*Opioids Agonists (Exam II) Flashcards
(129 cards)
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)
S7
3
Q
What two types of opioid chemical structures are there?
A
- Phenanthrenes
- Benzylisoquinolines
S8
4
Q
What types of drugs are Phenanthrenes?
A
Morphine & codeine
S8
5
Q
What types of drugs are Benzylisoquinolines?
A
Papaverine
S8
6
Q
What is Papaverine mostly used for?
A
Treating intra-arterial barbiturate administration
(dilates the highly constricted artery).
S8
7
Q
What portions of the brain are the source of Descending Inhibitory Signals?
A
- Thalamus
- PAG
- Locus Coeruleus
S9
8
Q
What endogenous substances have the same effect on receptors as Opioids?
A
Endorphins, Enkephalins, and Dynorphines.
S10
9
Q
Presynaptic inhibition of what neurotransmitters occurs with Opioid administration?
A
- Substance P
- ACh
- NE
- Dopamine
S10
10
Q
How do Opioids modulate pain at the cellular level?
A
- ↑ K⁺ conductance (hyperpolarization)
- Ca⁺⁺ channel inactivation
S10
11
Q
Where are Opioid receptors located in the brain?
A
- PAG
- Locus Ceruleus
- RVM (rostral ventral medulla)
- Hypothalamus
S11
12
Q
Where is the primary site of Opioid receptors in the spinal cord?
A
Substantia gelatinosa (aka Laminae 2)
where local anesthetics work
S11
13
Q
Where is/are Opioid receptors found outside the CNS?
A
Sensory neurons & immune cells
S11
14
Q
What are the four (most important) types of opioid receptors?
A
- Μu1 (μ₁)
- Μu2 (μ₂)
- Κappa (κ)
- Delta (δ)
S12
15
Q
Which opioid receptor(s) is/are responsible for respiratory depression & physical dependence?
A
- Μu2
- δ
S12
16
Q
Which receptors are responsible for constipation?
A
- Μu2 (primarily)
- δ (less)
S12
17
Q
Which receptors can cause urinary retention?
A
- Μu1
- δ (delta)
S12
18
Q
Are there any receptors that cause diuresis when bound?
A
κ (Kappa)
S12
19
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.
S12
20
Q
What opioid receptors have low abuse potential when bound?
A
Μu1 and κ
S12
21
Q
Which opioid receptor is responsible for euphoria, bradycardia, hypothermia, and miosis when bound?
A
Mu1
S12
22
Q
What agonists bind to the four opioid receptors?
A
- Mu1 & Mu2 = endorphins, morphine, synthetics.
- κ = dynorphins.
- δ = enkephalins.
S12
23
Q
Describe the adverse side effects of Opioids on the cardiovascular system.
A
- ↓SNS tone = ↓BP, VR, and CO & Orthostatic hypotension and sycope
- ↓HR + histamine release = ↓BP
+ N2O or Benzo = CV depression
S12
24
Q
What possible cardiovascular benefits do Opioids provide?
A
Myocardial ischemia protection
(won’t cause myocardial depression)
S13
25
What are the *respiratory effects* of Opioids?
- **Depressed CNS response to CO₂** causing a *right shift* of PaCO₂ (↑)
## Footnote
S14
26
What are the syptoms of Opioid overdose?
**- apnea**
- miosis
- hypoventilation
- coma
## Footnote
S14
27
What drug would treat opioid ventilatory depression but **not** reverse analgesia?
How?
**Physostigmine** would by increasing CNS levels of ACh
## Footnote
S14
28
What is normal PaO₂?
Normal PaO₂ is **80 mmHg**
## Footnote
S15
29
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 (need higher CO2 to make them breath)
## Footnote
S15
30
Why should caution be used when administering opioids to *head trauma patients*?
Opioids **↓CBF** and **possibly ↓ICP**
## Footnote
S16
31
What can happen when large doses of Opioid is given?
Myoclonus
## Footnote
S16
32
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 makes it worse
- *treat* with **Muscle relaxants and/or naloxone**
## Footnote
S16
33
What are Sphincter of Oddi spasms?
Which drugs can cause this?
- Biliary smooth muscle spasm
caused by:
- **Fentanyl** (99%),
- Morphine (53%)
- Meperidine (61%).
*I think maybe all opioids can cause this but these are the primary culprits*
## Footnote
S17
34
How are opioid-induced Sphincter of Oddi spasm's treated?
