Neuroscience Week 3: Anesthetics Flashcards
Be able to explain the stages of inhalational anesthesia and the pharmacokinetics of inhaled anesthetics (alveolar wash-in, uptake from the lungs, solubility in blood, tissue uptake, and elimination), including the concept of minimum alveolar concentration.
Be able to describe the mechanisms of action (including analgesic properties) and organ system effects (including effects on intracranial pressure) of inhaled and intravenous anesthetics, the uses of these agents and their adverse effects, including malignant hyperthermia and its treatment.
Be able to list the key differences between amide and ester local anesthetics, as well as to explain in detail the mechanism of action of local anesthetics, the influence of pH on their actions, which nerve fibers are more or less sensitive to them (e.g., small unmyelinated fibers are the most sensitive to block), their uses and adverse effects.
Balanced Anesthesia Definition
Combination of inhaled anesthetics and IV medications
Monitored Anesthesia Definition
Oral or parenteral sedatives + local anesthetics
Conscious Sedation Definition
Alleviation of anxiety and pain + altered levels of consciousness produced by small doses of sedatives (in ICU, neuromuscular blockers may be also used)
Deep Sedation Definition
Light state of anesthesia (also used in ICU)
Depth of Anesthesia: Stage I
Analgesia and subsequent amnesia.
Depth of Anesthesia: Stage II
Excitement
- delirium, combative behavior, increase in blood pressure and respiratory rate. To avoid, a shortacting I.V. anesthetic is given before.
- in part due to inhibition of the function of inhibitory neurons in the brain, excitatory neurons are disinhibited
Depth of Anesthesia: Stage III
Surgical Anesthesia
regular respiration, skeletal muscle relaxation, decrease in eye reflexes and movements, fixed pupils. Loss of motor and autonomic responses to pain.
Depth of Anesthesia: Stage IV
Medullary Paralysis
depression of respiratory and vasomotor centers. can be followed by Death.
Neuron type sensitivity to anesthesia
- Dorsal horn = analgesia
- Frontal cortex = sedation
- Thalamic neurons and midbrain reticular formation = hypnosis
- Ventral horn = immobility
MAC
- Potency of anesthetics is measured in minimum alveolar concentrations
- Potency is an expression of the activity of a drug in terms of the concentration or amount of the drug required to produce a defined effect,
- Efficacy. maximum effect that a drug can produce regardless of dose
In these examples NO is least potent and Isoflurane is the most potent example given on this slide
1 MAC
Alveolar concentration of anesthetic that renders immobile 50% of subjects exposed to a strong noxious stimulation
MAC examples
0.3 MAC
Analgesia
0.5 MAC
Amnesia
1.0 MAC
50% immobile
1.2 MAC
Sympathetically-mediated response to surgery is blunted
1.3 MAC
99% immobile
>/= 2.0 MAC
Potentially lethal
Most common Inhalational Anesthetics
- Sevoflurane (Volatile)
- Desflurane (Volatile)
- Isoflurane (Volatile)
- Nitrous Oxide (Gaseous)
Most common Intravenous Anesthetics
7 listed
- Benzodiazepines (Midazolam)
- Opioids (Fentanyl)
- Barbiturates (Thiopental)
- Propofol
- Ketamine
- Etomidate
- Dexmedetomidine
Pharmacokinetics of anesthesia
*higher the ventilatory rate/depth = shorter induction time
Blood solubility of anesthesia
Anesthetic type high arterial pressures are reached rapidly and shorter induction time
with an anesthetic w/ Low blood solubility
Anesthetics Tissue Uptake
also remember Meyer-Overton rule
Meyer-Overton rule
the higher the lipid solubility the more potent the anesthetic
Anesthetic Elimination
clearance by the lungs is the main elimination route
the rate of recovey from anesthesia depends on
the rate of elimination of the brain
bronchospasm and anesthesia
avoid pungent agents in patients with bronchospasm
malignant hyperthermia
Malignant Hyperthermia Etiology
- Autosomal dominant genetic disorder
- Caused by mutations of muscle ryanodine receptor that are activated by inhaled anesthetics, leading to uncontrolled release of Ca2+ from the sarcoplasmic reticulum
Malignant Hyperthermia Clinical Presentation
Characterized by tachycardia, hypertension, severe muscle rigidity, hyperthermia, hyperkalemia and acidosis
Common when volatile anesthetics are combined with succinylcholine
Malignant hyperthermia
Malignant Hyperthermia common anesthesia cause
Common when volatile anesthetics are combined with succinylcholine
Malignant Hyperthermia Treatment
- Treatment = dantrolene (blocks Ca2+ release via ryanodine receptor);
- cooling;
- oxygen;
- correction of acid-base disturbances.
