Opioids Flashcards
drugs which are naturally derived
for opium (extract from the poppy plant);
also refers to synthetically produced drugs
which have opium- or morphine-like
properties
opioids
derived from the Greek word
meaning stupor; used interchangeably with
opioid; has negative legal connotation
narcotics
4 favorable opioid properties
- Analgesia
2.Preservation of blood flow autoregulation
(CNS, heart, kidneys) - Minimal cardiac depression with
maintenance of hemodynamics
4.Blunting of autonomic responses to
sympathetic stimulation (laryngoscopy,
surgical stress)
MOA of opioids
Opioid agonists bind to opioid receptors at
presynaptic and postsynaptic sites in the
CNS (brainstem and spinal cord) and
peripheral sites (primary afferent neurons).
▪ Opioids act like the endogenous peptides
that normally activate these receptors:
enkephalins, endorphins, and dynorphins
what is the principal effect of opioid receptor activation?
decrease in neurotransmission
activation of opioid receptor causes these 2 things:
– Closure of voltage-gated Ca2+ channels on presynaptic
nerve terminals to cause a reduction of the release of
neurotransmitters (glutamate, acetylcholine, dopamine,
norepinephrine, serotonin, and substance P)
– Opening K+ channels to hyperpolarize the cell, thus
causing inhibition of the postsynaptic neurons
occurs through activation of opioid receptors in the
medulla, midbrain, and other areas, which causes inhibition of neurons
involved in pain pathways
supraspinal analgesia
occurs by activation of presynaptic ORs, which leads to
decreased calcium influx and decreased release of neurotransmitters involved
in nociception (sensory nervous system’s process of handling noxious stimuli)
spinal analgesia
explain the steps of the GPCR with opioids
– inhibit the activity of adenylate cyclase inside of cells. This results in a
decrease in intracellular cAMP, which decreases conductance of the voltagegated calcium channels (decreased neurotransmitters) and opens potassium
channels (hyperpolarization), resulting in decreased neuronal activity.
opioid analgesic effect 1
) directly inhibit the ascending transmission
of nociception information from the spinal
cord dorsal horn
opioid analgesic effect 2
activate pain control pathways that
descend from the midbrain, via the rostral
ventromedial medulla to the spinal cord
dorsal horn.
noxious stimuli (chemical, thermal, mechanical energy) is converted to an electrical impulse in sensory nerve endings
transduction
– conduction of electrical impulses
(action potential propagation) to the CNS – major
connections for these nerves in dorsal horn of the
spinal cord and thalamus with projections to the
cingulate, insular and somatosensory cortexes
(signal transmitted along myelinated A-delta fibers
and unmyelinated C fibers)
transmission
altering pain
transmission – both inhibitory and excitatory
mechanism modulates pain impulse
transmission in peripheral and CNS
modulation of pain
occurs at the thalamus
with the cortex important for discrimination
of specific sensory experiences
pain perception
▪ Effect: – Analgesia (spinal and supraspinal) – Euphoria – Miosis – Bradycardia – Hypothermia – Urinary retention
MU1 receptor
Effect: – Analgesia (spinal) – Respiratory depression – Physical dependence – Constipation (marked)
effects at MU2 receptor
what agonists affect mu1 and mu2
Endorphins, morphine, synthetic
opioids
Effects: – Analgesia (spinal, supraspinal) – Sedation – Dysphoria – Miosis – Diuresis – Respiratory depression
effects kappa receptor
what are the agonists of kappa receptors:
dynorphins, agonist-antagonists
▪ Effect: – Analgesia (spinal, supraspinal) – Respiratory depression – Physical dependence – Urinary retention – Constipation (mild)
effects at delta receptor
what is agonist for delta receptor?
enkaphalins
which receptors are present in high concentrations in the dorsal horn of the spinal cord
mu, kappa, delta
what 3 areas are receptors found supraspinal
▪ Rostral ventral medulla
▪ Locus ceruleus
▪ Midbrain periaqueductal gray area
the dose of a drug required to produce death in 50% of patients receiving the drug. Higher the number, safer it is to administer
LD50
what does the decrease in sympathetic tone and stimulation cause cardiovascular wise with opioid admin?
- Venous dilation, pooling
– Decreased venous return
– Decreased cardiac output and BP
– Orthostatic hypotension
what two opioids cause a relax in aortic smooth muscle
sufentanil and alfentanil
what causes the decrease in HR with opioids?
