Substance Use And Opioids Flashcards
What is the most clinically relevant opioid receptor
Mu
*mediates analgesia
*respiratory depression
*euphoria
*sedation
*miosis
*GI effects
What does the k (kappa) and delta opioid receptors mediate?
KOR
*mediates analgesia
*dysphoria
DOR
*mediates analgesia
*convulsions
*role in tolerance
When activating an opioid receptor what happens to the secondary signals?
- Reduce opening of voltage gates Ca2+ channels, thereby inhibiting calcium dependent neurotransmitter release
*less excitation - Stimulate K+ currents, bind open channels which will hyperpolarizes and inhibits postsynpatic neurons
*not as many messages being sent
What are the components of the ascending pathway (pain transmission)
- Senses painful stimuli
- Transmits pain signal to cortex
- Opioids will decrease emotional signal to the brain AND
- Opioids will block sensory neuron signals (less pain sensations)
What happens to the potassium channels in the ascending pathway?
- Agonists open channels causing neuronal hyperpolarization
What are the components of the descending pathway (pain transmission)
- Modulates pain signal
*opioids enchance inhibitory modulation (sensory)
*less pain sensation
What happens to the calcium channels in the descending pathway?
- Agonists reduce channel opening, thereby inhibiting calcium dependent neurotransmitter release
How do the mechanisms of opioids work?
- Bind and stimulate open K+ channels causing hyperpolarization
*less likely to fire - Bind and reduce Ca2+ channel opening thereby blocking Ca- dependent neurotransmitter release
*less excitatory signaling available
Opioids exert their analgesic effects in the human body by modulating the pain signal in both the ascending and descending pain pathways.
True
Definition of tolerance and dependency
Tolerance: higher opioid dose is needed to produce same level of analgesia
Dependency: chronic, relapsing brain disease characterized by compulsive drug seeking and use despite harmful consequences
Definition of addiction
- State where organism functions normally only in presence of substance
What effects will be shown with minimal/no tolerance, moderate tolerance, and rapid tolerance
Minimal
*pupillary miosis
Moderate tolerance
*constipation, emesis, analgesia, sedation
Rapid tolerance
*euphoria
What are the analgesic effects the opioids have?
- Continuous, dull pain better relived
- Opioids reduce sensory and emotional components of pain
What are the euphoric effects of opioids
- Pleasant feeling of well-being
What are the ‘respiratory depression’ effects of opioids?
- Primary consequence of opioid overdose
- Inhibition of respiratory controlling neurons in the brain stem
*dose related
What are the hypotension effects of opioids
- Agonists stimulate histamine release thereby causing low BP
*peripheral ad arterial vasodilation
What are the sedative opioid effects
- Drowsiness
- Mood alterations
- Mental clouding
What are other effects of opioids?
- Cough suppression (primary therapeutic effects)
- Miosis (pupil constriction)
- Emesis (N/V)
- Constipation
- Pruritis
Why does constipation happen while on an opioid?
- Opioid acts on nerves within the enteric nervous system to increase muscle tone and decrease peristaltic movement in small intestine and colon
What are the two predominate therapeutic uses of opioid medications?
- Analgesia
- Emesis
- Constipation
- Sedation
- Antitussive
*1 and 5
What is the “A” effects of opioids
Absorption
1. Modestly well GI absorption
2. Extensive first pass metabolism
3. Some are very lipohilic
What is the “D” effects of opioids
Distribution
1. 1/4 of morphine in plasma bound to proteins
2. Fails to redistribute into tissues very well
What is the “M” effect of opioids
- Morphine 6-glucuronide 2X potency as morphine
What is the “E” effects of opioids
Excretion
1. Glomerular filtration
2. Kidney ARDS in patient with significant renal hx
What are the neuropsychiatric opioid ARDS
- Sedation
- Clouded thoughts
- Euphoria
- Sleep-wake disturbances
- Mood changes
- Fatigue
What are the cardiopulmonary opioid ARDS
- Respiratory depression
- Dizziness
- Orthostatic hypotension
- Bronchoconstriction
What are the gastrointestinal opioid ADRs
- Nausea
- Vomiting
- Constipation
- Decreased GI motility
What are the ARDS of the urinary system and endocrine due to opioids
Urinary system
*urinary retention
Endocrine
*decreased testosterone levels
*reduced/absent menses
*hypogonadism
*infertility
*reduced libido
What are the allergic and immunologic ARDS
- Pruritus
What is the primary cause of morbidity to opioid therapy
Respiratory depression
*bc the duration of the opioid may be longer than analgesia
What type of patients should you monitor while on opioid therapy
- Asthma
- COPD
- Increased intracranial pressure
*bc all the stages of breathing are being depressed
What are the risk factors of opioid induced respiratory depression?
