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Flashcards in General & Local Anesthetics Deck (72)
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1
Q

What is anesthesia?

A
  • state where no movement occurs in response to what should be painful
  • patient is usually not consciousness
    • unaware of sensory input
2
Q

Components of the anesthetic state:

A
  1. Amnesia
  2. Unconsciousness
    • not always needed
  3. Analgesia
    • inability to interpret, respond to or remember pain
  4. Immobility in response to noxious stimuli
  5. Attenuation of autonomic responses to noxious stimuli
3
Q

How is anesthetic potency measured?

A
  • Potency is usually measured by determination of the concentration of anesthetic that prevents movement in response to pain
  • Dose of a gas is directly related to and determined by its concentration at the alveolus
    • defined as minimal alveolar concentration (MAC) that prevents movement in response to pain 50% of subjects
  • For IV anesthetics:
    • The free plasma concentration that produces loss of response to a surgical incision in 50% of patients (EC50)
4
Q

Advantages of MAC as a measure:

A
  1. Can be continuously monitored by measuring end-tidal anesthetic concentration
  2. Provides a direct correlate to anesthetic concentration at the site of action in CNS
  3. Simple to measure end-point
    • lack of movement
  4. Can be defined
    • ​​Ex:** **MACawake
5
Q

What are common effects shared by all anesthetics?

A
  • membrane hyperpolarization and effects on synaptic function:
    • inhibitory neurotransmission is increased
    • excitatory neurotransmission is reduced
6
Q

What type of receptors are likely targeted by anesthetics?

A
  1. GABAA receptors:
    • GABA-regulated chloride channel
    • function is enhanced by most, but not all anesthetics
    • anesthetics produce allosteric interactions
    • increased Cl- conductance results in hyperpolarization
  2. NMDA receptors:
    • Glutamate-regulated cation channel
    • Anesthetics that do not interact with GABA receptors (i.e. ketamine, nitrous oxide and xenon) all inhibit NMDA receptors
    • reduces Na+ and Ca2+ influx ⇒ some hyperpolarization of membrane potential
  3. Other membrane associated protiens
    • anesthetics fill hydophobic cavities
    • alter movement of proteins; alter transitions required for signaling and activation
7
Q

Stages of anesthesia:

A
  • Predmedication
  • Induction:
    1. Needs to be non-frightening, quick, painless
    2. Usually an i.v. anesthetic is used
    3. Can be other parenteral methods
    4. Emergency – via inhalational anesthetics
8
Q

Parenterally administered anesthetics:
Generalities

A
  1. All hydrophobic
  2. Single iv bolushigh concentration in brain and spinal cord within a single circulation time ⇒ rapid induction of anesthesia
  3. Subsequently, blood levels drop and the anesthetic redistributes back into the blood from the brain and winds up in other tissues where it is slowly released and metabolized
  4. As a result, the half-life of the anesthetic in the body and the duration of action are not the same
9
Q

Sodium thiopental:

Use

A
  • Used to induce anesthesia
    • typical induction dose produces unconsciousness in 10 to 30 sec
    • duration of action of a single dose is about 10 min
  • Activate GABAA receptors
  • long half life (12 hours) ⇒ produce residual effects (hang-over) after anesthesia has worn off
  • Can be administered to pediatric patients rectally if needed
10
Q

Sodium thiopental:

Contraindications

A
  • Depressants are additive
  • Dose should be reduced if patient has been premedicated with other CNS depressants
  • Intra-arterial injection can produce severe inflammation and can even be necrotic so this is not done
11
Q

Sodium thiopental:

Side effects

A
  • CNS:
    • **Reduces cerebral oxygen utilization **⇒ reduces cerebral blood flow and intracranial pressure
      • Has been tried as a protective agent for the treatment of cerebral ischemia
  • Cardiovascular: Produces vasodilation
    • venous dominant
    • Can produce severe drops in BP in patients with impaired ability to compensate for venodilation
      • reduced preload or cardiomyopathy
    • Not contraindicated in patients with coronary artery disease because demand is reduced; no arythmogenic effects
  • Respiratory depression
12
Q

