Exam 3 - L22-24 - Opioids Flashcards
3 types of opioid recptors
Mew, Kappa, Delta (dont worry about delta)
describe the characteristics of Mu receptor
1) mu receptor mediates pain relief
mu agonist have the best efficacy but also have potential to be overused
2) effects include:
euphoria, respiratory depression, sedation, tolerance, and dependence
3) located in brainstem, spinal chord
What receptors do Strong Analgesics interact with
Mu Receptors
List the Partial Agonist and Mixed Agonist/Antagonist
Pentazocine (Mixed Agonist )
Buprenorphine (partial agonist)
Tramadol (Partial agonist)
Trapentoadal (partial agonist)
Butorphanol (partial agonist)
Opioid Antagonist drugs
Naloxone, Naltrexone, Methylnatrexone, Naloxegol
Opiate
Derrived from opium
Opioid/ How it relieves pain
Properties similar to drugs derrived from opium
(synthetic)
- Opiods inhibit surges of Ca+ ultimately preventing release of neurotransmitters to block
Pain signals
Narcotic
Sleep inducing
What drugs have peptides that act as agonists on mew receptors
Opioid drugs
Opioid function
Uncouple the physical pain sensation by blocking substance P from conscious awareness and emotional response to pain
- Reduces conscious response
Substance P
NT which Crosses synaptic cleft and sends an action potential to the CNS inducing a pain feeling
A systemically administered opioid acts on what levels
(possible question)
Supraspinal levels
Mechanism: Acts as agonist at receptors for endorphins and enkephalins
Which receptors are linked with with some spinal and supraspinal analgesia, miosis, sedation, and dysphoria.
Kappa receptors
Which receptor is mainly envolved in the limbic system and is known to cause euphoria
Mu receptor
Activation of what receptor causes nausea in opioids
(CRTZ)hemoreceptor trigger zone in the medulla. (May also be some vestibular involvement)
** If a patient had heart surgery you would most likely not want to give them opioid due to the possible vomiting and nausea
What is the most common cause of death in opioid overdose
Depression of respiration (Mu receptor agonism)
At which dose of morphine can a patient not be aroused
When a patient has a overdose of morphine
*leads to mental clouding and sedation and death
in what cases does depression of respiration play a beneficial role
in cases of pulmonary edema small doses of morphine can be given to patient with pulmonary edema to reduce patient distress relaxing them improving cardiovascular function
(aka Compassionate Care Pack)
Dysphoria
Panic attacks and halucenations
Main sign of opioid overdose
Miosis (Pin-point pupils)
If a patient experiences a dysphoric response to morphine what drug could be used instead
ketoralac
Antitussive opiods effect/side effect:
1) Major drug + (mentioned another analogue)
2) H-1 affect / aggravation of asthma/ COPD (mentioned on this slide)
3) H-1 affect alleviation
1) Main drug at hand is Codeine ( he did also mention Hydrocodone analogue)
2) H-1 affect is when opiods literally move into MAST cells and displace the Histamine inside them. It occurs especially in IV admin causes itching.
3) Diphenhydramine (Benadryl) relieves itching
** Think bout tweakers or rappers like Yeat said the perc got him itching
Morphine therapuetic dose
10 milligrams with IV administration, subcutaneous, and intramuscular (injection)
(gold standard)
Chronic oral dose of morphine
10-30 mg
When dealing with patients who have a history of reoccurring seizure such as Epileptic patients the doctor:
Should be carful when administering opioids as they lower seizure threshold
This does not mean that the patient cannot take them at all.
What smooth muscle adverse effects are present in opioids
increased tone of circular smooth muscle and decrease in propulsive movement of longitudinal muscle
- Decreased intestinal motility (constipation peristalsis decreased)
- Urine retention
- Broncho constriction
- Increased biliary pressure due to constriction of Bile duct
What cardiovascular adverse effects
- Postural (orthostatic hypotension – going from laying to standing
- Cutaneous vasodilation
- increased CSF pressure
Skeletal Muscle Rigidity:
Problems which may occur during surgical anethesia with the use of opiods
A technique called Balanced Analgesia is used in surgeries where Anesthesia is used to KO person and the opioid is used to manage the pain during the operation:
- opioids increase skeletal tone -> patient is given neuromuscular blocker ( acts on Nicotinic)
In chronic use of opioids what adverse effect may arise
changes in endocrine function and immunosuppression
** affect females menstrual cycles
As tolerance to opioids develop the severity to most adverse effects lessen. Which two adverse effects don’t get better as tolerance is developed
Miosis and constipation
How much of morphine metabolized in first pass?
