Opiods Part 2 Flashcards
What is Meperidine (Demerol)?
A synthetic opioid agonist at mu and kappa receptors
- structurally similar to atropine
- fentanyl products are derived from the base of meperidine
How is meperidine metabolized?
Extensive hepatic metabolism —> normeperidine —> merperidinic acid, which has toxic effects
- primarily excreted by kidneys
- the worse the kidney, the more toxic the effects
- 1/ life is 3-5 hours
- 60% protein bound
What are the the analgesia and 1/2 life of normeperidine (first mepeperidine metabolite) like?
1/2 the analgesic properties of meperidine (still active)
Elimination time is 15 hours
—> >35 hours in renal failure (keeps extending and extending)
What are side effects of normeperidine?
- Produces CNS stimulation *
- CNS stimulation leads to myoclonus and seizures
- Demerol induced delirium-> confusion, hallucinations,
- worse in elderly
What is meperidine used for now?
Too dangerous to use routinely for pain
Mainly used for shivering
What are side effects of meperidine?
- increased HR (atropine like effect)
- orthostatic hypotension- frequent and profound
- interferes with compensatory SNS
- large doses decrease myocardial contractility
- dose dependent ventilatory impairment- worse than morphine
- Serotonin Syndrome ** especially when given with SSRIs, MAOIs, zyvox and ultram
What is Serotonin Syndrome?
- FEVER, HTN, CONFUSION ** hallmark signs (without other sources)
- tachycardia
- diaphoresis
- confusion, agitation
- hypereflexia
- coma, seizures
- coagulopathies
- metabolic acidosis
If planning to give meperidine, zyvox or ultram and your pt is on antidepressants (SSRI,MAOI), what can you do to prevent serotonin syndrome?
Hold antidepressant while pt is on zyvox, ultram or meperine
- 7 days for zyvox treatment usually
Is there currently a dose ceiling for opioids?
No
What is the mechanism of action for methadone?
Mu agonist with NMDA antagonism
- CYP metabolism—> inactive metabolites
- renal and fecal elimination
- variable 1/2 life (8-60 hours)
- causes QT prolongation (risk of tornadoes)
What are some opioid agonist-antagonists (mixed agents)?
- pentazocine
- but orphan oil
- nalbuphine
- bupresnorphine
- nalorphine
- bremazocine
- dezocine
Why are mixed agents important (opioid agonist-antagonist)?
Created in response to deaths from respiratory depression in pure opioid agonists
What is the mechanism of action for opioid agonist-antagonists?
Bind to mu receptors
- partial agonist produce LIMITED EFFECT AT MU RECEPTOR
- competitive antagonists produce NO EFFECT at mu receptor
- may cause partial agonist action at kappa and delta receptors **
- antagonistic property may effect other opioids
What is unique about opioid agonist-antagonists?
Glass ceiling: antagonist effect creates a maximum beyond which additional levels have no effect
What are the advantages of opioid agonist-antagonists?
- provides analgesia with limited ventilatory depression
- low potential fro physical dependence
- should be reserved for pts who cannot tolerate pure opioid agonists *
What is true of tolerance and dependence with opioids in general?
- major limitation of all opioids
- cross tolerance develops between all opioids
- tolerance can occur without dependence *
- dependence cannot occur without tolerance
What is the structure like in opioid antagonists?
- result from minor changes to structure of opioid agonist
- most commonly, substitution of an alkyl group for a methyl group
What are the 3 main opioid antagonists?
- nalaxone
- naltrexone
- nalmefene
- “nals” *
How do opioid antagonists work?
- competitive antagonism
- high affinity for opioid receptor
- displaces opioid from mu receptor
What is nalaxone?
Non-selective antagonist at all 3 opioid receptors
- useful in reversal of opioid (in neonates also) and in detecting suspected physical dependence
How is nalaxone metabolized?
Hepatic enzymes
- 1/2 life 60-90 minutes ( may need repeated doses for long acting opioids)
- duration of action = 30-45 minutes
What are side effects of naloxone?
- reversal of analgesia/sudden onset of pain
- N/V related to speed of injection
- increased SNS activity—> tachycardia, HTN, pulmonary edema, cardiac dysrhythmias
What are neuraxial opioids?
Opioids in the epidural or subarachnoid space
- mu receptors present in substantia gelatinosa of the spinal cord
What is unique regarding neuraxial opioids?
Analgesia from neuraxial opioids is NOT associated with:
- SNS denervation
- skeletal muscle weakness
- loss of proprioception (own sense of movement)
What is the significance of the epidural space being lipophillic?
- meds here can still absorb systemically (especially if lipophillic-> cell membranes are lipophillic)
- morphine is ionized and tends to stay in the epidural space
- vasoconstrictors (epi) given to keep med in
Epi is given to prevent epidural med from distributing systemically, but…….
It does not effect diffusion into CSF (depending on lipid solubility)
- coughing/straining causes quicker absorption
- positioning has no effect
When an opioid is given in epidural space there are similar blood/plasma concentrations as when given which other route?
I.M.
What are the 4 classic side effects on neuraxial morphine administration?
- ) pruritus
- ) N/V
- ) urinary retention
- ) depression of ventilation
* * neuraxial opioids can also cause shingles **
Which receptors does Ketorolac (toradol) work on and what effects do they have?
NSAID, COX 1 and 2 inhibitors
- COX participate in inflammatory and pain cascade
- also work on gut and kidneys
- COX 1 protects layer in GI tract—> NSAID use reduces this layer—> GIB
What are side effects of Ketorolac?
- BLACK BOX WARNING: NOR MORE THAN 5 DAYS OF USE DUE TO RISK OF GI BLEEDING*
- ARF
- GI
- CHF
- platelet malfunction
What are some considerations for acetaminophen (Ofirmev: IV)(Tylenol)?
- Hepatotoxicity * cause by metabolite Napqui
Give mucomyst for O.D.
What are maximum daily doses for acetaminophen?
Liver failure: 2 G daily
Elderly: 3 G daily
What is the mechanism of action for Tramadol (Ultram)?
Mu agonist, weak SNRI (serotonin norepinephrine reputable inhibitor)
- CYP metabolism: no active metabolite
- *contraindicated in seizures **
- lowers seizure threshold
- anyone with seizures should never take ultram