Propofol:

Use

A
  • Onset and duration of anesthesia are the same as barbiturates
  • GABAA mechanism
  • Is used to maintain and induce anesthesia
  • Is antiemetic, an advantage as many patients are nauseated following surgery
  • Has a shorter half-life than thiopental
    • used when a rapid return to normal mental status is desired
      • Ex: out-patient surgery
13
Q

Propofol:

Side effects

A
  • Elicits pain on injection
    • To avoid, can be given with lidocaine or administered into larger veins
  • Can produce excitation during induction
  • CNS: same as barbiturates
  • Cardiovascular: more severe decrease in blood pressure than thiopental
    1. Produces both vasodilation and depression of myocardial contractility
    2. Also blunts baroreceptor reflexes
    3. Therefore, needs to be used with caution in patients that are intolerant of decreases in blood pressure
  • produces more respiratory depression than thiopental
  • Has demonstrated abuse liability
14
Q

Etomidate:

Use

A
  • Primarily used to induce anesthesia in patients at risk for hypotension
  • High incidence of pain on injection and myoclonus
    • Pain is dealt with using lidocaine
    • myoclonus is reduced by premedication with benzodiazepines or opiates
15
Q

Etomidate:

Side effects

A
  • CNS: like thiopental
  • Cardiovascular:
    • Less than thiopental and propofol which is the major advantage of etomidate over them
    • Produces small increase in heart rate, little or no decrease in blood pressure
  • Less respiratory depression than thiopental
16
Q

Etomidate:

Drawbacks

A
  1. Significantly more nausea and vomiting than thiopental
  2. Increased post-surgical mortality due to suppression of the adrenocortical stress response
    • primarily when the anesthetic has been given for a prolonged period of time
    • only used to induce anesthesia in patients prone to hemodynamic problems
17
Q

Ketamine:

Characterstics

A
  • NMDA receptor antagonist
  • Produces a different hypnotic state; called “dissociative anesthesia”
  • Characterized by:
    1. profound analgesia
    2. unresponsiveness to commands, even though eyes can be open
    3. amnesia
    4. spontaneous respiration
  • typically administered iv
    • also can be via IM, oral or rectal
18
Q

Ketamine:

Use

A
  • Advantages: profound analgesia, very little respiratory depression, bronchodilator
  • Reserved for patients with bronchospasm
  • Children undergoing short, painful procedures
19
Q

Ketamine:

Side effects

A
  • Produces nystagmus, salivation, lacrimation, spontaneous limb movements and increased muscle tone
  • Increased intracranial pressure
  • Emergence delirium: hallucinations, vivid dreams, illusions (not as bad in children)
  • **Indirect sympathomimetic activity ⇒ **causes increased BP
20
Q

Midazolam:

Use

A
  • GABAA activator
  • Short-acting benzodiazepine:
    • half-life 1-5 hours
    • Used for conscious sedation, anxiolysis and amnesia during minor surgical procedures
    • Used as an induction agent
    • Used as an adjunct during regional anesthesia
    • Anti-anxiety effects make it useful preoperatively
  • Slower induction time and longer duration than thiopental
  • Metabolized by hydroxylation to an active metabolite
21
Q

Midazolam:

Side effects

A
  • Has been associated with respiratory depression and respiratory arrest especially when used intravenously to produce conscious sedation
  • Should be used with caution in patients with:
    • neuromuscular disease; Parkinson’s disease; bipolar disorder
  • Cardiovascular: Like thiopental
22
Q

What are the therapeutic indices for inhaled anesthetics?

