Term
| Which opioids are strong full agonists? |
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Definition
- Morphine/Kadian or MS Contin
- Hydromorphone/Dilaudid
- Oxycodone/Oxycontin
- Methadone/Dolophine
- Fentanyl/Duragesic or Sublimaze
- Levorphanol/Levo Dromoran
- Meperidine/Demerol |
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Term
| Which opioids are mild/moderate full agonists? |
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Definition
- Hydrocodone - Lortab or Norco
- Codeine
- Propoxyphene/Darvon
- Hydrocodone + Chlorpheniramine/Tussionex |
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Term
| Which opioids are partial or mixed agonists? |
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Definition
Pentazocine/Talwin - kappa > mu. Analgesic b/c of kappa
Nalbuphine/Nubain - IV, mu and kappa
Butorphanol/Stadol - more kappa activity, blocks mu.
Buprenorphine/Buprenex - mu agonist, kappa antagonist |
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Term
| Which opioids are antagonists? |
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Definition
Naloxone/Narcan
Naltrexone/Vivitrol
Methylnaltrexone/Relistor |
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Term
| Which opioids are 'misc'? |
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Definition
- Tramadol/Ultram
- Diphenoxylate + atropine - Lomotil
- Loperamide - Imodium
- Dextromethorphan
- Benzonatate - Tessalon |
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Term
| How do opioid receptors work? |
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Definition
- Opioids are relatively selective for the mu receptor
- Can be agonists or antagonists
- Receptors on PRIMARY afferents in the cord or brain
- Psychomimetic effects. SAME as endogenous opioids |
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Term
| What are the 3 main effects caused by opioids? |
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Definition
- Analgesia - mu receptor - increased threshold to pain
- Sedation - mu receptor - changes in mood, but easily awakened
- Euphoria - all 3 receptors - less anxiety and distress.
- 3 areas: VTA, prefrontal cortex, nucleus accumbens |
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Term
| How are the VTA, nucleus accumbens, and prefrontal cortex attached to opioids? |
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Definition
Opioids block GABA, allowing the VTA to express dopamine activity --> nerve goes to NAcc, release of more dopamine
Nacc attached to the limbic system, responsible for reward/euphoria |
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Term
| How do opioids produce respiratory and cough suppression? |
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Definition
- Respiratory - inhibition of respiratory center via mu receptor agonism - ALL opioids, an increase in CO2. What can kill people.
- Cough - reduced sensitivity of cough centers in the medulla, reduced transmission of impulse to CNS via vagus. NOT mu receptor mediated! Not antagonized by naloxone! |
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Term
| How do opioids cause nausea and vomiting? |
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Definition
In the brain stem, there is a center with several receptors: serotonin, histamine, Ach, Dopamine, Sub P,and Mu. Opioids bind to the Mu, can induce N/V.
- Zofran antagonizes 5HT-3 receptor, Emend antagonizes NK-1 (sub P) |
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Term
| What do opioids do to the eyes? What can block this? |
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Definition
- Miosis (pinpoint pupils), no tolerance. Mu and kappa receptors, inhibition of INHIBITORY nerves - activation of E-W nucleus on CN-III --> constriction of ciliary muscle and pupil.
- Muscarinic antagonist, opioid receptor antagonist, Ganglionic blocking agent. |
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Term
| How do opioids affect CV and GI? |
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Definition
- CV - inhibition of central vasomotor center, release of histamine --> decreases BP due to dilation
- GI - inhibition of Ach leads to CONSTIPATION, no tolerance, decreased motility.
- Contraction of sphincter of oddi leads to backup of secretions - similar to biliary colic. May be cholinergic?
- Decreases voiding/urination. An antidiuretic effect. |
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Term
| Do opioids affect unborn children? |
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Definition
| YES! Cross placental barrier. Dependence and withdrawal |
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Term
| How does tolerance develop? |
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Definition
Internalization of mu receptors/downregulation
NMDA activation
- An addicted individual requires higher doses, has less respiratory side effects.