- **Naloxone**
- **Glucagon** (2mg IV given incrementally) and causes no opioid antagonism.
35
What drugs should be used for ERCP cases?
- Non-opioids (multimodal approach w/ NSAIDs, gabapentin, etc.)
36
What is the side effect on GU with Opioids?
urinary urgency
## Footnote
S19
37
What are the effects on cutaneous with Opioid?
flushed face, neck, & upper chest
d/t Histamine release
## Footnote
S19
38
What are the side effects on the placenta with Opioids?
- neonate depression
- dependence (chronic)
## Footnote
S19
39
How long does it take (generally) to develop tolerance to Opioids?
What causes tolerance?
- **2-3 weeks**
- 25 days with Morphine
- Downregulation (↓ opioid receptors) causes tolerance
## Footnote
S20
40
What negative change can develop between all opioids?
Cross-tolerance
## Footnote
S20
41
Morphine is ____ standard with opioids
Gold standard
## Footnote
S27
42
What effects does Morphine have?
* Analgesia
* euphoria
* sedation,
* diminished ability to concentrate
* nausea
* feeling of body warmth
* heaviness of extremities,
* dryness of the mouth
* pruritis.
## Footnote
S27
43
What areas of the body does Morphine relieve?
* visceral
* skeletal muscles
* joints and integumental dull > sharp
* intermittent pain
## Footnote
S27
44
Morphine tends to relieve _____ type pain more than _____ type pain.
Dull: sharp
## Footnote
S27
45
What is the dosage of Morphine?
1 - 10 mg IV
## Footnote
S22/28
46
What is the onset of Morphine?
10 - 20 mins
## Footnote
S28
47
What is the IM and IV peak of Morphine?
IM: 45 to 90 mins
IV: **15-30 mins**
## Footnote
S28
48
What is the duration of Morphine?
4-5 hours
## Footnote
S28
49
What are the first past effects of Morphine in the liver and lungs?
* PO Hepatic 1st Pass: 25%.
* No first pass uptake in lungs
## Footnote
S28
50
Where does Morphine accumulate rapidly?
- kidneys
- liver
- skeletal muscles
## Footnote
S28
51
How is Morphine metabolized?
What are the metabolites and their significance?
- Glucuronidation in the liver
metabolites:
- **Morphine-6-glucuronide** = (5-25%) but is an ***active* anaglesic causing late resp depression**.
- Morphine-3-glucuronide (75% to 95%) but inactive
## Footnote
S29
52
What is the elimination 1/2 time of Morphine?
longer with morphine-3-glucuronide
## Footnote
S30
53
What would occur with Morphine overdose in a renal failure patient?
Prolonged ventilatory depression.
54
Which gender has more analgesic potency and slower speed of offset with Morphine?
Women
## Footnote
S30
55
What receptors does Meperidine agonize?
- **μ and κ receptors**
- α2 receptors as well
## Footnote
S31
56
What are the analogues of meperidine?
What other drugs does meperidine have a similar organic structure to?
-Analogues: **Fentanyl & it's derivatives**
- structure similarity: **Lidocaine & Atropine**
## Footnote
S31
57
How potent is Meperidine?
How long does it last?
- *10% as potent* as morphine
- Duration: **2-4 hours**
## Footnote
S32
58
What is the dose and primary indication for Meperidine?
**12.5 mg IV** for Post-operative shivering
## Footnote
S32/33
59
What are the effects of Meperidine?
* sedation
* euphoria
* N/V
* depression of ventilation
## Footnote
S32
60
What is the metabolism and how much is protein bound of Meperidine?
90 % hepatic metabolism
--> Normeperidine
60 % protein bound (consider with elderly)
## Footnote
S32
61
What is the elimination profile of Meperidine?
Elimination: **Renal** (acidic urine can speed elimination)
Elimination 1/2 time: **3 to 5 hour**s (35 hours with renal failure)
## Footnote
S32
62
What are the toxic effecs of Meperidine?
* delirium (confusion, hallucinations)
* myoclonus
* seizures
## Footnote
S32
63
When should Meperidine not be used?
- Bronchoscopies (promotes coughing)
- diarrhea
- cough suppressant
## Footnote
S33
64
What are the side effects of Meperidine?
