General Anesthesia B&B Flashcards
what factor determines the potency and onset/offset of an inhaled anesthetic?
solubility of gas for blood determines onset/offset - need to saturate blood to generate partial pressure (dissolved = no effect)
solubility of gas for lipids determines potency
Describe how blood solubility affects the efficacy of inhaled anesthetics
molecules dissolved in blood (higher solubility) = no anesthetic affect
Molecules NOT dissolved = anesthetic affect
Need to saturate blood to generate partial pressure… So more solubility in blood = longer to take effect
measured by the blood/gas partition coefficient (>1 = more likely to be found in blood, <1 = more likely to be found in alveoli/ gaseous form)
You have two inhaled anesthetics, drug A and drug B. Drug A is less soluble in blood then drug B. Which of the drugs will have a faster anesthetic effect?
Less soluble in blood = faster rise in partial pressure = faster anesthetic effect
Drug A will have a faster anesthetic affect
halothane has a blood/gas partition coefficient of 2.3, while desflurane has a blood/gas partition coefficient of 0.42 which of these inhaled anesthetics will have a faster onset of action?
> 1 = more likely to be found in blood
<1 = more likely to be found in alveoli/ gaseous form
halothane likes to stay in blood —> SLOW induction
desflurane quickly leaves blood —> FAST induction
How is the potency of an inhaled anesthetic measured?
via the oil/gas partition coefficient - represents the lipid solubility of the drug, higher = more potent (Meyer-Overton rule)
but in clinical use by the minimum alveolar concentration (MAC): concentration of anesthetic that prevents movement in 50% of subjects in response to pain
MAC = 1/lipid solubility
… this means low MAC = high potency
Isoflurane has an oil/gas partition coefficient of 98 while desflurane has an oil/gas, partition coefficient of 28. Which inhaled anesthetic is more potent?
represents the lipid solubility of the drug, higher = more potent (Meyer-Overton rule)
isoflurance is more potent than desflurane
minimum alveolar concentration (MAC)
concentration of anesthetic that prevents movement in 50% of subjects in response to pain
MAC = 1/lipid solubility
… this means low MAC = high potency
MAC changes with age (lower in elderly)
what are the common side effects of all inhaled anesthetics? (5)
- myocardial depression (low CO)
- respiratory depression
- N/V
- increased cerebral blood flow (high ICP)
- decreased GFR
what are the special side effects of each of the following inhaled anesthetic?
a. halothane
b. methoxyflurane
c. enflurane
a. halothane: hepatotoxicity (massive necrosis), malignant hyperthermia
b. methoxyflurane: nephrotoxicity (renal toxic metabolite)
c. enflurane: seizures
which inhaled anesthetic carries a risk of hepatotoxicity and malignant hyperthermia?
halothane; not really used anymore due to side effects
which 2 drugs can trigger malignant hyperthermia and what is this condition associated with?
- halothane: inhaled anesthetic
- succinylcholine: paralytic (for surgery)
—> fever, muscle rigidity/damage (high CK), tachycardia (high K+), HTN after surgery
due to AD mutation in ryanodine receptors in sarcoplasmic reticulum (Ca2+ channel) —> overactive, ATP consumption, heat generation, tissue damage
tx: dantrolene (muscle relaxant)
A pt receives halothane (inhaled anesthetic) for their surgery. After the surgery, they experience fever, muscle rigidity, and a rapid heart rate. BP shows they are hypertensive. What should they be treated with?
malignant hyperthermia: triggered by some anesthetics
—> fever, muscle rigidity/damage (high CK), tachycardia (high K+), HTN after surgery
due to AD mutation in ryanodine receptors in sarcoplasmic reticulum (Ca2+ channel) —> overactive, ATP consumption, heat generation, tissue damage
tx: dantrolene (muscle relaxant)
what are 2 contraindications for use of nitrous oxide as an inhaled anesthetic?
NO diffuses rapidly into air spaces and will increase volume
cannot use in patients with pneumothorax or abdominal distention as this can double the cavity size
what kind of drugs are desflurane, sevoflurane, halothane, enflurane, isoflurane, and methoxyflurane?
inhaled anesthetics
which barbiturate can be used as a general anesthetic? describe its properties
thiopental (Pentothal): binds GABA receptors
HIGH potency (high lipid solubility) + RAPID onset (rapid entry into brain) + ultra SHORT acting (rapidly distributes to muscle and fat)
what kind of drug is thiopental (Pentothal) and what is it used for?
barbiturate used for general anesthesia - binds GABA receptors
HIGH potency (high lipid solubility) + RAPID onset (rapid entry into brain) + ultra SHORT acting (rapidly distributes to muscle and fat)
how does the clinical use of midazolam, lorazepam, diazepam, and alprazolam differ when give orally vs intravenously?
