Lec. 1: Narcotic Analgesics Flashcards
1
Q
Name the three opioid antagonists.
A
Naloxone, Naltrexone, Nalmefene
2
Q
Name the seven strong opioid agonists.
A
Fentanyl, Hydromorphone, Meperidine, Morphine, Methadone, Buprenorphine, Oxymorphone.
3
Q
What opioid drug is considered the gold standard?
A
Morphine
4
Q
Name the three opioid antitussives.
A
Codeine, dextromethorphan, levopropoxyphene.
5
Q
Name the two moderate opioid agonists.
A
Codeine and oxycodone.
6
Q
Name the two weak agonists.
A
Propoxyphene and tramadol.
7
Q
Name the three mixed agonists/antagonists.
A
Pentazocine, Nalbuphine, and Butorphanol.
8
Q
The structure of the opioid determines what five factors?
A
- Water or lipid solubility
- Absorption in and outside of CNS
- Onset of action/duration of action
- Affinity for receptors
- Side effects
9
Q
Opium resin contains what three major alkaloids?
A
Morphine, codeine, and thebaine.
10
Q
What happens if you change the two R groups on morphine?
A
Becomes an opioid antagonist.
11
Q
Name the four endogenous opioid peptides.
A
Endorphins, Enkephalins, Dynorphins, and Endomorphins.
12
Q
Name the three main opioid receptors.
A
Mu (µ), kappa (κ), and delta (δ).
13
Q
Morphine and other pure agonists have the greatest affinity for ? receptors and lower affinity for ? and ? receptors.
A
- Mu
2. Kappa and delta
14
Q
Beta-endorphin is released from what precursor protein?
A
(POMC) Propiomelanocortin
15
Q
Enkephalins are made up of what two pentapeptides?
A
Met-enkephalin and Leu-enkephalin
16
Q
Name the sequence of events caused by binding of an opioid to the receptor.
A
- Decreased cAMP
- Opening of K+ channels (hyper-polarization)
- Closing of Ca++ channels (inhibits release of neurotransmitters)
17
Q
Dynorphin A (1-8) and dynorphin B (1-13) are produced from what?
A
Prodynorphin
18
Q
Are the endogenous opioid peptides responsible for excitatory or inhibitory signals?
A
Inhibitory signals
19
Q
Where are the opioid receptors (kappa, delta, mu) located?
A
At the 7-transmembrane domain-containing channels; coupled to heater-trimeric G-proteins.
20
Q
What is ORL-1 and what does it stand for?
A
It is an orphan receptor that stands for Opioid receptor like-1
21
Q
What are the three sites where opioid receptors can be found?
A
Peri-aqueductal gray, rostral-ventromedial medulla, and the dorsal horn of the spinal cord.
22
Q
What two substances block pain transmission?
A
Norepinephrine and 5HT (serotonin)
23
Q
What two pain stimuli activate the nociceptive neurons (ascending pathway)?
A
Prostaglandins and Substance P
24
Q
Name the fast (myelinated) and slow (not myelinated) fibers involved in pain transmission.
A
Fast: A-delta
Slow: C
25
Which pain pathway is INDIRECT?
Descending pain inhibition pathway
26
Briefly describe the mechanism behind the descending pain inhibition pathway.
The brain sends neurotransmitters to the spinal cord and nerves the block the "pain transmitting gates."
27
Where do NE and 5HT perform their action?
Spinal Cord
28
Pain in the orofacial region is transmitted by what four cranial nerves?
5th (trigeminal), 7th (facial), 9th (glossopharyngeal), and 10th (vagus)
29
Where is the relay site for the trigeminal nerve?
The nucleus caudalis, located in the medulla.
30
Cell damage to the orofacial region releases what four substances?
PG, substance P, bradykinin, serotonin --these activate the second neuron!
31
The endogenous pain system works at the peripheral, spinal, and ? sites?
