1- Opioids Flashcards
What is the role of endogenous opioid peptides?
Released in response to pain and lead to decreased responsiveness to pain
Endogenous opioids are found in areas of the brain involved in what?
Reward system
What are the 3 endogenous opioids?
Enkephalins, beta-endorphins, dynorphin
What is the role of enkephalins? (endogenous opioid)
↓ pain transmission in spinal cord
What is the role of beta-endorphins? (endogenous opioids)
↓ pain and facilitate DA → euphoria
What is the role of dynorphin? (endogenous opioid)
Bind to kappa receptors → analgesia or dysphoria
What are the effects of binding to the mu (𝝁) receptor?
Analgesia, euphoria, sedation, SE
What are the effects of binding to the kappa (𝜿) receptor?
Analgesia OR dysphoria (individual variance)
What are the effects of binding to the delta (𝛅) receptor?
Dysphoria
All opioid receptors are coupled to Gi/O. This leads to ↓ cAMP, ↓ release of excitatory NTs (in dorsal horn) by closing Ca voltage channels on presynaptic terminal and ultimately leads to what?
↓ neuronal activity in pain pathways
Opioids have a direction action at what tissue?
Inflamed and damaged
Opioids remove inhibition in periaqueductal grey area, resulting in what?
Release of endogenous opioids
What is the effect of opioids on GABA?
Block release → activation of descending pathway that inhibits pain transmission → ↓ pain transmission
What is the contribution of only mu (𝝁) receptors with respect to opioid activity?
Open K channels → hyperpolarization → inhibit nerve transmission → harder for neurons to respond to pain signals
Opioid effects are dependent on what?
Receptor distribution in the individual
What is the effect of opioids with respect to analgesia?
↓ sensation & reaction to pain, tolerance develops quickly
Are opioids used as sleep aids?
No- quality of sedation different
With respect to sedative effects, opioid overdose leads to what?
Graded depression of cortical function: mental clouding/ sedation → hypnosis/ stupor → coma → death
How can opioids lead to emesis?
Stimulate chemoreceptor trigger zone (CTZ), depression of cough reflex
When is respiratory depression more common w/ opioid use and what condition may this effect be useful in?
More common in OD, useful in pulmonary edema
Because opioids can result in elevated intracranial pressure, you should be cautious with use in who?
Pts with head trauma
What effect of opioids does not develop tolerance and why is this beneficial?
Miosis, can be used as dx tool
Do opioids have the potential to increase or decrease body temp?
Decrease
When can truncal rigidity occur with the use of opioids and what might this complicate?
If given too quickly, may interfere w/ respiration or attempts to ventilate patient
How can truncal rigidity with use of opioids be prevented?
Injecting slowly or using NM blockers
What are the CV effects of opioids?
- No direct effect (possible bradycardia)
- Hypotension from CNS depression or histamine release
What significant GI effect is seen with opioids?
Constipation (proactively tx/edu)
How do opioids affect the GU system?
Antidiuretic effect, increase sphincter and urethral tone
What populations should you avoid use of opioids with due to their effects on the GU system?
Avoid in pts w/ BPH or in pts passing kidney stone
(antidiuretic effect and increase sphincter and urethral tone)
What is the effect of opioids on the uterus?
Prolonged labor
What are the endocrine effects of opioids?
Increases AHD, prolactin, somatotropin
Inhibits LH
Opioids result in histamine release which may result in flushing, itching, or sweating. Is this considered an opioid allergy?
NO
(more common if injected)
How can the effects of histamine release from opioids be treated/ prevented?
Antihistamines
What are the SEs of opioids? (8)
N/V (take w/ food)
Constipation
Urinary retention
Itching
Respiratory depression
Postural hypotension
Restlessness
Dysphoria
When is respiratory depression (SE of opioids) worse and when should this lead to caution?
Worse w/ higher doses (dangerous if naive users)
Caution in pulmonary disease
When does tolerance to opioids develop?
Chronic use, occurs rapidly and more common w/ drugs that have lower efficacy → higher doses needed
To what opioid effects can an individual develop tolerance? (5)
Analgesia, sedation, euphoria, N/V, respiratory depression
To what opioid effects can an individual NOT develop tolerance? (3)
Miosis, constipation, seizures
Due to the fact that physical dependence to opioids can develop, when might withdrawal occur?
If stopped abruptly
(physical dependence due to desensitization of 𝝁 receptors)
How can physical dependence to opioids be decreased?
