Anesthetic Agents

ANESTHETIC
AGENTS
Perfecto B. Soriano, MD, FPPS, FPSECP, MSc.

Surgery Before Anesthesia
Fun and Frolics led to Early Anesthesia

GENERAL ANESTHETIC AGENTS
•  A. GENERAL ANESTHETIC AGENTS
 Act on the CNS or ANS to produce analgesia, amnesia, or
hypnosis, skeletal muscle relaxa<on and loss of reflexes
Ø  Used alone or in combina<on with other agents (e.g.
preanesthe<c medica<on
Ø  Can produce an op<mum depth of anesthesia for variety of
surgical procedures
Ø 1. Inhala(on anesthe(cs: e.g. ether and nitrous oxide
Ø 2. Intravenous anesthe(cs: are mostly used for induc<on
of anesthesia before administra<on of more potent
anesthe<c agents; however, they can be used for some
procedures of shorter dura<on (e.g. thiopental)
Ø a. Neuroleptanesthesia is induced by combining a
powerful narco<c analgesic with a neurolep<c
agent, and administering the combina<on in
conjunc<on with the inhala<on of nitrous oxide and
nitrogen.
Ø b. Dissocia(ve anesthesia, such as ketamine,
produces rapid analgesia and amnesia while
maintaining laryngeal reflexes.
Ø c. Preanesthe(c medica(on may include seda<ves,
opioids, tranquilizers and an<cholinergic agents
STAGES OF GENERAL ANESTHESIA
•  Stage I: Disorientation, altered consciousness. (ANALGESIA)
•  Stage II: Excitatory stage, delirium, uncontrolled movement, irregular
breathing. Goal is to move through this stage as rapidly as possible
(DISINHIBITION)
•  Stage III: SURGICAL ANESTHESIA; return of regular respiration.
•  Plane 1: “light” anesthesia
•  Plane 2: Loss of blink reflex, regular respiration . Surgical
procedures can be performed at this stage.
•  Plane 3: Deep anesthesia. Shallow breathing, assisted ventilation
needed. Level of anesthesia for painful surgeries
•  Plane 4: Diaphragmatic respiration only, assisted ventilation is
required. Cardiovascular impairment.
•  Stage IV: Too deep; essentially an overdose and represents
anesthetic crisis. This is the stage between respiratory arrest and
death due to circulatory collapse. (MEDULLARY DEPRESSION)
•  A. InhalaCon AnestheCcs
Ø  1. General Considera<ons
Ø  a. The rela<onship between the administered dose of an inhala<on
anesthe<c and the quan<ta<ve effect produced as the minimal alveolar
concentra-on (MAC) of the anesthe<c at 1 atm that will produce loss of
movement in 50% of subjects exposed to a noxious s<mulus. The MAC is
used as the measure of potency for all inhala<on anesthe<cs.
Ø  b. The concentra<on of an inhala<on anesthe<c in blood or <ssue is the
product of its solubility and par<al pressure. The solubility of an agent is
expressed most commonly terms of blood:gas or a <ssue:blood par<<on
coefficient.
Ø 1. An agent with blood:gas par<<on coefficient of 2 reaches twice
the concentra<on in the blood phase as in the gas phase when the
par<al pressure is the same in both phase (i.e. at equilibrium).
Ø Very soluble agents (e.g. ether) have a blood:gas par<<on
coefficient as high as 12; rela<vely insoluble agents (e.g. nitrous
oxide) have a coefficient of less than 1. The lower the blood:gas
par<<on coefficient of an anesthe<c, the more rapid the induc<on
of anesthesia with that agent, because high solubility constantly
lowers the alveolar gas pressure.
Ø  2. Most inhala<on agents are equally soluble in lean <ssue and in
blood, so that the <ssue-‐blood par<<on coefficient oYen
approximates 1. On the other hand, most anesthe<cs have a far
greater concentra<on in faZy <ssues that in blood at equilibrium.
Ø  3. Types: Halogenated and Nitrous