– due to stimulation of the vagal nucleus in the medulla
– SA node depression, slowed conduction through AV
node
– Opioid-induced bradycardia is responsive to atropine.
what opioid has muscarinic affect and causes tachycardia?
meperidine
you will see a synergistic decrease in BP when opioids combined with:
benzos (SVR) and nitrous (CO)
what two opioids are cardio protective
remifentanil and morphine
what receptor causes respiratory depression?
mu2
a decrease in responsiveness to PaCO2 causes
a right shift in the co2 curve which means a higher co2 is needed to stimulate breath
what medication can reverse respiratory depression without reversing analgesia?
physostigmine (using this because of decrease ACh release)
what type of patients do not tolerate a increase in paCO2 i.e: careful when giving opioids
– Patients with increased intracranial pressure
– Asthma, COPD, or cor pulmonale
what is cause of death of opioids
respiratory depression (mu2)
Mobilization of opioid from skeletal muscle following
rewarming, increased blood flow, and movement
re-narcotization (redistribution)
respirations are tied to …. during procedures
stimulation
what type of pain are opioids most effective with
visceral continuous dull pain
Can opioids be used as an anesthetic
NO THEY DO NOT CAUSE AMNESIA
when hypercarbia is avoided, opioids cause:
cerebral vasoconstriction,
a decrease in cerebral blood flow, and a decrease
in ICP
do opioids increase or decrease cerebral o2 consumption
decrease
what four reasons should you be careful when administering opioids to head trauma patients
– Sedative effects make neuro checks difficult
– Pupillary effects – miosis
– Hypoventilation effects – increased PaCO2 causes
vasodilation, increased ICP
– Increased sensitivity to opioids if blood-brain barrier is not intact
how do opioids cause miosis
excitatory action on the autonomic nervous
system.
an intensification of tone of large
muscles of the thorax and abdomen, “Stiff Chest
Syndrome, reduces compliance to ventilate
Trunchal rigidity
what is trunchal rigidity associated with
rapid administration of large doses of highly lipidsoluble opioids (fentanyl, sufentanil, alfentanil, remifentanil)
moa of trunchal rigidity
inhibited release of GABA in the muscles and increased dopamine production
how is trunchal rigidity prevented and treated
– Prevented with slow administration, avoidance of nitrous oxide
during induction
– Relieved with antagonist (Narcan) or relaxed with neuromuscular blockers
what medication causes closure of vocal cords
sufentanil (crap opioid to use for induction)
N/V is caused by
direct stimulation of the chemoreceptor trigger zone
floor of the fourth ventricle
reflect the effect of increased gastric secretions and
delayed emptying
what opioid depresses vomiting center in medulla
morphine
types of patients more at risk for n/v
ambulatory patients (especially young female gyn)
epidural
pca
what do you give if you want to diagnose biliary spasm (sphincter of oddi) vs angina pectoris
glucagon (1) , narcan, nitro
can opioids cross placenta
yes, be careful in use during delivery. safe for non-delivery procedures
Histamine release, urticaria, or a local
reaction more common with
morphine and meperidine
Reflex cough often seen with
administration of fentanyl-type on induction -
▪ No tolerance to these two effects
miosis
constipation
Opioid receptor desensitization* – Down-regulation of receptors – Up-regulation of the cAMP system – NOT due to enzyme induction (increase in the rate of metabolism of opioids occurs.) – Activation of NMDA receptors and downregulation of spinal glutamate transporters (treatment with small doses of NMDA antagonist, ketamine, to treat
theories of what causes opioid tolerance
4 withdrawal symptoms of opioids listed
– Yawning
– Diaphoresis
– Lacrimation
– Coryza – severe nasal congestion
what med is effective in hiding withdrawal signs
clonidine
effect opioids have on Hypothalamic-pituitary-adrenal axis
decreased plasma cortisol levels
Hypothalamic-pituitary-gonadal axis affects what 5 hormones
prolactin (increases)
decreases
-estrogen, d luteinizing hormone, follicle stimulating
hormone, testosterone
how does opioid exposure affect immune system
Alter the development, differentiation, and
function of bone marrow progenitor cells,
macrophages, T cells
triad of opioid overdose
miosis, hypoventilation, coma
overdose symptoms
Respiratory depression – principal symptom
▪ Pupils symmetric and constricted (if hypoxemia,
mydriasis)
▪ Muscles flaccid
▪ Likely airway obstruction
how to treat overdose
mechanical ventilation with O2
administration of opioid antagonist (naloxone,
Narcan), which may cause acute withdrawals
what organ plays significant role in first pass uptake
lungs
how much sufentanil is found in lungs immediately after injections
50%
Amount of uptake by the lungs is influenced by
▪ Prior accumulation of another drug (decreases)
▪ Smokers (increases)
▪ Inhalation anesthetic administration (decreases)
the effect of small doses of opioids is terminated by
redistribution
large doses of opioids are terminated by
metabolism
Most opioids are chiefly metabolized by the
liver (except for remifentanil)
what are the two metabolites of morphine?
morphine 3-glucuronide and
morphine 6-glucuronide
how are opioids excreted
kidneys!! different than metabolization
metabolite of meperidine
normeperidine (causes seizures)
When used in conjunction with propofol for
TIVA (total intravenous anesthesia),
clinically useful doses of propofol inhibit the
degradation of alfentanil and sufentanil by
50-60% and up to 90% with higher propofol
doses.