Example of Antagonist of Ryanodine Receptor
Dantrolene
How are different classes of anesthesia used in Balanced Anesthesia
Balanced Anesthesia Premedication
Midazolam (I.V. Benzodiazepine)
Balanced Anesthesia Induction reagents
Fentanyl IV opioid
Propofol IV anesthetic
Curare-like neuromuscular blocker (nondepolarizing blocker) (Pancuronium)
Tracheal intubation
Balanced Anesthesia Maintenance Reagents
Inhalational anesthetics
Sevoflurane 1-2% + Nitrous Oxide 66%
TIVA AKA
Total intravenous Anesthesia
Total Intravenous Anesthesia Premedication
Midazolam IV benzo
Total Intravenous Anesthesia Induction Reagents
- Remifentanil (loading dose)
- Propofol
Total Intravenous Anesthesia NMJ Blockade reagents
Rocuronium
Total Intravenous Anesthesia Maintenance Reagents
- Remifentanil
- Propofol
Total Intravenous Anesthesia complete procedure and reagents
After what reagent is a patient intubated?
NMJ Blockers
Rocuronium TIVA
Pancuronium Balanced Anesthesia
(Curare-like)
for what procedures can IV anesthetics used for?
Volatiles Mech. of Action
↑GABAAR, ↓NMDAR & CNS nAChRs
*N2O Mech. of Action
↑GABAAR, ↓NMDAR,
Midazolam Mech. of Action
↑ GABAAR
*Fentanyl Mech. of Action
R ↑ Opioid Rs
Thiopental Mech. of Action
↑ GABAAR
Propofol Mech. of Action
↑ GABAAR
Etomid. Mech. of Action
↑ GABAAR
Ketamine Mech. of Action
↓NMDAR
Dexmet Mech. of Action
α2 -adrenoceptor agonist
Volatiles Cardiovascular
- ↓Peripheral resistance
- ↓Myocardial O2 consumption
- Dilate coronaries
N2O Cardiovascular
↓Myocardial function
↑Sympathetic (effects cancel out-minimal effect)
Midazolam Cardiovascular
↓Peripheral resistance
Fentanyl Cardiovascular
↓Heart rate
Thiopental Cardiovascular
↓Peripheral resistance and myocardial contractility
Propofol Cardiovascular
↓Peripheral resistance
Etomidate Cardiovascular
Stability
Ketamine Cardiovascular
↑Peripheral resistance and heart rate
Dexmedetomidine Cardiovascular
↓Peripheral resistance and heart rate
Volatiles Respiratory
- Depression.
- ↓Response to hypoxia.
- ↓Mucociliary.
- Bronchodilation
N2O Respiratory
- Diffusional hypoxia.
- Diffuse into cavities (pneumothorax; also bowel loop).
can lead to increased pressure of the thorax or intestines
Midazolam Respiratory
Depression (particularly when given with opioids)
Fentanyl Respiratory
- Depression.
- ↓Response to hypoxia.
- Chest wall and laryngeal rigidity.
Thiopental Respiratory
Depression.
↓Response to hypoxia.
Propofol Respiratory
Depression.
↓Response to hypoxia.
Etomidate Respiratory
Less pronounced depression.
