Barb/Non-Barb EXAM REVIEW Flashcards
What is a common side effect associated with the use KETAMINE? (MUPU)
-Unique in its ability to stimulate the CV system
-Unique in its ability to cause emergence delirium
- May ⇧ ICP placing pts with intracranial pathology at
risk
- Produces CV effects that resemble sympathetic
nervous system stimulation (INCREASES HR and BP)
What is a common side effect associated with the use ETOMIDATE?
CV stability is characteristic with 0.3mg/kg IV
induction dose
• Minimal changes in HR, stroke volume or cardiac
output
MYOCLONUS: Excitatory effects that manifest as spontaneous movements, dystonia and tremor
• ⇩ cerebral blood flow and CMRO2
• ⇩ ICP
What is a common side effect associated with the use PRECEDEX?
Hypotension, transient HTN
Nausea, bradycardia, fever, vomiting, hypoxia
Tachycardia, anemia, dry mouth, thirst
What is a common side effect associated with the use PROPOFOL?
CNS
⇩cerebral metabolic rate for oxygen (CMRO2)
⇩ ICP and cerebral blood flow
⇩burst suppression)
⇩ somatosensory evoked potentials (SSEP) and
motor evoked potentials (MEPs)
CV
⇩ in systemic BP( ⇩ preload) greater than
equivalent thiopental dose
⇩ BP often accompanied by changes in cardiac
output and SVR
BRADYCARDIA
- Relaxation of smooth muscle is due to inhibition of
sympathetic vasoconstrictor nerve activity
• Stimulation of laryngoscopy and intubation reverses
BP effects of propofol
• BP effects exaggerated in hypovolemic, elderly, & pt
with compromised LV function due to CAD
• Adequate hydration recommended prior to administering propofol
RESP
Maintenance doses of propofol ⇩ Vt and RR
• Causes bronchodilation and ⇩ incidence of
intraoperative wheezing in asthma pt
• ⇩Ventilatory response to CO2 & arterial hypoxemia
What is a common side effect associated with the use METHOHEXITAL?
High dose associated with seizures
Normovolemic pt- transient 10-20 mmHg ⇩ in BP
and offset by compensatory 15-20BPM ⇧ in HR
Overdose or large dose to ⇩ ICP may cause direct
myocardial depression
Induction- mild, transient ⇩ BP due to peripheral
vasodilation (mostly venous), reflecting depression
of the medullary vasomotor center and ⇩
sympathetic nervous system outflow
Propofol dose :_______equivalent _________ thiopental or __________Methohexital
• 1.5-2.5mg/kg IV is equivalent to 4-5mg/kg
thiopental or 1.5 mg/kg methohexital
What is the most likely mechanism of action for Ketamine?
• NMDA receptor, member of the glutamate receptor,
ligand gated ion channel
• Ketamine- inhibits activation of the NMDA receptor by
glutamate, ⇩presynaptic release of glutamate and
potentiates GABA
• Ketamine- noncompetitive antagonist of NMDA receptor
• Interacts with the phencyclidine-binding receptor site,
leading to inhibition of NMDA activity
What is the most likely mechanism of action of ETOMIDATE?
Binds GABA and enhances the affinity of the inhibitory
neurotransmitter (GABA) for these receptors
• Etomidate does not modulate other ligand gated ion channels at clinically relevantconcentrations
What is the most likely mechanism of action PRECEDEX?
• Highly selective, specific and potent full alpha 2
adrenergic agonist(1600 times the affinity for the
receptor)
• Indicated as an adjunct for anesthesia and ICU sedation
Produces hypnotic, sedative and analgesic effects
Produces pharmacologic effects similar to
clonidine-
clonidine is partial alpha 2 agonist
What is the most likely mechanism of PROPOFOL ?
Sedative-hypnotic effects via GABA activation
• Selective modulator of GABA receptors
• GABA receptor activated= ⇧chloride ions=
hyperpolarizes cell= functional inhibition
• Propofol may also ⇩ the rate of GABA dissociation
from the GABA receptor
What is the most likely mechanism of action METHOHEXITAL ?
