*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