- NO tolerance to miosis, convulsions, constipation
- Dependence - adapts to presence of the drug, cannot tolerate withdrawal. 2+ weeks |
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Term
| What is the clinical triad of acute toxicity? |
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Definition
Respiratory depression
Sedation
Miosis - Pinpoint pupils |
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Term
| Which opioids can be used to treat neuropathic pain? |
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Definition
- Methadone/Dolophine - also used in addicts, a full mu agonist as well as an NMDA antagonist, SERT and NET antagonist
- Levorphanol/Levodromoran - also blocks NMDA
- Tramadol - a codeine analog. Binds to mu, inhibits NET and SERT. Stimulates alpha 2. NOT antagonized by naloxone |
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Term
| Which opioid is not antagonized by naloxone? |
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Definition
| - Demerol/Meperidine - metabolite has extremely long half life. Rapid onset, accumulating metabolite, caution w/ SSRIs |
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Term
Why does Lomotil have atropine in it?
What is the difference with Loperamide? |
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Definition
Used only for constipating activity, atropine prevents abuse.
- Loperamide - used for constipating activity, does not penetrate CNS so low abuse. |
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Term
| How does DM suppress cough? |
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Definition
Non-opioid. works on cough reflex center, not antagonized by naloxone. DOES work on NMDA
- Can be abused - dissociative sedation |
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Term
How do partial/mixed agonists produce their effects?
Why is this important? |
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Definition
- Partial agonism on the mu receptor
- mu receptor antagonism
- Kappa receptor agonism and antagonism. Kappa agonism results in dysphoria
- Low ceiling - compete with full agonists to reduce the activity of a full agonist. Can precipitate withdrawal symptoms! |
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Term
|
Definition
Prialt/Ziconotide - mimics cone snails. No opioid receptor activity. 1000x as potent as morphine!
Blocks N-type calcium channels on afferent nerves |
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Term
| How are opioid antagonists used? |
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Definition
- Narcan/naloxone - competitive antagonists, reverses respiratory depression. Can produce withdrawal. Reverses toxicity
- Naltrexone/Revia - treatment of alcohol dependence. Can reduce a narcotic to no activity
- Methylnaltrexone/Relistor - mu antagonist in the GI tract, reducing ONLY constipation
- Embeda - morphine/naltrexone - naltrexone core prevents incorrect use/abuse. Naltrexone mixes with morphine if crushed, otherwise not. |
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Term
| What are symptoms of neuropathic pain? |
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Definition
Allodynia - pain to normally non-painful stimuli
Hyperalgesia - exaggerated response
Dysesthesia - abnormal sensation
Paresthesia - numbness tingling |
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Term
| What is used for therapy of neuropathic pain? |
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Definition
- TCAs - amitriptyline/nortriptyline. Inhibits SERT and NET
- Anticonvulsants - Tegretol inhibits sodium channels, Phenytoin/trileptal/Lamictal also block sodium and calcium. Gabapentin and Pregabalin inhibit calcium and increase GABA.
- Local anesthetics - reversibly blocks sodium channels
- Neuropeptide antagonists - Capsaicin
- NMDA antagonists - Ketalar (psychomimetic), symmetrel/amantadine, dextromethorphan |
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Term
How does Topamax/Topiramate work?
Depakote?
Clonidine? |
|
Definition
anticonvulsant for neuropathic pain and prevention of migraine
- Inhibits sodium and L-calcium channels
- Potentiates GABA and K efflux
- Inhibits NMDA
- Depakote - blocks sodium and increases GABA
- Clonidine - inhibits pain mediators |
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Term
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Definition
| Nucynta/Tapentadol is a mu agonist as well as an SNRI |
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Term
| How does capsaicin have an AIF effect? |
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Definition
| Initial pain, binds to TRPV1, depletion of nerve ending of Sub P. |
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Term
| Are NK-1 antagonists analgesic? |
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Definition
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