Ketamine Respiratory
Stable but laryngospasm can occur
Dexmet Respiratory
Little effect
Volatiles GI
Nausea/vomiting
N2O GI
Nausea/vomiting
Midazolam GI
N/A
Fentanyl GI
Nausea Constipation
Thiopental GI
Nausea/ vomiting
Propofol GI
Antiemetic
Etomidate GI
N/A
Ketamine GI
N/A
Dexmedetomidine GI
N/A
Volatiles CNS
- ↓Metabolic rate
- ↑Cerebral blood flow and intracranial pressure
*
N2O CNS
↑Cerebral blood flow and intracranial pressure via sympathetic
Midazolam CNS
N/A
Fentanyl CNS
↑ intracranial pressure in head trauma patients
Thiopental CNS
- ↓Metabolic rate
- ↓Cerebral blood flow & intracranial pressure
- decreases metabolic rate and decreases cerebral blood flow and intracranial pressure which can be neuroprotective
Propofol CNS
↓Metabolic rate.
↓Cerebral blood flow & intracranial pressure.
Etomidate CNS
↓Metabolic rate.
↓Cerebral blood flow & intracranial pressure.
Ketamine CNS
↑Metabolic rate.
↑Cerebral blood flow & intracranial pressure.
Dexmedetomidine CNS
↓Cerebral blood flow but little effect on intracranial pressure
Volatiles Liver/ Kidneys
↓blood flow
N2O Liver/ Kidneys
↓blood flow
Midazolam Liver/ Kidneys
Failure slows elimination
Fentanyl Liver/ Kidneys
Caution in liver failure
Thiopental Liver/ Kidneys
N/A
Propofol Liver/ Kidneys
N/A
Propofol Liver/ Kidneys
Failure slows elimination
Etomidate Liver/ Kidneys
(Adrenocortical suppression)
Ketamine Liver/ Kidneys
N/A
Dexmet Liver/ Kidneys
N/A
Volatiles Uterus
- ↓contraction
- can be useful if you need to do an emergency C-section
Anesthetics that increase intracranial pressure
have to be careful with patients with intracranial injuries
decreases metabolic rate and decreases cerebral blood flow and intracranial pressure which can be neuroprotective
- Thiopental
- Propofol
- Etomidate
DONT use Ketamine because it does the opposite
Local Anesthetic classes
Esters (1 I)
Amides (2 I’s)
Esters
Amides
Esters Medium Duration
Cocaine
Amides Medium Duration
Lidocaine
Esters Short Duration
Procaine
Esters Long Duration
Tetracaine (2 a’s)
Amides Long Duration
Bupivacaine (2 a’s)
Local anesthetics lipophilic
Lipophilic agents are more potent and longer lasting for esters and amides alike
Esters Metabolism
Hydrolized plasma esterases
Amides Vs Esters
Amides are longer lasting
Local Anesthetics Mechanism of Action
- Mechanism of Action: open channel blockers of voltage-gated sodium channels
- Local anesthetics block from the inside when channel is open; fibers with high firing frequency are blocked first (i.e. pain fibers)
- Decrease action potential propagation. Cause nerve conduction to fail.
Local Anesthetics are dependent upon?
pH
only the uncharged base can cross the membrane
the charged form will go and blocks the channel from the inside
Local Anesthetics and Henderson Haselbach EQ
Local Anesthetics Caveats
REMEMBER!!!!!!!!!!
In general, smaller fibers are blocked more easily than larger fibers, and myelinated fibers are blocked more easily than unmyelinated fibers.
- Activated pain fibers fire rapidly; thus, pain sensation appears to be selectively blocked by local anesthetics.
- Fibers located in the periphery of a thick nerve bundle are blocked sooner than those in the core because they are exposed earlier to higher concentrations of the anesthetic.
Order of blockade: Pain (fibers have high firing rate and long action potentials) →Other sensations → Motor
Concurent injection of ________ with local anesthetics
Epinephrine
It causes vasoconstriction via activation of α1 adrenergic receptors, decreasing removal of the local anesthetic via absorption into circulation. This increases duration of the local anesthetic’s effect
- It activates presynaptic α2 adrenergic receptors, decreasing release of pain mediators such as Substance P
- It provides local bleeding control (vasoconstriction)
Adverse Effects of Local Anesthetics
Restlessness and tremor. At high doses: convulsions (pre-medicate with benzodiazepine but could mask serious reactions), respiratory depression.
