The (δ/κ/μ) opioid receptor is less well defined than the others. It modulates both spinal and supraspinal analgesia while also exhibiting less capacity for dependence formation.
The (δ/κ/μ) opioid receptor primarily deals with supraspinal analgesia. It also causes miosis, respiratory depression, euphoria, and development of dependence.
The (δ/κ/μ) opioid receptor primarily modulates spinal analgesia. It may cause weak supraspinal analgesia, along with weak miosis, sedation, weak respiratory depression, and dysphoria.
Opioid receptors are G-protein coupled receptors that span the membrane ___ times.
A(n) ______________ is an endogenous opioid that has the highest affinity for μ-receptors. It possesses decreased affinity for δ-receptors.
A(n) ______________ is an endogenous opioid that has the highest affinity for δ-receptors. It possesses decreased affinity for μ-receptors.
A(n) ______________ is an endogenous opioid that has the highest affinity for κ-receptors. It possesses decreased affinity for both δ-receptors and μ-receptors.
In the presynaptic terminal, μ-receptor activation (increases K+ conductance/decreases Ca2+ influx) in response to an incoming action potential.
Decreases Ca2+ influx
In the postsynaptic terminal, μ-receptor activation (increases K+ conductance/decreases Ca2+ influx) and thereby inhibits postsynaptic response to excitatory neurotransmission.
Increases K+ conductance
Analgesia caused by opioids is more effective against (dull/sharp) pain.
Stimulation of the μ-receptors (increases/decreases) the pain threshold while also (increasing/decreasing) the response to pain.
- Increase pain threshold
- Decrease response to pain
Analgesic effects modulated by the μ-receptors are primarily produced at the (spinal/supraspinal) level.
Stimulation of the μ-receptor causes (increased/decreased) tone and (increased/decreased) motility in one's GI tract.
- Increased tone
- Decreased motility
(T/F) Opioids acting at μ-receptors may be used as anti-diarrheals due to their constipative effects.
Opioids that act at μ-receptors may cause miosis by activity at the ________________ nucleus.
After chronic opioid use, (little/substantial) tolerance is developed to the miosis-inducing effects of opioids.
_______________ is the only opioid that does not cause miosis.
Direct stimulation of μ-receptors in the chemoreceptor trigger zone (area postrema) may result in ___________.
Opioids have (profound/minimal) cardiovascular effects.
(T/F) Opioids may cause urinary retention by inhibition of the urinary voiding reflex. After chronic use, tolerance may be developed to this effect.
Physical dependence (withdrawal) symptoms begin ___ hours after the last opioid dose. These symptoms peak at ___ hours and then decline for ___ days.
- Begin at 6 hours
- Peak at 48 hours
- Decline for 10 days
What are the most common withdrawal symptoms seen in opioid dependence?
"OperiOLD" mnemonic. Most withdrawal symptoms resemble premenstrual symptoms.
(Codeine/Morphine/Heroin) is the prototype μ-agonist. It is poorly absorbed through oral routes and undergoes extensive first-pass metabolism. It possesses a half life of 2-3 hours, but its effects persist for 3-6 hours after administration.
(Codeine/Meperidine/Heroin) is the di-acetylated, semi-synthetic form of morphine. It is 5-10 times more potent than morphine, leading to its abuse. It also possesses a greater lipid solubility and increased absorption, contributing further to its popularity. It has a half life of 0.5 hours, and a duration of 4-5 hours.
(Codeine/Meperidine/Heroin) is an orally effective opioid that may be used as an analgesic or antitussive. It possesses a lower potency and efficacy than morphine. It has a half life of 2-4 hours, and a duration of 3-6 hours.
(Codeine/Meperidine/Heroin) is an opioid that is less potent and has a slightly shorter duration than morphine. The anticholinergic effects of this opioid lead to dry mouth and mydriasis, as opposed to the miosis commonly seen with other opioids. Its metabolite, _______________, is excitatory. Overdose can lead to convulsions, and overdose effects are not blocked by typical opioid antagonists due to its action at sites other than μ-receptors. It has a 2-3 hour half life and a duration of 3-6 hours.
