Lecture 7-Local and General Anesthetics

DRUGS USED IN DISORDERS OF THE
CENTRAL NERVOUS SYSTEM AND

TREATMENT OF PAIN
Lecture 7:
Pain, Local and General Anesthetics
Marc Imhotep Cray, M.D.
CNS Pharmacology
Lecture 7
Learning Objectives:
LOCAL ANESTHETICS
1. The mechanisms by which local anesthetics block nerve conduction.
2. An understanding of how the physiochemical properties of local anesthetics
influence the pharmacodynamics and pharmacokinetics of these drugs.
3. What undesirable side effects may occur with the use of local anesthetics and why
these side effects happen.
4. The unique characteristics and the common clinical use for each prototypical local
anesthetic.
5. The most commonly caused severe complications of local anesthetics when they
are systemically absorbed or injected intravenously.
Marc Imhotep Cray, M.D. 2

CNS Pharmacology
Lecture 7
Learning Objectives cont.
GENERAL ANESTHETICS
1. The definition of general anesthesia and how it can be achieved.
2. A working understanding of the pharmacokinetics for inhalational anesthetics.
3. The various stages of anesthesia.
4. How the blood: gas coefficient influences the onset of action (and termination of
anesthesia) for inhaled anesthetics.
6. How blood flow to a tissue influences the tension of an anesthetics gas in that tissue.
7. The definition of minimum alveolar concentration (MAC) and what information it
provides about a volatile anesthetic.
8. The pharmacokinetic properties of the ultrashort-acting hypnotics and how these
properties make this class of drugs popular general anesthetic agents.
9. The advantages and disadvantages for clinically used inhaled and intravenously
administered general anesthetics. When they should be used and when they are
contraindicated.
10. The concept that inhalational and intravenous anesthetics cause varying degrees of
respiratory depression with an exception being ketamine.

CNS Pharmacology
Classification Schema: Lecture 7
Local and General Anesthetics

Local Anesthetics General Anesthetics General Anesthetics cont.
A. Esters: A. Halogenated D. Sedative-Hypnotics
Procaine Hydrocarbons: Ketamine
Cocaine Isoflurane Etomidate
Tetracaine Sevoflurane Propofol
Benzocaine Desflurane E. Opioids
B. Amides: B. Inert Gas Morphine
Lidocaine Nitrous Oxide Fentanyl
Mepivacaine C. Ultrashort-Acting F. Benzodiazepines
Bupivacaine Barbiturates Midazolam
L-Bupivacaine Thiopental
Ropivacaine Methohexital
A “Functional” Classification Schema of Anesthetics:
PREANESTHETIC MEDICATIONS GENERAL ANESTHETICS:
LOCAL ANESTHETICS: AMIDES
Antacids INTRAVENOUS
Bupivacaine MARCAINE
Anticholinergics Barbiturates
Lidocaine XYLOCAINE
Antiemetics Benzodiazepines
Mepivacaine CARBOCAINE
Antihistamines Dexmedetomidine PRECEDEX
Ropivacaine NAROPIN
Benzodiazepines Etomidate AMIDATE
LOCAL ANESTHETICS: ESTERS
Opioids Ketamine KETALAR
Chloroprocaine NESACAINE
GENERAL ANESTHETICS: Opioids
Procaine NOVOCAINE
INHALED Propofol DIPRIVAN
Tetracaine PONTOCAINE
Desflurane SUPRANE NEUROMUSCULAR BLOCKERS
Cocaine
Halothane FLUOTHANE (An ANS Lecture)
Isoflurane FORANE Cisatracurium, pancuronium,
Nitrous oxide NITROUS OXIDE rocuronium, succinylcholine,
Sevoflurane ULTANE vecuronium
5
CNS Pharmacology
Lecture 7
Pain Pathways:
 Tissue injury can lead to cellular changes involving release of
chemicals (e.g., histamine) that start or quicken neuronal impulses
that are interpreted as pain
 Many neuronal pathways transmit pain sensation