Pathway for General Anesthe<cs
(Inhaled Anesthe<cs)
•  Par<al Pressure in brain quickly
equilibrates with par<al pressure in
arterial blood which has equilibrated
with par<al pressure perfused alveoli.
Furthermore, the DEPTH of anesthesia
induced by an inhaled anesthe<c
depends primarily on the PARTIAL
PRESSURE. Of the anesthe<cs in the
brain, and the rate of induc<on and
recovery from anesthesia depends on
the rate of change of par<al pressure in
the brain.
•  à These drugs are small lipid-‐soluble
molecules that cross the alveolar
membrane easily. Move into and out of
the blood based on the par<al pressure
gradient.
Pharmacokine<cs of Inhaled Anesthe<cs
1.  Amount that reaches the brain
§  indicated by oil:gas ra<o (lipid solubility)
2.  Solubility of gas into blood
§  The lower the blood:gas ra<o, the more anesthe<cs
will arrive at the brain
•  Agents
•  1. Halothane
Ø  a. Pharmacokine<cs
•  1. MAC of .075%, is a potent anesthe<c agent
Ø  2. Excre<on
Ø a. Approximately 70% of halothane is eliminated unchanged in
exhaled gas in the first 24 hours aYer administra<on.
Ø b. Approximately 5% is biotransformed by the cytochrome P-‐450
system in the endoplasmic re<culum of the liver
Ø  b. Pharmacologic effects. Halothane lacks significant analgesic potency
and, thus, is most frequently used with another anesthe<c.
Ø  1. Respiratory effects
Ø a. Respira<ons become rapid and shallow, and there is a reduc<on
in the minute volume
Ø b. Halothane produces bronchiolar dila<on.
Ø  2. CNS effects. As halothane anesthesia deepens, fast, low voltage EEG
waves are replaced by slow, high voltage waves.
Ø  3. Muscular effects
a. Halothane causes skeletal muscle relaxa<on by both central and
peripheral mechanisms.
Ø b. It appears to increase the sensi<vity of end-‐plates to the ac<on
of compe<<ve neuromuscular blocking agents
Ø c. It relaxes uterine smooth muscle
Ø  c. Prepara<ons and therapeu<c uses
Ø  1. Halothane is not irrita<ng to the larynx; thus, induc<on of
anesthesia with this agent is smooth and bronchospasm is uncommon
Ø  2. Halothane administra<on is oYen supplemented with thiopental for
induc<on of anesthesia. Nitrous oxide, oxygen, and muscle relaxants
are normally used with halothane.
Ø  3. Halothane is a safe anesthe<c for children and may be administered
via mask because it is the least pungent vola<le agent.
Ø  d. Adverse effects
Ø  1. Halothane is a highly potent, nonflammable general anesthe<c with
a rela<vely high blood:gas par<<on coefficient; thus, induc<on of and
recovery from anesthesia with this agent may be prolonged
Ø  2. Respiratory effects. Halothane causes a reduc<on in the ven<latory
response to carbon dioxide. This effect appears to result from depression
of central chemoreceptors.
Ø  3. Cardiovascular effects
Ø  a. causes a dose-‐dependent decrease in arterial blood pressure
Ø  b. cutaneous blood flow may increase as blood vessels dilate
Ø  c. myocardial contrac<lity is depressed
Ø  d. interferes with the ac<on of norepinephrine and, thus, antagonizes
the sympathe<c response to arterial hypertension
Ø  e. depresses cardiac sympathe<c ac<vity→ slow heart rate
Ø f. arrhythmias are uncommon
Ø g. can increase the automa<city of the heart-‐exacerbated by
adrenergic agonists, cardiac disease, hypoxia, and electrolyte
abnormali<es
Ø  4. CNS effect
Ø a. cerebral blood vessel dilate, increasing cerebral blood flow and
CSF pressure. A maldistribu<on of cerebral blood flow and altered
metabolism can occur
Ø b. shivering during recovery is common
Ø  5. Renal effects
Ø a. At a level of 1 MAC, halothane causes renal blood flow and
filtra<on to drop to about 50% of normal
Ø b. these effect are mi<gated by adequate hydra<on
Ø  6. Hepa<c effects
Ø a. depresses liver func<on-‐ this effect is rapidly reversed when
administra<on of the anesthe<c is stopped
Ø b. Hepa<c necrosis that cannot be aZributed to known causes can
occur with halothane anesthesia. Two to five days postopera<vely,
an affected pa<ent develops fever, anorexia, and vomi<ng.
Eosinophilia and biochemical abnormali<es characteris<c of