A

Very low: LD50/ED50 values are 2-4

23
Q

Describe the pharmacokinetics of inhaled anesthetics:

A
  • Easily vaporized at room temperature or gases
  • Rather than a concentration gradient across a barrier, the partial pressure of the anesthetics determines transmembrane movement
  • Equilibrium is reached when partial pressures are the same
    • not necessarily equivalent to equal concentrations on each side of the membrane
24
Q

List the 3 partition coefficents:

A
  1. blood:gas
  2. blood:brain
  3. blood:fat
25
Q

What does the blood:gas partition coefficient determine?

A

determines absorption in the lung

  • Measure of the solubility of the anesthetic in an aqueous versus gaseous environment
  • Low blood:gas partition coefficient ⇒ rapid equilibration in blood
    • need high amounts in inspired air
    • drug moves out of the blood and into gas readily
    • induction & recovery are quick
  • High blood:gas partition coefficient:
    • need less in inspired air
    • induction & recovery are slow
  • Therefore, rate of induction is inversely related to the blood:gas partition coefficient
26
Q

What does the **blood:brain **partition coefficient determine?

A

determines distribution to the brain

27
Q

What does the blood:fat partition coefficient determine?

A

determines redistribution and recovery from anesthetic effect

  • high blood:fat PC:
    • Half-­‐life will be long (hang over) due to slow release into the blood
    • Enough gets into the brain to make the patient feel sleepy
28
Q

Factors that affect induction:

A
  1. Anesthetic concentration in the inspired air
  2. Pulmonary ventilation
  3. Pulmonary blood flow
  4. Arteriovenous concentration gradient
  5. Elimination (rate of recovery from anesthesia)
29
Q

How does the anesthetic concentration in the inspired air affect induction?
:

A
  1. Affects the partial pressure of the gas in air
  2. Also affects the partial pressure in the blood
  3. The rate of transfer will increase as the concentration is increased
  • Therefore, rapid induction can be achieved with higher concentrations
30
Q

How do pulmonary ventilation and blood flow affect induction?

A
  1. Pulmonary ventilation:
    • Affects moderately blood soluble anesthetics more than low soluble agents
  2. Pulmonary blood flow:
    • Increased blood flow slows the rate of rise in arterial partial pressure
      • shorter time for equilibration
    • Effect is most dramatic for moderately soluble anesthetics
31
Q

How does arteriovenous concentration gradient affect induction?

A
  • Dependent upon rate and extent of tissue uptake
  • Determined by partition coefficients, rate of blood flow to that tissue and concentration gradient
  • During induction, highly perfused tissues exert the greatest effect
32
Q

How does the elimination of inhaled anesthetics affect induction?

A
  1. Reverse of induction
    • blood:gas partition coefficient is the most important determinant
    • gas needs to get into the blood to be eliminated
    • Low solubility anesthetics are eliminated fastest
  2. Duration of exposure
    • Because of tissue accumulation
    • Longer the exposure the longer it takes to eliminate the anesthetic
    • low fat solubility ⇒ quicker recovery
33
Q

Anesthesia is achieved when:

A

brain partial pressure = MAC

  1. Brain is well perfused
    • partial pressures of the anesthetic in alveolar gas and in the brain become equal in a short period of time
  2. Anesthesia is reached shortly after MAC is achieved in the alveolae
  3. In clinical practice, the equilibration of the patient with the gas is determined
    • ​​Equilibration occurs when the concentration of anesthetic in the inspired gas mixture is the same as the end-tidal (alveolar) concentration
    • no net movement of anesthetic occurs
    • This will occur more slowly for agents that are very fat-soluble and more quickly for those agents with less fat solubility
34
Q

Recovery from inhaled anesthesia is the opposite process:

A
  1. For agents with low blood and tissue solubility:
    • recovery is rapid and unrelated to the length of anesthetic exposure
  2. For agents with high blood and fat solubility
    • recovery will be a function of the duration of anesthetic administration
      • because of fat accumulation
35
Q

Inhaled anesthetic agents (4):