W/ use of NMDA receptor antagonists
When does hyperalgesia occur with opioid use?
Chronic use
How can hyperalgesia be decreased with chronic opioid use?
NMDA receptor antagonist
Do patients who develop a tolerance to opioids have an addiction?
Not necessarily, but patients with addiction are also tolerant
In addiction with opioids, the brain responds by decreasing dopamine receptors. What does this result in?
Substance doesn’t provide as much pleasure anymore but craving for it is worse
What is defined as compulsive use of drugs (in spite of adverse consequences) that are no longer required medically?
Addiction
Abondoning responsibilities, constipation, depression, mood swings, slurred speech, poor coordination, needle marks from injection, and infections from injection are all signs of what?
Addiction
Addiction to opioids is more likely under what circumstance?
If UNDERprescribed, pt develops severe pain → relieved by opioids → reinforcement and reward pathway activated
What is important to prevent addiction to opioids?
Stay ahead of the pain
The following are sxs of what?
Dysphoria, anxiety, insomnia, anorexia, yawning, chills, goosebumps, vomiting, diarrhea, rhinorrhea, lacrimation, increased BP/ HR/ temp, muscle aches/ twitches
Opioid withdrawal
Sxs of opioid withdrawal can be reduced with the use of what?
Clonidine (or another opioid- Methadone)
Opioid antagonists can precipitate what if dependent?
Withdrawal
What are the signs of opioid overdose?
CNS depression, respiratory depression, pinpoint pupils (may dilate if severely hypoxic)
How do you treat opioid overdose?
Supporting respiration + opioid antagonist (Narcan)
What are the routes of administration for opioids? (5)
Patient controlled analgesia, transdermal patch, intranasal spray, buccal-lollipop, sublingual
In order to maximize effectiveness, opioids should be combined with what?
Non-opioids
What is the protocol for opioid use in terminal illness?
Use enough drug to control pain and relieve suffering
Aside from analgesia, what are the clinical uses of opioids?
Acute pulmonary edema, relief of cough, treatment of diarrhea, anesthesia
How are opioids used in anesthesia?
General- adjunct to control pain
Spinal- epidural with local anesthetics
What drug interactions should you be cautious of with use of opioids?
Sedative hypnotics, antipsychotics, MAO inhibitors, CYP2D6 inhibitors
Opioids + sedative hypnotics will have what what effects?
Increased CNS and respiratory depression
Opioids + antipsychotics will have what effects?
Sedation
What are the contraindications to opioid use? (5)
- Partial agonist + full agonist
- Head injuries (increased IC pressure)
- Pregnancy
- Impaired pulmonary/ hepatic/ renal fxn
- Some endocrine diseases
When does withdrawal occur with opioids?
Abrupt discontinuation after chronic treatment, or with administration of an antagonist or partial agonist
Relapse with opioids is often prevented with what?
Another opioid (buprenorphine or methadone)
Why do addicts often go back to using drugs?
Not b/c drugs are working but b/c they don’t want withdrawl or lack of drug causes dysphoria
What opioid gets into the brain well, can be injected, snorted or smoked, and is commonly abused because it produces euphoria?
Heroin
What opioid stimulates all opioid receptors, is a strong agonist, and produces all of the effects of opioids?
Morphine
What is the use of Morphine and what route of administration is most effective?
Severe pain (ER long acting if chronic/ terminal pain)
More effective when injected due to high first pass metabolism
What opiois has rapid onset after parenteral administration, max analgesic action w/i 1 hr of injection and duration of analgesia of ~4-6 hrs?
Morphine
Morphine is primary excreted via what?
In the urine as metabolites
How is morphine metabolized?
In liver by CYP2D6
What are the SEs of morphine if injected?
Itching or vomiting
Morphine and other opioids readily cross the placental barrier and can affect the fetus how?
Respiratory depression or drug dependence with chronic use
Why is Hydromorphone a good alternative to morphine? (3)
More potent, metabolites don’t accumulate so good if renal dysfunction, less likely to cause histamine release and itching
What opioid has a long half life/ duration of actio, stimulates mu receptors, and may also block NMDA receptors and inhibit NE/5-HT reuptake?
Methadone
What is the use of Methadone? (3)
Maintenance treatment of addicts, long-term control of pain, low does used to prevent withdrawal sxs (withdrawal milder but prolonged)
What opioid is effective in “hard-to-treat” types of pain?
Methadone
What are the SEs of Meperidine (Demerol)?