 For example, pain from peripheral injury reaches CNS via primary afferent
neurons, whose cell bodies form the dorsal root ganglia (DRG)
 Disorders such as phantom limb pain may involve abnormal DRG structure or
function
 Primary afferents end mainly in the dorsal horn of the spinal cord
Secondary neurons cross spinal cord and ascend in pathways to the
thalamus, the cerebral cortex, and other sites

CNS Pharmacology
Lecture 7
Pain Pathways(2)
A descending system of opioid (endorphins, enkephalins), 5-HT
(e.g., from raphe nuclei), and noradrenergic (e.g., from locus
ceruleus) pathways can lessen afferent signals
Drugs that act at pathways mediating pain sensation or

perception are:
 local (e.g., lidocaine) and
 general (e.g., halothane) agents,
 opioids (e.g., morphine), and
 nonopioids (e.g., aspirin and acetaminophen)

CNS Pharmacology
Pain Pathways Lecture 7

CNS Pharmacology
Lecture 7
Local Anesthetics
Modified from: Trevor and Katzung. Pharmacology Examination & Board Review 10th ed. 2013

CNS Pharmacology
Lecture 7
Local Anesthetics: Spinal Afferents and
Mechanisms of Action
 Local anesthetics cause temporary loss of pain sensation without loss
of consciousness by blocking conduction along sensory nerve fibers
 Some selectivity for pain afferents is achieved partly by using agent

close to target neurons (local administration)
 All currently used drugs block voltage-dependent Na+ channels in
excitable cells, which decreases likelihood of an action potential
 Target site of drugs is on cytoplasmic side of neuron membrane, so

drug molecules must pass through membrane ( must have lipophilicity)

CNS Pharmacology
Lecture 7
Local Anesthetics (2)

 Local anesthetics are both lipophilic and hydrophilic and are weak
bases (amides or esters) that exist in equilibrium between ionized
(hydrophilic) and nonionized (lipophilic) forms
 nonionized (lipophilic) forms diffuse more readily through
membrane
 ionized (hydrophilic) form diffuse more readily through cytoplasm
 Esters are metabolized by plasma cholinesterases
(butyrylcholinesterases)
 Amides are hydrolyzed in liver (amidases)
 Because local anesthetics act on all excitable cells, they can cause
toxicity, including fatal cardiovascular effects or seizures

CNS Pharmacology
Lecture 7
A. REDUCTION OF SODIUM AND POTASSIUM ION PERMEABILITY (PNa
AND PK) in activated nerve membranes leads to local anesthesia
1. There are no effects on resting membranes
2. Effects on nerve action potential of both sensory and motor
nerve fibers include:
o Reduction in amplitude
o Reduction in rate of rise
o Reduction in conduction velocity
o Blockade of axonal conduction
3. Sensory neurons are blocked before motor neurons because sensory
axons are usually smaller and have less myelin

CNS Pharmacology
Lecture 7
B. Local anesthetics, except for benzocaine, have three common structural
components:
1. The aromatic residue is lipophilic, which is important for good
membrane penetration
2. The amino group is hydrophilic
a. It can become charged by picking up a proton
b. pH and pKa determine whether the local anesthetic is present
predominantly in the charged or uncharged forms
Lidocaine

CNS Pharmacology
Lecture 7
i. Only uncharged form crosses nerve cell membrane
ii. It is converted to charged form inside axon, which then interacts with binding
sites within ion channels
iii. Stock solutions of local anesthetics are acidic (local anesthetic is ionized)
 Acidity must be neutralized before anesthesia can occur
iv. Local anesthetics will be less effective for inducing anesthesia in areas of
inflammation because:
a. pH is low
b. Most of anesthetic will be charged and unable to penetrate nerve cell
membrane

CNS Pharmacology
Lecture 7
Local Anesthetic Mechanism of Action

CNS Pharmacology
Lecture 7

v. Mucous membranes have a low buffering capacity and cannot
readily neutralize acidity of local anesthetic solution
 As a result, mucous membranes are relatively difficult to
anesthetize
c. The pKa must be between 7 and 9 so that some of local
anesthetic is in the charged form and some is in uncharged
form at physiological pH