- History of previous overdose
- Substance abuse
- Using large doses (>50 morphine milligram)
- Use with benzodiazepines (gabapentin, Pregabalin)
- Comorbid respiratory or psychiatric disease
What SE do all opioids cause?
- Constipation
- Does not improve over time
*anticipate and treat
*no tolerance develops over time
*if opioids are timed around the clock use prophylaxis
What is the first line stool softener
Stimulant laxatives
1. Sienna
2. Bisacodyl
What are the top 4 essential opioids ADE
- N/V
- Constipation
- Respiratory depression
- Sedation
What drugs will cross react with on another
COD or MORPH in the name
*include heroin
What is the onset of analgesia, duration of effect, and T 1/2 of morphine, Oxycodone, hydrocodone
Morphine
*onset = 20-40
*duration = 4 hours
*T 1/2 = 2
Oxy
*onset = 10-30
*duration = 3-6 hours
*T 1/2 = 3
Hydro
*onset = 10-20
*duration = 4-6 hours
*T 1/2 = 4 hours
What is the onset of analgesia, duration of effect, and T 1/2 of oxymorphone, hydromorphone, methadone
Oxymorphone
*onset = 10-30
*duration = 4-6 hours
*T 1/2 = 9
Hydromorphone
*onset = 15-30
*duration = 4 hours
*T 1/2 = 2.5
Methadone
*onset = 10-15
*duration = 4-8 hours
*T 1/2 = 12-50 hours
What is the onset of analgesia, duration of effect, and T 1/2 of Fentanyl transmucosal, IM, IV
Transmucosal
*onset = 5-10
*duration = 1-2 hours
*T 1/2 = 7
IM
*onset = 5-10
*duration = 1-2 hours
*T 1/2 = 4
IV
*onset = immediate
*duration = 30mins - 1 hour
*T 1/2 = 4 hours
Which of the following are key side effects of oxycodone?
- Diarrhea
- Nausea
- Respiratory depression
- Excitation
- Sedation
*2, 3, 5
What is tramadol (ultram) MOA
- Agonizes mu-opioid receptors to produce moderate analgesia
What is the maximum dose of tramadol and the ADRs
Max = 300mg
ADRS
*constipation
*dizziness
*nausea
*somnolence
What are the DDI of tramadol
- Caution with other drugs that can increase serotonin
*SSRI, SNRI leads to serotonin syndrome - Caution in patients with seizure disorder or taking anticonvulsants
What are the components of methadone
- Long acting mu agonist
- Effective in severe chronic pain
- Very long half-life (50 hours)
*sticks around after analgesia wears off
What do equinanalgesic dose of methadone cause>
- It decreases progressively the higher of the previous opioid dose
What opioid medication has a “quick on, quick off” pharmacokinetic profile?
Fentanyl
How does age related to opioid therapy
- PD changes with aging
*increase sensitivity to opioids - Children <2 should not receive transdermal fentanyl
How dos cognitive status relate to opioid therapy
- Ability to self-assess and report pain, take break-through analgesia
How does pregnancy/breastfeeding relate to opioid therapy
- Opioids cross through the breast milk
- Developmental outcomes are unknown
What genetic factors can effects opioid therapy
- CYP2D6
What does dopamine mediate?
- Drug reinforcement by binding to D1 receptors in the NA (nucleus accumbens)
*sensitizing dopaminergic neurons
*all addictive substance increases dopamine in the NA
What is the cycle of a SUD
- Drug use
*dopamine surges - Positive reinforcement
- Decrease use or wanting to stop
- Negative reinforcement
*withdrawal symptoms
What is the correct drug to use during intoxication / overdose phase
Naloxone
*will reserve the effect
What are the correct drugs to use during the withdrawal phase?