Works on GABA in the CNS
• Produces sedative-hypnotic effects
• GABA hyperpolarizes postsynaptic cell
• Barbiturates and propofol ⇩ dissociation of GABA
from receptor and ⇧duration of GABA activated
opening of chloride channels
How does Ketamine affect ventilation and management of a patient’s airway?
• Upper airway skeletal tone is well maintained
• ⇧ salivary secretions=need to protect airway
• Bronchodilator activity- successful treatment of
status asthmaticus has been reported with
ketamine
How does Ketamine affect ventilation and management of a patient’s airway?
NO SIGNIFICANT RESPIRATORY DEPRESSION
• Upper airway skeletal tone is well maintained
• ⇧ salivary secretions=need to protect airway
• Bronchodilator activity- successful treatment of
status asthmaticus has been reported with
ketamine
What are major warnings, disadvantages and contraindications with the use of Barbiturates?
High dose = hypotension = ⇩ cerebral perfusion
pressure ‘•
Intra-Arterial Injection –>Immediate, intense vasoconstriction and excruciating pain that radiates along the distribution of the artery
What are major warnings, disadvantages and contraindications with the use of Barbiturates?
High dose = hypotension = ⇩ cerebral perfusion
pressure ‘•
Intra-Arterial Injection –>Immediate, intense vasoconstriction and excruciating pain that radiates along the distribution of the artery
(Gangrene and permanent nerve damage may result
• Risk ⇧ with ⇧ drug concentrations)
Venous thrombosis
Cross placenta
This ⇧ production of Heme, and may exacerbate
acute intermittent porphyria
For induction of anesthesia, barbs produce a dose
dependent depression of the medullary and pontine
ventilatory centers
• Leads to ⇩ response to hypercarbia
• Low RR and Low tidal volumes
⇧Apnea risk when used with other CNS depressant
drugs used for preop medication
Large doses needed to suppress laryngeal reflexes
& cough
Laryngospasm or bronchospasm may occur during
intubation attempts- no LMA
Barbiturate use is declining due to
• Lack specificity of effect in the CNS
• Lower therapeutic index than benzodiazepines
• Result in tolerance more easily than benzodiazepines
• Greater liability for abuse
• High risk for drug interaction
• Paradoxical excitation especially in the elderly
• ⇩ in pain threshold with small doses
• Hangover effect
• No skeletal muscle relaxation- to be effective
clinically
What IV induction agent should be avoided in a hypovolemic patient?
BARBITURATES
What are the cardiovascular effects of Methohexital?
⇩ in BP and offset by compensatory 15-20BPM
⇧ in HR
What are the cardiovascular effects Propofol ?
⇩ in systemic BP( ⇩ preload) greater than
equivalent thiopental dose
⇩ BP often accompanied by changes in cardiac
output and SVR
BRADYCARDIA
What are the cardiovascular effects PRECEDEX?
Hypotension
Transiet HTN
Brady/Tachy
What is a common concern regarding the use of etomidate?
MYOCLONUS• Can ⇩ myoclonus incidence with 1-2mcg/kg fentanyl or a benzodiazepine prior to etomidate
injection
What are all the advantages with the use of propofol?
• Rapid and complete awakening compared to other induction agents
• Minimal residual CNS effects
• No MH activation
• Doesn’t affect steroid synthesis or ACTH response
• Does not alter hepatic or fibrinolytic function
• Does not cause histamine release
• Context sensitive half time is minimally influenced by
duration of infusion (<40 minutes for up to 8hr infusion)
• Antiemetic and antipruritic effects
What are all the disadvantages with the use of propofol?
Dose dependent ventilatory depression
• Allergic reaction to phenol nucleus and diisopropyl
side chain
• May lead to anaphylaxis
May lead to bronchoconstriction
• Prolonged myoclonus has been reported in pt with
meningismus
• Potential for bacterial contamination. Propofol
strongly supports the growth of E-coli and
pseudomonas aeruginosa
• Use aseptic technique
• Discard unused portion in 6 hours
• Change infusion line q 12 hours
• HIGH abuse potential- high risk of death
Propofol infusion syndrome
• s/s Lactic acidosis, bradycardia unresponsive to
treatment, fat infiltrated liver, rhabdomyolysis
Pain at injection site
How is the primary action of barbiturates terminated?
Redistribution terminates action of methohexital (barb)
How is the primary action of propofol terminated?