CNS Pharmacology
Lecture 7
3. The intermediate chain determines how a local anesthetic is
metabolized and can be either an ester or an amide
a. Esters are broken down by butyrylcholinesterases in blood
i. Cocaine is only used for topical anesthesia
ii. Procaine (Novocain) is metabolized to para-aminobenzoic
acid (PABA) It can induce an allergic reaction
iii. Chloroprocaine (Nesacaine) is metabolized most rapidly, has
the shortest duration of action, and theoretically has the
lowest risk of systemic toxicity
iv. Tetracaine (Pontocaine) is 10 times as potent as procaine and
10 times as toxic Lidocaine

CNS Pharmacology
Lecture 7

b. Amides, which are metabolized by amidases in liver, include:
i. Lidocaine (Xylocaine)
ii. Mepivacaine (Carbocaine)
iii. Bupivacaine (Marcaine), which is cardiotoxic

CNS Pharmacology
Lecture 7

C. TOXIC EFFECTS are very uncommon but can be serious if systemic
absorption of local anesthetic is excessive:
1. Myocardial depression is due to sodium channel blockade in
myocardial muscle
2. Vasodilation leads to a fall in blood pressure
3. Anxiety, depression, and convulsions can occur due to CNS
neurotoxicity
4. Hypersensitivity reactions are rare and occur primarily with
esters, which contain PABA derivatives

CNS Pharmacology
Lecture 7

D. EPINEPHRINE (EPI) IS FREQUENTLY COMBINED WITH LOCAL
ANESTHETICS
1. EPI reduces blood flow in anesthetized area which
a. Reduces bleeding, making it useful during some types of
surgeries
b. Prolongs anesthesia by slowing the loss of anesthetic from
area of injection
c. Reduces systemic concentration of the anesthetic, thereby
lowering the incidence of toxicity
2. EPI is not used with cocaine because cocaine by itself has
vasoconstrictor activity, and it is not used on end-appendages
where ischemia can be induced

CNS Pharmacology
Lecture 7

E. Symptoms of local anesthetic toxicity must be treated aggressively
1. Oxygen reduces hypoxia
2. Vasopressors or intravenous fluids increase blood pressure
3. Diazepam reduces convulsions
F. During spinal anesthesia, blood pressure may fall due to blockade of

sympathetic pathways in spinal cord

CNS Pharmacology
Lecture 7
General Anesthetics:
Modified from: Trevor and Katzung. Pharmacology Examination & Board Review 10th ed. 2013

CNS Pharmacology
Lecture 7
General Anesthetics: Properties

 General anesthetics (inhalational and intravenous agents) have a rapid,
smooth onset of action and clinically desirable rapid reversal of effect
 Concentrations of inhalational agents in body and pharmacokinetics

depend on drugs’ partial pressure in lungs and solubility in blood and
brain tissue
 Induction of anesthesia is more rapid for drugs with high partial

pressure in lungs and high solubility in blood (e.g., nitrous oxide,
desflurane, sevoflurane)
 Onset of anesthesia is slowed when pulmonary blood flow is reduce

CNS Pharmacology
Lecture 7
General Anesthetics Properties (2)

 Site of drug action is brain; exact mechanism is unknown but may be
related to lipid solubility and activation of GABAA receptors (enhanced
Cl− influx, hyperpolarization of neurons) (recent theories vs classic
theories)
 Elimination from brain and exhalation from lungs stop effect of drug
 Redistribution to other tissues delays elimination and may increase

occurrence of adverse effects
 Intravenous agents include barbiturates, benzodiazepines, ketamine,

opioids, and propofol

CNS Pharmacology
Lecture 7
Principles of General Anesthesia:

A. THE PRIMARY OBJECTIVES of general anesthesia are:
1. Amnesia
2. Analgesia
3. Unconsciousness
4. Suppression of autonomic reflexes
5. Muscle relaxation
B. Due to blood–brain barrier, all CNS drugs including general

anesthetics must either be lipid soluble or carried across barrier by
active transport (e.g., P-glycoproteins) in order to be effective

CNS Pharmacology
Lecture 7
Principles of General Anesthesia (2)

C. Mechanism of action of general anesthetics has been difficult to
determine
1. Classical theories involve a physical association of anesthetics with
cell membranes leads to several implications
a. Potency of inhaled anesthetics is defined in terms of minimal
alveolar concentration (MAC)
i. MAC is anesthetic alveolar partial pressure required to prevent
movement in 50% of patients in response to a skin incision
ii. It is inversely related to oil–water partition coefficient for that
anesthetic
b. Association of anesthetic with cell membranes reduces
excitability of membranes
c. Important receptors for inhalation anesthetics are not known
d. There are no specific antagonists for inhalation anesthetics
2. Recent theories involve an enhancement of effects
of inhibitory neurotransmitters (e.g., gamma-
aminobutyric acid, GABA)
3. At low concentrations of a general anesthetic, CNS

is depressed more than other tissues
 as concentration is increased, all excitable cells
are eventually depressed
27
CNS Pharmacology
Lecture 7

D. Factors to considered when selecting anesthetics:
1. Patient’s kidney and liver function
2. Patient’s respiratory function, since anesthetics are respiratory
depressants
3. Cardiac or CNS abnormalities
4. Family or personal history of malignant hyperthermia
5. Pregnancy status of patient, to avoid harm to the fetus
6. Other drugs being taken by patient, both legal and illegal

CNS Pharmacology
Lecture 7
E. Anesthetics induce characteristic stages of anesthesia:
 Stage 1 involves analgesia patient is conscious
 Stage 2 involves excitement, due to blockade of inhibitory pathways in

brain can be a dangerous phase due to vomiting, restlessness,
delirium, and other hyperexcitable effects that may occurpatient is
unconscious
 Stage 3 is stage at which surgery is usually performed patient is
unconscious, and skeletal muscles are relaxed
 Stage 4 involves respiratory and cardiovascular depression, which, if

pronounced, can lead to death

CNS Pharmacology
Lecture 7

 Loss of eyelash reflex and a pattern of respiration that is regular
and deep are most reliable indications of stage III (surgical
anesthesia)
 Analgesia and amnesia are characteristics of stage I anesthesia,
whereas
 Loss of consciousness is associated with stage II anesthesia
 Maximum papillary dilation also occurs during stage III anesthesia,

but closer to progression to stage IV anesthesia
 stage IV anesthesia is an undesirable stage associated with

respiratory and cardiovascular failure

CNS Pharmacology
Lecture 7
F. The three steps of anesthesia are induction, maintenance, and
recovery:
1. Induction describes period from beginning of anesthetic
administration until effective surgical anesthesia is achieved
2. Maintenance involves sustained surgical anesthesia, which is often

performed with inhalation anesthetics because they provide a high
degree of control
3. Recovery describes period from discontinuation of anesthesia until

patient has regained consciousness anesthesiologist continues to
monitor patient during this period

CNS Pharmacology
Lecture 7
G. Rate of induction of inhaled anesthesia is dependent on blood
solubility of an anesthetic, assuming that anesthetic is being
administered as only agent Note that this is generally not the case in
most surgeries
1. Blood solubility can be determined by measuring blood–gas partition coefficient
λ
2. High blood solubility leads to a slow rise in partial pressure of anesthetic in body
and a slow induction
a. undesirable because it prolongs Stage 2 of anesthesia
b. Halothane has high blood solubility slow induction, whereas nitrous oxide
(N2O) has low blood solubility rapid induction
3. Induction of highly blood soluble anesthetics is most readily hastened by
“overpressuring” (using a high concentration of anesthetic)

