Opioid Analgesics Flashcards
____ is known as the “fifth vital sign”
Pain
Mu opioid receptors regulate…
-Analgesia
-Well-being
-Respiratory depression
-Physical dependence
Mu-1 receptors are responsible for ___ and ___
Analgesia and euphoria
Mu-2 receptors are responsible for ___ and ___ depression
Respiratory and cardiac
Delta opioid receptors have a similar profile to mu receptors; they are primarily responsible for analgesia to ____ ____
Thermal pain
Kappa opioid receptors are responsible for…
-Analgesia
-Sedation
-Anesthesia
-Miosis
Sigma receptors are nonopioid receptors that mediate the ____ effects of opioids
Dysphoric
Epsilon receptors have a high affinity for ____
Endorphins
Interactions of drugs with opioid receptors can be ____
Selective
Drugs can act as agonists, partial agonists, or antagonists ____ at each receptor
Independently
Depending on the spectrum of interactions, there is a wide spectrum of ____ effects that may be seen with drugs
Pharmacological
Opiate receptors outside of the CNS (like in the intestine and bladder) may mediate non-analgesic actions of the opiates like _____
Constipation
What is a drug that treats opioid-induced constipation?
Naloxegol
Immodium is designed to not get into the ____, but if it is abused, it will be able to
CNS
With partial agonist antagonists, the receptors can’t become _____
Desensitized
Opioid receptors are linked to ___ ___ and therefore are able to affect ion gating, intracellular Ca2+ disposition, and protein phosphorylation
G protein
What are the two well-established direct actions that opioids have on neurons?
-Close voltage-gated calcium channels on presynaptic nerve terminals
-Opening potassium channels (hyperpolarize=inhibit) on postsynaptic neurons
The net result of the cellular decrease in calcium is a decrease in the release of…
-Dopamine
-Serotonin
-Nociceptive peptides (substance P)
The decrease in dopamine, serotonin, and nociceptive peptides results in a blockage of ____ transmission
Nociceptive
Mu, kappa, and delta agonists reduce transmitter release from ____ terminals of nociceptive primary afferents
Presynaptic
Mu agonists also ____ second-order pain transmission neurons by increasing potassium conductance, evoking and inhibitory postsynaptic potential
Hyperpolarize
The net result of opioids on spinal sites is the blockage of ___ ___ to higher centers
Pain transmission
Opioids are well absorbed from the ____ ____ and ____
GI tract and transcutaneously (skin)
Drugs such as morphine that have a free ____ group in position 3 undergo first-pass effects (glucuronidation) and have reduced bioavailability
OH
Opioids distribute to all tissues depending on ____
Lipophilicity
Some opioids may sequester ___ and extend half-life relative of effect
Fat
____ and ____ pass readily into the blood-brain barrier
Heroin and codeine
____ is slow to pass through the blood-brain barrier
Morphine
____ and ____ can be redistributed into the brain
Fentanyl and methadone
Opioids readily cross the ____, so they should be used with caution during pregnancy and delivery
Placenta
The fetus is slow to _____ (similar to how an adult with reduced liver function)
Glucuronidate
The majority of opioid metabolites are ____
Inactive
What are three active metabolites of opioids?
-Morphine-6-glucuronide (analgesic)
-Normeperidine and norpropoxyphene (excitatory but not analgesic)
-6-beta-naltexol (less active than parent, but prolongs the effect)
Opioids are excreted through the ____ system
Renal
What effects might be seen from the interaction of sedative-hypnotics with opioids?
-Increased CNS depression, particularly respiratory depression
What effects might be seen from the interaction of antipsychotics with opioids?
-Increased sedation
-Variable effects on respiratory depression
-Accentuation on cardiovascular effects
What effects might be seen from the interaction of MAO inhibitors and opioids?
