Opioids Agonists (Exam II) Flashcards
(125 cards)
1
Q
What are opioids effects on the CO₂ medullary center?
A
- Opioids inhibit the CO₂ medullary center.
2
Q
Three opiates from Papaver somniferum (Opion)
A
Morphine - 1803
Codeine - 1832
Papaverine - 1848
3
Q
Differentiate opioids from narcotics.
A
- Opioids = all exogenous substances that bind to endogenous opioid receptors.
- Narcotic = any substance that can produce physical dependence (stupor)
4
Q
What two types of opioid chemical structures are there?
A
- Phenanthrenes
- Benzylisoquinolines
5
Q
Which drugs are Phenanthrenes?
Which drugs are benzylisoquinolines?
A
- Phenanthrenes: Morphine & codeine, and Thebaine
- Benzylisoquinoline: Papaverine and Noscapine
6
Q
What is papaverine mostly used for?
A
Treating intra-arterial barbiturate administration (dilates the highly constricted artery).
7
Q
What portions of the brain are the source of descending inhibitory signals?
A
- Hypothalamus
- PAG
- RVM
- Locus Coeruleus
8
Q
What endogenous substances have the same effect as or use the same receptors as opioids?
A
Endorphins, Enkephalins, and Dynorphines.
9
Q
Presynaptic inhibition of what neurotransmitters occurs with opioid administration?
A
- ACh
- Dopamine
- NE
- Substance P
10
Q
How do opioids modulate pain at the cellular level?
A
- ↑ pK⁺ (hyperpolarization)
- Ca⁺⁺ channel inactivation
11
Q
Where are opioid receptors located in the brain?
A
- PAG
- Locus Ceruleus
- RVM (rostral ventral medulla)
- Hypothalamus
12
Q
Where is the primary site of opioid receptors in the spinal cord?
A
Substantia gelatinosa (aka Laminae 2)
13
Q
Where is/are opioid receptors found outside the CNS?
A
- Sensory neurons & immune cells
14
Q
What are the four (most important) types of opioid receptors?
A
- Μu1 (μ₁)
- Μu2 (μ₂)
- Κappa (κ)
- Delta (δ)
15
Q
Which opioid receptor(s) is/are responsible for respiratory depression & physical dependence?
A
- Μu2 and δ (delta)
16
Q
Which receptors are responsible for constipation?
A
- Μu2 primarily
- δ (less)
17
Q
Which receptors can cause urinary retention?
Are there any receptors that cause diuresis when bound?
A
- Retention: Μu1 and δ
- Diuresis: κappa
18
Q
All opioid receptors induce analgesia at both the brain the spinal cord. T/F?
A
- False. Μu2 receptors only cause at analgesia at the spinal cord level.
19
Q
What opioid receptors have low abuse potential when bound?
A
Μu1 and κ
20
Q
Which opioid receptor is responsible for euphoria, bradycardia, hypothermia when bound?
A
Mu1
21
Q
An agonist binding to Mu1 and Kappa receptors result in
A
Low abuse potential
Miosis
22
Q
What agonists bind to the four opioid receptors?
A
- Mu1 & Mu2 = endorphins, morphine, synthetics opioids.
- κ = dynorphins.
- δ = enkephalins.
23
Q
What 3 meds are antagonists of all 4 major opioid receptors?
A
Naloxone
Naltrexone
Nalmefene
24
Q
What does this graph show?
A
That if you add nitrous or a benzodiazepine (diazepam) with an opioid like fentanyl –> depression in MAP and SVR
25
Describe the adverse side effects of opioids on the cardiovascular system.
- ↓BP from ↓SNS tone - orthostatic **hypotension** and syncope
- ↓HR or histamine release = ↓BP
26
What possible cardiovascular benefits do opioids provide?
- Myocardial ischemia protection (won't cause myocardial depression)
27
What are the respiratory effects of opioids?
What would symptoms of overdose be?
- Depressed CNS response to CO₂ causing a right shift of PaCO₂ (↑)
- Overdose = apnea, miosis, ↓RR, coma.
28
What drug would treat opioid ventilatory depression but **not** reverse analgesia?
How?
- **Physostigmine** would by increasing CNS ACh levels.
29
What is normal PaO₂?
What shift in PaO₂ would be seen with metabolic acidosis?
What shift in PaO₂ would be seen with general anesthesia?
- Normal PaO₂ is 80 mmHg
- Left shift
- Right shift
30
What would cause a leftward shift in PaO₂?