Supra-spinal
32
Opioid receptors are present in the mainly in the ?. They are also present in the autonomic nervous system, peripheral nerves, and the GI tract where they mediate effects on ?, ?, and ?.
1. CNS
2. Heart rate
3. Nociception
4. GI motility
33
Where in the cerebral cortex are mu receptors found?
Striatum, hippocampus, dorsal horn, and midbrain
34
Where in the cerebral cortex are kappa receptors found?
Striatum, hippocampus, dorsal horn, and midbrain
35
Where in the cerebral cortex are delta receptors found?
Striatum, hippocampus, dorsal horn, and amygdala.
36
What pharmacologic function is seen at each opioid receptor?
Analgesia
37
What pharmacologic functions are associated with mu receptors?
Analgesia, sedation, miosis, euphoria, constipation, respiratory depression, and pruritus (itching)
38
What pharmacologic functions are associated with kappa receptors?
Analgeisa, sedation, miosis, dysphoria, micturition, diuresis, and hallucinations.
39
What pharmcologic functions are associated with delta receptors?
Analgesia, emotion/reward, and seizures (?)
40
***What are the prototypic ligands for mu receptors?
Morphine, methadone, and endorphin
41
***What are the prototypic ligands for kappa receptors?
Dynorphin A and Ethylketocyclazocine
42
***What are the prototypic ligands for delta receptors?
Enkephalins and Deltorphin II
43
Morphine acts as a agonist on the ? receptor and a weak agonist on the ? receptor.
1. Mu
| 2. Kappa
44
Buprenorphine acts as a ? on the mu receptor, a ? on the kappa receptor, and a ? on the delta receptor.
1. Partial agonist
2. Antagonist
3. Antagonist
45
Pentazocine acts as a ? on the mu receptor and a ? on the kappa receptor.
1. Weak antagonist
| 2. Agonist
46
Nalbuphine acts as a ? on the mu receptor and a ? on the kappa receptor.
1. Antagonist
| 2. Agonist
47
Naloxone acts on all receptors as a ?.
Antagonist
48
Name the two natural opioid drugs.
1. Morphine
| 2. Codeine
49
What is the potency of morphine and codeine.
Morphine: 1.0
Codeine: 0.5
50
Name the 6 semi-synthetic opioid drugs.
1. Diacetylmorphine
2. Hydrocodone
3. Oxycodone
4. Hydromorphone
5. Oxymorphone
6. Buprenorphine
51
Name the four synthetic opioid drugs.
1. Meperidine
2. Fentanyl
3. Methadone
4. Tramadol
52
What is the potency of diacetylmorphine?
2-4
53
What is the potency of hydrocodone?
0.6
54
What is the potency of oxycodone?
2.0
55
What is the potency of hydromorphone?
7-11
56
What is the potency of oxymorphone?
7.0
57
What is the potency of buprenorphine?
40
58
What is the potency of meperidine?
0.1
59
What is the potency of fentanyl?
50-100
60
What is the potency of methadone?
7.5
61
What is the potency of tramadol?
0.5-1
62
Rate the potency of morphine from most to least given: orally, IV/IM, or intra-thecally.
1. Intra-thecal
2. IV or IM
3. Oral
63
Morphine is converted to what two substances and what are their percentages?
55% Morphine-3-glucouronide
| 10 % Morphine-6-glucouronide
64
Which is more potent, morphine-3-glucuronide or morphine-6-glucoruonide?
Morphine-6-glucouronide is twice as potent analgesic as morphine.
65
T or F. The BBB keeps most morphine out.
True
66
Opioids are contraindicated with what?
Mono-amine oxidase inhibitor antidepressants
67
CNS depression is enhanced by morphine and what three types of drugs?
Sedative-hypnotics, antipsychotic drugs, and antidepressants
68
Morphine and sedative hypnotics may interfere with what?
Opioid-induced analgesia
69
Morphine and tricyclic antidepressants and antihistamines will have what effect on analgesia?
Enhance the analgesic effect.
70
What is an example of a sedative-hypnotic?