Euphoria, tachycardia, pupil dilation
(Normeperidine can cause seizures)
What is the caution with Meperidine (Demerol)?
Do not use for > 48 hrs, in high doses, or in renal failure (due to accumulation of metabolites)
What is the use of Meperidine (Demerol)?
Obstetrics- less respiratory depression in baby
(also no cough suppression)
What is the caution with Meperidine (Demerol) and MAOIs or other anti depressants?
Serotonin syndrome
What opioid is very lipid soluble, highly potent, has a short duration of action and half life, and high abuse potential?
Fentanyl
What is the use of Fentanyl?
Short surgical procedures (w/ midazolam), longer surgeries (good CV profile)
What are the SEs of Fentanyl?
Truncal rigidity (if given rapidly IV), drug interactions (CYP3A4)
What are available routes of admin for Fentanyl?
IV, transdermal patches, lollipops
What opioids is used for mod to severe pain, often combined w/ acetaminophen, given orally/ well absorbed, and has a fairly short half life and duration of action?
Hydrocodone and Oxycodone
Conversion by what is needed for some of the analgesic effect of Hydrocodone?
CYP2D6 (therefore doesn’t work as well in some pts on SSRIs)
Why is it recommended to prescribe Hydrocodone, Oxycodone or Codeine w/o acetaminophen?
Risk of acetaminophen toxicity
Oxycodone, Hydrocodone, and Codeine must be metabolized by what in order to become active and to increase analgesic effectiveness?
CYP2D6
How has oxycodone changed to decrease abuse potential?
Delivery forms modified, Naloxoen or naltrexone added to prevent effect if injected
What is the use of Codeine?
Cough suppresant, mild to mod pain
What is the caution with Codeine?
Shouldn’t be used in small children
What opioids are generally given orally in combo with acetaminophen or aspirin?
Codeine, Oxycodone, Hydrocodone
How can genetic differences in CYP2D6 lead to different drug effects?
Ultra metabolizers (convert more than they should)
Extensive metabolizers (normal)
Poor metabolizers (basically useless)
What opioid is a kappa receptor agonist, and a mu receptor partial agonist?
Pentazocine/ naloxone
What is the use of Pentazocine/ naloxone?
Moderate pain, oral or injected
What are the benefits of using Pentazocine/ naloxone over some other opioids?
Fewer SEs (less sedating, resp depression, and GI effects)
What are the cautions with use of Pentazocine/ naloxone?
May cause dysphoria, may cause withdrawl in pts dependent on opioids (partial mu agonist)
What opioid is a partial agonist on mu and has a ceiling effect (therefore not causing much euphoria)?
Buprenorphine
What is the use of Buprenorphine?
Maintenance treatment of opioid addiction- decreases craving for drug
Buprenorphine is typically combined with what other drug?
Naloxone
What is the MOA of Tramadol?
Weak mu agonist, inhibits NE/5-HT reuptake (contributes to analgesic effect)
What is the use of Tramadol?
Mild to mod pain
What drug interactions should you be cautious of when using Tramadol?
Combo with antidepressants- seizures
Combo with MAOIs, TCAs, SSRIs- serotonin syndrome
What is the MOA for Dextromethorphan?
Blocks NMDA receptors, decreases 5-HT reuptake
What is the use of Dextromethorphan?
Cough suppressant (not an analgesic)
What drug is associated with abuse in teenages and has even caused some deaths (robotripping)?
Dextromethorphan (in some OTC meds)
With respect to SEs, what is a benefit of Dextromethorphan?
Not likely to cause constipation
What is the MOA of opioid antagonists?
Bind to opioid receptors and prevent agonists from acting
When will mixed opioid agonists/ antagonists exert their effects?
Alone will cause stimulation of receptor
Antagonism if other stronger agonist used concurrently
What is the DOC for opioid overdose?
Narcan (reverses resp depression, consciousness, awareness of pain, miosis, constipation)
How is Narcan administered?
Must be injected, give until pupils dilate
What is the duration of action of Narcan?
Short (2 hrs)
What is the use for Naltrexone?
Treatment of opioid addicts (esp HCPs), decreases craving in recovering alcoholics
What are the pharmacokinetics of Naltrexone?
Effective orally and long-acting
Long acting prep injected to treat addiction
What effect might Naltrexone have in patients dependent on opioids?
Will precipitate withdrawal
What is the caution with use of Naltrexone chronically?
Liver toxicity (concern in alcoholics)
