DATA:

A. Differentiate local from general anesthetics using specific points of comparison. Tabulate your
answers.
POINTS OF COMPARISON
a. Regions of the body
covered or affected
b. Manner it is given
c. Type of surgeries done
when it is used
d. Effect caused
e. Period of time it is effective Effective only for a short period of Effective for a longer period of
or used
f. Examples
LOCAL ANESTHETICS GENERAL ANESTHETICS
Applied for small regions of the
Affects the whole body
body
Injection into the surgical site or an
Inhalation and intravenous drugs
area near nerves transmitting pain
are given and maybe used in
stimulation from the injected
combination
region
Given for small surgeries and small Given for surgeries for the
injuries abdomen, thorax, and brain
Sedation, numbness Sleep or unconsciousness
time time
Articaine (Septocaine ) Desflurane (Suprane)
Lidocaine (Xylocaine) Diazepam (Valium)
Dyclonine (Dyclone) Halothane (Fluothane)
Procaine (Novocaine) Methohexital (Brevital)

Reference:
Goodman & Gilmans Manual of pharmacology & Therapeutics
Katzung, B.G. and Trevor, A.J. (2015). Basic & Clinical Pharmacology. 13 Ed. pp. 421-445

B. Give the various methods of administering local anesthetics. Describe each briefly and give
advantages and disadvantages. Tabulate.
METHOD DESCRIPTION ADVANTAGES DISADVATAGES
Topical Anesthesia Used method for Rapidly absorbed Always carries the
Cocaine anesthesia of into the circulation risk of systemic
Lidocaine mucous following topical toxic reactions.
Tetracaine membranes of the application to Have poor
nose, mouth, mucous penetration.
throat, membranes or Application on
tracheobronchial denuded skin. abraded skin may
tree, esophagus, & Shrinking of result in systemic
genitourinary tract mucous toxicities.
which can be membranes
produced by direct decreases
application of operative bleeding
aqueous solutions while improving
of salts of many surgical
local anesthetics visualization.
or by suspension
of poorly soluble
local anesthetics.
Infiltration Anesthesia It is the injection Provides Relatively large
 Lidocaine of local anesthetic satisfactory amounts of drug
Procaine directly into tissue anesthesia without must be used to
Bupivacaine without taking disrupting normal anesthetic
into consideration bodily functions. relatively small
the cause of It can be so areas.
cutaneous nerves. superficial as to It should not be
include only the injected into
skin. tissues supplied by
Also, include end arteries
deeper structure (fingers & toes,
intra-abdominal ears, nose, penis)
organ. if combined with
epinephrine
because it may
cause gangrene.
Field Block Anesthesia It is produced by Fewer drugs can It may not reach
subcutaneous be used to provide the site of action.
injection of a greater area of It may affect other
solution of local anesthesia than areas of the body.
anesthetic in order when infiltration
to anesthetize the is used.
region distal to the Better pain control
injection site. than IV or IM
opioids
(narcotics).
Nerve Block Anesthesia Injection of local Produces even The drug may be
anesthetic into or greater areas of injected into the
around individual anesthesia than do nerve
peripheral nerves the techniques unintentionally /
or nerve plexuses. described above. accidentally that
Blockade of Produces skeletal would cause pain
mixed peripheral muscle relaxation & nerve damage.
nerves & nerve which is essential Potential for
plexuses. Also, for some surgical systemic toxicity
usually procedures. & direct neural
anesthetizes toxicity.
somatic motor
nerves.
Spinal Anesthesia It follows the Minimized Difficulty in
injection of local potential for direct achieving visceral
anesthetic into the nerve trauma. analgesia.
cerebrospinal fluid Safe & effective There are many
in the lumbar technique factors that needs
space. For a especially during to be considered
number of surgery involving because they may
 reasons, including the lower affect the heights
the ability to abdomen, the of the block, rate
produce lower extremities of distribution,
anesthesia of a & the perineum. etc.
considerable Lesser potential
fraction of the harm than those
body with a dose associated with
of local anesthetic general anesthesia.
that produces
negligible plasma
levels.
Epidural Anesthesia Administered by Continuous The dose of local
injecting local infusion or anesthetic used
anesthetic into the repeated bolus can produce high
epidural space administration is concentration in
the space bounded allowed with the blood following
by the ligamentum use of epidural absorption from
flavum, catheters, to epidural space,
posteriorly, the provide more thus, leading to
spinal periosteum control over systemic toxicity.
laterally & the duration of block. Epidurals may
dura anteriorly. Normally, an cause blood
It can be epidural will allow pressure to
performed in the the birthing suddenly drop.
sacral hiatus or in mother to stay
the lumbar, alert and remain
thoracic, or an active
cervical regions of participant during
the spine. the birthing stage.
Primary site of
action is at the
spinal nerve roots.
Intravenous Regional This technique It is an attractive Pain from
Anesthesia (Biers Block) relies on using the technique due to tourniquet may
vasculature to its simplicity. experience.
bring local Used most often Potential for
anesthetic solution for the surgery of ischemic nerve
to the nerve trunks the forearm & injury.
& endings. hand. Can only be used
An extremity is Can also be for few anatomical
exsanguinated adapted for the regions.
with an Esmarch foot and distal leg. Premature
(elastic) bandage release / failure of
& proximally the tourniquet can
located tourniquet produce toxic
 is inflated to 100- levels of the drug.
150mmHg above
the systolic BP.
The bandage is
removed & the
drug is injected.