CNS Pharmacology
Lecture 7
F. Factors affecting distribution vary with the phase:
1. Initial distribution of an anesthetic will depend on relative tissue blood flow;
more anesthetic will go to areas with higher blood flow (e.g., heart, brain,
endocrine organs)
2. Final distribution will be dependent on tissue–blood partition coefficients,
although tissue–blood partition coefficient for most anesthetics in most
tissues is approximately 1
a. An exception is fat–blood partition coefficient, which is usually high
b. Movement of an anesthetic into fat will be slow due to low blood supply
to fat only after long anesthesias will significant amounts of anesthetic
be sequestered in fat
c. Recovery from long anesthesias may be slower than anticipated due to
slow elimination of anesthetic from fat
CNS Pharmacology
Lecture 7
Inhalation Anesthetics:
A. Inhalation anesthetics act as gases in body and follow gas laws:
1. Dalton’s Law. An anesthetic exerts a partial pressure that is
proportional to percent of anesthetic in mixture.
2. Fick’s Law. The anesthetic diffuses down its concentration
gradient.
3. Henry’s Law. The amount of anesthetic dissolved in a liquid is
proportional to partial pressure of anesthetic in the gaseous
mixture

CNS Pharmacology
Lecture 7
Inhalation Anesthetics (2)

B. DIETHYL ETHER was the first useful anesthetic
1. It has several major disadvantages, including:
a. Very slow induction (λ =16)
b. Flammability
c. Respiratory irritation, which frequently leads to enhanced
secretions, nausea, and vomiting
2. It is, however, a complete anesthetic, meaning that it
a. Induces muscle relaxation, due to actions on the spinal cord
and neuromuscular junction
b. Induces analgesia
c. Induces unconsciousness

CNS Pharmacology
Lecture 7
Inhalation Anesthetics (3) Halogenated
Hydrocarbons
C. As compared to diethyl ether, newer inhalation anesthetics, which are
halogenated hydrocarbons, are
1. Less soluble in blood, resulting in faster rates of induction and recovery
2. Nonflammable
3. Less irritating to the respiratory tract
D. Common disadvantages of newer inhalation anesthetics are that they
1. Depress respiration
2. Decrease blood pressure in a dose-related fashion
3. Dilate cerebral blood vessels, which can increase intracranial pressure
4. Relax the uterus during pregnancy
5. Induce a low incidence of malignant hyperthermia, which can be treated with
dantrolene
6. Have weaker analgesic actions

CNS Pharmacology
Lecture 7
Hydrocarbons
1. Halothane (Fluothane) was first anesthetic in group (Prototype)
a. It is a poor skeletal muscle relaxant and a poor analgesic; thus
usually combined with other drugs (e.g., muscle relaxants and
analgesics) combination is called balanced anesthesia
b. Halothane sensitizes myocardium to catecholamines arrhythmias
may occur when catecholamines are administered
c. Metabolism of halothane to halogenated products is high, which
may account for infrequent hepatotoxicity
d. For these reasons, it is not commonly used in the United States any
longer

CNS Pharmacology
Lecture 7
Hydrocarbons
2. Enflurane (Ethrane) can induce seizure patterns during anesthesia
and is also no longer used in United States
3. Isoflurane (Forane) has respiratory irritant effects
4. Sevoflurane (Ultane) is partially metabolized by liver and may be

hepatotoxic
5. Desflurane (Suprane) has fastest onset of and recovery from

anesthesia It also has respiratory irritant effects

CNS Pharmacology
Lecture 7
Hydrocarbons
F. NITROUS OXIDE is a gas with
1. Rapid onset and recovery (λ =0.4)
2. Excellent analgesic activity
3. No effect on the function of most vital systems
4. Inadequate potency, leading to
a. Unconsciousness only when used with other anesthetics
b. A second gas effect during induction, which accelerates
onset of anesthesia by other inhalation anesthetics
c. Diffusion hypoxia during recovery, due to filling of lungs
with nitrous oxide so that inadequate oxygen is inhaled
This can be avoided by administering 100% oxygen for a
short time at conclusion of nitrous oxide anesthesia
CNS Pharmacology
Lecture 7
Inhalation Anesthetics (7)