75% is metabolized in first pass.
half life of opioids is and is primarily excreted in
half like is 2-3 hours it is primarily excreted in the urine
Major drug interactions of opiods, antidepressents, and an example of a drug mixture tweakers use
-additive effects like drinking with a benzo, antipsychotics
-“speedball” addy + coke kinda lit (idk how this is related to content but he said to know in lecture)
-Duloxotene SNRI antidepressent effects which enhance analgesic effects of opiods by inhibiting synaptic reuptake of serotonin and dopamine
Combining NSAID and Acetaminophen with opioids
enhance analgesic effect
Treatment for overdose
Support respiration and NARCAN (naloxone)
Codeine properties and uses
Given orally
1/12 the potency of morphine common doses are 30-60 orally
Metabolized to morphine (CYP2D6) Under metabolizers may not be effective
over metabolizers may be fatal
mild pain
Hydromorphone
10x more potent then morphine
- Strong Mu agonism
-same use as morphine in pain relief
-
Oxycodone
50% more potent then morphine used orally for mild moderate pain 0
Oxycotin in sustain release oral pill
Hydrocodone
*similar to morphine and codeine used as an antitussive
*oral use for mild moderate pain
*widely used in combination with NSAIDS + Acetominophen
Meperidine
Synthetic drug given orally
1/10 potency of morphine
Weaker smooth muscle effect then morphine
Used in obstetrics
Short acting 1-3 hours NOT GOOD CHRONIC PAIN
can cause SEIZURES In long term use
Heroin
1)More potent and more euphoric than morphine
2) Heroin is an attractive substance for abuse due to it’s ability to pass through the BBB easily giving intense high (Acetal side chain)
last 4-6 hours
SCHEDUALE 1
injection and snorting or smoking is method used to take drug
Methadone
Can be used as an Analgesic and to treat opioid addiction (not common)
*Methadone clinic stigma
Less euphoric than Morphine
when used in opioid addiction (Methadone maintenance treatment) lasts long time (12-24 hours)
For analgesic use last 4-6 hours
used for severe pain
Fentanyl
Synthetic potent mu receptor agonist
100x more potent then morphine
Administered during surgical anesthesia
also given in a Transdermal preparation
Can be found in street drugs to make them more potent
In opioid Combination Preparations what drugs are usually used? Why do these drugs exist? Why cant they be used in high doses for severe pain?
- These drugs either have acetaminophen, Aspirin or ibuprofen in combination with an opioid. Opioids used (Codeine, hydrocodone, oxycodone, or propoxyphene
- allow for the less than 10mg of morphine equivalent to be used while still providing sufficient analgesia. Used for moderate pain
- When used in high doses Acetaminophen and NSAID toxic metabolites can build up. (Renal/Liver damage)
NOT recommended for severe pain
Mixed agonist/antagonist drugs
Pentazocine, Buprenorphine, Butorphenol,Tramadol, Tapentadol
Pentazocine
A mixed Agonist-Antagonist:
1) Partial agonist at LOW doses=weak effect on Mu receptors.
2) At the same time its Antagonist traits in HIGH doses.
3) Less effective than morphine, but less sedation and respiratory depression.
4) Acts agonistically on Kappa receptors causing dysphoric effects
+ Increased CNS stim and hallucinations.
5)Less risk for physical dependence than morphine. Can precipitate withdrawal syndrome in opioid addicts.
Buprenorphine
Partial Agonist at mu and kappa.
Less analgesic effect than morphine, but less potential for abuse.
Reduces drug craving, so used to treat opioid addiction.
- Has a plateau effect which decreases overdose likelihood
- Office based treatment
*more accesible than methadone (forgot why, someone add…
it could be related to stigma of methadone clinics)
what does a presense of naloxone in oral drugs provide?
naloxone will be metabolized if taken orally if addicts were to try to administer a drug intravenously naloxone would prevent overdose.
* Therefore detering addicts
Tramadol
Newer drug for mild/moderate pain.
Weak mu agonist and inhibits reuptake of norepinephrine and serotonin.
Good analgesic with minimal side effects.
Lower abuse potential.
Tapentadol
Similar to tramadol, but a stronger agonist of mu receptors.
Inhibits reuptake of NE and serotonin
More effective than tramadol, but greater abuse potential.
Beneficial for neuropathic pain
Naloxone
Treats opioid poisoning
Given parenterally in ED or intranasally by EMTs
Short acting (1-2 hours) after levels will begin to increase again
Patient goes right into withdrawal
(ex: Heroin has a 6 hour 1/2 life)
Naltrexone
Treatment of alcohol poisoning by reducing cravings
Risk of hepatotoxicity and poor patient compliance
Patient must be entirely detoxified before naltrexone can be initiated.
Physical drug dependence
Patient tolerent to drug
upon stopping you see withdrawl
Main characteristic of withdrawl
Dialated pupils, drug craving, GI hypermotility, sweating, yawning,
patient has turkey/chicken skin (Opposite effects of what opiods do)
clonidine
Tones down CNS and treats withdrawal symptoms like sweating and hypertension
Naloxegol
-Approved for opioid induced constipation
-Taken orally, so has few systemic effects
-Useful for out patients
Duration and Intensity of Acute Withdrawal
Short acting drug: intense symptoms for 2-3 days
Long acting drug: moderate symptoms for 4-7 days.
Acute withdrawal is followed by prolonged symptoms including anxiety, sleep disturbances, and autonomic excitability.
Spinal Morphine
- just remember that inhibits the release of substance P (NT) to shutoff pain impulses and given often post operatively
Methylnaltrexone
Analog of Naloxone approved to treat constipation
Must be given parenterally
Only used for severe symptoms caused by potent opioids
