Anesthesia Pharm II Flashcards
Opioid receptors
mu, delta, and kappa
Opioid mechanism of action
- opioid binds receptor
- Ca2+ channels close
- K+ channels open
- cells hyperpolarize
- transmission blocked
primary effect is a decrease in neurotransmission
Where are opioid receptors located
brain, spinal cord, and peripheral nerves
Common clinical effects of Opioids (8)
- impairs sympathetic compensatory responses
- itching
- depression of ventilation
- increased CO2 increases ICP
- sedation
- biliary spasm
- nausea/vomiting
- urinary retention
Meperidine
(Demerol)
- antispasmodic effect
- renal excretion
- CNS stimulant
- shivering
- serotonin syndrome
- demethylation to normeperidine in the liver
Fentanyl
- renal excretion
- stable hemodynamics
- no amnestic effect
- depression of ventilation
- skeletal muscle rigidity possible
Sufentanil
- renal and biliary excretion
- bradycardia
- skeletal muscle rigidity
Rank in order of duration
morphine, meperidone, fentanyl
fentanyl < meperidone < morphine
Remifentanil
- ester linkage susceptible to hydrolysis
- rapidly titratable
- respiratory depression
- no change in ICP
*must add a longer acting agent to cover post-op pain
Context-Sensitive half-time of Remifentanil
4 minutes
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Sufentanil
Fentanyl
Alfentanil
Remifentanil
Rank in order of increasing context-sensitive half time:
Sufentanil, Fentanyl, Alfentanil, Remifentanil
Remifentanil
Sufentanil
Alfentanil
Fentanyl
Codeine
- interindividual variability
- cough supressant
Hydromorphone
(Dilaudid)
- 5x more potent than morphine
- faster onset
- oral dose every 4 hours
- agitiation/restlessness
- dangerous when combind with other sedatives
Oxycodone
moderate to severe pain
high abuse potential
Hydrocodone
high abuse potential
Methadone
- used for chronic pain
- prolonged duration of action
- overdose possible
- used to control withdrawal symptoms
Opioid Agonist-Antagonist
- binds to mu receptors, but produce limited effects
- may antagonize effects of other narcotics
- may produce dysphoric effects
- low abuse potential
- limited respiratory depression
Pentazocine
(Talwin)
combined with naloxone to prevent “powdering”
can develop phyiscal dependence
Suboxone
treats opioid addiction
Naloxone
- nonselective antagonist of all 3 opioid receptors
- treats depression of ventilation
Naltrexone
treats alcoholism
Q24 hour dosing
PCA pumps
(patient-controlled anesthesia)
- Settings
- drug concentration
- loading dose
- lockout interval
- basal rate
Which opioid has a cephalad movement?
Morphine
less lipid soluble compared to fentanyl/sufent
Side effects of Neuraxial Opioids
- itiching
- urinary retention
- nausea/vomiting
- depression of ventilation
*does not appear in breast milk
*may be reversed by naloxone
Masimo Acoustic Monitor
alarm that triggers when patient stops breathing
- 81% sensitive
- do not give to a person at risk of hypoventilation
Withdrawal symptoms
- yawning
- diaphoresis
- lacrimation
- coryza (stuffy nose)
- insomnia
- abdominal cramps
- nausea/vomiting
What can cause an increase of NMB activity?
CO2 retention
- patient can hypoventilate in PACU and become “recurarized”
- Treatment
- increase FIO2
- sit patient up
- assist ventilation
- additional reversal
What can reverse a spasm of the sphincter of Oddi?
naloxone or glucagon (2mg IV)
4 Parts in a Nociceptive system
- transduction
- transmission
- modulation
- perception
What accounts for perception of sensory-discriminative component of peripheral pain stimuli?
forebrain somatosensory cortex
What accounts for the perception of motivational affective components of pain?
Limbic cortex and Thalamus
(3) Primary afferent nocicpetors
A-beta, A-delta, and C fibers
A-alpha fibers
proprioception
myelinated
wide diameter
fastest conduction speed
A-beta Fiber
touch
myelinated
wide diameter
fast conduction speed
A-delta fiber
pain (mechanical and thermal)
myelinated
narrow diameter
slow conduction speed
C fiber
pain (mechanical, thermal, and chemical)
non-myelinated
narrowest diameter
slowest conduction speed
sensory nerves travel to what part of the spine?