* tachycardia
* mydriasis with dry mouth
* (-) inotropy
* serotonin syndrome (MAOIs & TCAs)
* impaired ventilation
* crosses placenta
65
True or False: Meperidine develops withdrawal symptoms more rapidly than Morphine?
True
## Footnote
S33
66
How potent is fentanyl?
- 75 - 125 x Morphine.
## Footnote
S34
67
What is the *blood-brain equilibration* of fentanyl?
What does this mean?
- **6.4 minutes**
- Potent with rapid onset and ↑ lipid solubility.
## Footnote
S34
68
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.
## Footnote
S34
69
What organs are reservoirs and affect the drug's pharmacokinetics' dispositional phase?
Lungs
## Footnote
S35
70
What is removal of endogenous compounds form the pulmonary arterial blood?
Pulmonary Uptake/Extraction
## Footnote
S35
71
What is the term for 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?
Lung First-Pass
## Footnote
S35
72
Where is fentanyl metabolized?
What is its principal metabolite?
- Liver via CYP3A
- Norfentanyl is the principal metabolite
## Footnote
S 36
73
Where is Fentanyl excreted?
Kidneys
## Footnote
S36
74
What is the Vd of Fentanyl?
**Large Vd**
IV ( *< 5 mins 80% is gone*)
--> highly vascular tissues
--> inactive tissue sites
## Footnote
S36
75
How does fentanyl dosing change for the elderly or liver patients?
**No change in elderly or cirrhotic patients.**
## Footnote
S36
76
Describe what the graph below is showing.
Fentanyl has the greatest context-sensitive half-time of any of the Fentanyl derivatives.
| d/t saturation of inactive tissue
## Footnote
S37
77
What is the analgesia dosage of Fentanyl?
1 - 2 μg/kg IV
## Footnote
S38
78
What is the induction dose of Fentanyl?
1.5 - 3 μg/kg IV
## Footnote
S38
79
What is the dose of Fentanyl with inhaled anesthetics?
**2 to 20 µg/kg IV**
* Direct laryngoscopy during intubation
* Sudden changes in surgical stimulation level
## Footnote
S38
80
What is the surgical anesthesia dose of Fentanyl?
50 to 150 µg/kg IV
## Footnote
S39
81
What is the intrathecal dosage of Fentanyl?
25 mcg
## Footnote
S39
82
What is the adult oral dose of Fentanyl?
Pediatric?
- Adult: **5 - 20 mcg/kg**
- Peds: **15 - 20 mcg/kg**
## Footnote
S39
83
1mg of PO Fentanyl = ____ mg of IV Morphine
5
## Footnote
S39
84
What is the transdermal dose of Fentanyl?
75 - 100 μg (18 hours steady state)
## Footnote
S39
85
What cardiovascular side effects should be known about Fentanyl?
- no histamine release
- depress carotid sinus baroreceptor reflex
- no significant bradycardia
- ↓BP & ↓CO
## Footnote
S40
86
What CNS side effects of Fentanyl should be known?
* Can cause seizures
* modestly increase ICP (6-9 mmHg)
## Footnote
S41
87
What are synergism effects of Fentanyl?
* Potentiate Benzodiazepines
* Decrease dose requirements with Propofol
## Footnote
S41
88
How much more potent is Sufentanil than Fentanyl?
5-12 times more potent.
## Footnote
S42
89
How much of Sufentanil is subject to first pass effects?
60% lung first-pass
## Footnote
S42
90
How much of Sufentanil is protein bound? What protein is it bound to?
**92.5% α-1 acid glycoprotein bound.**
## Footnote
S42
91
What is the metabolism and excretion of Sufentanil?
Metabolism: hepatic
Excretion: renal and fecal (caution in chronic renal failure)
## Footnote
S42
92
What is the context-sensitive half-time and Vd of Sufentanil?
* Context-sensitive half-time: shorter
* larger Vd > alfentanil
## Footnote
S42
93
What is the analgesia dose of Sufentanil?
0.1 - 0.4 μg/kg IV
## Footnote
S43
94
What is the induction dose of sufentanil?
18.9 mcg/kg IV
## Footnote
S43
95
What is the intraop dose of Sufentanil?
0.3 to 1 µg/kg IV
## Footnote
S43
96
What is the infusion dose of Sufentanil?
0.5 to 1 µg/kg/hr IV
## Footnote
S43
97
What are the side effects of Sufentanil?
- Bradycardia (↓ C.O.)