Reference:
Japanese Society of Anesthesiologists. (2007). Anesthesia types suitable for various types of surgery.
Retrieved on March 8, 2017 from www.anesth.or.jp

C. Enumerate the local and general anesthetics.

1. General Anesthetics
a. Inhaled
- Desflurane (Suprane)
- Halothane (Fluothane)
- Isoflurane (Forane)
- Sevoflurane (Ultane)
- Nitrous Oxide

b. Intravenous
- Barbiturates
- Benzodiazepine
- Dexmedetomidine (Precedex)
- Etomidate (Amidate)
- Ketamine (Ketalar)
- Propofol (Diprivan)
2. Local Anesthetics
a. Amides
- Bupivacaine (Marcaine)
- Lidocaine (Xylocaine)
- Mepivacaine (Carbocaine)
- Ropivacaine (Naropin)
b. Esthers
- Chloroprocaine (Nesacaine)
- Procaine (Novocaine)
- Tetracaine (Pontocaine)

Reference:
Jones, J.A., MD. (2015, Sept). Types of Anesthesia. Retrieve March 8, 2017 from m.kidshealth.org

QUESTIONS:
1. Give the mechanisms of action of:
a. Local Anesthetics
These are drugs which produce insensitivity in a limited area by blocking the generation and
conduction of nerve impulses. They interrupt pain impulses in a specific region of the body without
loss of consciousness. They decrease the permeability of cell membrane to sodium thus prevents
depolarization. They inhibit the conduction of action potentials in all afferent & efferent nerve fibers.
 The local anesthetic binds to the channel in an area just beyond the selectivity filter of P region.
When the drug binds, it blocks sodium ion passage into the cell and thus blocks the formation &
propagation of the action potential. This blocks the transmittance of the pain or even touch.

b. General Anesthetics
These are drugs that inhibit CNS neural activity. But their precise mechanism of neuronal inhibition
is not clear. Several mechanisms were proposed to explain this:
Lipid Theory According to this theory the more lipid soluble general anesthetics
concentrate in hydrophobic regions in neural cell membrane and causes swelling of these
membranes. Due to this swelling of structure of membrane alters, thereby blocks the Na +
channels. Thus the generation of action potential is inhibited and produces anesthesia. Meyer
& Overton correlated the potency of general anesthetics with their lipid solubility. The higher
the value of partition coefficient of the compound, more will be its general anesthetic
potency.
Protein Theory anesthetics bind to the hydrophobic sites of protein molecules of neuronal
cell membrane, thus the membrane function is altered and produces anesthesia.

Reference:
Goodman & Gilmans Manual of pharmacology & Therapeutics
Katzung, B.G. and Trevor, A.J. (2015). Basic & Clinical Pharmacology. 13 Ed. pp. 421-445

2. What is balanced anesthesia? Give its purpose.

It is a technique of general anesthesia based on the concept that administration of a mixture of small
amounts of several neuronal depressants (narcotics & inhalational agents) maximizes the advantages,
but not the disadvantages of the individual components of the mixture. Its purpose is achieving the goal
of anesthesia & minimizing the side effects of using large doses of a medication, instead using smaller
doses of many different kinds of medication.