What would cause a rightward shift?
- Leftward: Metabolic acidosis (to breathe off all that CO₂)
- Rightward: sleep → opiates → anesthesia
31
What level of PaCO2 do we want to avoid?
PaCO2 of 60 (CO2 narcosis)
32
Why should caution be used when administering opioids to head trauma patients?
- Opioids ↓CBF and possibly ICP
Myoclonus (with large doses)
33
What musculoskeletal abnormality occurs with opioid administration?
What makes this condition worse or severe?
How is it treated?
- **Skeletal chest wall and abdominal muscle rigidity.**
- Mechanical ventilation
- Muscle relaxants and/or naloxone
34
What are sphincter of Oddi spasms?
Which drugs can cause this?
- Biliary smooth muscle spasm
- **Fentanyl** (99%), Morphine (53%), and Meperidine (61%).
*I think maybe all opioids can cause this but these are the primary culprits*
35
What drugs should be used for ERCP cases?
- Non-opioids (multimodal approach w/ NSAIDs, gabapentin, etc.)
| To avoid the Sphinctre of Oddi spasms
36
How are opioid-induced sphincter of Oddi spasm's treated?
- Naloxone (will differentiate between Oddi spasm or angina)
- **Glucagon** (2mg IV given incrementally, ,don't give all 2 mg at once) and causes no opioid antagonism.
37
Treatment of Oddi spasms per TWU reference guide
Glucagon 2 mg IV
Naloxone 40 mcg IV
Atropine 0.2 mg IV
NTG 50 mcg IV
38
How do opioids effect N/V?
They directly stimulate the Chemoreceptor trigger zone (CTZ)
- increases GI secretions and results in delayed emptying
39
Opioid side effects
GU:
Cutaneous:
Placenta:
GU: Urinary urgency
Cutaneous: histamine release --> flushed face, neck, upper chest
Placenta: Neonate depression, dependence (chronic)
40
How long does it take (generally) to develop tolerance to opioids?
What causes tolerance?
- 2-3 weeks
- Morphine: 25 days
- Downregulation
41
T/F: Cross tolerance can happen with all opioids.
True
42
Initial symptoms of opioid withdrawal: (5)
Yawning
diaphoresis
lacrimation
coryza
restlessness
43
opioid withdrawal symptoms after 72hrs:
72 hrs: ABD cramps, N/V, diarrhea
44
Which two drugs have the same **shortest** Onset, Peak intensity, and Duration of withdrawal symptoms?
Fentanyl
Meperidine
onset: 2-6 hrs
Peak intensity: 6-12 hrs
Duration: 4-5 days
45
Which two drugs have the same **medium** Onset, Peak intensity, and Duration of withdrawal symptoms?
Morphine
Heroine
onset: 6-18 hrs
Peak intensity: 36-72 hrs
Duration: 7-10 days
46
Which drug has the longest Onset, Peak intensity, and Duration of withdrawal symptoms?
Methadone
24-48 hrs
3-21 days
6-7 weeks
47
What is the dosage of morphine?
Duration?
- 1 - 10 mg IV Intraop
- 5 - 20 mg post op
- Duration: 4-5 hours
48
When does morphine peak?
- IV Peak: **15 - 30 minutes**
49
Onset of morphine
10-20 min
50
Morphine works on the ____ more then the other fibers
Unmyelinated C-fibers
51
Fentanyl
Intraop dose:
Onset:
Duration:
Intraop dose: 1.5-3 mcg/kg
Onset: 30-60 sec
Duration: 1-1.5 hrs
52
Sufentanil
Intraop dose:
Onset:
Duration:
Infusion dose:
Intraop dose: 0.3-1 mcg/kg
Onset: 30-60 sec
Duration: 1-1.5 hr
Infusion dose: 0.5-1 mcg/kg/hr
53
Remifentanil
Intraop dose:
Onset:
Duration:
Infusion:
Intraop dose: Load: 0.5 - 1 mcg/kg over 1 min
Onset: 30-60 sec
Duration: 6-8 min
Infusion: 0.125 - 0.375 mcg/kg/min
54
Meperidine
Post op dose:
Onset:
Duration:
Post op dose: 12.5 mg (shivering)
Onset: 5 - 15 min
Duration: 2 - 4 hrs
55
Naloxone
Intraop OR Post op dose:
Onset:
Duration:
Intraop OR Post op dose: 40 - 80 mcg
Onset: 1 - 5 min
Duration: 30 min
56
Hydromorphone
Intraop, Post op:
Onset:
Duration:
Intraop, Post op: 1 - 4 mg, 1.5 - 4 mg
Onset: 5 - 15 min
Duration: 2 - 4 hrs
57
What is the gold standard of opioids?