Neurotoxic injury. • Transient neurological symptoms (transient pain or dysesthesia) has been linked to lidocaine in spinal anesthesia.
Allergy - Especially, ester-type local anesthetics (very important)
Cardiovascular Adverse Effects of Local Anesthetics
Lipid Emulsion can act as a sink and remove and sequester anesthetics
Local Anesthetics Overview Table
Question 1
Question 2
Question 3
Question 4
Question 5
Question 6
Question 7
Question 8
Question 9
Question 10
Question 11
Question 12
Question 13
Question 14
Question 15
Question 16
MAC to %anesthetic
1 MAC = 100% N2O so .3 MAC = 30% N2O
1 MAC = 1.4% Isoflurane so .3 MAC = .42% Isoflurane
Alveolar Wash-in
↑Ventilatory rate/depth = shorter time to exchange lung gases with anesthetic mixture
increase the concentration and increase the depth of ventilation
If you need to anesthetize quickly choose?
an anesthetic with a low blood solubility because high arterial pressures are reached rapidly and shorter induction
Which tissues absorb Anesthetic most quickly
- highly perfused tissues rapidly achieve a steady-state with the partial pressures in blood
- muscles accumulate anesthetics more slowly due to lower perfusion rates and larger volume
- Adipose tissue accumulates anesthetics more slowly due to lower perfusion rates but most anesthetics have high lipid solubility (patient will recover from anesthesia less quickly)
the higher the lipid solubility of the anesthetic the more _______ is
Potency
so
the
lower
the
MAC
Potency is inversely related to MAC
Major route of anesthetic clearance from the body
unchanged by the lungs
Avoid pungent anesthetics in patients with
Bronchospasm
Pungent
Very strong odor but sensitive
Ach Antagonist Malignant Hypothermia
wont work because the Ca2+ release is from inside the cell
Opioids
larynx rigidty preventing intubation, tracheostomy , naloxone antidote!
Benzodiazepines
Barbiturate anesthetics: Thiopental
rapid ultra short-acting
Propofol
milk of amnesia
antiemetic (postoperative vomiting is uncommon)
Propofol intracranial pressure
↓Intracranial pressure
Propofol analgesic properties
not a good analgesic
Ketamine
Only IV anesthetic that produces cardiovascular stimulation (increases heart rate and cardiac output)
Ketamine
Ketamine analgesic properties
good analgesic
Ketamine respiratory effects
minimal effects on respiration
upper airway reflexes
Don’t give ketamine to patients with?
patients with cardiovascular issues or vascular issues stroke, psychosis or schizophrenia
Etomidate
Etomidate Caveat
can use in anesthetic induction in patients at risk of hypotension because it produces minimal cardiovascular and respiratory depression
Etomidate Side effects
- Vomiting
- pain on injection
- Myoclonus
- Decreases plasma levels of hydrocortisone
Dexmedetomidine
used for short term sedation of intubated and ventilated ICU patients or during regional anesthesia
For an opiod tolerant patient what type of anesthesia
propofol perhaps
Two Is
Amide Local anesthetics
Two As
long-acting local anesthetic
How to treat arrhythymias from local anesthetics
lipid resuscitation
pH has a major effect on?
Local anesthetic effect
If patient has liver problems would an amide be appropriate
maybe not or decrease the dose
because amides are metabolized in the liver
where do local anesthetics have their therapeutic effect
on the internal Na+ channels
pH can block local anesthetics where?
intra and extracellularly because if it is charged it cannot get in
if it is not charged inside the cell then it cannot block the channel
Actions of local anesthetics
Why do you coinject with epinephrine
1 is extremely important
aspirate before
putting in a local anesthetic
Pre-medicate with ____________ to prevent convulsions but it could mask serious reactions
benzodiazepines
Adverse effects of local anesthetics
IV Lipid Emulsion
lidocaine is used to treat _____
ventricular arythmias maybe
