Opioid Analgesics

Front 1

What does NSAIDS treat?

Back 1

headache, mild-mod arthritic pain

Front 2

what does Anticonvulsants, Tricyclic antidepressants, Serotonin/norepinephrine re-uptake inhibitors treat?

Back 2

Neurogenic pain

Front 3

What do opioids treat?

Back 3

Severe, chronic, malignant pain

Front 4

What kind of compounds are opioids? What kind of effects do they have?

Back 4

natural (opium poppy) or synthetic compounds that produce morphine-like effects

Front 5

What 4 diverse functions Opioid Analgesics treat?

Back 5

Sensory component (inhibiting response to pain stimuli)
Modulation of GI, endocrine and autonomic functions
Emotional component (powerful rewarding and addicting properties)
Cognitive component (learning and memory)

Front 6

What are the 3 families of classical opioid peptides?

Back 6

Enkephalins(Pro-enkephalin)

Endorphins (POMC)(pre-opiomelanocortin)

Dynorphins (Pro-dynorphin)

Front 7

What is the common NH2 terminal “opioid motif” sequence?

Back 7

TYR-GLY-GLY-PHE-(MET or LEU)

Front 8

how many ligands and major receptors are there in Endogenous opioid system?

Back 8

>12 ligands (Table 21-1); 3 major receptor types

Front 9

What may be a critical functional variable in opioids?

Back 9

Duration of action of endogenous ligands may be a critical functional variable

Front 10

what is more important than activation of single receptor may be important?

Back 10

Pattern or profile of activation of multiple receptors by a ligand

Front 11

Intracellular trafficking of the receptors may vary as a function of what?

Back 11

receptor and the ligand

Front 12

Opioid Receptors are what kind of receptors? What do they inhibit? What chanels are they involved in?

Back 12

1)G-Protein coupled receptors
2)Inhibit adenylyl cyclase
3)Associated with ion channels

Front 13

Opioid receptors increase what efflux and and decreasewhat influx? What does this impede?What is released?

Back 13

↑ post-synaptic K+ efflux (hyper-polarization) or ↓ pre-synaptic Ca2+ influx → impedes neuronal firing and transmitter release

Front 14

How do opioid receptors signal?

Back 14

May also signal via MAP kinase and Phospholipase C signaling pathways

Front 15

what does Chronic opioid exposure result in?

Back 15

myriad signaling adaptations that may be important in tolerance, sensitization and withdrawal symptoms

Front 16

What are the three opioid receptor families?

Back 16

(Mu)
(Kappa)
(Delta)

Front 17

Enkephalins interact more selectively with what receptors?

Back 17

 receptors in periphery

Front 18

Analgesic properties of opioids mediated via which receptor?

Back 18

MU and K receptors in the dorsal horn

Front 19

What is the MOA of the mu-opioid Receptor agonists?

On the pre-synaptic neuron and the post synaptic neuron

Back 19

Activation of the opioid receptor ↓ Ca2+ influx in response to incoming action potential. This decreases release of excitatory neurotransmitters such as glutamate.

Activation of the opioid receptor ↑ K+ efflux and decreases the response of the post-synaptic neuron to excitatory neurotransmitters such as glutamate

Front 20

Transient opioid administration can result in what? What kind of time frame can it occur in?

Back 20

acute tolerance.
Can occur w/in hours

Front 21

Sustained opioid administration can result in what? How long does it take?

Back 21

classical tolerance (following days-weeks of treatment)

Front 22

What two things play a role in development of tolerance?

Back 22

Acute receptor desensitization and down-regulation likely

Front 23

How does Phosphorylation of μ and δ receptors occur?

Back 23

PKC, PKA and/or βARK

Front 24

What receptors can opioid receptors can undergo rapid agonist-mediated internalization via classical endocytic pathway?

Back 24

μ and δ but not κ

Front 25

Different ligands induce different what? What does this lead to?

Back 25

Different ligands induce different conformational changes in the receptors leading to divergent signaling pathways.

Front 26

In the brain stem, what do opioid receptors influence?

Back 26

respiration, cough, nausea and vomiting, blood pressure, pupillary diameter (miosis), control of gastric secretion)

Front 27

In the medial thalamus, what do opioid receptors mediate?

Back 27

mediates deep pain that is poorly localized and emotionally influenced

Front 28

In the Spinal cord, what receptors are involved? What are they involved in? What does it lead to?

Back 28

receptors in the substantia gelatinosa are involved with the receipt and integration of incoming sensory information, leading to the attenuation of painful afferent stimuli

Front 29

What do opioid receptors in the hypothalamus affect?

Back 29

affect neuroendocrine secretion

Front 30

Where are the the greatest concentration of opiate receptors in the limbic system located? What do they influence?