Benxodiazepines
71
What is an example of an opioid that is contraindicated with MAOI antidepressants?
Meperidine
72
What are the three effects of morphine on the CNS?
1. Analgesia
2. Euphoria
3. Stupor or torpor
73
What is euphoria?
Relief from pain and a feeling of well.
74
What is stupor or torpor?
Lethargy, apathy, dulled mental function
75
Morphines analgesic effect on the CNS peaks at ? minutes and lasts ?-? hours.
1. 60 minutes
| 2. 4-5 hours
76
What is the effect of morphine on the respiratory center depression?
Causes respiratory center to become less sensitive to CO2.
77
T or F. Morphine is recommended in patients with asthma, emphysema, pulmonary edema, head injury, or coma?
False. Morphine causes respiratory center depression and should be avoided in these patients.
78
What drug is likely being abused if the patient experiences hypercapnea and what are their symptoms?
Morphine; Patient will have dilated cerebral arteries, and elevated intra-cranial pressure.
79
What is morphines antitussive effect?
Morphine depresses the cough reflex center.
80
What is morphines effect on the vomiting center?
Morphine stimulates chemoreceptor trigger zone, and may cause nausea and vomiting
81
What is morphines effect on the eyes?
Causes miosis - narrowing of the pupils. Note: tolerance of miosis does not develop with use!
82
What is morphines effect on the GI tract? (5 things)
1. Decreased gastric motility
2. Decreased gastric secretion
3. Decreased intestinal secretion
4. Increased tone of intestinal smooth muscle
5. Decreased peristaltic contractions of intestine
83
What are the effects of morphine on the cardiovascular system?
Causes vasodilation and orthostatic hypertension.
84
When taking morphine, cerebral vessels can dilate via ? and peripheral vessels can dilate via ?.
1. Hypercapnea
| 2. Mu receptors
85
What is morphines two effects on the skin?
1. Facial and neck flushing
| 2. Itching and sweating
86
What is morphines three effect on the urinary tract?
1. Urinary retention
2. Increased tone of bladder sphincter
3. Increased detrussor muscle tone leading to increased urgency
87
What is morphines effect on the uterus and how is this complicated in pregnancy?
Decreased uterine contractions, which may cause distress to the infant during L and D.
88
What is morphines effect on the neuroendocrine system?
Decreased GnRH and CRF release (lower LH, FSH, and ACTH).
Decreased cortisol and testosterone
Increased prolactin secretion
89
What drug is used in cough suppression, has 1/10th the potency of oral morphine, and is metabolized in the liver?
Codeine
90
What drug is 1/2 the potency of morphine, has good oral bioavailability (70%), and is converted to hydromorphone?
Hydrocodone
91
What three drugs are manufactured in combination with acetaminophen?
Codeine, hydrocodone, and oxycodone
92
What drug is used for acute pain, has 7-10X potency at Mu receptor sites, high water solubility, and acts very quickly?
Hydromorphone
93
What drug has 2X potency of M, has high abuse potential, active ONLY orally, bioavailability of 80%, and has multiple receptor sites?
Oxycodone
94
What drug is 7X more potent that M, used to treat chronic pain, acts quickly, and has extended action.
Oxymorphone
95
What drug is 1/10th potency of M, has anti-spasmodic activity, does not prolong labor but may cause respiratory depression in neonates, and was the first fully synthetic drug?
Meperidine
96
What drug is used in opiate dependence treatment?
Buprenorphine
97
What drug has high lipid solubility, crosses the BBB rapidly, 25-50X more potent than M, long half-life, and has high lipid solubility.
Buprenorphine
98
Suboxone is a mixture of what two drugs that is used to deter IV abuse?
Buprenorphine and naloxone in a 4:1 ratio
99
What drug is the most potent opioid?
Fentanyl
100
What drug is used to treat sever pain relief, fully synthetic, 100X more potent than M, highly lipophilic, crosses BBB fast, and is used in trans-dermal skin patches?
