*Opioids Agonists (Exam II) Flashcards
What are opioids effects on the CO₂ medullary center?
- Opioids inhibit the CO₂ medullary center.
Differentiate opioids from narcotics.
- Opioids = all exogenous substances that bind to endogenous opioid receptors.
- Narcotic = any substance that can produce dependence (stupor)
S7
What two types of opioid chemical structures are there?
- Phenanthrenes
- Benzylisoquinolines
S8
What types of drugs are Phenanthrenes?
Morphine & codeine
S8
What types of drugs are Benzylisoquinolines?
Papaverine
S8
What is Papaverine mostly used for?
Treating intra-arterial barbiturate administration
(dilates the highly constricted artery).
S8
What portions of the brain are the source of Descending Inhibitory Signals?
- Thalamus
- PAG
- Locus Coeruleus
S9
What endogenous substances have the same effect on receptors as Opioids?
Endorphins, Enkephalins, and Dynorphines.
S10
Presynaptic inhibition of what neurotransmitters occurs with Opioid administration?
- Substance P
- ACh
- NE
- Dopamine
S10
How do Opioids modulate pain at the cellular level?
- ↑ K⁺ conductance (hyperpolarization)
- Ca⁺⁺ channel inactivation
S10
Where are Opioid receptors located in the brain?
- PAG
- Locus Ceruleus
- RVM (rostral ventral medulla)
- Hypothalamus
S11
Where is the primary site of Opioid receptors in the spinal cord?
Substantia gelatinosa (aka Laminae 2)
where local anesthetics work
S11
Where is/are Opioid receptors found outside the CNS?
Sensory neurons & immune cells
S11
What are the four (most important) types of opioid receptors?
- Μu1 (μ₁)
- Μu2 (μ₂)
- Κappa (κ)
- Delta (δ)
S12
Which opioid receptor(s) is/are responsible for respiratory depression & physical dependence?
- Μu2
- δ
S12
Which receptors are responsible for constipation?
- Μu2 (primarily)
- δ (less)
S12
Which receptors can cause urinary retention?
- Μu1
- δ (delta)
S12
Are there any receptors that cause diuresis when bound?
κ (Kappa)
S12
All opioid receptors induce analgesia at both the brain the spinal cord. T/F?
- False. Μu2 receptors only cause at analgesia at the spinal cord level.
S12
What opioid receptors have low abuse potential when bound?
Μu1 and κ
S12
Which opioid receptor is responsible for euphoria, bradycardia, hypothermia, and miosis when bound?
Mu1
S12
What agonists bind to the four opioid receptors?
- Mu1 & Mu2 = endorphins, morphine, synthetics.
- κ = dynorphins.
- δ = enkephalins.
S12
Describe the adverse side effects of Opioids on the cardiovascular system.
- ↓SNS tone = ↓BP, VR, and CO & Orthostatic hypotension and sycope
- ↓HR + histamine release = ↓BP
+ N2O or Benzo = CV depression
S12
What possible cardiovascular benefits do Opioids provide?
Myocardial ischemia protection
(won’t cause myocardial depression)
S13
What are the respiratory effects of Opioids?
- Depressed CNS response to CO₂ causing a right shift of PaCO₂ (↑)
S14
What are the syptoms of Opioid overdose?
- apnea
- miosis
- hypoventilation
- coma
S14
What drug would treat opioid ventilatory depression but not reverse analgesia?
How?
Physostigmine would by increasing CNS levels of ACh
S14
What is normal PaO₂?
Normal PaO₂ is 80 mmHg
S15
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)
S15
Why should caution be used when administering opioids to head trauma patients?
Opioids ↓CBF and possibly ↓ICP
S16
What can happen when large doses of Opioid is given?
Myoclonus
S16
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
S16
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
S17
How are opioid-induced Sphincter of Oddi spasm’s treated?
- Naloxone
- Glucagon (2mg IV given incrementally) and causes no opioid antagonism.
What drugs should be used for ERCP cases?
- Non-opioids (multimodal approach w/ NSAIDs, gabapentin, etc.)
What is the side effect on GU with Opioids?
urinary urgency
S19
What are the effects on cutaneous with Opioid?
flushed face, neck, & upper chest
d/t Histamine release
S19
What are the side effects on the placenta with Opioids?
- neonate depression
- dependence (chronic)
S19
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
S20
What negative change can develop between all opioids?