Back 30

Ithe amygdala. Influence emotional behavior.

Front 31

In the Periphery what do opioids also bind to? What do they inhibit the release of?

Back 31

sensory nerve fibers and their terms. Inhibit Ca2+ dependent release of excitatory proinflammatory substances (e.g. substance P) from these nerve endings.

Front 32

Morphine and clinically used opioid agonists exert what? What do they affect and what do they alter?

Back 32

Exert clinical and adverse effects via μ opioid receptors
Affect mood and rewarding behavior (euphoria)
Alter respiratory, cardiovascular, GI and neuroendocrine function

Front 33

Δ opioid receptor agonists are potent what?

Back 33

analgesics in animal models

Front 34

What do K receptors produce? What kind of effects do they produce?

Back 34

agonists produce analgesia mediated primarily at spinal sites (animal models)

Produce dysphoria and psychotic effects

Front 35

What are strong agonist opioid analgesics? What are moderate agonists?

Back 35

Alfentanil, Fentanyl, Heroin, Meperidine, Methadone ,Morphine, Oxycodone, Remifentanil, Sufentanil

Codeine, Propoxyphene

Front 36

analgesia of morphine and related opioid agonists occurs without what?

Back 36

Pain relief occurs w/o loss in consciousness

Front 37

Analgesia of morphine and related opioid agonists raises pain threshold at what level?

Back 37

at the level of the spinal cord and alter brain’s perception of pain.

Front 38

When therapeutic Rx of morphine and related opioid agonistsis given to normal, pain-free individual what happens?

Back 38

→ unpleasant experience
Nausea, vomiting, drowsiness, difficulty in mentation, apathy. With ↑ dose, toxic effects including respiratory depression may become pronounced.

Front 39

Neural systems that mediate opioid reinforcement are distinct from those involved in what?

Back 39

involved in physical dependence and analgesia

Front 40

What is involved in involved in drug-induced reward? what does the data show?

Back 40

Dopaminergic pathways, particularly involving the nucleus accumbens,

Data show interaction between opioids and dopamine in mediating opioid-induced reward.

Front 41

Morphine and related agonists cause what? how is this done? Where does this occur?

Back 41

respiratory depression by ↓sensitivity of brainstem respiratory center neurons to CO2.
Occurs at therapeutic Rx and is dose-dependent.

Front 42

What is the most common cause of death w/acute opioid overdose?

Back 42

Respiratory depression

Front 43

In Miosis Pinpoint pupil results from what?

Back 43

stimulating μ and κ receptors

Front 44

In Miosis, what does morphine excite?
What does this result in the increase of?

Back 44

excites the Edinger-Westphal nucleus of the oculomotor nerve → ↑ parasympathetic stimulation to the eye

Front 45

morphine and related opioid agonists have what kind of effect in Depression of cough reflex?

Back 45

direct effect on a cough center in the medulla

Front 46

morphine and related opioid agonists have what kind stimulation during Emesis? What does it cause?

Back 46

direct stimulation of the chemoreceptor trigger zone in the area postrema of the medulla that causes vomiting.

Front 47

morphine and related opioid agonists decrease and increase what in GI tract? What does this result in?

Back 47

μ agonists ↓ acid secretion in stomach, ↓ gastric motility, ↓ motility and ↑ tone of SI circular smooth muscle. Results in constipation w/little tolerance. Can also increase biliary tract pressure due to contraction of gallbladder and constriction of biliary sphincter.

Front 48

morphine and related opioid agonists have what kind of cardiovascular affect? What does respiratory depression?

Back 48

morphine causes hypotension and bradycardia.
Respiratory depression results in dilation of cerebral vessels and ↑ CSF pressure

Front 49

What does morphine stimulate? Contradicted in what patients?

Back 49

morphine stimulates histamine release form mast cells.

Asthmatics

Front 50

morphine and related opioid agonists have what kind of effects in the endocrine?

Back 50

many effects including ↓ GNRH, corticotrophin releasing hormone, LH, FSH, adrenocorticotropic hormone, β-endorphin, testosterone and cortisol. ↑ GH, prolactin and antidiuretic hormone (urinary retention)

Front 51

What can morphine prolong? How?

Back 51

morphine may prolong 2nd stage of labor by transiently decreasing the strength, duration and frequency of uterine contractions

Front 52

How does Morphine help treat diarrhea?

Back 52

↓ motility and ↑tone of intestinal smooth muscle (can cause constipation)

Front 53

How does morphine help with acute pulmonary edema?

Back 53

IV morphine dramatically relieves dyspnea caused by pulmonary edema associated w/left ventricular failure presumably via vasodilation

Front 54

Absorption of morphine from the GI tract is____? What kind of metabolism does it go through? What kind of dosing is there?