Redistribution terminates action of propofol
How is the primary action of ketamine terminated?
Redistributed
How is the primary action of etomidate terminated?
Prompt awakening is the result of REDISTRIBUTION to
inactive tissues
How is the primary action of precedex terminated?
?
How is naloxone classified?
Opiod antagonist
What is mechanism of action of the neurotransmitter GABA?
GABA hyperpolarizes postsynaptic cell
Major INHIBITORY NEUROTRANSMITTER IN the BRAIN
What is mechanism of action of the neurotransmitter GABA?
GABA Major INHIBITORY NEUROTRANSMITTER IN the BRAIN
GABA receptor is a CHLORIDE ION CHANNEL –> When GABA binds to the receptor , CHLORIDE IONS enters cell
GABA hyperpolarizes postsynaptic cell
Decrese NEURON’s action potential
Which of the neurotransmitters are excitatory? Which of the neurotransmitters are inhibitory?
Excitatory: GLUTAMATE
Inhibitory : GABA
Which IV induction agents lead to severe tissue damage when given intra-arterially? How can those be prevented? How can this be treated?
Methohexital,
• Gangrene and permanent nerve damage may result
• Risk ⇧ with ⇧ drug concentrations
Treatment
Immediate attempts to dilute drug, prevention of arterial spasm, general measures to maintain blood flow
–>Lidocaine, papaverine, phenoxybenzamine
–>sympathectomy of the upper extremity
produced by a brachial plexus block
Prevented by using dilute concentrations
• 1% methohexital
Explain differences between thiobarbiturates and oxybarbiturates?
• Oxybarbiturates metabolized only in hepatocytes
Thiobarbiturates are more potent than oxybarbiturates as they are more lipid soluble (the exception is methohexital which is an oxybarbiturate & is actually more potent than thiobarbiturates d/t ionization and physiologic pH)
EXTRA Avantageous characteristic/characteristics of thiopental (Pentothal) and methohexital (Brevital):
Short duration
Rapid onset of action
EXTRA: Barbiturate pharmacology: pulmonary effects
Respiratory depression
Laryngospasm
EXTRA: Avoid in pt with Acute Intermittent Porphyria
Methohexital
Barbiturate causes
Vasodilation
EXTRA: Enhancement of neuronal inhibition by barbiturates occur at synapses using this neurotransmitter.
GABA
How do barbiturates affect ICP and CMRO2?
DECREASE BOTH
• Barbs used to ⇩ ICP, along with hyperventilation &
diuresis
• ⇩ ICP by ⇩ cerebral blood volume through drug
induced cerebral vasoconstriction and associated ⇩
in cerebral blood flow
• Barbs ⇩ metabolic oxygen requirements (CMRO2)
• Isoelectric EEG=max barb effect and ⇩ CMRO2 55%
• No improved outcomes for head trauma pt
In patients with what comorbid conditions would it be recommended to decrease the dose of methohexital?
Uremic
Cirrhosis
LIVER ISSUES
What IV induction agent would be best for placing an LMA?
PROPOFOL
What is expected next if a patient yawns while increasing the dose of propfol?
APNEA
What clinical effects are expected with induction doses of ketamine?
Eyes remain open
nystagmic gaze
Increased oral secretions
amnesia, bronchodilation, increased HR and CO, increased ICP and emergence delerium.
How does propofol affect ventilation
Dose dependent depression of ventilation
• Apnea occurring in 25-35% of pts after induction
• Effect enhanced with preoperative opioids
• Painful stimuli may counteract this effect
• Maintenance doses of propofol ⇩ Vt and RR
• Causes bronchodilation and ⇩ incidence of
intraoperative wheezing in asthma pt
• ⇩Ventilatory response to CO2 & arterial hypoxemia
How are barbiturates classified? What drugs fall into each class?
Oxybarbiturates: Methohexital,phenobarbital and pentobarbital
Thiobarbiturates: Thiopental, thiamylal
What are the IV/IM induction doses of Ketamine?
1-2mg/kg IV
4-8mg/kg IM
What is the mechanism of action of ketamine? Where in the CNS does ketamine work?