A
  1. isoflurane
  2. desflurane
  3. sevoflurane
  4. nitrous oxide
36
Q

Isoflurane:

Pharmacokinetics

A
  1. Moderate blood:gas partition coefficient
  2. 99% excreted unchanged from the lungs
37
Q

Isoflurane:

Use

A
  1. Commonly used inhalational anesthetic in the US
  2. Can be used to induce and maintain anesthesia
    • ​​mostly maintenance
  3. Co-administration of nitrous oxide allows for a reduction in the dose of isoflurane
38
Q

Isoflurane:

Side effects

A
  • Respiratory:
    1. Is an airway irritant, can cause coughing
    2. Decreases tidal volume and increases respiratory rate
    3. All volatile anesthetics are respiratory depressants and increase PaCO2
  • Cardiovascular
    1. Myocardial depression leading to a decrease in blood pressure
    2. Arrythmias
      • ​​sensitizes the heart to catecholamines
    3. Dilates cerebral blood vessels increasing intracranial pressure
39
Q

Desflurane:

Pharmacokinetics

A
  1. Very volatile at room temperature, requires special equipment to administer
  2. Very low blood:gas partition coefficient
    • ​​very rapid induction and recovery
  3. Predominantly excreted unchanged
40
Q

Desflurane:

  • Use:
  • Side effects:
A
  • Use:
    • outpatient surgeries
    • can cause coughing and bronchospasm in awake patients
    • not used to induce because of respiratory irritation
    • produces direct skeletal muscle relaxation
  • **Side effects: **
    • Cardiovascular: Similar to isoflurane
    • Respiratory: similar to isoflurane
      • worse as a respiratory irritant
      • bronchospasm
41
Q

Sevoflurane:

Pharmacokinetics

A
  1. Very low blood:gas partition coefficient
  2. About 5% of administered dose is metabolized to fluoride ion in the liver
    • may cause renal damage
  3. Ex vivo degradation by CO2 absorbents in the anesthesia circuit forms “compound A”
    • nephrotoxic in rats
42
Q

Sevoflurane:

  • Use:
  • Side effects:
A
  • Use:
    • Inpatient and outpatient
    • Induction and maintenance
    • Children and adults
    • Not a respiratory irritant
  • Side effects:
    • ​Cardiovascular: similar to isoflurane
    • Respiratory: similar to isoflurane, but not much respiratory depression
43
Q

Nitrous Oxide:

Pharmacokinetics

A
  1. True gas
  2. Moderate blood:gas PC
  3. Very insoluble in blood and other tissues so results in a rapid equilibration
    • very rapid induction and recovery
  4. Its rapid uptake from the alveolae results in the “concentration” of gases that are administered at the same time
    • This is why it is often co-administered with other inhalational anesthetics ⇒ enhances induction
  5. Can also dilute oxygen when its use is discontinued
    • ​​need to place patients on 100% O2 during emergence
  6. 99% excretion through the lungs
44
Q

Nitrous Oxide:

Use

A
  1. Weak anesthetic, only gets to full efficacy under hyperbaric conditions
    • Cannot be used at greater than 80% due to oxygen requirements
  2. Used to produce sedation and analgesia in outpatient dentistry (50% conc. in inspired air)
  3. Used as an adjunct with other inhalational anesthetics, allows for a reduction in their dose (70% conc. in inspired air)
45
Q

Nitrous Oxide:

Side Effects

A
  1. Can exchange with nitrogen in any air-containing cavity
    • contraindicated in pneumothorax
  2. Negative inotrope but also sympatho-stimulant
  3. Respiratory effects are minimal except for the oxygen dilution issue
  4. Abuse liability
46
Q

Local Anesthetic: Definition

A
  • Bind reversibly to a site within the pore of Na+ channels in nerves
    • blocking ion movement through the pore
  • When applied locally, act on any part of the nervous system and any nerve fiber
    • reversibly blocking action potential responsible for nerve conduction
  • Can cause sensory and motor paralysis of the area innervated
47
Q