dorsal root (posterior)
also dorsal root ganglion
Gate Theory of Pain
painful stimuli can only be reached when “gate” is open
- can be closed by inhibitory impulses
- rubbing painful area
- A-beta fibers faster than C fibers
“wind up” sensitization
repeated peripheral noxious stimuli where the pain increases with each stimulus, but the intensity of that stimulus remains the same
Heterosynaptic activity-dependent plasticity
a brief intense stimulus increases the efficiency of the dorsal horn synapses causing subsequent subthreshold inputs to result in pain
(4) ascending pathways of pain perception
–spinothalamic tracts (STT)
–spinomedullary projections
–spinobulbar projections
–spinohypothalamic tract (SHT)
Spinothalamic Tract (STT)
- originates in dorsal horn
- travel up contralateral side
Spinobulbar projections
the integration of nociceptive activity with processes that serve homeostasis and behavior
Spinohypothalamic Tract (SHT)
important for autonomic, neuroendocrine, and emotional aspects of pain
Neurotransmitters involved in Pain
glutamine
enkephalin
norepinephrine
GABA
Somatic Stimuli
easily localized and a distinct sensation
Visceral pain
diffuse and poorly localized
Complex Regional Pain Syndrome (CRPS)
reflex sympathetic dystrophy
- Type I - absence of major nerve injury
- Type II - specific nerve injury
- hyperalgesic
Perfusion pressure
MAP - CVP
Transmural pressure
pressure outside the tube minus pressure inside the tube
GABA mechanism of action
increases Cl- conductance
hyperpolarizes and inhibits postsynaptic neuron
(6) GABA agonists
- propofol
- etomidate
- benzodiazepines
- nonbenzodiazepines and benzodiazepines
- barbituates
- alcohol
Diprivan pH
7 - 8.5
uses disodium edetate and sodium hydroxide
Generic Propofol pH
4.5 - 6.4
uses sodium metabisulfite
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propofol’s context sensitive half-time with 8 hour infusion is less than 40 minutes
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6 effects of Propofol
- decreases cerebral metabolic rate
- decreases cerebral blood flow
- decreases ICP
- autoregulation maintained
- does NOT modify evoked potentials
- tolerance does not develop
6 Cardiovascular effects of Propofol
- decreases:
- BP
- SVR
- contractility
- does not alter SA or AV node function
- does NOT prolong QTc interval
Propofol infusion syndrome
lactic acidosis with infusions over 24 hours
Etomidate
- GABAA receptor
- rapid in onset
- hydrolyzed in the liver and plasma esterases
- involuntary myoclonic movements
- NO analgesic properties
Effects of Etomidate
- lowers ICP and CMRO2
- minimal effects on contractility
- nausea
- adrenocortical supression
What occurs after a decrease in SVR?
lower blood pressure
reduced filling of the LV secondary to increased pericardial pressure prevents a compensation in stroke volume to maintain BP
Midazolam
- water soluble
- metabolized by P450 and excreted by kidneys
- anticonvulsant
Effects of Midazolam
- decreases CMRO2
- decreases cerebral blood flow
- decreases hypoxic drive
- especially with fentanyl
Lorazepam
slow onset and long duration
- delays emergence
- suitable for withdrawal symptoms
Flumazenil
competitive antagonist of benzodiazepines
- may result in seizures
- no negative cardiovascular side effects
(3) Nonbenzodiazepine Benzodiazepine drugs
Zaleplon (sonata)
Zolpidem (ambien)
eszopiclone (lunesta)
what classification do the “sleeping agents” fall under?
nonbenzodiazepine benzodiazepine
Ketamine Characteristics
- intense analgesia at “sub-anesthetic” doses
- emergence delirium
- hemodynamically stable
- not a respiratory depressant
What receptor does Ketamine bind?
NMDA
(N-methyl-D-aspartate)
* Glutamate is the neurotransmitter and glycine is the co-agonist
Which sedative is useful in patients who are unable to be monitored or have a maintained airway?
Ketamine
Ketamine cautions
- aspiration risk
- hypersensitive reflexes
- delirium
Dexmedetomidine
(Precedex)
- potent alpha2 agonist
- mainly on pontine locus ceruleus
- inhibitory
- decreases plasma catecholamines
- decreases MAC
spasm of the muscles causing backward arching of the head, neck, and spine, as in severe tetanus, some kinds of meningitis, and strychnine poisoning
opisthotonos
Artery of Adamkieqicz
provides the major blood supply of the lumbar and sacral cord
- located between T8 and L1
Ideal anesthetic for aortic insufficiency
- decreased SVR
- preserved or increased HR
Ideal anesthetic for aortic stenosis
- preserved SVR
- prevent tachycardia
Aortic Stenosis concerns
- left ventricular hypertrophy
- vasodilators are hard to recover from
- CPR is ineffective
- easy to kill someone
- avoid spinals
Ideal anesthetic for Mitral Regurge
decreased SVR and preserved HR
Ideal anesthetic for Mitral Stenosis
preserved SVR and decreased HR
Causes of QT prolongation
- Sevo and Iso
- Type 1A and III antiarrhythmic agents
- hypokalemia
- hypocalcemia
- Droperidol
Normal QTc interval
< 430 in male and < 450 in females
Equation for QTc
QTc = QT / sqrt(RR)
Which is the best inhalational agent for a cardiac ablation?
Sevo
(TIVA even better)
Which inhalational agent causes “steal”
Isoflurane
does minute ventilation increase/decrease with inhalational agents?
decrease