hepa<<s occur. This syndrome is known as halothane hepa<<s.
Ø i. halothane hepa<<s has an incidence of 1 in 7000 individuals
receiving halothane anesthesia, and it is associated with a
20-‐50% mortality rate.
Ø ii. it is likely that halothane induced hepa<c damage is
metabolic in origin. The possibility of gene<c suscep<bility has
been suggested and would provide evidence that the rate of
halothane metabolism is gene<cally determined
Ø iii. pa<ent characteris<cs that increase the poten<al for liver
damage include middle age, obesity, and female sex.
Ø iv. repeated administra<on of halothane increases the poten<al
for liver damage
Ø v. children do not appear to be suscep<ble to the liver damage
associated with halothane
Ø  7. Muscular effects-‐ can trigger malignant hyperthermia, a poten<ally
fatal condi<on believed to be autosomal dominant, in which, in
response to anesthesia, a sudden, rapid rise in blood temperature and
signs of increased muscle metabolism occur
•  2. Enflurane
Ø  a. Pharmacokine<cs:
Ø  1. MAC of 1.68%
Ø a. approximately 80% of enflurane is eliminated unchanged as
expired gas
Ø b. because enflurane’s oil:gas par<<on is less than that of other
halogenated anesthe<cs, enflurane leaves faZy liver more rapidly
Ø c. approximately 5% of enflurane is metabolized in the liver. Free
flouride ion is released, but poses liZle danger of renal toxicity
Ø  b. Pharmacologic effects
Ø 2. Muscular effects
Ø a. Enflurane, which act directly on the neuromuscular junc<on,
provides adequate muscular relaxa<on for most surgical
procedures
Ø b. Enflurane relaxes uterine smooth muscle
•  c. Therapeu<c uses
Ø  is a potent general anesthe<c
Ø  beZer skeletal relaxant than halothane
Ø  enflurane can cause seizure ac<vity
Ø  1. causes mild s<mula<on of saliva<on and tracheobronchial
secre<ons
Ø  2. it suppresses laryngeal reflexes
Ø produces dose-‐dependent respiratory depression
Ø at level of 1 MAC, respiratory responses to hypoxia and
hypercapnia are less than those with halothane
Ø a. dose-‐dependent depression of the arterial blood pressure and
depressed baroreceptor responses are similar to those caused by
halothane
Ø b. dose-‐dependent myocardial depression also occurs and is
similar to that caused by halothane
Ø c. causes a lower incidence of arrhythmias and less sensi<za<on of
the myocardium to catecholamines than halothane
Ø  4. CNS effects
Ø a. can lead to an EEG paZern characteris<c of seizure ac<vity or to
frank seizures
Ø i. the seizure are self-‐limited and can be prevented by
avoiding both high concentra<ons of enflurane and
hyperven<la<on, which can lead to hypocapnia
Ø ii. contraindicated in seizure disorder
Ø b. causes cerebral vasodila<on and increased intracranial pressure as
long as the arterial blood pressure remains normal
Ø  5. Renal effects
Ø at a level of 1 MAC, enflurane anesthesia causes a reduc<on in renal
blood flow and glomerular filtra<on similar to halothane
Ø  6. Hepa<c effects
Ø liver impairment has been reported but usually reversible
Ø hepa<c necrosis also has been reported, especially aYer repeated
administra<on of enflurane
•  3. Isoflurane
Ø  a. Chemistry: dialkyl-‐haloether-‐ vola<le anesthe<c agent
Ø  1. is an isomer of enflurane and has similar physical proper<es-‐ MAC is
1.15%
Ø  2. provides beZer muscle relaxant than either halothane and enflurane
Ø  c. Therapeu<c uses
Ø for adults, has largely replaced halothane and enflurane as
anesthe<c agent, it offers rapid induc<on and emergence and has
liZle postanesthe<c organ toxicity
Ø does not cause seizure ac<vity
Ø does not sensi<ze the myocardium to epinephrine or induce
arrhythmias
Ø 1. produces significant respiratory depression
Ø because of hypercapnia resul<ng from respiratory depression,
cardiac output may increase
Ø peripheral vascular resistance is decreased by isoflurane, resul<ng
in a full in arterial blood pressure
Ø  4. Desflurane
Ø  is a newly approved inhala<on anesthe<c that differs from isoflurane in
that a flourine atom is subs<tuted for a chlorine atom
Ø 1. has the lowest blood:gas par<<on coefficient of any inhala<on
anesthe<c, producing the most rapid induc<on