Back 54

Absorption from GI tract is erratic; high first pass hepatic metabolism → IV, sc or IM dosing optimal

Front 55

Mepiridine is agonist to what receptors? What does it tx?

Back 55

Agonist to μ and κ.
Rx for acute, severe pain

Front 56

Methadone is what kind of opioid? What is its potency compared to Morphine? Induces less what? Has a longer what?

Back 56

synthetic, orally active opioid (μ agonist) equal in potency (analgesia) to morphine but induces less euphoria and has longer duration of action.

Front 57

Fentanyl: chemically related to what? Describe its potency compared to morphine? What is it used as?

Back 57

related to meperidine, 100X more potent than morphine (analgesia) and is used in anesthesia.

Front 58

Describe fentayl lipophilicy? What kind of onset does it have? What kind of duration on action does it have?How is fentanyl administered?

Back 58

Highly lipophilic; rapid onset and short duration of action (15-30 min)
IV, epidural, intrathecal injection

Front 59

When is an example that fentayl is used?

Back 59

Cardiac surgery → minimal effect on myocardial contractility
Oral transmucosal (cancer patients w/breakthrough pain) and transdermal patch are available

Front 60

What substrate is fentanyl have?

Back 60

CYP3A4 substrate (DDI)

Front 61

What is oxycodone?

Back 61

Oxycodone: Orally-active semi synthetic derivative of morphine.

Front 62

What is the most widely used opioid

Back 62

codeine

Front 63

What is codeine?

Back 63

moderately potent agonist from opium poppy.

Front 64

What are three reasons why codeine is the most used opioid?
What is it commonly formulated with?

Back 64

Less euphoria than morphine, lower potential for abuse, rarely produces dependence (at commonly used doses)
Commonly formulated with aspirin or acetaminophen

Front 65

Heroin does what to morphine? Describe its potency compared to morphine?
It leads to the increase of what 3 things compared to morphine?

Back 65

Deacetylation of morphine → 3X↑potency vs. morphine.
↑ lipid solubility ↑ access to BBB ↑ euphoria vs. morphine.

Front 66

What does Mixed agonist-antagonist equal?

Back 66

Mixed agonist-antagonist = drugs that activate one receptor and block another.

Front 67

How do Mixed agonist-antagonist differ from mu-receptor agonists?

Back 67

1.Effects depend upon previous exposure to opioids
2.naïve patients→ agonist/analgesia
3.Opioid dependent patients → agonist/antagonist drugs may cause withdrawal symptoms due to antagonist activity

Front 68

what was the goal of development of Opioid Agonists/Antagonists and Partial Agonists

Back 68

< respiratory depression and addictive potential.
Clinical use limited by side effects and limited analgesic efficacy.

Front 69

Nalbuphine and butorphanol are what kindof receptors? What do they exert? What do they act as to do this?

Back 69

competitive μ-receptor antagonists but exert analgesic actions by acting as agonists at κ receptors.

Front 70

Buprenorphine is a ____ _____ at μ receptors?

Back 70

Buprenorphine is a partial agonist at μ receptors.

Front 71

when is Buprenorphine used?
What are advantages of it compared to methadone?

Back 71

Used in opiate detox → less severe and shorter duration withdrawal symptoms vs. methadone

Front 72

Pentazocine is what kind of opioid agonist/antagonist?
What can it cause?
Used for the tx of what?

Back 72

Pentazocine is κ receptor agonist and weak antagonist at μ and δ

Can cause dysphoria and psychosis-like side effects
Used for treatment of moderate pain

Front 73

What do opioid antagonists bind with to opioid receptors?

Back 73

Opioid antagonists bind with high affinity to opioid receptors

Front 74

what 3 components do the Pharmacological effect of opioid antagonists depend upon:

Back 74

Whether or not an opioid agonist has been administered
The pharmacological profile of that opioid
The degree to which physical dependence upon the opioid has developed

Front 75

During shock or stress, what are activated?

Back 75

During shock or stress, endogenous opioid systems are activated and antagonists may have visible consequences

Front 76

Naloxone and naltrexone are what kind of receptors?

Back 76

competitive opioid receptor antagonists

Front 77

What do Opioid antagonists have use in treatment of?

Back 77

opioid toxicity
(Rapidly reverse respiratory depression)

Front 78

Naltrexone is FDA approved for treatment of what?
Naloxone is used to treat what?

Back 78

alcoholism
opioid overdose

Front 79

What can naloxone decrease when used in a pregnant mother?

Back 79

Can be used to ↓ neonatal respiratory depression 2° to opioid consumption by the mother

Front 80

what are three signs of Acute Opioid Toxicity

Back 80

Coma
Pinpoint pupils
Depressed respiration

Front 81

What can antagonists be used to help diagnose?

Back 81

help diagnose physical dependence on opioids