these are benzodiazepines: bind GABA receptors (increase Cl- influx)
orally = anti-anxiety (anxiolytic)
IV = general anesthesia (sedation, amnesia, anticonvulsant)
name 4 benzodiazepines that can be used for general anesthesia
midazolam, lorazepam, diazepam, and alprazolam (”-zolam/zepam”)
bind GABA receptors (increase Cl- influx)
orally = anti-anxiety (anxiolytic)
IV = general anesthesia (sedation, amnesia, anticonvulsant)
what is the treatment for benzodiazepine overdose (ex, midazolam, lorazepam, diazepam, and alprazolam)
bind GABA receptors (increase Cl- influx)
Flumazenil is a selective competitive antagonist of the gamma-aminobutyric acid (GABA) receptor and is the only available specific antidote for benzodiazepine (BZD) toxicity
which benzodiazepine is used as general anesthetic for short procedures such as endoscopy?
midazolam (Versed) - washes out very quickly
bind GABA receptors (increase Cl- influx)
what is an important consideration when prescribing opioids as general anesthesia or sedatives for procedures? (ex: morphine, fentanyl, hydromorphone)
will NOT cause amnesia - the patient will remember everything, so if undergoing a dangerous procedure, should also be given something to cause amnesia
what side effects will patients experience who are given opioids as sedatives or analgesics for procedures? (ex: morphine, fentanyl, hydromorphone)
act on opioid (mu) receptors in brain
side effects: decreased respiratory drive, decreased blood pressure, nausea/vomiting, ileus, urinary retention.
what is the effect of opioids bindings Mu receptors? (ex: morphine, fentanyl, hydromorphone)
Mu receptors are GPCR, cause increase in K+ efflux which hyper-polarizes the neuron for less pain transmission
which side effects of opioids persist, even after chronic use and tolerance?
Constipation and meiosis
What are the effects of ketamine?
PCP derivative (“angel dust”) - antagonist of NMDA receptors (glutamate)
“Dissociative drug” – patient enters trancelike state, analgesia and amnesia, can increase BP/HR but few respiratory or CV effects
“Emergence reactions” occur afterwards – disorientation, dreams, hallucinations… if given as anesthetic for surgery, co-administer midazolam (benzodiazepine) to mitigate
which IV general anesthetic is often co-administered with midazolam (benzodiazepine) to mitigate “emergence reactions,” including disorientation, dreams, and hallucinations?
ketamine: PCP derivative (“angel dust”) - antagonist of NMDA receptors (glutamate)
what is the effect of etomidate? when is it most often clinically used?
IV general anesthetic - modulates GABA receptors to block neuroexcitation
induces anesthesia but NOT analgesia! (patient can still feel pain), but has rapid onset so often used for rapid sequence intubation
relatively hemodynamically stable - good for hypotensive patients
side effect: blocks cortisol synthesis (secondary adrenal insufficiency)
which 2 IV drugs are used in combination for rapid sequence intubation in the hospital?
etomidate (puts patient to sleep) + succinylcholine (paralyzes patient)
both are rapid onset and wash out quickly
what are the effects of propofol as an anesthetic?
GABA modulator, causes sedation and amnesia
can cause myocardial depression and hypotension
what types of anesthetics are used for induction vs maintenance?
IV used for induction (ex: propofol, etomidate, ketamine)
inhaled used for maintenance (ex: propofol, sevoflurane, desflurane)
what is the drug rocuronium used for?
paralytic used for surgery
what are the 4 possible functions of an anesthetic drug?
- analgesia
- loss of consciousness
- amnesia
- muscle relaxation
4 types: inhaled, IV, local, neuromuscular blockers
what are the clinical uses and adverse effects of desflurane, isoflurane, and sevoflurane?
halogenated volatile general anesthetics used for maintenance of general anesthesia + induction of general anesthesia in pediatrics
adverse effects: N/V, bronchospasm, reduced systemic vascular resistance (SVR), malignant hypothermia
for what aspect of anesthesia are desflurane, isoflurane, and sevoflurane used?
halogenated volatile general anesthetics
used for maintenance of general anesthesia + induction of general anesthesia in pediatrics
what is the mechanism of action and clinical uses (4) of propofol?
GABA agonist used as IV anesthetic
causes sedation, induction + maintenance of general anesthesia, antiemetic (low dose)
side effects: decreased SVR, cardiac inotropy, respiratory drive, ability to protect airway reflexes
name an IV anesthetic that can be used as an antiemetic at low dose
propofol: GABA agonist
causes sedation, induction + maintenance of general anesthesia, antiemetic (low dose)
what is the MOA and clinical use of etomidate?
GABA agonist used as IV anesthetic for induction of general anesthesia
side effects: burning on injection, N/V, diminished respiratory drive, dose dependent cortisol suppression
what is the MOA and clinical uses (3) of ketamine?