Ø 2. recovery <me is 5 minutes with desflurane, as opposed to 10
minutes with isoflurane
Ø  b. Therapeu<c use
Ø may offer some advantage over isoflurane in that induc<on and
emergence are more rapid, permigng rapid anesthesia adjustment
Ø  c. Adverse effects
Ø causes myocardial and respiratory depression
Ø dilates peripheral, coronary and cerebral arteries
Ø it is pungent, thus preven<ng mask induc<on in children
•  5.Nitrous oxide
Ø  1. inorganic inert gas that supports combus<on
Ø  2. MAC is 105.2%,meaning that hyperbaric condi<ons would be
required to reach a level of 1 MAC with this drug. For maintaining
anesthesia, a concentra<on of 75-‐80% nitrous oxide is required
Ø  3. not effec<ve for anesthesia as a single agent, and aZemp<ng to use
it in this manner is likely to induce hypoxia
Ø  4. to achieve complete anesthesia with this agent, administra<on of
opioids to supplement analgesia, the use of thiopental for narcosis,
and a neuromuscular blocking agent for muscular relaxa<on are all
required.
Ø eliminated primarily as an expired gas
Ø the amount of nitrous oxide subject to biotransforma<on is not
known
•  b. Therapeu<c uses
Ø  It is an important and powerful analgesic that is well tolerated. Its onset
of ac<on is rapid, as is recovery from its effects. Because of this, it is
frequently used for OPD dental procedures
Ø  It is used as a supplement to more potent anesthe<c agents and, in this
capacity, is probably the most widely used general anesthe<c agent. The
effects of nitrous oxide on respira<on are minimal when a concentra<on
of 50% is used. When nitrous oxide is combined with thiopental or
another anesthe<c agent for induc<on of anesthesia, the respiratory
s<mulant response to carbon dioxide is depressed more than when
thiopental or the other anesthe<c agent is used alone
Ø  1. Cardiovascular effects. When combined with a potent inhala<on
anesthe<c, ac<va<on of the sympathe<c nervous system results; blood
pressure and total vascular resistance rise, and cardiac output is reduced.
Ø  2. Because of its high par<al pressure in blood and its low blood: gas
par<<on coefficient, nitrous oxide diffuses into air-‐containing body
cavi<es and can increase the pressure or expand the volume of gas in
air pockets. This ac<on can result in: disten<on of the bowel,
expansion or rupture of a pulmonary cyst, rupture of the tympanic
membrane in an occluded middle ear, pneumocephalus
Ø  3. When nitrous oxide is dissolved in blood, it can enlarge the volume
of air emboli.
Ø  4. Diffusion hypoxia can occur at the termina<on of nitrous oxide
anesthesia if a pa<ent abruptly begins to breathe room air. This
hypoxia is caused by a rapid outward diffusion of nitrous oxide from
<ssues into the bloodstream and then into the alveoli, where it
decreases alveolar tension and consequently lowers arterial oxygen
levels. This problem can be avoided by administra<on of 100% oxygen
for a short period following nitrous oxide anesthesia
Ø  5.Nitrous oxide is associated with a high incidence of postopera<ve
nausea and vomi<ng
Ø  6. Inac<va<on of Vitamin B₁₂
Ø  7. Leukopenia with chronic nitrous abuse
Ø  8. Nitrous oxide is contraindicated in pregnant women,
immunosuppressed pa<ents, and pa<ents with pernicious anemia
Ø  6. Diethyl ether
Ø  a. Chemistry: highly flammable and explosive anesthe<c agent that
essen<ally has been replaced by halogenated anesthe<cs
Ø a. increased sympathe<c ac<vity produced by diethyl ether results
in bronchodila<on
Ø b. the respiratory response to carbon dioxide, although reduced, is
maintained spontaneously by reflex excita<on at peripheral sites.
Ø  2. Cardiovascular effects. Although diethyl ether is a myocardial
depressant, cardiac output and arterial blood pressure are maintained
because of sympathe<c ac<va<on
Ø  3. Muscular effects
Ø a. Good skeletal muscle relaxant because it causes CNS depression
at synap<c pathways in the spinal cord
Ø b. In addi<on, diethyl ether has a curare-‐like ac<on, allowing a
lower dose of neuromuscular blockers; several aminoglycoside
an<bio<cs augment this effect

