Opioids Flashcards
What are the types of opioids
endorphins, Enkephalins, and Dynorphins
What is POMC
it is a precursor for ACTH, MSH, beta lipoprotein, endogenous opioids. cleaved into subunits that are pharmacologically active.
What are the opioids receptors
are G-coupled receptors found in the brain, spinal cord and the digestive tract. activation of opioid receptors reduces pain transmission and produces other characteristic effects.
What are the types of opioid receptors
Mu, Kappa and Delta
What is the function of Mu
responsible for most of the effects and side effects of opiates, euphoria, respiratory, depression,sedation, miosis, dependence, constipation.
What has the highest affinity with Mu?
Endorphins and enkephalin
what are the full agonist?
Morphine, Meperidine, Fentanyl and analogues, oxycodone and Hydrocodone, Oxymorphone, methadone
What are the antagonist?
Naloxone, Naltrexone and Nalmephene
What is the function of Kappa-
spinal analgesia, anticonvulsant effect, depression, sedation, dysphoria and hallucination, and inhibition of ADH secretion. found in the limbic system, spinal cord, brainstem and hypothalamus
What are the main endogenous agonist for Kappa?
Dynorphins (Nalbuphine and Pentazocine)
What is the function of the Delta?
responsible for analgesia, antidepressant, dependence, convulsions. inhibits motility of gastro-intestina
What has the highest affinity for delta receptors?
enkephalins. found in the factory bulb, nucleus accumbent and cerebral cortex
What is the mechanism of the opioid receptors
stimulation of opioid receptor lead to their effect through mobilization of the alpha and the beta gamma subunit of the trimeric G protein. they beta-gamma subunit leads to opening of G protein inward rectifying potassium channels.
also inhibits adenylate cyclase, voltage gated Ca+ channels, activation of MAP kinases and Phospholipase C.
it inhibits the release of NTS from the presynaptic neuron by inhibition of the calcium influx. inhibits the depolarization of the post synaptic neurons by causing hyper polarization through opening of inward rectifying potassium channels.
What NTS are inhibit through the G-proteins
decrease the release of Glutamate, substance, ACh, NE and Serotonin
What is morphine
it is agonist for Mu receptor that acts at laminae I and II of the dorsal horn. important points are depresses cough reflexes, decreased peristalsis, emesis, induce histamine release. vasodilation, increased biliary pressure.
What are the ADR of Morphine
Apnea and severe respiratory depression, constipation, vomiting, Urticaria, addiction. signs of acute toxicity: pinpoint pupil, respiratory depression and coma
What manages the ADR of Morphine
IV Naloxone
What is Mepheridine?
it is also called pethidine that binds to both Mu and Kappa receptors. it functions in increased sympathetic stimulation ( Interaction with MAO)
What is Normeperidine
it is the metabolite of meperidine and it is an inhibitor of serotonin re-uptake. can change seizures, hyperactive reflexes and tremors
What is methadone?
it is an antagonist of NDMA receptor. it is a agonist at Mu receptors that is potent and long duration analgesia. used to manage opioid withdrawals symptoms
What are the synthetic opioids
Fentanyl- 100x more potent than morphine
Alfentanyl - 10x more potent
Sufentanyl - 1000x more potent
What are semisynthetic opioids?
hydrocodone, oxycondone, hydromprohpne, oxymorphone, codeine, propoxyphene. metabolized by CYP3A4 and other enzymes
What are partial agonist?
ex. Buprenorphine. it is useful only in weak pain due to it partial agonist effects. it treats addiction through suboxone - that is a combination of bupreorphine and naloxone.
What are mixed agonist/ antagonist?
ones that work on one receptor but not another. doesn’t cause too much respiratory depression, ceiling analgesic effect and causes psychoactive effects.
What are examples of an mixed agonist and antagonist
ex. Pentazocine- agonist at kappa and antagonist at Mu receptor
Nalbuphine and butorphanol - antagonist to Mu but agonist to Kappa
What is loperamide
synthetic opioid receptor agonist and acts on the u-opiod receptors in the enteric plexus of the large intestine to treat diarrhea.
What is dextromethorphan?
Dextromethorphan. Antitussive. μ, δ, and κ-opioid receptor agonist. Also, a nonselective serotonin reuptake inhibitor. Its major metabolite, dextrorphan, is an NMDA receptor antagonist.
What is tramadol
weak analgesic that acts partially at mu receptors but also blocks reuptake of NE and 5-HT.Contraindicated with MAOIs. Much less addictive potential
What is tapentadol
–synthetic weak analgesic similar to Tramadol. Works at mu receptors and also NE reuptake inhibitor .