Topical: Anesthesia

A
  • Applied to the skin, mucous membranes, or ulcerated surfaces
  • Ophthalmic
    • produce anesthesia of the cornea and conjunctiva
48
Q

Local Infiltration Anesthesia

A
  • local injection of an agent into tissues irrespective of the course of cutaneous nerves
  • provides regional anesthesia around sites of injection
49
Q

Nerve Block Anesthesia

A

injection around individual nerves or nerve plexuses that leads to operative site

50
Q

Spinal and Epidural Anesthesia

A
  • Spinal
    • injection into the cerebrospinal fluid in the lumbar space
  • Epidural
    • local injection into the epidural space in the sacral, thoracic, lumbar, or cervical regions
51
Q

Local Anesthetics:

Act directly on nerve cells to block their ability to conduct impulses

A
  • act on every type of nerve fiber
  • by blocking action potential propagation on nociceptic neurons, eliminate pain sensation
  • completely reversible; no nerve damage
52
Q

Local Anesthetics:

Bind directly to voltage-dependent sodium channels

A
  • bind to a site on the intracellular side of the channel (segment 6 in domain IV)
  • bind in the cationic form, but must reach their site of action by penetrating the nerve sheath and axonal membrane in the unionized species
  • are all weak bases
53
Q

Local Anesthetics:

Effects on the action potential

A
  • slows rate of depolarization
  • reduces height of action potential
  • reduces rise of action potential
  • slows axonal conduction
  • ultimately prevents propagation of the action potential
  • does not alter the resting membrane potential
  • increases the threshold potential
54
Q

**Local Anesthetics: **

Frequency- and voltage-dependence

A
  • degree of block depends on the frequency of nerve stimulation and the resting membrane potential
  • resting nerves much less sensitive to block compared to one that is repetitively stimulated
  • nerves with more positive membrane potential more sensitive to block
  • occurs because:
    • gain access to the channel binding site more easily when the channel is open
    • have higher affinity for the inactivated channel than for resting channels
55
Q

Local Anesthetics:

Effect of pH

A
  • charged form binds to the channel but uncharged form penetrates into the nerve
    • alterations in the extracellular pH can influence efficiency
  • sites of inflammation or infection have lower pH
    • local anesthetic is in the ionized form
    • less diffusion across membranes producing less effective block
56
Q

How do local anesthetics affect vasoconstrictors?

A
  • many times used in combination with vasoconstrictors
    • decreases rate of vascular absorption
    • increases the depth of anesthesia
  • less systemic absorption so less toxicity and increases the maximal dose that can be given
  • most common vasoconstrictor used with local anesthetics – epinephrine
57
Q

Sensitivity of specific nerve fibers to local anesthetics:

A
  • in general, autonomic fibers, small non-myelinated C fibers (mediating pain sensation), and small myelinated Aδ fibers (mediating pain and temperature sensation) are blocked before larger myelinated Aδ, Aβ, and Aα fibers (mediating postural, touch, pressure, and motor information)
  • spacing of nodes of Ranvier increase with size of nerve fibers and a fixed number of nodes must be blocked to prevent conduction
58
Q

General order of block (recovery in reverse order):

A
  1. pain
  2. cold
  3. warmth
  4. touch
  5. deep pressure
  6. motor
59
Q

Local Anesthetics:

TOXICITY AND SIDE EFFECTS

A
  • local anesthetics interfere with the function of all organs in which conduction or transmission of impulses occurs
  • systemic toxic reactions are related to high concentrations of the local anesthetic in the circulation
    • use the smallest amount that effectively blocks pain sensation
  • accidental intraneuronal injection can produce irreversible damage
  • in general, the S-enantiomer is less toxic that the R-enantiomer in local anesthetics with chiral centers
60
Q

Local Anesthetics:

Central nervous system toxicity

A
  • if absorbed systemically, may cause CNS stimulation
    • producing restlessness and tremor that may progress to convulsions
  • central stimulation is followed by depression
  • death with severe toxicity is usually caused by respiratory depression
61
Q

Local Anesthetics:

Cardiovascular toxicity

A
  • general depression of the cardiovascular system
  • usually seen after CNS effects are produced
  • can develop hypotension and arrhythmias leading to cardiac arrest
62
Q

Local Anesthetics:

Hypersensitivity

A
  • rare individual are hypersensitive to local anesthetics
    • allergic dermatitis or a typical anaphylactic-like reaction
  • must distinguish from the effects of co-administered vasoconstrictors
  • more frequent with ester local anesthetics
    • extends to chemically related compounds
  • preservatives such as methylparaben may provoke an allergic reaction
63
Q

Local Anesthetics:

Metabolism of local anesthetics

A
  • metabolic fate important
    • toxicity depends largely on the balance between the rate of absorption into the systemic circulation and elimination
  • ester local anesthetics primarily inactivated by plasma esterases
  • amide local anesthetics metabolized in the liver
    • use with caution in patients with severe liver disease
64
Q

Ester Local Anesthetics (4):

A
  1. Cocaine
  2. Procaine
  3. Tetracaine
  4. Benzocaine
65
Q

Cocaine:

A
  • exhibits local anesthetic activity and also blocks norepinephrine uptake into presynaptic adrenergic nerves
  • local anesthetic with potent vasoconstrictor properties
  • toxicity and potential for abuse have decreased its clinical use
  • used for topical anesthesia of the upper respiratory tract
    • actions as both a vasoconstrictor and local anesthetic provide anesthesia and shrinking of the mucosa limiting bleeding
66
Q

Procaine:

A
  • short acting ester local anesthetic
  • first synthetic local anesthetic (1905)
  • has been supplanted by newer agents but still used for infiltration anesthesia
  • low potency, slow onset, and short duration of action
67
Q

Tetracaine:

A
  • long acting ester local anesthetic
  • more potent and longer duration of action than procaine
  • widely used in spinal anesthesia and in topical and ophthalmic preparations
    • not irritating when placed in the eye unlike some other local anesthetics
  • rarely used for peripheral nerve block
    • large doses are necessary increasing the potential for toxicity
68
Q

Benzocaine:

A
  • anesthetic with low solubility in water
    • too slowly absorbed when applied topically to be toxic
  • applied to wounds and ulcerated surfaces where it provides relief for long periods of time
69
Q

Amide Local Anesthetics (3):

A
  1. Lidocaine
  2. Bupivacaine
  3. Ropivacaine
70
Q

Lidocaine:

A
  • intermediate duration of action
  • produces faster, more intense, longer lasting, and more extensive anesthesia than does an equal concentration of procaine
  • use with epinephrine decreases the rate of absorption decreasing toxicity
  • metabolized in the liver
  • standard toxicity associated with local anesthetics
  • has a wide range of clinical uses:
    • used in almost any application where a local anesthetic of intermediate duration of action is needed
71
Q

Bupivacaine:

A
  • long acting amide local anesthetic
    • capable of producing prolonged anesthesia
  • long duration of action plus its tendency to provide more sensory than motor block has made it use popular for providing prolonged analgesia
  • more cardiotoxic than equi-effective doses of lidocaine
    • severe ventricular arrhythmias and myocardial depression following large doses
  • **bupivacaine dissociates from Na+ channels slowly **
    • increased potency for blocking cardiac conduction
    • S-enantiomer is less cardiotoxic
72
Q

Ropivacaine:

A
  • long acting amide local anesthetic
  • consists of the S-enantiomer
  • anesthetic actions similar to bupivacaine with less cardiotoxicity
  • suitable for both epidural and regional anesthesia
  • even more motor-sparing than bupivacaine