G. Miscellaneous anesthetics are of historical interest
1. Methoxyflurane is
a. most potent anesthetic available for clinical use
b. best analgesic anesthetic
c. Nephrotoxic and thus seldom used
2. Cyclopropane is an explosive gas.
3. Chloroform is
a. A complete anesthetic
b. Hepatotoxic

CNS Pharmacology
Lecture 7
Intravenous General Anesthetics:

CNS Pharmacology
Lecture 7
Intravenous General Anesthetics (2)

A. BARBITURATES, such as thiopental (Pentothal), have a rapid onset of
anesthesia due to high lipid solubility
1. When administered they go primarily to areas of high blood flow, such as brain
2. Short duration of anesthesia is due to redistribution from brain to more

soluble peripheral tissues with less blood flow, such as skeletal muscle and fat
3. Clearance from body by metabolism is very slow
4. Duration of anesthesia becomes longer with repeated administrations because

less redistribution can occur As a result, primary uses of thiopental are for
a. Induction of anesthesia
b. Procedures of short duration

CNS Pharmacology
Lecture 7
5. Thiopental has the following properties:
a. Marked respiratory and cardiovascular depression, especially
with a rapid bolus injection
b. Weak skeletal muscle relaxant activity
c. Antianalgesic activity (increases sensitivity to pain)
d. Pharyngeal stimulation
e. Very alkaline solution, which causes severe tissue injury if
given through an infiltrated IV

CNS Pharmacology
Lecture 7

B. PROPOFOL (Diprivan) also has a rapid onset of action and recovery.
1. Although the anesthesia is terminated by redistribution, there are
fewer cumulative
effects compared with barbiturates, and it can be used for long
anesthesias.
2. The postoperative complications (e.g., nausea, vomiting, residual
drowsiness)
are less than with other IV anesthetics.
3. It can markedly reduce blood pressure.

CNS Pharmacology
Lecture 7

C. OPIOIDS, such as fentanyl (Duragesic), sufentanil (Sufenta), and alfentanil (Alfenta),
are narcotic analgesics. They are often used with other anesthetics.
1. Following anesthetic properties:
a. Good analgesia
b. Euphoria
c. Respiratory depression, which can be reversed by naloxone
d. Muscle rigidity
e. Nausea and vomiting
2. Anesthesia is very safe with little cardiovascular depression
3. Droperidol (Inapsine), an antipsychotic (neuroleptic), can be combined with
fentanyl (Innovar) to induce neuroleptanalgesia
a. Patient is sometimes conscious and can respond
b. It can be supplemented with nitrous oxide to induce unconsciousness
(neuroleptanesthesia)

CNS Pharmacology
Lecture 7

D. MIDAZOLAM (Versed) is a water-soluble benzodiazepine with a
rapid onset of action and a shorter duration than other
benzodiazepines It is used for sedation
1. Pt. remains conscious at low doses, but experiences amnesia
during anesthesia
2. At high doses, some LOC is induced
3. Can induce respiratory depression that is reversible by
administration of benzodiazepine antagonists, such as flumazenil
(Romazicon)

CNS Pharmacology
Lecture 7

E. KETAMINE (Ketalar) is an analog of phencyclidine, a hallucinogen
1. It induces a dissociative anesthesia
a. Pt. may look awake but is unresponsive
b. Analgesic effects are excellent
c. Muscle tone is either unchanged or increased
d. Respiration is not affected
2. Ketamine can be administered intravenously or intramuscularly
3. Side effects are related to hallucinogenic activity, which leads to
a. Vivid dreams
b. Hallucinations, which can be reduced by diazepam

CNS Pharmacology
Lecture 7

F. ETOMIDATE (Amidate) is a hypnotic that lacks analgesic activity
1. It is used in patients with coronary artery disease (CAD) and
other cardiac diseases
2. Etomidate inhibits enzyme 11β-hydroxylase, leads to
decreased synthesis of glucocorticoids and mineralocorticoids

