OPIOIDs Flashcards
Activation of u receptors cause what behavioral changes?
Analgesia
euphoria
respiratory depression
Physiological dependence
delta and kappa receptors contribute to what effect?
and at what level do they act?
Contribute to analgesia particularly at the spinal level.
mu kappa and delta receptors (all are G protein) assert functional effects on:
supraspinal analgesia
spinal analgesia
mu asserts functional effects on:
Respiratory depression Supraspinal analgesia spinal analgesia reduced GI motility Sedation
mu and delta assert functional effects on:
reduced motility
Kappa
psychotomimesis (symptoms of psychosis)*
sedation
spinal analgesia
supraspinal analgesia
mu and Kappa receptors assert functional effects on:
sedation
- At high concentrations what drug is known to cause seizures?
- What may cause the increase in concentration?
- Normeperidine a metabolite of meperidine.
2. Decreased renal function causes the accumulation of the metabolite
What are opioids converted to before they get excreted by the kidneys?
Example?
Glucuronides
example Morphine is conjugated to Morphine-3-glucuronides (M3G)- a compound with neurotoxicity.
How are esters like heroine and remifentanil hydrolyzed?
They are hydrolyzed by tissue esterases
example: Heroin is hydrolyzed to monoacetylmorphine–> morphine–>conjugated to glucuronic acid.
What happens to patients w/ decreased renal function?
accumulation of meperidine and normoperidine may occur. Causes seizures at high doses!!!
Where and what metabolizes Fentanyl?
and what are it metabolites?
CYP 3A4 in the liver.
Fentanyl has no active metabolites
100 times more potent than morphine!!.
Rapid onset short duration.!!!
Where and what metabolizes Codeine/Oxycodone and hydrocodone?
and what are it metabolites?
CYP 2D6 in the liver.
Metabolites with greater potency are formed eg. morphine from codeine.
opioid derivatives most commonly used as antitussives are:
Dextrometorphan and codeine
Most commonly used drugs to control diarrhea?
What receptors mediate actions of these drugs?
Do they have analgesic effects at their usual doses?
Loperamide (imodium) and diphenoxylate (AKA Lomotil-formulated with Atropine to reduce abuse potential) mu and delta
they lack analgesic effects!
Adverse effects of the opioid analgesics include:
Nausea* Vomiting* Sedation* Itching* Constipation* Urinary retention Hypotension Respiratory depression *=reported AEs
CIs of opioid use:
Patients with head injuries (CNS area of action)
Pregnancy: Fetus may become dependent
Patients with impaired pulmonary function (due to respiratory depression)
Patients w/ impaired hepatic function (Metabolic enzymes)
Patients w/ impaired renal function (site of excretion)
Patients with endocrine disease
Drug interactions
- Sedative
- Antipsychotics
- MAOI + Opioids
Sedative-hypnotics: increased CNS depression particularly respiratory depression.
Antipsychotics: Increase sedation
- variable effects on respiratory depression
- Accentuation of CV effects (antimuscarinic and alpha blocking actions).
MAOI:
Meperidine and MAOI–>resulted in life threating reactions
Tramadol and MAOI–>similar interactions
Strong Agonists:
- Morphine
- Hydromorphone and Oxymorphone
- Heroin
Morphine: high affinity for mu* receptors and lower affinity for delta and kappa receptors
-standard of opioid measurement
Hydromorphone and Oxymorphone: usefull in treating severe pain
Heroin: rapidly hydrolyzed to 6 MAM–>morphine
- both heroin and 6-MAM are more liposoluble than morphine and enter the brain more readily.***
- Heroin and 6-MAM responsible for pharmacological actions of heroin.
Meperidine: mu* receptor agonist.
- No longer recommended for Tx. of chronic pain due to metabolite toxicity
Meperidine drug Interactions:
The most prominent is an excitatory reaction (“serotonin syndrome”) w/: delirium; hyperthermia; headache; hyper or hypotension; rigidity; convulsions; coma and death.
- due to ability of meperidine to block reuptake of serotonin.
- do not take with MAOI
Strong mu* agonist a 100 times more potent than morphine?
Fentanyl
rapid onset and short duration of action (15-30 minutes)
100 times more potent than morphine
strong mu* agonist w/ equal potency to morphine?
Methadone
less euphoria and longer duration of action
Also and NMDA antagonist and serotonin and norepinephrine reuptake inhibitor.
Interesting choice for chronic pain
prolonged abstinence syndrome but less severe.
methadone AE:
QT prolongation
torsades de pointes and death have been reported
Mild to moderate agonists:
codeine
oxycodone and
hydrocodone
- rarely used alone: combined w/ acetaminophen aspirin or other drugs.
- codeine has low affinity for opioid receptors
- CYP2D6 converts to morphine for analgesic effects
Tramadol: weak mu agonist and serotonin norepinephrine reuptake inhibitor*
- Useful in NEUROPATHIC PAIN*
- increased risk of seizures in patients with seizure disorder and those taking meds that lower seizure threshold.
- “Serotonin syndrome”*- do not use with serotonergic drugs
Mixed agonist-antagonist:
Whats common to all Mixed agonist-antagonist?
Whats common to only 3 of them?
Pentazocine: k agonist and u antagonist or partial agonist.
Butorphanol
Nalbuphine - u antagonist
Buprenorphine*: partial mu agonist and kappa antagonist.
- potent analgesic in opioid naive patients.
- ppt withdrawal in patients who are physically dependent on opioids.
- developed to reduce addiction potential of the opioids
- mild to moderate pain
CEILING EFFECT* is common to all
Tx. of acute opioid overdose
Naloxone
Tx. for opioid addiction
Naltrexone
decreases craving for alcohol in chronic alcoholics and its approved for this purpose.
Naltrexone
What are opioids metabolized to
Gucuronides which are then excreted by kidneys
what is morphine metabolized to?
What are the effects of the metabolite?
Are the effects mediated by opioid receptors?
- Morphine-3-Glucuronide (M3G) 10% metabolized to M6G
- Neuroexcitatory effects-M3G and analgesic effects with M6G (4-6 times potent)
- No for M3G and yes for M6G
how are opioid analgesics in anesthesia used?
- Premdicant drugs before anethesia and surgery because of their sedative anxiolytic and analgesic properties?
Intraoperatively both as adjuncts to other anesthetic agents and as primary component of the anesthetic regimen.
Regional analgesics by intraspinal administration.
Do Antitussive use the same receptors as other opioids?
No. they differ