What god is it named after?
Morphine
Greek god of morpheus (1806)
58
Which opioid does **not** have first pass in the lungs?
morphine
59
How is morphine metabolized?
What is the active metabolite and its significance?
- Glucuronidation in the kidneys.
- **Morphine-6-glucuronide** = comprises only 5-25% of morphine metabolites but is an **active anaglesic causing late resp depression**.
60
What would occur with morphine overdose in a renal failure patient?
- Prolonged ventilatory depression
61
Morphine analgesic potencey and slower speed of offset with ____
women more than men
62
Elimination half-time is longer if morphine contains the ____
Take extra caution in giving this type to pts with _____
morphine-3-glucuronide
renal dysfunction
63
What receptors does meperidine agonize?
- μ and κ receptors
- α2 receptors as well
64
What are the analogues of meperidine?
What other drugs does meperidine have a similar organic structure to?
- Fentanyl & it's derivatives
- Lidocaine (tertiary amine, ester group, and lipophilic phenyl group) & Atropine
65
How potent is Meperidine?
How long does it last?
- 10% as potent as morphine
- Duration: 2-4 hours
66
What is the primary indication for meperidine?
What dose is used?
- Post-operative shivering
- 12.5 mg IV
67
When should meperidine not be used?
- Bronchoscopies (promotes coughing)
- diarrhea
- cough suppressant
68
meperidine metabolism is by
Hepatic 1st pass = 80%
90% hepatic --> normeperidine
69
T/F: Withdrawal symptoms develop more rapidly with morphine than with Meperidine.
False
70
Demerol is ____ protein bound
60%
Caution in the elderly
71
Meperidine elimination half time
3-5 hours
35 hours with renal failure pt
72
How potent is fentanyl?
- 75 - 125 x morphine.
73
What is the blood-brain equilibration of fentanyl?
What does this mean?
- 6.4 minutes
- Potent with rapid onset and ↑ lipid solubility.
74
What percent of fentanyl is subject to lung first-pass effect?
What does this mean?
- 75%
- Drug is taken up into lung tissue and possibly subjected to breakdown via pulmonary esterases.
75
Where is fentanyl metabolized?
What is its principal metabolite?
- Liver via CYP3A
- Norfentanyl
76
The following definition is known as ____
"Drug gets retained/accumulated and removed/cleared/metabolized at a specific location in the body that result in a reduced concentration of the active drug upon reaching its site of action"
First pass effect
77
How does fentanyl dosing change for the elderly or liver patients?
**No change in elderly or cirrhotic patients.**
| according to the book. He said gives less in elderly
78
Describe what the graph below is showing.
Fentanyl has the greatest context-sensitive half-time of any of the fentanyl derivatives.
79
What is the reason for the context-sensitive half time of fentanyl?
d/t the saturation of inactive tissue --> return to plasma replaces those metabolized
80
What is the analgesia dosage of fentanyl?
Induction dose?
- Analgesia: 1 - 2 μg/kg IV
- Induction: 1.5 - 3 μg/kg IV 5 min prior to induction
81
dose of fentanyl with inhaled anesthetics as an adjunct
2 - 20 µg/kg IV
82
Dose of fentanyl if ONLY giving it SOLO for surgical anesthesia:
50 - 150 mcg/kg IV
83
1mg of PO fentanyl = ____ mg of IV morphine
5
84
What is the intrathecal dosage of fentanyl?
25 mcg
85
What is the adult oral dose of fentanyl?
Pediatric?
- Adult: 5 - 20 mcg/kg
- Peds: 15 - 20 mcg/kg
86
What is the transdermal dose of fentanyl?
- 75 - 100 μg (18 hours steady state)
87
What cardiovascular side effects should be known about fentanyl?
What CNS side effects should be known?
- ↓BP & ↓CO
- Can cause seizures
- depressed carotid sinus baroreceptor reflex (graph)
- Can cause muscle or **chest wall rigidity** (Sufentanil does as well)
88
Does fentanyl increase or decrease ICP?
Increase by 6 - 9 mmHg
89
How much more potent is sufentanil than fentanyl?
- 5-12 times more potent.