Cross-tolerance
S20
Morphine is ____ standard with opioids
Gold standard
S27
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.
S27
What areas of the body does Morphine relieve?
- visceral
- skeletal muscles
- joints and integumental dull > sharp
- intermittent pain
S27
Morphine tends to relieve _____ type pain more than _____ type pain.
Dull: sharp
S27
What is the dosage of Morphine?
1 - 10 mg IV
S22/28
What is the onset of Morphine?
10 - 20 mins
S28
What is the IM and IV peak of Morphine?
IM: 45 to 90 mins
IV: 15-30 mins
S28
What is the duration of Morphine?
4-5 hours
S28
What are the first past effects of Morphine in the liver and lungs?
- PO Hepatic 1st Pass: 25%.
- No first pass uptake in lungs
S28
Where does Morphine accumulate rapidly?
- kidneys
- liver
- skeletal muscles
S28
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
S29
What is the elimination 1/2 time of Morphine?
longer with morphine-3-glucuronide
S30
What would occur with Morphine overdose in a renal failure patient?
Prolonged ventilatory depression.
Which gender has more analgesic potency and slower speed of offset with Morphine?
Women
S30
What receptors does Meperidine agonize?
- μ and κ receptors
- α2 receptors as well
S31
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
S31
How potent is Meperidine?
How long does it last?
- 10% as potent as morphine
- Duration: 2-4 hours
S32
What is the dose and primary indication for Meperidine?
12.5 mg IV for Post-operative shivering
S32/33
What are the effects of Meperidine?
- sedation
- euphoria
- N/V
- depression of ventilation
S32
What is the metabolism and how much is protein bound of Meperidine?
90 % hepatic metabolism
–> Normeperidine
60 % protein bound (consider with elderly)
S32
What is the elimination profile of Meperidine?
Elimination: Renal (acidic urine can speed elimination)
Elimination 1/2 time: 3 to 5 hours (35 hours with renal failure)
S32
What are the toxic effecs of Meperidine?
- delirium (confusion, hallucinations)
- myoclonus
- seizures
S32
When should Meperidine not be used?
- Bronchoscopies (promotes coughing)
- diarrhea
- cough suppressant
S33
What are the side effects of Meperidine?
- tachycardia
- mydriasis with dry mouth
- (-) inotropy
- serotonin syndrome (MAOIs & TCAs)
- impaired ventilation
- crosses placenta
True or False: Meperidine develops withdrawal symptoms more rapidly than Morphine?
True
S33
How potent is fentanyl?
- 75 - 125 x Morphine.
S34
What is the blood-brain equilibration of fentanyl?
What does this mean?
- 6.4 minutes
- Potent with rapid onset and ↑ lipid solubility.
S34
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.
S34
What organs are reservoirs and affect the drug’s pharmacokinetics’ dispositional phase?
Lungs
S35
What is removal of endogenous compounds form the pulmonary arterial blood?
Pulmonary Uptake/Extraction
S35
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
S35
Where is fentanyl metabolized?
What is its principal metabolite?
- Liver via CYP3A
- Norfentanyl is the principal metabolite
S 36
Where is Fentanyl excreted?
Kidneys
S36
What is the Vd of Fentanyl?
Large Vd
IV ( < 5 mins 80% is gone)
–> highly vascular tissues
–> inactive tissue sites
S36
How does fentanyl dosing change for the elderly or liver patients?
No change in elderly or cirrhotic patients.
S36
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
S37
What is the analgesia dosage of Fentanyl?
1 - 2 μg/kg IV
S38
What is the induction dose of Fentanyl?
1.5 - 3 μg/kg IV
S38
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
S38
What is the surgical anesthesia dose of Fentanyl?
50 to 150 µg/kg IV
S39
What is the intrathecal dosage of Fentanyl?
25 mcg
S39
What is the adult oral dose of Fentanyl?
Pediatric?
- Adult: 5 - 20 mcg/kg
- Peds: 15 - 20 mcg/kg
S39
1mg of PO Fentanyl = ____ mg of IV Morphine
5
S39
What is the transdermal dose of Fentanyl?
75 - 100 μg (18 hours steady state)
S39
What cardiovascular side effects should be known about Fentanyl?
- no histamine release
- depress carotid sinus baroreceptor reflex
- no significant bradycardia
- ↓BP & ↓CO
S40
What CNS side effects of Fentanyl should be known?