- Normeperidine metabolite
(Propoxyphene/Methadone/Fentanyl) is a very potent opioid (100-1000x more potent than morphine) that is also relatively short acting. It is often used as an anesthetic adjuvant due to its cardiovascular stability. It has an onset of around 15 minutes, while other similar drugs, referred to as ____________, have been developed for more rapid onsets.
(Propoxyphene/Methadone/Fentanyl) is a very popular opioid analgesic for mild to moderate pain. It is atypical from most other opioids in that its dextro form is the active analgesic. It has a 6-12 hour half life and a duration of 4-6 hours.
(Propoxyphene/Methadone/Fentanyl) is an opioid that is relatively well absorbed through oral routes. Its use is primarily maintenance therapy for opioid addicts due to its oral activity and long duration of action. Tolerance to this drug also develops more slowly than tolerance to morphine. It has a half life of >12 hours and a duration of 6-8 hours.
(Buprenorphine/Pentazocine/Tramadol) functions as a partial agonist or antagonist at μ-receptors. Its analgesic activity is primarily mediated at κ-receptors. This causes it to possess a lower addiction liability than other μ-agonist opioids. Due to the difference in receptor activity, it also possesses distinct withdrawal symptoms relative to the other opioids. It is often combined in oral tablets with naloxone, has a half life of 4-5 hours, and a duration of 3-6 hours.
(Buprenorphine/Pentazocine/Tramadol) is a partial agonist at μ-receptors and an antagonist at κ-receptors. It has been approved as an alternative to methadone maintenance therapy, but may precipitate withdrawal symptoms in patients currently taking high doses of methadone or other μ-agonist opioids. It has a half life of 2-3 hours and a duration of 12-36 hours.
(Buprenorphine/Pentazocine/Tramadol) is a weak partial agonist at μ-receptors that also blocks norepinephrine uptake and produces release of serotonin. It has a lower addiction liability than other μ-agonist opioids, and thus it is not a DEA-scheduled drug. It is used to treat a variety of conditions in addition to pain, such as: restless leg syndrome, fibromyalgia, acid reflux, and premature ejaculation.
Morphine's active metabolite is _______________.
Meperidine's active metabolite is _______________.
- Overdose can lead to convulsions, effects not blocked by typical opioid antagonist
Heroin's active metabolite is _______________.
Hydrocodone's active metabolite is _____________.
Oxycodone's active metabolite is ______________.
(Methylnaltrexone/Naloxone/Naltrexone) is a "pure" μ-antagonist. It possesses a very high affinity for μ-receptors, and as such, displaces most other opioids. At relatively higher doses, it also blocks δ- and κ-receptors. It causes an instant reversal of μ-opioid overdose, but its duration of action is only 1-2 hours, so multiple doses may need to be given based upon which drug was taken. This drug will precipitate withdrawal symptoms in opioid addicts.
(Methylnaltrexone/Naloxone/Naltrexone) is a newer, longer-acting μ-antagonist. It is often used in maintenance therapy for addicts who are not physically dependent and also for treatment of alcoholics. Its duration of action is around 24 hours.
- NalTrexone for Tipsy addicts
(Methylnaltrexone and Alvimopan/Naloxone and Naltrexone) are both "pure" μ-antagonists that are restricted to the periphery. These drugs antagonize peripheral, but not central, μ-receptors. This reduces postoperative ileus or constipating effects in patients with chronic opioid use.
Methylnaltrexone and Alvimopan
Do not cross BBB
(Loperamide/Dextromethorphan/Oxycodone) is a special dextro-isomer opioid that is effective in use as an antitussive. Its actions are not mediated via opioid receptors, and therefore has little abuse liability. Use of this drug produces dysphoric effects.
(Loperamide/Dextromethorphan/Oxycodone) is a controlled release μ-agonist analgesic that is receiving current publicity for abuse.
(Oxycodone and Dextromethorphan/Loperamide and Diphenoxylate) are aqueous, insoluble meperidine derivatives used to treat diarrhea. They exhibit poor GI absorption, thus they remain concentrated at their site of action in the gut.
Loperamide and Diphenoxylate
Opioids that bind to μ-receptors (stimulate/depress) the brain stem respiratory centers. This causes a(n) (increased/decreased) response to carbon dioxide.