- Methadone
- Buprenorphine
What are the correct drugs to use during the maintenance phase
- Methadone
- Buprenorphine
- Naltrexone
*keep system empty
What is Naloxone (narcan)
- Opioid antagonist
*used to treat overdose and prevent - Injection (Naloxone)
- Nasal spray (narcan)
- Monthly IM (vivitrol) is naltrexone (maintenance)
When to use then IV/IM/SubQ, or nasal spray
IV/IM/SubQ
*every 2-3 minutes (0.4 - 2mg)
Nasal spray
*every 2-3 minutes (4 to 8mg )
Which of the following medications can be used for opioid withdrawal?
1. Methadone
2. Naloxone
3. Buprenorphine
4. Oxycodone
5. Clonidine
Methadone
Buprenorphine
Clonidine
What is the MOA and SE of buprenorphine (belbuca)
MOA: partial mu opioid receptor agonist
SE
*sedation
*HTN
*N/V/D
What are the warnings, and clinical pearls of buprenorphine (belbuca)
Warnings
*CNS depression
*hepatic events
*Qtc prolongation
Clinical pearls
*Subq requires 7 days of induction with PO
*must be in withdrawal
*oral cancer reported
What are the contraindication of buprenorphine (belbuca)
- Respiratory depression
- GI obstruction
- Acute or severe asthma in unmonitored setting
What are the clinical pearls and ADRs of methadone (dolophine, methadose)
Clinical pearls
*clinic records dont show in OARRS
ADRS
*QTc prolongation
*sedation
*respiratory depression
What are the warnings of methadone (dolophine, methadose)
- Decompensated liver disease
- Concomitant substance use disorders
- Respiratory insufficiency
- Low levels of physical dependence to opioids
What are the CI to methadone (dolophine, methadose)
- Respiratory depression
- Acute bronchial asthma or hypercapnia
- Known or suspected paralytic ileus
What is the MOA and SE of naltrexone (ReVia PO, Vivitrol SR injection)
MOA = mu opioid receptor antagonist
SE
1. Nausea
2. Increased LFTs
3. Insomnia
4. Injection site reactions
What are the warnings of naltrexone (ReVia PO, Vivitrol SR injection)
- Hepatotoxicity
- Suicidal thoughts ‘ depression
- Bleeding disorders (IM)
- Caution in renal impairment
What are the clinical pearls of naltrexone (ReVia PO, Vivitrol SR injection)
- Can be used for both alcohol and opioid use disorders
- Not used for withdrawal, used to prevent euphoria in relapses
- Avoid with opioids or if in acute opioid withdrawal
Which of the following medications should not be used in a patient with a prolonged QTc?
Buprenorphine
Naltrexone
Naloxone
Methadone
Buprenorphine
Methadone
What is the treatment of alcohol intoxication mild-mod, severe
Mild/mod
1. Supportive care, symptom control, reassurance
Severe
1. Cardiac monitoring
2. Fluids
3. Respiratory support
What should be used during severe alcohol intoxication
- Benzodiazepines (want to prevent seizures)
- Diazepam
- Lorazepam
- Midazolam
*use thiamine before dextrose (or else there will be brain encephalopathy)
What is wernicke-korsakoff syndrome
Caused from a thiamine deficiency, there will be
1. Mental confusion
2. Amnesia
3. Ataxia of gait
4. Nystagmus
5. Opthalmoparesis
What can administration of glucose cause?
- Rapidly deplete existing thiamine stores
*if pre-existing thiamine deficiency can precipitate wernicke disease
How to treat wernicke-korsakoff syndrome
- Always give thiamine before dextrose-containing fluids
- Banana bag (thiamine + folate + multivitamin)
What is the first line treatment of AUD
- Acamprosate
- Naltrexone
What is the MOA and indication of use for acamprosate (Campari)
MOA = GABA agonist/glutamate antagonist
Indication
*moderate to severe AUD
What is the dosage, SE, and CI of Acamprosate (Campari)
Dosage = 666TID
SE = anxiety/depression, diarrhea, insomnia, weakness, suicidal thoughts
CI = CrCl<30
What is the MOA of disulfiram (Antabuse)
Aldehyde dehydrogenase inhibitor
What are the clinical pearls of disulfiram (Antabuse)
- Need a BAC of zero