Ketamine- inhibits activation of the NMDA receptor by glutamate, ⇩presynaptic release of glutamate and potentiates GABA
• Ketamine- noncompetitive antagonist of NMDA receptor
• Interacts with the phencyclidine-binding receptor site,
leading to inhibition of NMDA activity
Works on Mu, Kappa and Delta receptors
What are the IV induction doses of methohexital, propofol, precedex, etomidate?
Methohexital dose 1-1.5mg/kg
Propofol dose is 1.5-2.5 mg/kg
What are the IV induction doses PRECEDEX?
Precedex
Initial dose 1mcg/kg IV, load over 10 minutes then 5-10mcg/kg/hour= TIVA without ventilatory
depression
0.2-1.5mcg/kg/hr -postop sedation
What are the IV induction doses of ETOMIDATE
0.2-0.4 mg/kg
What patients are at risk for emergence reactions? How can this be prevented?
- Pts treated with ketamine dose > 2mg/kg
- > 15 years of age
- female
- Hx of personality disorder or frequent dreaming
What IV induction agent has anticholinergic side effects
KETAMINE
What are advantages of the iv induction agent ketamine
Increases SVR, PVR, and SBP 20-40 mmHg.
No significant depression of ventilation and upper airway skeletal tone is well maintained.
Useful for burn dressing changes and hypovolemic patients.
PREVENTION OF EMERGENCE DELIRIUM -KETAMINE
•
Benzodiazepine- most effective
Midazolam > diazepam
Give benzo 5 min prior to induction Inclusion of thiopental or inhalational agents may⇩incidence
ATROPINE or DROPERIDOL may ⇧ incidence of
emergence delirium with ketamine
Methohexital vs thiopental
Methohexital has higher hepatic clearance than thiopental because of a Higher extraction ratio (3-4X more)
Methohexital vs thiopental recovery of motor function
Earlier return to psychomotor recovery than thiopental
Non-ionization of thiopental vs Methohexital
Thiopental 65
Thio vs Metho reflecting less lipid soluble
More rapid metabolism than thiopental,
Distribution half time of thiopental vs Methohexital
Methohexital 5.6 mins
Thiopental 8.5mins
Elimination half time of Methohexital vs Thiopental
Methohexital 3.9 hours
Thiopental 11.6 hours
Clearance Methohexital vs Thiopental
Methohexital 2.2 L/kg
Thiopental 2.5 L/kg
Oxybarbiturates
Oxygen in the pyrimidine nucleus at carbon 2 position’
Methohexital
Thiobarbiturates
Sulfur atom at the Carbon 2 position (Thiopental)
Barbiturates are
Sodium salts
You cannot mix barbiturates with
- Acidic solution
- LR
- water soluble drugs
Can lead to precipitation and occlusion of an IV line
Use to induce seizures
Barbiturates and methohexital
2 major contraindications to Barbiturates
Porphyrias
Hypovolemia
Intra arterial injection
Thiopental or Methohexital
Methohexital redistribution
Redistribution- terminates action- about 8.5
minutes
Intra-arterial Injection immediate treatment
Treatment-immediate attempts to dilute drug,
prevention of arterial spasm, general measures to
maintain blood flow
Lidocaine, papaverine, phenoxybenzamine
sympathectomy of the upper extremity
produced by a brachial plexus block
Cirrhosis , renal failure and barbiturates
Increase concentration of free barbiturates, RECUE DOSE by 50%
Acidosis and BARBITURATES
Acidosis will INCREASE the NONIONIZED fraction and favor transfer of these agents into the brain
ALKALOSIS and Barbiturates
Increase the dose.
What induce oxidative microsomal enzymes
Chronic Use of barbiturates
Reason why people awaken more quickly from Methohexital infusion relates to
Higher rate of hepatic clearance
Barbiturates metabolism
Conjugated into water soluble metabolites , excreted in urine
First order
a constant fraction
Zero order
a constant amount
Barbiturates are (acids vs bases)
Weak acids
Barbiturates toxicity
Sodium bicarbonate to accelerate elimination
High doses of methohexital associated with
Seizures
Barbiturates on Pulmonary system
Brief period of apnea lasting 30-45 sec
60-90 second after admin
Full recovery in 15 mins
Capable of brain protection
Barbiturates
Focal cerebral ischemia protection
Barbiturates
Barbiturates contraindicated in
Acute porphyria