Ø  1. when used as a sole agent to induce anesthesia, diethyl ethyl
increases salivary secre<ons, vomi<ng, and laryngospasm
Ø  2. Vagal blockade occurs with diethyl ether administra<on, resul<ng in
tachycardia
Ø  3. Diethyl ether is a strong s<mulant of ADH
Ø  4. Sympathe<c ac<va<on results in increased hepa<c glycogenolysis.
•  Malignant Hyperthermia
§  Malignant hyperthermia (MH) is a pharmacogene<c
hypermetabolic state of skeletal muscle induced in
suscep-ble individuals by inhala<onal anesthe<cs and/or
succinylcholine (and maybe by stress or exercise).
§  Gene<c suscep<bility-‐Ca+ channel defect (CACNA1S) or
RYR1 (ryanodine receptor)
§  Excess calcium ion leads to excessive ATP breakdown/
deple<on
§  Signs: tachycardia, tachypnea, metabolic acidosis,
hyperthermia, muscle rigidity, swea<ng, arrhythmia
§  May be fatal
§  Treated with Dantrolene
•  Intravenous AnestheCcs
•  1. Neuroleptanesthesia
Ø  a. General considera<ons
Ø 1. When a neurolep<c agent is combined with a powerful narco<c-‐
neuroleptanalgesia is produced. Diagnos<c and surgical
procedures can be accomplished under neuroleptanalgesia. When
these procedures require anesthesia, neuroleptanalgesia can be
converted to neuroleptanesthesia by the concurrent
administra<on of 65% nitrous oxide in oxygen
Ø 2. The agents most frequently used to achieve neuroleptanalgesia
are droperidol and fentanyl. A premixed combina<on of the two
drugs is available as a product called Innovar.
•  b. Pharmacologic effects
Ø a. Droperidol slightly decreases the respiratory rate but increases <dal
volume
Ø b. Fentanyl reduces both respiratory rate and <dal wave
Ø c. The marked respiratory depressant effect of the two drugs outlasts
the analgesic effect
Ø a. Droperidol can produce mild α-‐adrenergic blockade, causing some
hypotension
Ø b. Fentanyl has a parasympathomime<c effect that can cause
bradycardia and hypotension
Ø c. Innovar can cause bradycardia. However, it rarely causes other
cardiac arrhythmias, and, in general, it has liZle effect on the
cardiovascular system
Ø  c. Prepara<on and therapeu<c uses
Ø  1. Fentanyl should be administered as a lower intravenous infusion
(given over 5-‐10 minutes), because rapid injec<on may cause
respiratory muscle spasm.
Ø  2. AYer induc<on of neuroleptanalgesia, nitrous oxide administra<on
is begun. Supplementary fentanyl may be required for prolonged
analgesia because fentanyl has a short dura<on of ac<on.
Ø  1. Confusion and mental depression are the most common complaints
aYer neuroleptanesthesia.
Ø  2. Respiratory depression is a frequent occurrence, and adequate
ven<la<on and oxygena<on may require use of mechanical measures
Ø  3. Extrapyramidal symptoms occur rarely
Ø  2. DissociaCve Anesthesia
Ø  a. General considera<ons. Dissocia<ve anesthesia is a state similar to
neuroleptanalgesia in which anesthe<zed pa<ents feel totally
dissociated from their surroundings.
Ø Phencyclidine was the original dissocia<ve anesthe<c
Ø The structurally similar ketamine is the only drug presently used to
produce this state
Ø 1. Ketamine produces profound analgesia and amnesia.
Ø 2. It has no effect on laryngeal reflexes.
Ø 3. Skeletal muscle tone, heart rate, arterial blood pressure and CSF
pressure can be increased by ketamine.
Ø 4. The respiratory cycle is maintained near normal.
Ø  c. Prepara<ons and therapeu<c uses
Ø 1. Ketamine is used mainly in children and young adults for
diagnos<c procedures of short dura<on.
Ø 2. Premedica<on with atropine reduces salivary secre<ons;
premedica<on with a narco<c analgesic decreases the dose of
ketamine needed for anesthesia
Ø 1. Because of its hallucinogen-‐like structure, ketamine frequently
produces unpleasant dreams, especially in adults. Recovery from
ketamine anesthesia oYen is accompanied by emergence of
delirium and psychomotor ac<vity.
Ø 2. Contraindica<ons to the use of ketamine include psychiatric
disorders, a history of cardiovascular disease (to avoid the risk of
hypertension-‐induced stroke), and respiratory infec<on
•  3. Barbiturates
Ø  1. Thiopental is the barbiturate most frequently used for general
anesthesia.
Ø It provides rapid and pleasant induc<on and, thus, oYen is used
before administra<on of stronger agents.
Ø It can be used alone to provide anesthesia for short procedures,
but thiopental and other barbiturates are poor analgesics.
Ø  2. Once barbiturate is injected, liZle can be done to facilitate its
removal. Termina<on of its effects depends on redistribu<on of the
drug from the brain to other <ssues and, to a lesser extent, on
biotransforma<on.
•  4. Propofol
Ø  a. Pharmacokine<cs. Onset of unconsciousness occurs within 1
minute, and dura<on of ac<on is only 3-‐5 minutes because of rapid
redistribu<on.
Ø  b. Pharmacologic effects. The hemodynamic and respiratory effects
are similar to those occurring with barbiturate induc<on.
Ø 1. Propofol is a short-‐ac<ng IV anesthe<c that can be used for
induc<on of anesthesia or maintenance as part of a balanced
anesthesia regimen.
Ø 2. The clarity of mental status upon recovery makes propofol
par<cularly useful for ambulatory surgical pa<ents.
Ø  d. Adverse effects: hypotension, irrita<on on IV administra<on
Ø  5. Medazolam
Ø  a. Medazolam is a parenteral benzodiazepine that is 3-‐4 <mes as
potent as Diazepam. It does not cause local irrita<on aYer IM or IV
injec<on.
Ø  b. Pharmacokine<cs
Ø  1. Medazolam is highly lipid-‐soluble and rapidly crosses the blood-‐
brain barrier.
Ø 2. It is metabolized in the liver and has a half-‐life of 1-‐4 hours.
Ø used for seda<on during short procedures, seda<on before
general anesthesia, induc<on of general anesthesia, and as a
hypno<c drug in balanced anesthesia regimens.
Ø  d. Adverse effects. Medazolam can cause respiratory depression, and
anterograde amnesia lasts for at least 2 hours
Ø  6. Etomidate
Ø  is an ultra-‐short ac<ng hypno<c used for induc<on of anesthesia
Ø  cardiovascular effects are virtually absent
Ø  Adverse effects: pain on injec<on, myoclonic movements, and
postopera<ve nausea and vomi<ng, especially with opioid use;
embryocidal ac<vity
•  PreanestheCc medicaCons can foster an uncomplicated anesthe<c and

