Exam 1 Opioids Flashcards
What are the endogenous opioid peptides and their cause
- enkephalin: analgesia
- Beta endorpin: runners high
- Dynorphin: hyperalgesia
Receptors: Mu, Kappa, Delta, their effect and their MOA
Mu: analgesia, euphoria, sedation, SE
K: euphoria or dysphoria
Delta: dysphoria
- all R coupled to Gi
- all close voltage gated Ca channels on PREsynaptic nerve terminals (decrease NT release, decreasing pain signaling)
- Mu often K channels on Postsynaptic neuron causing hyperpolarization, inhibiting n transmission and pain signal
- alpha2 receptors also decrease pain transmission in this region
How do opioids influence pain transmission
a. directly at inflammed and damaged tissue
b. inhibition of release of excitatory NT in dorsal horn aka SPINAL ANESTHESIA
c. Thalamic action
How do opioids modulate pain?
d. Periaqueductal gray may release endogenous opioids
e. Rostral ventral medulla
* NE path from LOCUS COERULEAS to dorsal horn may decrease pain
* inhibition of inhibitory neurons (GABA) may increase activity of pathways that inhibit pain (decreases pain transmission in dorsal horn)
Analgesic effect of opioid?
decrease sensation of and reaction to pain
TOLERANCE dev to analgesia
Sedation/mental clouding effect of opioids?
Not sleep aid disrupt REM Morphine --> CNS depression in OD Codeine and meperidine may cause excitement in OD *tolerance dev
Euphoria or dysphoria effect of opioids
Sense of floating, pleasure
- depends on receptor distribution in diff individuals
- tolerance develops to euphoria
Emesis effect of Opioid
N/V in some bc opioids stim chemoreceptor trigger zone in the brain (CTZ)
Will dev tolerance to N/V
*helps to take with food
Depression of cough reflex (antitussive) in opioids
Lower dose than those for analgesia
CODEINE and DEXTROmethorphan
- dextromethorphan not an analgesic
- meperidine doesn’t suppress cough
Tolerance develops to?… not to?
analgesia, sedation, euphoria, N/V, resp depression
NOT to miosis, constipation, seizures
Respiratory depression and opioid
more common in OD, but also with therapeutic; dose dependent
Decreases response of brain stem to CO2
USEFUL IN PULMONARY EDEMA
not good for people with pulm dz (COPD, asthma etc)
May cause bronchoconstriction
Tolerance may dev to resp depression
Elevated ICP and Opioids
Increased CO2 causes vasodilation, increase cerebral blood flow and pressure
*caution giving morphine/opioids to pt with head trauma
Decrease in body temp and opioids
opioids cause dysregulation in hypothalamus
Miosis and opioids
Common in OD but may convert to dilation in comatose pt
- no tolerance develops
- miosis (PNS) blocked by atrophine (anticholinergic)
- no mioisis with meperidine
Truncal rigidity and opioids
think fentanyl (highly lipid soluble)
- supraspinal effect increases tone of large trunk muscles, may interfere with resp or ventilation attempts
- USE NEUROMUSCULAR BLOCKERS to prevent truncal rigidity
Cardiovascular effect of opioids
May cause bradycardia
- hypoTN common (release histamine)
- may result from CNS vasomotor depression or vasodilation from histamine
*Tachycardia with Meperidine (anticholinergic property)
GI effects of opioids
decreased gastric activity local and CNS CONSTIPATION decreased motility Biliary colic, constriction of sphincter of Oddi, decreased secretions *prepare pt and be proactive
GU and Opioids
opioids have ADH effect, decrease urine and renal blood flow
- increase sphincter tone (harder to urinate), worse if BPH present
- increase urethral tone (harder to pass kidney stone)
Uterus and Opioids
Opioids may prolong labor
*meperidine doesn’t
Tolerance and Dependence with Opioids?
Yes, tolerance dev quickly when opioids used chronically (not to all effects)
- physical dependence also occurs (may result from desensitization of mu receptors)
- NMDA R antag may decrease development of tolerance (Methadone)
- Hyperalgesia may occur with long term use (increase in dynorphine maybe?)
Allergic to opioids? or what is the real cause of flushing, itching, sweating
- Opioids can produce histamine release that can cause flushing, itching, sweating. NOT a true allergy!
- more common with injected opioids
- Treat or pretreat with diphenydramine (benadryl)
Addiction is more likely if opioids are…
UNDERrx
*severe pain relieved by opioid provides reinforcement and activation of reward pathway. If tx before pain gets too severe, bypass the pathway
what are some opioid withdrawal sx
dysphoria, anxiety insomnia
- anorexia, yawning, chills, piloerection
- vomiting, diarrhea, rhinorrhea, lacrimation
- HTN, tachycardia, hyperpyrexia
- muscle ache, twitches
- Reduce sx with clonidine (alpha 2 adrenergic agonist used to tx HTN) or another opioid such as methadone
- opioid antagonists can precipitate withdrawal if pt is dependent
Signs of opioid OD
CNS depression, Resp depression, pin point pupils *may dilate if severely hypoxic
ABCS! support respiration, use opioid antagonist like Naloxone (Narcan)
Tx of opioid withdrawal? OD?
