Term
| Can you list the 7 essential opioids we must know? |
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Definition
Morphine
Codeine
Fentanyl
Methadone
Buprenorphine
Meperidine
Tramadol |
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Term
| What are the opioid antagonists? |
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Definition
Naloxone (Narcan)
Naltrexone |
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Term
| What are some uses of opioids? |
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Definition
Opioids are used in pain management both outside of and within anesthetic regimens.
They are also used to treat diarrhea. |
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Term
| What is the MoA of the analgesic effect of opioids? |
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Definition
Opioids can indirectly inhibit pain by binding to presynaptic mu1 receptors of gaba-ergic interneurons. These neurons normally depress pain inhibitory neurons. When opioids inhibit the gaba-ergic neurons (via Gi/Go -> hyperpolarization), the pain inhibitory neurons are free to act, and they block pain pathways.
(draw it out)
Opioids can also directly inhibit ascending pain pathways |
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Term
| At which opioid receptors do the "essential 7 drugs" mainly act? |
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Definition
There are multiple opioid receptors, including Mu, Kappa, Sigma, and Delta.
The opioids act mainly on the Mu receptors. This receptor is responsible for the majority of opioid effects, including physical dependence.
Kappa receptors are stimulated in spinal analgesia, Sigma receptors are responsible for psychotic effects. |
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Term
| Which opioid receptor does morphine act on to produce dependence? |
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Definition
| The opioid Mu receptor is involved in dependence |
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Term
| Why does opioid withdrawal produce an adrenergic storm? |
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Definition
| Opioids act on presynaptic Mu receptors of norepinephrine cells. Mu receptors result in the hyperpolarization of the neuron, and this inhibits NE release. There is a reactionary increase in NE receptors postsynaptically. When opioids are withdrawn, the release of NE is no longer prevented, and increased NE levels act at increased NE receptors! |
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Term
| Describe the development of tolerance to morphine's emetic, respiratory depression, pupillary constriction, and poikilothermia-inducing effects. |
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Definition
Rapid and complete tolerance develops to the nausea-producing effects of morphine. This tolerance is also rapidly lost during abstinence from the drug, so somebody that has stopped taking opioids and then goes back to their normal dose will likely suffer nausea and vomiting.
Tolerance to respiratory depression is also rapid, but incomplete.
The tolerance to the other effects is minimal. This means chronic morphine abusers will still suffer from constipation and pinpoint pupils etc.
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Term
| Describe morphine's impact on nociceptive vs. neuropathic pain |
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Definition
| Morphine (and other opioids) have a great effect on nociceptive pain, but are not as effective against neuropathic pain. |
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Term
| What effect does morphine have on the cardiovascular system? How/why? |
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Definition
Morphine's depressive effects on the cardiovascular system occur mainly at high doses.
Morphine causes a drop in blood pressure.
This is achieved mainly through stimulation of histamine release, resulting in vasodilation.
Additionally, morphine blocks the baroreceptor mechanism (postural hypotension)
HR is also slightly decreased |
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Term
| What effect does morphine have on the GIT? |
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Definition
Morphine causes constipation by increasing the tone of the GIT smooth muscle. These are nonpropulsive contractions:
"squeeze but no push"
Opioids also decrease GIT secretions and cause nausea and vomiting (CRTZ stimulation). |
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Term
| How do opioids affect respiration? |
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Definition
Opioids depress everything to do with respiration. This includes minute respiration, tidal volume, respiratory rate.
This is accomplished by reduced sensitivity of central receptors to CO2.
In large doses, opioids can produce bronchoconstriction!... Recall that they stimulate mast cell release of histamine.
(important to remember for asthmatics) |
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Term
| How is morphine metabolized? |
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Definition
Morphine suffers a large first pass metabolism, and is therefore preferentially given by IV or intramuscular injection. (codeine has good oral bioavailability)
Morphine is metabolized in the liver to morphine-3-glucoronide and morphine-6-glucoronide. Morphine-6-glucuronide, the active compound is responsible for the potent analgesic effects. They are excreted mainly by the kidney. |
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Term
| Which opioid acts as a good antitussant? |
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Definition
| All opioids suppress the cough reflex, but codeine is the best. |
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Term
| What opioid is preferred to morphine in cases of cardiac surgery? |
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Definition
Fentanyl is the preferred opioid for cardiac surgery. It has minimal stimulation of histamine release, thereby causing minimal vasodilation and minimal BP changes. (It has good hemodynamic stability)
Minimal histamine release is also beneficial in asthmatics
(methadone also causes minimal histamine release) |
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Term
| What opioid drug is used to treat chronic pain? |
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Definition
| Fentanyl is used to treat chronic pain because it is available in a patch, making long term administration easier. |
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Term
| Which opioid is absolutely contraindicated in someone taking an MAOI? |
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Definition
| Never use meperidine with an MAOI. It can precipitate serotonin syndrome. |
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Term
| What are the therapeutic uses of diphenoxylate and loperamide? |
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Definition
| These are the opioids that specifically exert their effect on the GIT, and are therefore used to treat diarrhea. |
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Term
| Which opioid is unique in that it causes an increase in BP and HR? |
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Definition
Pentazocine increases BP and HR, this makes it contraindicated in patients with angina or MI. The other opioids all tend to decrease these parameters.
Pentazocine is also the opioid with the greatest stimulation of sigma opioid receptors, and therefore is the most likely to cause psychomimmetic effects and dysphoria! |
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Term
| Which opioid cannot readily be displaced from Mu receptors by naloxone? |
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Definition
Buprenorphine is a partial mu-agonist that dissociates very slowly from opioid receptors. Therefore, naloxone does not readily displace it and does not counteract buprenorphine well.
This slow dissociation also means that buprenorphine has an extended duration of action. |
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Term
| Why can buprenorphine, an opioid, precipitate withdrawal symptoms in someone on a different opioid? |
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Definition
| Buprenorphine is a partial mu-agonist. If someone is on a full agonist (morphine, fentanyl) and then takes buprenorphine, buprenorphine can outcompete for the mu-receptor and cause much less stimulation, precipitating withdrawal symptoms! |
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Term
| Which opioid has been found effective for neuropathic pain? |
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Definition
Recall that opioids are very effective against nociceptive pain, and not so effective against neuropathic pain. However, Tramadol has been found useful in treating neuropathic pain.
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Term
| What are some important toxicities of/ contraindications to tramadol? |
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Definition
Tramadol inhibits uptake of 5HT and NE, and should therefore be avoided in patients taking SSRIs or MAOIs (serotonin syndrome risk)
Tramadol also lowers the seizure threshold and should therefore be used with extreme caution in epileptics. |
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Term
| What are presenting symptoms/signs of opioid overdose? |
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Definition
Pinpoint pupils
Respiratory Depression
Coma
*give Naloxone as the antidote to opioid toxicity
(death from opioid overdose is from respiratory failure) |
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Term
| What are symptoms of opioid withdrawal? |
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Definition
Opioids are depressants, so withdrawal symptoms will be opposite:
Restlessness
Anxiety
Dysphoria
Mydriasis
Tachycardia
Hypertension
Hyperpnea
Hyperthermia |
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Term
| What are some important contraindications to opioids/ situations requiring cautious use? |
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Definition
Because opioids greatly depress the respiratory center, beware of patients whose respiration is already impaired. This includes COPD, kyphosis, cor pulmonale. edema, asthmatic patients!
Hypovolemics/hypotensives (because impairs baroreceptor reflex, and depresses cardiovascular function even further)
Constipation (worsens)
BPH (furthers urinary retention)
Head trauma, because they vasodilate, causing increased ICP
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