Opioids Agonists (Exam II) Flashcards
1
Q
What are opioids effects on the CO₂ medullary center?
A
- Opioids inhibit the CO₂ medullary center.
2
Q
Differentiate opioids from narcotics.
A
- Opioids = all exogenous substances that bind to endogenous opioid receptors.
- Narcotic = any substance that can produce dependence (stupor)
3
Q
What two types of opioid chemical structures are there?
A
- Phenanthrenes
- Benzylisoquinolines
4
Q
What types of drugs are Phenanthrenes?
What types of drugs are benzylisoquinolines?
A
- Phenanthrenes: Morphine & codeine
- Benzylisoquinoline: Papaverine
5
Q
What is papaverine mostly used for?
A
Treating intra-arterial barbiturate administration (dilates the highly constricted artery).
6
Q
What portions of the brain are the source of descending inhibitory signals?
A
- Thalamus
- PAG
- Locus Coeruleus
7
Q
What endogenous substances have the same effect as opioids?
A
Endorphins, Enkephalins, and Dynorphines.
8
Q
Presynaptic inhibition of what neurotransmitters occurs with opioid administration?
A
- ACh
- Dopamine
- NE
- Substance P
9
Q
How do opioids modulate pain at the cellular level?
A
- ↑ pK⁺ (hyperpolarization)
- Ca⁺⁺ channel inactivation
10
Q
Where are opioid receptors located in the brain?
A
- PAG
- Locus Ceruleus
- RVM (rostral ventral medulla)
- Hypothalamus
11
Q
Where is the primary site of opioid receptors in the spinal cord?
A
Substantia gelatinosa (aka Laminae 2)
12
Q
Where is/are opioid receptors found outside the CNS?
A
- Sensory neurons & immune cells
13
Q
What are the four (most important) types of opioid receptors?
A
- Μu1 (μ₁)
- Μu2 (μ₂)
- Κappa (κ)
- Delta (δ)
14
Q
Which opioid receptor(s) is/are responsible for respiratory depression & physical dependence?
A
- Μu2 and δ
15
Q
Which receptors are responsible for constipation?
A
- Μu2 primarily
- δ (less)
16
Q
Which receptors can cause urinary retention?
Are there any receptors that cause diuresis when bound?
A
- Retention: Μu1 and δ
- Diuresis: κ
17
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.
18
Q
What opioid receptors have low abuse potential when bound?
A
Μu1 and κ
19
Q
Which opioid receptor is responsible for euphoria, bradycardia, hypothermia, and miosis when bound?
A
Mu1
20
Q
What agonists bind to the four opioid receptors?
A
- Mu1 & Mu2 = endorphins, morphine, synthetics.
- κ = dynorphins.
- δ = enkephalins.
21
Q
Describe the adverse side effects of opioids on the cardiovascular system.
A
- ↓BP from ↓SNS tone
- ↓HR + histamine release = ↓BP
22
Q
What possible cardiovascular benefits do opioids provide?
A
- Myocardial ischemia protection (won’t cause myocardial depression)
23
Q
What are the respiratory effects of opioids?
What would symptoms of overdose be?
A
- Depressed CNS response to CO₂ causing a right shift of PaCO₂ (↑)
- Overdose = apnea, miosis, ↓RR, coma.
24
Q
What drug would treat opioid ventilatory depression but not reverse analgesia?
How?
A
- Physostigmine would by increasing CNS ACh levels.
25
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
26
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
27
Why should caution be used when administering opioids to head trauma patients?
- Opioids ↓CBF and possibly ICP
28
What musculoskeletal abnormality occurs with opioid administration?
What makes this condition worse?
How is it treated?
- Skeletal chest wall and abdominal muscle rigidity.
- Mechanical ventilation
- Muscle relaxants and/or naloxone
29
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*
30
What drugs should be used for ERCP cases?
- Non-opioids (multimodal approach w/ NSAIDs, gabapentin, etc.)
31
How are opioid-induced sphincter of Oddi spasm's treated?
- Naloxone
- **Glucagon** (2mg IV given incrementally) and causes no opioid antagonism.
32
How long does it take (generally) to develop tolerance to opioids?
What causes tolerance?
- 2-3 weeks
- Downregulation
33
What is the dosage of morphine?
When does it peak?
How long does it last?