opera<ve course by improving the rapidity and smoothness of induc<on,
reducing anxiety, providing analgesia and amnesia, and compensa<ng for
the saliva<on, bradycardia, and other side effects of anesthesia.
Preanesthe<c agents include seda<ves, opioids, tranquilizers, and
an<cholinergic agents
Ø  1. Barbiturates, such as secobarbital and pentobarbital are the
preopera<ve seda<ves most frequently employed. These agents produce
less nausea and vomi<ng than opioids.
Ø  2. Opioids, such as morphine, fentanyl and alfentanil,oYen given to
pa<ents who are to be anesthe<zed with general anesthe<cs of fairly low
potency, such as the combina<on of nitrous oxide and thiopental. They
can be administered with a barbiturate or diazepam for regional
anesthesia. They provide analgesia.
Ø  Alfentanil may offer advantages over fentanyl for longer procedures.
Response and recovery appear to be more rapid.
Ø  3. Phenothiazine deriva(ves, such as promethazine and the an<histamine
hydroxyzine, oYen are administered concomiZantly with opioids because
they poten<ate the analgesic effect without increasing side effect.
Ø  4. Tranquilizers, such as diazepam, are useful in a wide variety of
anesthe<c situa<ons. They can provide preopera<ve seda<on, help to
prevent and treat the CNS s<mula<on caused by local anesthe<cs, and
provide amnesia.
Ø  5. An(cholinergic agents.
Ø  atropine and scopolamine, glycopyrrolate are used rou<nely to
decrease the flow of saliva.
Ø  glycopyrrolate has lower incidence of undesirable side effects. It is
recommended as the an<cholinergic agent of choice for
bronchoscopy.
LOCAL ANESTHETIC AGENTS
•  B. Local AnestheCcs
Ø 1. act by blocking both sensory and motor
nerve conduc<on to produce a temporary loss
of sensa<on without a loss of consciousness
Ø 2. they normally do not cause CNS depression
Ø  LOCAL ANESTHETICS
Ø  1. Structurally, all local anesthe<cs consist of a hydrophilic amino group
linked through a connec<ng group to a lipophilic aroma<c residue. The
greater the length of the connec<ng and amino groups, the greater the
potency and the toxicity of the local anesthe<c.
Ø  2. Local anesthe<cs are weak bases and, thus, are usually water-‐insoluble.
The drug maybe dispensed as a crystal but usually is prepared as an acidic
salt solu<on, which is highly water-‐soluble and stable.
Ø  3. At <ssue pH, depending on the pKa of the agent, the drug exists as
either an uncharged ter<ary or secondary amine or a posi<vely charged
ammonium ca<on. The former state is lipophilic and crosses connec<ve
<ssue and enters nerve cells; the ca<on is thought to block the genera<on
of ac<on poten<als via membrane-‐ receptor complex.
Ø  Mechanism of AcCon
Ø  1. Local anesthe<cs slow the propaga<on of nerve impulses by reducing the
rate of rise of the ac<on poten<al and the rate of repolariza<on.
Ø  a. The increased threshold for electrical excitability results in a complete
block of conduc<on.
Ø  b. Local anesthe<cs specifically block nerve conduc<on by interfering the
cell membrane permeability to sodium, par<cularly voltage-‐dependent Na
channels. Two theories may explain the mechanism of interference with
membrane permeability.
Ø 1. The specific receptor theory postulates that the local
anesthe<c displaces Ca from a site near the Na channel and then
block the adjacent Na channel.
Ø 2. The membrane expansion theory hypothesizes that local
anesthe<cs, because of their lipophilic proper<es, incorporate
into the cell membrane, preven<ng the opening of pores and,
thus, interfering with the passage of electrolytes.
Ø  2. A differen<al sensi<vity of nerve fibers to local anesthe<cs has been