CNS Pharmacology
Lecture 7
THE END

CNS Pharmacology
Lecture 7
Further study (SDL):
MedPharm Digital Guidebook: Unit 3-Drugs Used for CNS Disorders
Companion eNotes: CNS- Central Nervous System Pharmacology
Textbook Reading: Eilers H & Yost S. Ch. 25. General Anesthetics, 429-47,
Kenneth Drasner K. Ch. 26 Local Anesthetics,449-62
In: Katzung BG, ed. Basic & Clinical Pharmacology. 12th ed.
Online resource center: Medical Pharmacology Cloud Folder
Lectures/discussions to follow:
8. Analgesics
9. Drugs of Abuse

Lecture 7-Local and General Anesthetics

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Lecture 7-Local and General Anesthetics

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DRUGS USED IN DISORDERS OF THE

CENTRAL NERVOUS SYSTEM AND

Marc Imhotep Cray, M.D. 2

Marc Imhotep Cray, M.D. 3

Classification Schema: Lecture 7

Local and General Anesthetics

 Many neuronal pathways transmit pain sensation

Marc Imhotep Cray, M.D. 6

Drugs that act at pathways mediating pain sensation or

Marc Imhotep Cray, M.D. 7

Marc Imhotep Cray, M.D. 8

Marc Imhotep Cray, M.D. 9

 Some selectivity for pain afferents is achieved partly by using agent

 Target site of drugs is on cytoplasmic side of neuron membrane, so

Marc Imhotep Cray, M.D. 10

Local Anesthetics (2)

Marc Imhotep Cray, M.D. 11

Marc Imhotep Cray, M.D. 12

Marc Imhotep Cray, M.D. 13

Marc Imhotep Cray, M.D. 14

Local Anesthetic Mechanism of Action

Marc Imhotep Cray, M.D. 15

Local Anesthetics (6)

Marc Imhotep Cray, M.D. 16

Marc Imhotep Cray, M.D. 17

Local Anesthetics (8)

Marc Imhotep Cray, M.D. 18

Local Anesthetics (9)

Marc Imhotep Cray, M.D. 19

Local Anesthetics (10)

Marc Imhotep Cray, M.D. 20

Local Anesthetics (11)

F. During spinal anesthesia, blood pressure may fall due to blockade of

Marc Imhotep Cray, M.D. 21

Marc Imhotep Cray, M.D. 22

General Anesthetics: Properties

 Concentrations of inhalational agents in body and pharmacokinetics

 Induction of anesthesia is more rapid for drugs with high partial

 Onset of anesthesia is slowed when pulmonary blood flow is reduce

Marc Imhotep Cray, M.D. 23

General Anesthetics Properties (2)

 Redistribution to other tissues delays elimination and may increase

 Intravenous agents include barbiturates, benzodiazepines, ketamine,

Marc Imhotep Cray, M.D. 24

Principles of General Anesthesia:

B. Due to blood–brain barrier, all CNS drugs including general

Marc Imhotep Cray, M.D. 25

Principles of General Anesthesia (2)

3. At low concentrations of a general anesthetic, CNS

Principles of General Anesthesia (4)

Marc Imhotep Cray, M.D. 28

 Stage 2 involves excitement, due to blockade of inhibitory pathways in

 Stage 4 involves respiratory and cardiovascular depression, which, if

Marc Imhotep Cray, M.D. 29

Principles of General Anesthesia (6)

 Maximum papillary dilation also occurs during stage III anesthesia,

 stage IV anesthesia is an undesirable stage associated with

Marc Imhotep Cray, M.D. 30

2. Maintenance involves sustained surgical anesthesia, which is often

3. Recovery describes period from discontinuation of anesthesia until

Marc Imhotep Cray, M.D. 31

Marc Imhotep Cray, M.D. 32

Marc Imhotep Cray, M.D. 34

Inhalation Anesthetics (2)

Marc Imhotep Cray, M.D. 35

Marc Imhotep Cray, M.D. 36

Marc Imhotep Cray, M.D. 37