90
How much of sufentanil is subject to first pass effects?
- 60% lung first-pass
91
How much of sufentanil is protein bound? What protein is it bound to?
Vd compared to fentanyl?
**92.5% α-1 acid glycoprotein bound.**
Smaller Vd than fentanyl
92
What is the analgesia dose of sufentanil?
- Analgesia: 0.1 - 0.4 μg/kg IV
93
What is the induction dose of sufentanil?
18.9 mcg/kg IV
*What an odd number*
*I don't think that this is right, a quick google search shows completely different numbers*.
94
What is the potency of alfentanil?
What is its onset?
- 20% as potent as fentanyl
- Onset: 1.4 min (faster than all derivatives except remifentanil)
95
Is Alfentanil more or less lipid soluble than fentanyl?
Less lipid solube
- 90% nonionized at normal pH --> lower lipid solubility
96
What is the alfentanil induction dose?
What about laryngoscopy dose?
What about maintenance?
- Induction alone: 150 - 300 mcg /kg IV
- with Laryngoscopy: 15 - 30 mcg/kg IV
- Maintenance: 25 - 150 mcg/kg/hr with inhaled anesthetics
97
What drug can cause acute dystonia when given to a Parkinson's patient?
Alfentanil
98
Which drug is 15 - 20 times as potent as Alfentanil?
Remifentanil
99
What receptor affinity does remifentanil have?
How potent is it?
μ opioid agonist that is equipotent to fentanyl
| with less context sensitve half time than fent
100
What is remifentanil's structure and why is it important?
**Ester Structure** = hydrolyzed by plasma & tissue esterases.
- Rapid onset & recovery (15 min offset)
- Very titratable
- No accumulation
101
What drug was said to be a great choice for carotid procedures in lecture? (carotid endarterectomy)
Remifentanil
102
Answer the following characteristics of remifentanil below:
Clearance:
Peak effect:
- Clearance: 3-L/min (8x faster than alfentanil)
- Peak or Blood/brain equilibration: 1.1 min (fastest fentanyl derivative) (Table 7.4)
103
What is the induction dose of remifentanil?
- 0.5 - 1 mcg/kg IV over 1 min
104
How is remifentanil dosed by weight?
using IBW
105
Remifentanil can cause ______ ______ of ventilation with propofol
**Synergistic depression**
106
What is the maintenance dosing of remifentanil?
- 0.005 - 2 μg/kg/min IV
107
Remifentanil side effects: (5)
- Seizure like activity
- N/V
- Depression of ventilation
- Decreased BP and HR
- Hyperalgesia d/t previous large dose opioid use and tolerance
108
How potent is hydromorphone?
What dose should be given?
What benefits does hydromorphone have over morphine?
- 5x more potent than morphine
- 0.5mg → 1-4 mg total
- **No histamine release & no active metabolites.**
109
Before stopping Remifentanil, give a
longer acting opioid
110
Why is codeine not given IV?
- Induced hypotension via histamine release.
111
What is the dose of codeine for cough suppression?
Analgesia?
- Cough: 15mg
- Analgesia: 60mg (= about 5mg morphine)
112
Which opioid is most cleared?
- Remifentanil (3-4L/min)
113
Which opioid(s) is/are the most protein bound?
Which is the least?
- Sufentanil, alfentanil, & remifentanil
- Least = morphine
114
Which opioid is the highest percent non-ionized at pH of 7.4?
- Alfentanil (89%)
115
Morphine tends to relieve _____ type pain more than _____ type pain.
Dull: sharp
116
Other opioid agonists: (6)
Oxymorphone
oxycodone
methadone - (used in opioid withdrawal and chronic pain)
Propoxyphene
Tramadol - Interacts with coumadin
Heroin
117
What is the most important factor to consider when determining onset of action? (table 7.4)
Effect-Site
(blood/brain equilibration time in min.)
118
which opioid has the largest partition coefficient?
Sufentanil (1,727)
119
which opioid has the smallest partition coefficient?
Morphine (1)
120
which opioid has the fastest clearance?
Remifentanil
121
which opioid has the slowest clearance?
Alfentanil (238 mL/min)
122
which opioid has the smallest volume of distribution?
Alfentanil (27L)
123
which opioid has the largest Vd?
Fentanyl (335L)
124
which opioid has the shortest context sensitive half-time?
Remifentanil
125
which opioid has the slowest Effect-site time?
Fentanyl (6.8 min or 6.4 min)