iden<fied and characterized.
Ø  a. The smallest unmyelinated fibers, which conduct impulses for pain,
temperature and autonomic ac<vity, conducts slowly and are the first
to be blocked by local anesthe<cs.
Ø  b. Cri<cal length is the exposure <me required by an anesthe<c in
order for it to exert its ac<on; smaller nerve fibers have a
propor<onally smaller cri<cal length.
•  Agents
•  1. Cocaine
Ø  a. Chemistry: an ester of benzoic acid
Ø  1. quickly degraded by plasma esterases and has a half-‐life of
approximately 1 hour.
Ø  2. metabolized in the blood by ester hydrolysis using
pseudocholinesterase.
Ø  c. Pharmacologic Effects. In addi<on to local anesthe<c ac<vity, the
spectrum of ac<vity of cocaine includes the following:
Ø  1. CNS effects
Ø  ini<ally produces euphoria and some<mes dysphoria
Ø  the ini<al effect is followed by posts<mulatory depression
•  2. Cardiovascular effects
Ø  blocks the uptake of catecholamines at adrenergic nerve terminals
Ø  this causes sympathe<cally mediated tachycardia and vasoconstric<on
leading to hypertension. The vasoconstric<on also decreases
intraopera<ve mucous membrane bleeding.
Ø  d. Prepara<on and therapeu<c uses: 4%-‐10% concentra<on, crystal,
topical anesthesia of nose, pharynx, and tracheobronchial tree; use
limited by abuse poten<al
Ø  e. Adverse effects
Ø  1. tolerance, abuse, and poisoning occur with cocaine overuse.
Ø  2. hyperpyrexia
Ø  3. anorexia
•  2. Procaine
Ø  a. Chemistry: is an ester of diethylaminoethanol and
paraaminobenzoic acid (PABA)
Ø 1. well-‐absorbed following parenteral administra<on and is
rapidly metabolized by pseudocholinesterase. It has a short
dura<on of ac<on.
Ø 2. the metabolic product of procaine hydrolysis is PABA, which
inhibits the ac<on of sulfonamides
Ø 3. the drug lack topical ac<vity
Ø 4. procaine administra<on causes minimal systemic toxicity and no
local prepara<on
Ø  c. Prepara<on and therapeu<c uses: 1%-‐2% solu<on, nerve block,
infiltra<ve anesthesia, 5-‐10% solu<on for spinal anesthesia
Ø  Procaine hydrochloride is available with or without epinephrine.
Epinephrine, a vasoconstrictor, decreases the rate of anesthe<c
absorp<on in the bloodstream and so approximately doubles the
dura<on of anesthesia produced by a given dose.
•  3. Tetracaine
Ø  a. Chemistry: an ester and deriva<ve of PABA
Ø  1. approximately 10 <mes more potent (and more toxic) than
procaine.
Ø  2. its onset of ac<on is approximately 5 minutes, and its dura<on of
ac<on is between 2 and 3 hours
Ø  c. Prepara<ons and therapeu<c uses:10% dextrose solu<on for spinal
anesthesia,2% solu<on for topical anesthesia of mucous membrane
Ø  1. Tetracaine HCl is a commonly used local anesthe<c for spinal
anesthesia and, in this context, usually is combined with 10% dextrose
to increase the specific gravity so that the solu<on is heavier than CSF
•  4. Lidocaine
Ø  a. Chemistry: an amide local anesthe<c and an acetanilid deriva<ve.
Ø  b. Pharmacokine<cs: rapidly absorbed aYer parenteral administra<on and
is metabolized in the liver by microsomal mixed-‐func<on oxidases
Ø  c. Pharmacologic effects:
Ø  1. rapid onset of anesthesia
Ø  2.minimal local irrita<on
Ø  3. a greater potency and longer dura<on of ac<on than procaine
Ø  4. moderate topical ac<vity
Ø  d. Prepara<ons and therapeu<c uses: 1-‐2% solu<on, ointment-‐ jelly or cream-‐
topical anesthesia of mucous membranes; nerve block anesthesia, 0.5%
solu<on-‐ infiltrita<ve anesthesia, <5% solu<on-‐ spinal anesthesia.
Ø  Lidocaine HCl can be administered with or without epinephrine.
Ø  The major clinical uses of lidocaine are as a local anesthe<c and,
intravenously, as an an<arrhythmic
•  5. Prilocaine