Fentanyl
101
What drug has high tissue binding, fully synthetic, is used to minimize withdrawal symptoms, and is a one a day pill.
Methadone
102
What opioid is considered atypical and inhibits the reuptake of NE and 5HT?
Tramadol
103
What drug is a chemical analog of codeine, has high oral bioavailability, is 0.1-0.5X potency of M, and has a less liability for respiratory depression and constipation?
Tramadol
104
What two drug combinations are best for mild to moderate pain relief?
1. Propoxyphene + Acetaminophen
| 2. Codeine + Aspirin
105
What three drug combinations are best for moderate to moderately severe pain?
1. Hydrocodone + Acetaminophen
2. Oxycodone + Aspirin
3. Dihydrocodone + Acetaminophen + caffeine
106
What two drug combinations are best for pain of bone metastasis?
1. Opioids + NSAIDS
| 2. Pamidronate, Calcitonin
107
What three drug combinations are best for neuropathic pain?
1. Tricyclic antidepressants
2. Anti-convulsants
3. Anti=arrhythmic drugs
108
What drug combinations are best for soft tissue infiltration, nerve compression?
Corticosteroids
109
What opioid receptor antagonist has a short duration of action, used for the overdose of opioids, has high affinity for mu, paraenteral administration only, and has no effect if given alone?
Naloxone
110
What opioid receptor antagonist has a longer duration of action and parenteral administration only?
Nalmefene
111
What opioid receptor antagonist has a longer duration of action, used for treatment of opioid and alcohol detox, and is given as an oral administration only?
Naltrexone
112
What is paraenteral administration?
Taken into the body in a manner other than through the digestive canal.
113
When using the opioid receptor antagonist, what system is being activated?
The dopamine reward system
114
Drugs can be categorized based on what four categories?
1. Route of Admin
2. Duration of action
3. Elimination half-life
4. Active Metabolite
115
What patient is at the greater risk for drug-drug interactions and NSAID toxicities?
Elderly
116
T or F. It is easier to prevent pain than it is to treat pain.
True
117
What is the pathway in prescribing pain medicine?
Non-opioid + adjuvant --> weak opioid+non-opioid+adjuvant --> strong opioid+non-opioid+adjuvant
118
Tolerance can develop to what three effects of opioids?
1. Analgesia
2. Sedation
3. Respiratory depression
119
Tolerance can not develop to what three opioid effects?
1. Miotic effects
2. Convulsant effects
3. Constipation effects
120
Define a physical dependence of opioids.
Body requires their continual presence to function normally.
121
Define a psychological dependence of opioids.
Euphora and indifference to stimuli and sedation
122
How soon can opioid withdrawal syndrome be observed and what are some of its symptoms?
7-10 days. Exhibits flu-like symptoms, gooseflesh, tremor, muscle twitches, cramps, diarrhea, tachycardia, and hyperventilation.
123
T or F. Physical dependence and addictive behaviors are common in short-term use of opioids.
False. Physical dependence can develop with long term use but is RARE in short term use of opioids.
124
T or F. Children are no more likely to become physically dependent or addicted to opioid than adults.
True
125
What types of opioids are mainly used for analgesia in dentistry? Name four.
Orally administered opioids.
1. Codeine
2. Hydrocodone
3. Oxycodone
4. Pentazocine
126
What three parenterally administered drugs are most common in dentistry?
1. Morphine
2. Fentanyl
3. Meperidine
127
In dentistry, what are the two preferred analgesics for mild pain?
Ibuprofen and aspirin
128
T or F. Acetaminophen does have anti-inflammatory properties.
False. It does not have anti-inflammatory properties.
129
What combination can cause severe and immediate excitation, rigidity, hypertension, and occasionally death?
Meperidine and MAOI drugs
130
Co-administratoin of ? and opioids produces summation of effects.
CNS depressants
131
Give four examples of CNS depressants.
1. Anti-psychotic drugs
2. Tricyclic anti-depressants
3. MAOIs
4. Local anesthetics