- Rigidity chest wall and abdominal muscles)
## Footnote
S43
98
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)
## Footnote
S44
99
What are the pharmacokinetics of Alfentanil?
* Cirrhosis: ***prolongs elimination half-time***
* 90% nonionized at normal pH --> **lower lipid solubility**
* **Higher protein binding**
* Metabolite: **Noralfentanil** (Hepatic P450 3A4)
## Footnote
S44
100
What is the Alfentanil induction dose?
Induction: 150 - 300 mcg /kg IV
## Footnote
S45
101
What is laryngoscopy dose of Alfentanil?
15 - 30 mcg/kg IV (90 seconds prior)
## Footnote
S45
102
What about is the maintenance dose of Alfentanil?
25 - 150 mcg/kg/hr with inhaled anesthetics
## Footnote
S45
103
What drug can cause acute dystonia when given to a Parkinson's patient?
Alfentanil
## Footnote
S45
104
What receptor affinity does Remifentanil have?
How potent is it?
μ opioid agonist that is equipotent to fentanyl
## Footnote
S46
105
What is Remifentanil's structure and why is it important?
**Ester Structure** = hydrolyzed by plasma & tissue esterases.
- Rapid onset & recovery
- rapid titratable effect
- No accumulation
- rapid recovery when discontinued
## Footnote
S46
106
What drug was said to be a great choice for carotid procedures in lecture?
Remifentanil
107
What is the clearance of Remfentanil?
3-L/min
(8x faster than Alfentanil)
## Footnote
S47
108
What is the peak effect of Remifentanil?
30 - 60 seconds
## Footnote
S47
109
Where is Remifentanil excreted?
kidneys
(unchanged by renal or hepatic disease)
## Footnote
S47
110
What is the elimination half-time of Remifentanil?
6.3 minutes
## Footnote
S47
111
What is the induction dose of Remifentanil?
0.5 to 1 µg/kg IV over 30-60 seconds
## Footnote
S48
112
What is the maintenance dosing of Remifentanil?
- 0.005 - 2 μg/kg/min IV
## Footnote
S48
113
What do you need to give before stopping Remifentanil?
give longer-acting opioid
## Footnote
S48
114
What use is not recommended for Remifentanil?
spinal or epidural use
## Footnote
S48
115
What are the side effects of Remifentanil?
* Seizure-like activity
* N/V
* Depression of ventilation
* Decreased BP and HR
* Hyperalgesia d/t
-Previous acute exposure to large opioid doses
-Tolerance
## Footnote
S49
116
How potent is Hydromorphone?
What benefits does hydromorphone have over morphine?
- 5x more potent than morphine
- **No histamine release & no active metabolites.**
## Footnote
S50
117
What is the dose of Hydromorphone?
0.5mg → 1-4 mg total
*Redose every 4 hours*
## Footnote
S50
118
Why is codeine not given IV?
Induced hypotension via histamine release.
119
What is the elimination 1/2 time of Codeine?
3 to 3.5 hours
## Footnote
S51
120
Where is Codeine metabolized?
Liver
## Footnote
S51
121
What are the side effects of Codeine?
* physical dependence
* minimal sedation
* N/V
* constipation
* dizziness
## Footnote
S51
122
What is the dose of codeine for cough suppression?
Analgesia?
- Cough: 15mg
- Analgesia: 60mg (= about 5mg morphine)
## Footnote
S51
123
Which opioid is most cleared?
Remifentanil (3-4L/min)
## Footnote
S53
124
Which opioid(s) is/are the most protein bound?
Which is the least?
- most = Sufentanil, alfentanil, & remifentanil
- least = morphine
## Footnote
S53
125
Which opioid is the highest percent non-ionized?
Alfentanil
## Footnote
S53
126
What are the other Opioid Agonists?
* Oxymorphone
* Oxycodone
* Hydrocodone
* Methadone
* Propoxyphene
* Tramadol
* Heroin
## Footnote
S52
127
Which Opioid Agonist is used in opioid withdrawal & chronic pain?
Methadone
## Footnote
S52
128
What are the drug facts about Tramadol?
* 5 -10x less (Morphine)
* µ with weak κ & δ
* **PO: 3 mg/kg**
* Interacts with Coumadin
## Footnote
S52
129
What are drug facts of Heroin?
* More rapid onset
* less N/V
* **great potential for dependency**
## Footnote
S52