Ø  a. Chemistry: an amide local anesthe<c
Ø  b. Pharmacokine<cs. The onset and dura<on of ac<on of prilocaine are slightly
longer than those of lidocaine
Ø  c. Prepara<ons and therapeu<c uses: 1-‐3% solu<on-‐ infiltrita<ve, regional and
spinal anesthesia
Ø  d. Adverse effects: The major disadvantage of prilocaine is the produc<on of
methemoglobinemia and shiY to the leY of the oxygen-‐dissocia<on curve for
hemoglobin
•  6. ECdocaine
Ø  a. Pharmacokine<cs: similar to lidocaine except for its greater potency and
longer dura<on of ac<on
Ø  b. Prepara<on and therapeu<c uses: 0.5-‐1.5% solu<on-‐infiltrita<ve,
regional and epidural anesthesia. Available with or without epinephrine
Ø  The drug usually blocks motor fibers before sensory fibers
•  7. Mepivacaine
Ø  a. Chemistry: is an amide-‐type local anesthe<c
Ø  b. Pharmacokine<cs:
Ø  1. similar to lidocaine; it does not have an<arrhythmic ac<vity
Ø  2. in onset of ac<on, mepivacaine is more rapid than lidocaine, and
dura<on of ac<on is about 20% longer
Ø  c. Prepara<ons and therapeu<c uses: 1-‐4% solu<on-‐infiltrita<ve and
regional nerve block anesthesia. Epinephrine is rarely used with the drug
•  8. Bupivacaine
Ø  a. Chemistry: an amide local anesthe<c, bupivacaine is structurally similar
to mepivacaine.
Ø  b. Pharmacokine<cs: more potent and has a longer dura<on of ac<on than
mepivacaine, las<ng for more than 24 hours in some situa<ons, possibly
as a result of increased <ssue binding.
Ø  the onset of ac<on is slower than that of mepivacaine
Ø  c. Prepara<ons and therapeu<c uses:0.25-‐0.75% solu<on-‐ regional nerve
block anesthesia
Ø  d. Adverse effects: similar to tetracaine; cardiac arrest has been reported
in associa<on with a 0.75% solu<on of bupivacaine used for obstetric
epidural anesthesia
•  9. Diducaine
Ø  a. Chemistry: subs<tuted amide and a quinolone deriva<ve
Ø  b. Pharmacokine<cs: potent anesthe<c with a long dura<on of ac<on
Ø  it has a systemic toxicity and is used only as a topical anesthe<c
Ø  c. Prepara<on: 0.2% solu<on-‐ topical anesthesia of mucous membranes
Ø  d. Adverse systemic effects of local anesthe<cs result from absorp<on of
toxic amounts of these agents into the bloodstreams. Adding epinephrine
to the op<mal concentra<on of a local anesthe<c reduces the rate of
systemic absorp<on, thereby decreasing systemic toxicity.
Ø  1. Seizures, the result of absorp<on of the local anesthe<c and
s<mula<on of the CNS, are the most serious side effects. Seizures are
treated with basic suppor<ve measures including ven<la<on and
oxygena<on, and with IV diazepam
Ø  2. Respiratory failure secondary to CNS depression is a late stage of
intoxica<on
Ø  3. A quinidine-‐like effect on the myocardium
Ø  4. Hypotension is a late effect that can occur as the result of myocardium
depression and peripheral arterial vasodila<on; affected pa<ents are
treated with appropriate parenteral vasopressor agents
Ø  5. Allergic reac<ons-‐rarely occur
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ANESTHETIC

Perfecto B. Soriano, MD, FPPS, FPSECP, MSc.

Ø  3. Types: Halogenated and Nitrous

•  PreanestheCc medicaCons can foster an uncomplicated anesthe<c and

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Anesthetic Agents

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Anesthetic Agents

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ANESTHETIC

Perfecto B. Soriano, MD, FPPS, FPSECP, MSc.

Ø 3. Types: Halogenated and Nitrous

• PreanestheCc medicaCons can foster an uncomplicated anesthe<c and

You might also like

Ø  3. Types: Halogenated and Nitrous

•  PreanestheCc medicaCons can foster an uncomplicated anesthe<c and