Reference:
Goodman & Gilmans Manual of pharmacology & Therapeutics

3. What patient factors are considered when choosing an anesthetic agent?

Safe, effective & efficient anesthetic regimen based on:
a. The nature of the surgical or diagnostic procedure.
b. Status of health of organ systems: patients physiologic, psychologic, pathologic & pharmacologic
state.
e.g. IHD, HTN, hypovolemic shock, bronchial asthma

STATUS OF ORGAN SYSTEMS:

Liver & Kidney: the release of fluoride, bromide & other metabolic products of the halogenated
hydrocarbons can affect these organs, especially with repeated anesthesia / anesthetic
administration over a short period of time.
Respiratory System: all inhaled anesthetics depress the respiratory system. Interestingly, they are
bronchodilators.
 Cardiovascular System: whereas the hypotensive effects of most anesthetics are sometimes
desirable, ischemic injury of tissues could follow reduced perfusion pressure.
Nervous System: the existence of neurological disorders such as epilepsy or myasthenia gravis &
a patient history of a genetically determined sensitivity to halogenated hydrocarbon-induced
malignant hyperthermia.
Pregnancy: nitrous oxide can cause aplastic anemia in the unborn child while benzodiazepines
can cause oral clefts in the fetuses of women. Diazepam should not be used routinely during
labor because it results in temporary hypotonia and altered thermoregulation in the newborn.

References:
Goodman & Gilmans Manual of pharmacology & Therapeutics
Katzung, B.G. and Trevor, A.J. (2015). Basic & Clinical Pharmacology. 13 Ed. pp. 421-445

4. Give the toxicities of anesthetics and explain the occurrence of each.

I. GENERAL ANESTHETICS
A. Acute Toxicity
1. Nephrotoxicity
Inhaled anesthetics tend to decrease glomerular filtration rate (GFR) and urine flow therefore
metabolism of these anesthetics like enflurane & sevoflurane may generate compounds that
are potentially nephrotoxic. Sevoflurane may be degraded by CO 2 absorbents in anesthesia
machines to form nephrotoxic vinyl ether compounds which, in high concentrations, have
caused proximal tubular necrosis in rats during clinical trial.