NMDA receptor antagonist used as IV anesthetic
used for sedation + induction of general anesthesia + adjunct to general anesthesia
side effects: hallucinations, increased ICP
what are 2 important side effects of ketamine?
NMDA receptor antagonist used as IV anesthetic (sedation + induction)
side effects: hallucinations, increased ICP
name an IV anesthetic which may cause hallucinations as a side effect
ketamine: NMDA receptor antagonist
used for sedation + induction of general anesthesia + adjunct to general anesthesia
what is the MOA and clinical use of dexmedetomidine?
alpha2 agonist used as IV anesthetic
induces sedation + analgesia, also used for attenuation of anesthesia
side effects: bradycardia and possible hypotension
name an alpha2 agonist used for sedation and analgesia
dexmedetomidine: alpha2 agonist used as IV anesthetic
side effects: bradycardia and possible hypotension
how would the following factors affect the pharmacokinetics of local anesthetics?
a. lipophilicity
b. pKa
c. protein binding
a. high lipophilicity (hydrophobic) = high potency, longer duration, slower onset of action
b. high pKa = slower onset of action
c. high protein binding = longer duration
describe how pH affects the pharmacokinetics of local anesthetics
local anesthetics are weak bases which are protonated in acidic pH and neutral in basic pH
the neutral form is required to diffuse to site of action, but charged form is required for activity!! - neutral form enters cells then is trapped within as pronated form, which is able to bind Na+ channels from within
the more acidic the extracellular medium (sepsis, local infection, DKA, etc), the higher the proportion of the charged form
sort the following types of nerve fibers as easiest to block with local anesthetics to hardest to block:
A fibers
B fibers
C fibers
B fibers = small, myelinated —> easiest to anesthetize
A fibers = large, myelinated —> middle of the road
C fibers = small, unmyelinated —> hardest to block (minimal Na+ channels)
injection of local anesthetics where produces greater blood concentration? injection where produces lease blood concentration? [mnemonic]
Injection of local anesthetics into very vascular areas leads to greater blood concentrations than the same dose injected into less vascular areas - remember with ICE BALL
Intercostal - greatest max blood concentration
Caudal
Epidural
BrAchial plexus
Lower Legs - least max blood concentration
why is epinephrine sometimes mixed with local anesthetics?
epinephrine = vasoconstrictor —> slows absorption at injection site to increase blood availability (does not help long-acting agents)
also increases HR, allowing for immediate recognition of intravascular injection —> STOP INJECTING (build up in cardiac muscle —> lethal via arrhythmias)
which type of local anesthetic has a shorter duration of action, esters or amides? which is more likely to cause an allergic reaction
esters have a shorter duration of action
… also more likely to cause allergic reactions - PABA metabolite can cause hapten formation —> IgE mediated anaphylaxis
what occurs in Local Anesthetic Systemic Toxicity (LAST)
inadvertent IV injection or systemic absorption of local anesthetics —> bind/inhibit Na+ and Ca2+ channels
build up in cardiac muscle —> lethal via arrhythmias
neurologic signs first, followed by cardiac signs (HTN/tachycardia —> hypotension/bradycardia —> ventricular dysrhythmias)
in what state of activity do local anesthetics bind Na+ channels?
active or inactive (NOT resting)
cross membrane as neutral, become protonated and trapped within, and bind intracellular aspect of channel
lipophilic, have pKa’s above neutral pH
how are esther vs amide local anesthetics eliminated?
esthers: plasma pseudocholinesterase breaks down to PABA (4-aminobenzoic acid) and derivatives
amides: metabolized by cytochrome P450 in liver, water soluble metabolizes excreted by kidneys
name a local anesthetic used for dental procedures
procaine, aka Novocain - has quick onset; esther
name a local anesthetic used for emergency C-sections
chlorprocaine - short acting with quick onset; esther
name an esther local anesthetic that is potent, long-acting, and has a low therapeutic index
tetracaine: esther local anesthetic that is potent, long-acting, and has a low therapeutic index
name a topical local anesthetic that is associated with risk of methemoglobin
benzocaine: esther local anesthetic
methemoglobin causes “chocolate blood”, treat with methylene blue + oxygen
name a local anesthetic that is antiarrhythmic at low dose
lidocaine: amide, given IV
ropivicaine vs bupivicaine
both are amide local anesthetics
ropivicaine: long-acting, less cardiotoxic
bupivicaine: very long acting, very cardiotoxic
which amide local anesthetic has the lowest pKa, and is thus quickest acting?
mepivicaine: low pKa = quick acting
sort the following local anesthetics into either esther or amide:
a. procaine
b. mepivicaine
c. lidocaine
d. chlorprocaine
e. benzocaine
f. ropivicaine
g. bupivicaine
h. tetracaine
esthers have 1 “i”: procaine, chlorprocaine, tetracaine, benzocaine
amides have 2 “i”: lidocaine, ropivicaine, bupivicaine, mepivicaine