withdrawal sx treat with CLONIDINE
OD treat with ABC and Naloxone (Narcan)
General uses for opioids
- Analgesia (stay ahead of pain, give enough esp in terminal illness)
- Acute pulmonary edema (relieves dypsnea nad air hunger)
- Relief cough (codeine and dextromethorphan)
- Diarrhea (Loperamid (imodium) and diphenoxylate/atropine (Lomotil))
- Anesthesia (adjunct to control pain or spinal epidural with local anesthetics)
Drug interactions with Opioids
- Sedative hypnotics (increased CNS and respiratory depression)
- Antipsychotics (sedation, maybe resp depression)
- MAOI - especially Meperidine and dextromethorphan - Serotonin Syndrome
- CYP2D6 inhibitors (Fluoxetine, paroxetine) - caise cpdeome. pxucpdpme. judrpcpdpme tp mpt ne ,etanp;ozed tp actove cp,[pimts
Contraindications for Opioids include
- Do not use partial agonist with full agonist bc can impair analgesia, cause withdrawal
- Not for Pt with head injury (increase ICP)
- Not for Preg pt (esp at delivery)
- not for pt with impaired pulmonary or hepatic or renal function
- not for some endocrine diseases
Precautions with Opioids include
severe liver/kidney dz Pulm dz Biliary tract problems Seizures (esp Meperidine) Pain of unknown cause (esp abdominal) Head trauma Chronic non terminal pain? IBD Preg/breast feeding Urinary retention/ BPH
Morhpine: MOA, use, metab
- stim all opioid receptors, STRONG agonist
- useful in severe pain
- oral/ IV/ rectal/ intrathecal/ epidural
- best when injected bc high first pass
- short half life; use ER long acting oral prep in chronic/terminal pain
Hydromorphone (Dilaudid) effect, use, admin
- Strong analgesic (more potent than morphine); moderate to severe pain
- metabolites don’t accumulate, so good option if renal dysfunction pt
- less likely to cause Histamine release
Oral, SQ, IV, Rectal, IM
similar DOA as morphine (short half life)
Methadone (Dolophine) MOA, metab, use
- Stimulates Mu R, may also lock NMDA and inhibit NE and 5HT (less likely to dev tolerance to analgesia)
- Maintenance tx of addicts (prevent withdrawal sx, but more prolonged)
- now used in long term pain control and hard to treat types of pain
Meperidine (Demerol) MOA, effect, use, caution
- Mu agonist, can cause euphoria
- also inhibits NE/5HT reuptake - Serotonin syndrome with MAOIs!
- don’t use longer than 2d, in high dose or in renal failure (produce normeperidine, a toxic seizure causing metabolite)
- anticholinergic effects: tachy, mydriasis
- no cough suppression
- pref in OB bc less resp depression in baby
- less constipation/urinary retention than morphine
Fentanyl (Sublimaze): MOA, use, SE
Very lipid soluble and potent, short DOA and half life (highly abused by anesthesiologists)
- used in short surg procedures w midazolam
- may cause truncal rigidity if given rapidly IV
- available in transdermal patches or lollipops
- metab by CY3A4
other “tanils” are the same
Hydrocodone use, admin, metab, schedule
Mod to severe pain; often comb with APAP
*Hydrocodone-APAP (Vicodin) schedule III, alone hydrocodone is Schedule II
- sometimes comb with homatropine to decrease abuse potential
- oral, good abs, sort half life and DOA
- CYP2D6 metab needed for some analgesic effect (less effective if pt on SSRI esp fluoxetine or paroxetine)
Oxycodone (Oxycontin)- use, metab, schedule
- Schedule II, often abused
- Mod to severe pain, Tourettes, restless leg
- oral, may be extended release (oxycontin)
- Oxycodone- APAP (Percoset) or Oxycodone-ASA (Percodan)
- metab by CYP2D6 increases analgesic effectiveness - fluoxetine inhibits, decreases effectivenss
- half life 4 hr unless ER
- oxymorphone similar to oxycodone, also ER and schedule II
Codeine
good cough suppresant, mild to mod pain
- CYP2D6 metab to be active (inhibited by fluoxetine), some abuse
- converted to morphine
- oral, often comb with APAP or ASA
- not for kids
- schedule II if alone, III combined, IV in cough suppressants
Naltrexone (Revia)
Oral, long acting, tx opioid addicts
*precipitate withdrawal!!
Decreases craving in recovering alcoholics
*may cause liver toxicity
*Nalmefene similar to naloxone, with slighlt longer DOA and less liver toxicity
Naloxone (Narcan)
DOC for opioid OD
*reverse resp depression, consciousness, awareness of pain, miosis, constipation
INJECT, until pupils dilate
short DOA (2 hr)
*may beed repeat doseing
*now being ocmbined with some agonists to prevent abuse
*sometimes injective with agonsit to preven SE of the agonist but still allow anlagesia
Dextromethorphan
not an analgesic, a cough suppressant
*often comb with guafenisen (expectorant)
*no constipation
*blocks NMDA r - abuse potential
*decreases 5HT reuptake - serotonin syndrome with MAOIs
*drug of abuse in teens
OTC cough syrup, tablet/internet concentrated form w/o Rx
**has caused some death in teens
Pentazocine (Talwin) MOA, use, SE
K receptor agonist
- Mu receptor PARTIAL agonist
- moderate pain, oral or injected
- less sedating than other opioids
- less respiratory depression, GI
- low abuse potential schedule IV
- May cause dysphoria
- may cuase withdrawal in pt dependent on opioids bc is a partial Mu agonist
Buprenorphine MOA, use, admin
PARTIAL agonist on Mu and maybe K
- ceiling, doesn’t cause much euphoria
- low abuse, used for tx of opioid addiction
- inj, SL or intranasal
*if combined with naloxone: inje it, it won’t work, but SL admin will
Tramadol use, MOA, SE
mild to mod pain; weak Mu agonist
*nibits NE, 5HT reuptake
Contributes to analgesic effect
SE mild: dizzy, sedation, constipation, Nausea
com with antidepressants - seizures
combine with MAOIs, TCAs, SSRI - serotonin syndrome
Low abuse potential
Tapentadol similar, but schedule II