-Relative contraindication to all opioid analgesics because of the high incidence of hyperpyrexic coma
-Hypertension has also been reported
____ is the opioid prototype
Morphine
Minor alterations in the ____ of morphine lead to major changes in drug effects (morphine, codeine, oxycodone, and heroin are all basically the same molecule with very small differences)
Structure
The binding of opioids to the mu receptor causes…
-Analgesia
-Euphoria
-Respiratory depression
-Physical dependence of morphine
Most of the currently available opioid analgesics act primarily at the ____ receptor
Mu
Delta and kappa receptors can also contribute to _____
Analgesia
The primary clinical use of opioids is for ____
Analgesia
Opioids are most effective against constant, moderate-severe ____
Pain
Opioids suppress perception of pain by eliminating or altering the ____ aspects of pain and inducing euphoria
Emotional
Opioids may produce ____ and ____ when given in the absence of pain
Dysphoria and nausea
Codeine can be used for ____ ___, but the mechanism of action is not understood
Cough suppression
Opioids can also be used for the treatment of _____ as they increase the tone of the small and large intestine with decreased propulsive movement
Diarrhea
Opioids can also be used for ____ ____, as epidural or subarachnoid administration can produce regional analgesia with decreased side effects
Spinal analgesia
Opioid adverse effects include things like…
-Respiratory depression
-Miosis
-Nausea and vomiting
-Constipation
-Biliary colic
-Increased bladder and ureteral tone, urinary retention, exacerbation of ureteral colic caused by kidney stones
-Additive CNS depression
-Gynecomastia in men
-Itching sensation (often around the nose)
Respiratory depression from opioids is due to direct effects on the brain stem respiratory centers via the mu2 receptor at the level of the ____
Medulla
The respiratory depression is ____ with an opioid overdose
Fatal
Respiratory depression is the ___-___ side effect
Dose-limiting
____, or “pinpoint pupils” have little clinical significance, but are a good indicator of opiate abuse; no tolerance to this effect has been observed
Miosis
Opioids can also cause ____ and ____ due to stimulation of the chemoreceptor trigger zone in the brain stem
Nausea and vomiting
____ is a drug with no analgesic activity, but is a potent emetic agent
Apomorphine
Opioids can cause constipation by ____ sphincter tone and ____ gastric motility
Increasing; decreasing
Opioids mixed with sedatives/hypnotics, antidepressants, and antipsychotics can cause additive ____ ____
CNS depression
Stimulation of some opioid receptors in the hypothalamus causes the release of dopamine which cause ____ secretion, leading to gynecomastia in men
Prolactin
Opioids induce the release of ____, which leads to an itching sensation, often around the nose (this is often associated with the use and abuse of opioids)
Histamine
Symptoms of opioid dependence/withdrawal are related to the development of _____ followed by an abrupt withdrawal
Tolerance
Exaggerated rebound from the effects of opioids include…
-Chills
Hyperthermia
-Mydriasis
-Anxiety
Intensity of withdrawal depends on the ____, ____, and ____ of use
Drug, dose, duration
Opioids are classified by agonist/antagonist activity; the four classifications are:
-Strong/pure agonists
-Mild-moderate agonists
-Mixed agonist/antagonist or partial agonist
-Pure opioid antagonist
What are three examples of strong or pure agonists?
-Morphine
-Methadone
-Meperidine
_____ acts as a complete agonist primarily at mu, but also at delta and kappa receptors
Morphine
Morphine produces a typical “narcotic profile”, which causes symptoms like…
-Analgesia
-Euphoria
-Sedation
-Respiratory depression and miosis
Long-acting preparations of morphine (MS Contin and Ora-Morph) are used for ____ ____
Cancer pain
The biggest problem with patient-controlled anesthesia is that people give themselves ____ drug because people fear they will become addicted
Less
Signs of morphine overdose:
-Respiratory depression
-Miosis
-Hypotension
-Coma
We can use IV ____ to reverse morphine toxicity
Naloxone
People who have overdosed on morphine may require multiple doses of naloxone due to the short ___-___ of naloxone
Half-life
____ is less potent than morphine with a more consistent oral absorption
Meperidine (Demerol)
Meperidine (Demerol) has a rapid onset and a shorter duration than morphine, therefore withdrawal symptoms appear ____
Faster
The primary metabolite of Meperidine (Demerol) is ____
Normeperidine
The active metabolite normeperidine may be responsible for…
-CN excitation
-Tremors
-Delirium
-Hallucinations
-Convulsions
Meperidine (Demerol) has significant ____ activity
Anticholinergic
The sign of Meperidine (Demerol) overdose is ____, not seizure
Sedation
Meperidine (Demerol) has ____ antitussive, GI, and GU tract side effects
Less
Related phenylpiperidines (loperamide in Imodium, diphenoxylate in Lomotil) poorly enter the CNS but produce peripheral opioid effects, and are therefore used as ____
Antidiarrheals
Methadone (Dolophine) is a synthetic mu opioid _____
Agonist
Methadone (Dolophine) is similar to morphine, but with a ____ duration of action and a longer, but less intense withdrawal syndrome
Longer
Methadone (Dolophine) is used primarily in ___ ___
Heroin detoxification