- Can cause seizures
- modestly increase ICP (6-9 mmHg)
S41
What are synergism effects of Fentanyl?
- Potentiate Benzodiazepines
- Decrease dose requirements with Propofol
S41
How much more potent is Sufentanil than Fentanyl?
5-12 times more potent.
S42
How much of Sufentanil is subject to first pass effects?
60% lung first-pass
S42
How much of Sufentanil is protein bound? What protein is it bound to?
92.5% α-1 acid glycoprotein bound.
S42
What is the metabolism and excretion of Sufentanil?
Metabolism: hepatic
Excretion: renal and fecal (caution in chronic renal failure)
S42
What is the context-sensitive half-time and Vd of Sufentanil?
- Context-sensitive half-time: shorter
- larger Vd > alfentanil
S42
What is the analgesia dose of Sufentanil?
0.1 - 0.4 μg/kg IV
S43
What is the induction dose of sufentanil?
18.9 mcg/kg IV
S43
What is the intraop dose of Sufentanil?
0.3 to 1 µg/kg IV
S43
What is the infusion dose of Sufentanil?
0.5 to 1 µg/kg/hr IV
S43
What are the side effects of Sufentanil?
- Bradycardia (↓ C.O.)
- Rigidity chest wall and abdominal muscles)
S43
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)
S44
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)
S44
What is the Alfentanil induction dose?
Induction: 150 - 300 mcg /kg IV
S45
What is laryngoscopy dose of Alfentanil?
15 - 30 mcg/kg IV (90 seconds prior)
S45
What about is the maintenance dose of Alfentanil?
25 - 150 mcg/kg/hr with inhaled anesthetics
S45
What drug can cause acute dystonia when given to a Parkinson’s patient?
Alfentanil
S45
What receptor affinity does Remifentanil have?
How potent is it?
μ opioid agonist that is equipotent to fentanyl
S46
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
S46
What drug was said to be a great choice for carotid procedures in lecture?
Remifentanil
What is the clearance of Remfentanil?
3-L/min
(8x faster than Alfentanil)
S47
What is the peak effect of Remifentanil?
30 - 60 seconds
S47
Where is Remifentanil excreted?
kidneys
(unchanged by renal or hepatic disease)
S47
What is the elimination half-time of Remifentanil?
6.3 minutes
S47
What is the induction dose of Remifentanil?
0.5 to 1 µg/kg IV over 30-60 seconds
S48
What is the maintenance dosing of Remifentanil?
- 0.005 - 2 μg/kg/min IV
S48
What do you need to give before stopping Remifentanil?
give longer-acting opioid
S48
What use is not recommended for Remifentanil?
spinal or epidural use
S48
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
S49
How potent is Hydromorphone?
What benefits does hydromorphone have over morphine?
- 5x more potent than morphine
- No histamine release & no active metabolites.
S50
What is the dose of Hydromorphone?
0.5mg → 1-4 mg total
Redose every 4 hours
S50
Why is codeine not given IV?
Induced hypotension via histamine release.
What is the elimination 1/2 time of Codeine?
3 to 3.5 hours
S51
Where is Codeine metabolized?
Liver
S51
What are the side effects of Codeine?
- physical dependence
- minimal sedation
- N/V
- constipation
- dizziness
S51
What is the dose of codeine for cough suppression?
Analgesia?
- Cough: 15mg
- Analgesia: 60mg (= about 5mg morphine)
S51
Which opioid is most cleared?
Remifentanil (3-4L/min)
S53
Which opioid(s) is/are the most protein bound?
Which is the least?
- most = Sufentanil, alfentanil, & remifentanil
- least = morphine
S53
Which opioid is the highest percent non-ionized?
Alfentanil
S53
What are the other Opioid Agonists?
- Oxymorphone
- Oxycodone
- Hydrocodone
- Methadone
- Propoxyphene
- Tramadol
- Heroin
S52
Which Opioid Agonist is used in opioid withdrawal & chronic pain?
Methadone
S52
What are the drug facts about Tramadol?
- 5 -10x less (Morphine)
- µ with weak κ & δ
- PO: 3 mg/kg
- Interacts with Coumadin
S52
What are drug facts of Heroin?
- More rapid onset
- less N/V
- great potential for dependency
S52