2. Hematotoxicity
All inhaled anesthetics can produce some CO from their interaction with strong bases in dry
CO2 absorbers. CO binds to hemoglobin with high affinity reducing oxygen delivery to
tissues. Dental personnel are exposed to nitrous oxide and prolong exposure to this
compound decreases methionine synthase activity which could cause megaloblastic anemia.
3. Malignant Hyperthermia
This is heritable genetic disorder of skeletal muscles that occur in susceptible individuals
exposed to volatile anesthetics while undergoing general anesthesia. The specific
biochemical abnormality is an increase in free cytosolic calcium concentration in skeletal
muscle cells, which causes muscle rigidity, hyperkalemia, rapid onset of tachycardia, &
hypercapnia.
4. Hepatotoxicity
Volatile anesthetics cause a concentration-dependent decrease in portal vein blood flow
therefore hepatic dysfunction following surgery and general anesthesia may occur. Hepatic
dysfunction is most likely caused by hypovolemic shock (infection conferred by blood
transfusion) or other surgical stresses rather than by volatile anesthetic toxicity. Studies in
animals implicate the formation of reactive metabolites that either cause direct hepatocellular
damage or initiate immune-mediated responses.
B. Chronic Toxicity
1. Mutagenicity, Teratogenicity, & Reproductive Effects
Halothane, enflurane, isoflurane, desflurane, & sevoflurane may be teratogenic as a result of
physiologic changes associated with the anesthesia rather than through direct teratogenic
effect. The pharmacologic effect of nitrous oxide during labor / delivery can be helpful when
 profound uterine relaxation is required for intrauterine fetal manipulation or manual
extraction of retained placenta during delivery. However, it can lead to increase uterine
bleeding.
2. Carcinogenicity
Epidemiologic studies suggested an increase in the cancer rate in operating room
personnel who were exposed to trace concentrations of anesthetic agents. However, no
study has demonstrated the existence of a causal relationship between anesthetics and
cancer. Most operating rooms now use scavenging systems to remove trace
concentrations of anesthetic released from anesthetic machines.
II. LOCAL ANESTHETICS
A. Systemic Toxicity
1. CNS Toxicity
Local anesthetics apparently cause depression of cortical inhibitory pathways, thereby
allowing unopposed activity of excitatory neuronal pathways. An early symptom of local
anesthetic toxicity is circumoral & tongue numbness & a metallic taste. At higher
concentrations, nystagmus and muscular twitching occur, followed by tonic-clonic
convulsions.
2. Cardiotoxicity
The most feared complications associated with local anesthetic administration result from the
profound effects these agents can have on cardiac conduction and function. Animal studies
demonstrate doses of bupivacaine & etidocaine as low as 2/3 those producing convulsions
could induce arrhythmias, while the margin between CNS & cardiac toxicity was less than
half for lidocaine.
3. Reversal of Bupivacaine Toxicity
Therapy for resistant bupivacaine cardiotoxicity using IV infusion of lipid appears to have
applications that extend beyond bupivacaine cardiotoxicity to the cardiac or CNS toxicity
induced by an overdose of any lipid-soluble drug.
B. Localized Toxicity
1. Neural Injury
The mechanism of local anesthetic neurotoxicity has been extensively investigated in cell
culture, isolated axons, & in-vivo models. These studies have demonstrated myriad deterious
effects including conduction failure, membrane damage, enzyme leakage, cytoskeletal
disruption, accumulation of intracellular calcium disruption of axonal transport, growth cone
collapse, & apoptosis.
2. Transient Neurologic Symptoms (TNS)
Devastating neural complications occur with neuraxial (spinal & epidural) administration of
local anesthetics (syndrome of transient pain or dysesthia or both) has been linked to spinal
anesthesia. The pain can be quite severe often exceeding that induced by surgical procedure
TNS occurs even at modest doses of anesthetic, & has been documented in 1/3 of patients
receiving lidocaine with increased risk associated with certain patient positions during
surgery, & with ambulatory anesthesia.

Reference:
Basic & Clinical Pharmacology (13th Ed) by Katzung & Trevor

5. Enumerate the adjuncts to anesthetics & rationalize the use of each.

 Diphenhydramine is one of a diverse group of drugs that competitively blocks H 1 receptors. Many
drugs with H1-receptor antagonist properties have considerable antimuscarinic, or atropine-like,
activity (eg, dry mouth), or antiserotonergic activity (antiemetic).

H2 blockers reduce the perioperative risk of aspiration pneumonia by decreasing gastric fluid volume
and raising the pH of gastric contents.

Metoclopramide increases lower esophageal sphincter tone, speeds gastric emptying, and lowers
gastric fluid volume by enhancing the stimulatory effects of acetylcholine on intestinal smooth
muscle.

Ondansetron, granisetron, and dolasetron selectively block serotonin 5-HT3receptors, with little or
no effect on dopamine receptors. 5-HT3 receptors, which are located peripherally and centrally,
appear to play an important role in the initiation of the vomiting reflex.

Ketorolac is a parenterally administered nonsteroidal antiinflammatory drug that provides analgesia

by inhibiting prostaglandin synthesis.

Clonidine is a commonly used antihypertensive agent but in anesthesia it is used as an adjunct for
epidural and peripheral nerve block anesthesia and analgesia. It is often used in the management of
patients with chronic neuropathic pain to increase the efficacy of epidural opioid infusions.

Dexmedetomidine is a parenteral selective 2 agonist with sedative properties. It appears to be more

selective for the 2 receptor than clonidine.

Doxapram - Selective activation of carotid chemoreceptors by low doses of doxapram stimulates

hypoxic drive, producing an increase in tidal volume and a slight increase in respiratory rate.
However, doxapram is not a specific reversal agent and should not replace standard supportive
therapy (ie, mechanical ventilation).

Naloxone reverses the agonist activity associated with endogenous or exogenous opioid compounds.

Flumazenil is useful in the reversal of benzodiazepine sedation and the treatment of benzodiazepine
overdose.

Reference:
http://accessmedicine.mhmedical.com/content.aspx?bookid=564&sectionid=42800548