- 1 - 10 mg IV
- Peak: 15 - 30 minutes
- Duration: 4 hours
34
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**.
35
What would occur with morphine overdose in a renal failure patient?
- Prolonged ventilatory depression.
36
What receptors does meperidine agonize?
- μ and κ receptors
- α2 receptors as well
37
What are the analogues of meperidine?
What other drugs does meperidine have a similar organic structure to?
- Fentanyl & it's derivatives
- Lidocaine & Atropine
38
How potent is Meperidine?
How long does it last?
- 10% as potent as morphine
- Duration: 2-4 hours
39
What is the primary indication for meperidine?
What dose is used?
- Post-operative shivering
- 12.5mg IV
40
When should meperidine not be used?
- Bronchoscopies (promotes coughing)
41
How potent is fentanyl?
- 75 - 125 x morphine.
42
What is the blood-brain equilibration of fentanyl?
What does this mean?
- 6.4 minutes
- Potent with rapid onset and ↑ lipid solubility.
43
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.
44
Where is fentanyl metabolized?
What is its principal metabolite?
- Liver via CYP3A
- Norfentanil
45
How does fentanyl dosing change for the elderly or liver patients?
**No change in elderly or cirrhotic patients.**
46
Describe what the graph below is showing.
Fentanyl has the greatest context-sensitive half-time of any of the fentanyl derivatives.
47
What is the analgesia dosage of fentanyl?
Induction dose?
- Analgesia: 1 - 2 μg/kg IV
- Induction: 1.5 - 3 μg/kg IV
48
1mg of PO fentanyl = ____ mg of IV morphine
5
49
What is the intrathecal dosage of fentanyl?
25 mcg
50
What is the adult oral dose of fentanyl?
Pediatric?
- Adult: 5 - 20 mcg/kg
- Peds: 15 - 20 mcg/kg
51
What is the transdermal dose of fentanyl?
- 75 - 100 μg (18 hours steady state)
52
What cardiovascular side effects should be known about fentanyl?
What CNS side effects should be known?
- ↓BP & ↓CO
- Can cause seizures & modestly increase ICP.
53
How much more potent is sufentanil than fentanyl?
- 5-12 times more potent.
54
How much of sufentanil is subject to first pass effects?
- 60% lung first-pass
55
How much of sufentanil is protein bound? What protein is it bound to?
**92.5% α-1 acid glycoprotein bound.**
56
What is the analgesia dose of sufentanil?
- Analgesia: 0.1 - 0.4 μg/kg IV
57
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*.
58
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)
59
What is the alfentanil induction dose?
What about laryngoscopy dose?
What about maintenance?
- Induction: 150 - 300 mcg /kg IV
- Laryngoscopy: 15 - 30 mcg/kg IV
- Maintenance: 25 - 150 mcg/kg/hr with inhaled anesthetics
60
What drug can cause acute dystonia when given to a Parkinson's patient?
Alfentanil
61
What receptor affinity does remifentanil have?
How potent is it?
μ opioid agonist that is equipotent to fentanyl
62
What is remifentanil's structure and why is it important?
**Ester Structure** = hydrolyzed by plasma & tissue esterases.
- Rapid onset & recovery
- Very titratable
- No accumulation
63
What drug was said to be a great choice for carotid procedures in lecture?
Remifentanil
64
Answer the following characteristics of remifentanil below:
Clearance:
Peak effect:
- Clearance: 3-L/min (8x faster than alfentanil)
- Peak: 1.1 min (fastest fentanyl derivative)
65
What is the induction dose of remifentanil?
- 0.5 - 1 mcg/kg IV over 1 min
66
What is the maintenance dosing of remifentanil?
- 0.005 - 2 μg/kg/min IV
67
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.**
68
Why is codeine not given IV?
- Induced hypotension via histamine release.
69
What is the dose of codeine for cough suppression?
Analgesia?
- Cough: 15mg
- Analgesia: 60mg (= about 5mg morphine)
70
Which opioid is most cleared?
- Remifentanil (3-4L/min)
71
Which opioid(s) is/are the most protein bound?
Which is the least?
- Sufentanil, alfentanil, & remifentanil
- Least = morphine
72
Which opioid is the highest percent non-ionized?
- Alfentanil
73
Morphine tends to relieve _____ type pain more than _____ type pain.
Dull: sharp
