drug of abuse.
It is a morphine that is acetylated at two hydroxyl residues.
Codeine
What receptors does it agonize/antagonize?
What formulation is used?
What is its clinical indication?
Compare its structure to morphine.
Codeine
(weakly) agonizes μ receptors.
Primarily oral (pills).
Mild to moderate analgesia in conjunction with NSAIDs. Also a mild cough suppressant.
It is morphine, methylated at one hydroxyl residue.
Oxycodone (Oxycontin)
What receptors does it agonize/antagonize?
What formulation is used?
What is its clinical indication?
Oxycodone (Oxycontin)
Primarily μ receptors.
Primarily oral (pills).
Moderate to heavy analgesia. Sometimes formulated with NSAIDs.
