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Drugs For Anesthesia, Muscle Relaxation
Drugs For Anesthesia, Muscle Relaxation
ANESTHESIA, MUSCLE
RELAXATION
A. Local anesthesia
As the name implies, local anesthetics are
applied locally and function to block nerve
conduction.
1. General information
The mechanism by which local anesthetics
work is well known
Recall that the concentration of sodium
ions is normally higher on the outside of
neurons than on the inside.
A rapid flood of sodium ions into cells is
necessary for neurons to fire and conduct
an action potential.
Local anesthetics act by blocking sodium
channels.
This blocking is nonselective, which
means that both sensory and motor
impulses are affected.
This blocking is brought about by the
anesthetic reversibly binding to and
inactivating sodium channels.
Sodium influx through these channels is
necessary for the depolarization of nerve
cell membranes and subsequent
propagation of impulses along the course
of the nerve.
When a nerve loses depolarization and
capacity to propagate an impulse, the
individual loses sensation in the area
supplied by the nerve.
Example: An injectable local anesthetic
which combines capsaicin with QX-314, a
variation of lidocaine
All local anesthetics have an amine
functional group, an aromatic ring, and
either an ester or amide group linking
them.
amine
aromatic ring
ester
amide
Therefore, all local anesthetics are
classified as esters or amides.
This is important because the amides are
chemically stable in vivo, whereas the
esters are subject to hydrolysis.
In addition, the hydrolysis of an ester local
anesthetic leads to the formation of PABA,
which causes an allergic response in
some individuals.
Local anesthetics may be administered
topically (i.e. nasal mucosa);
through infiltration (injection into the
dermis and soft tissues located near
peripheral nerve endings);
and in/near the spinal cord (includes
caudal block, epidural block, and spinal
nerve block).
Which local anesthetic should be used
generally depends on the duration of
action of the procedure.
For short procedures, procaine would be
recommended.
An intermediate duration of action is found
with cocaine, lidocaine, and mepivacaine.
Long- acting local anesthetics include
bupivacaine (and levobupivacaine),
ropivacaine, and tetracaine.
2. Ester local anesthetics
Commonly used local anesthetics
containing the ester functional group are
benzocaine, cocaine, procaine, and
tetracaine.
a. procaine(Novocain)
4. Adverse effects
Advantages:
rapid onset and recovery of anesthesia
(useful for outpatient procedures)
one of least metabolized to toxic
byproducts
Disadvantages:
low volatility, so requires a special
vaporizer
pungent and irritating to the airway
(leading to more coughing, laryngospasm,
so it is not as useful for extended surgical
procedures)
In addition, when high inspired gas
concentrations are administered, there is a
significant increase in the patients blood
pressure and heart rate.
sevoflurane:
Advantages:
rapid onset and very rapid recovery of
anesthesia (useful with children)
Not as pungent as desflurane (also useful
with children)
Has good bronchodilating properties and
is the agent of choice in patients with
asthma, bronchitis, and COPD. It has little
effect on the heart rate.
Disadvantages:
Its metabolism results in F1- which may
reach toxic levels in kidneys
In addition, carbon dioxide absorbents in
anesthesia machines degrade sevoflurane
to a fluorinated hydrocarbon, which is
degraded by renal lyase enzymes to a
thioacylhalide.
This compound has been observed to
cause necrosis of the proximal tubule in
rats.
isoflurane:
Advantages:
It causes peripheral vasodilation and
increased coronary blood flow (useful in
patients with ischemic heart disease)
one of least metabolized to F1-
Disadvantages:
moderate solubility, so recovery from
anesthesia may be delayed
Isoflurane can make the heart more
sensitive to circulating catecholamines
(like epinephrine).
This could lead to a ventricular arrhythmia
in patients with heart disease who are
given epinephrine in combination with an
anesthetic, or in chronically anxious, Type
A patients (they have higher circulating
levels of endogenous epinephrine).
C. Intravenous anesthesia
Intravenous anesthesia is used for the
rapid induction of, but not the maintenance
of anesthesia.
The maintenance of anesthesia is with an
inhalation anesthetic.
There are 5 categories of drugs used as
intravenous anesthetics:
1. Benzodiazepines (BZ)
The 3 main drugs used in this category are
diazepam, lorazepam and midazolam.
They sedate, relieve anxiety, and control
acute agitation, therefore their primary
indication is for premedication.
They are inadequate for use in surgical
anesthesia on their own, and must
therefore be used with another anesthetic
agent (i.e. an inhalation anesthetic).
a. diazepam (Valium)
Rapid induction of
analgesia (similar to
Fentanyl)
c. alfentanil (Alfenta)
Compared to fentanyl and sufentanil,
alfentanil has a shorter duration of action
because its high protein binding and
relatively low lipid solubility favor its
sequestration in plasma
d. remifentanil (Ultiva)
Remifentanil is ultra short acting and
rapidly cleared because its ester linkages
are susceptible to hydrolysis by esterases
in tissues and RBCs.
This converts the ester functional group
into an inactive carboxylic acid metabolite.
This particular opioid is useful when
dealing with patients with liver or kidney
failure.
Less potent opioids such as morphine and
demerol have fallen into disfavor because
of their adverse effects when given in high
doses.
Demerol may cause V-tach
Morphine may produce hypotension and
bronchoconstriction as a consequence of
its histamine-releasing action.
One of the most serious drawbacks of the
opioid anesthetics overall, is the possibility
of inadequate anesthetic depth.
Signs of this include sweating, wrinkling of
the forehead, and opening of the eyes.
To prevent this, the high dose opioid
techniques may be supplemented with
inhalation anesthetics or hypnotics such
as benzodiazepines (midazolam for
shorter cases, lorazepam for cases longer
than 4 hours), or more recently, propofol.
However, the use of these may result in
some loss of cardiovascular stability.
4. Dissociative anesthetics
This relates to a type of general
anesthesia that is characterized by
amnesia, sedation, and analgesia,
although the patient appears to be awake.
One of the dissociative anesthetics
commonly used is ketamine (Vetalar,
Ketaset).
Ketamine, is an N-methyl-D-aspartate
(NMDA) receptor antagonist.
Ketamine blocks the ion channel in the
following diagram
It increases blood pressure and increases
cardiac output (useful in patients
experiencing shock)
Ketamine has both very poor muscle
relaxation and analgesic activity.
Ketamine may be used, along with
diazepam for cosmetic/reconstructive
surgery anesthesia.
It is not widely used for anesthesia as it
tends to induce postoperative
hallucinations.
It is sometimes used as a recreational
drug, but it has a number of adverse
effects:
loss of coordination
exaggerated sense of strength
blank stare
slurred speech
A BBC report in May 2000 claimed that
medical research had shown that
controlled tests on ketamine users had
revealed impaired memory and mild
schizophrenia several days after taking the
drug.
Ketamine was classified as a Class C drug
in 2005.
Other class C drugs include cannabis and
anabolic steroids
Ketamine plays an extensive role in the
season 2 finale of House, M.D, titled No
reason
5. Propofol (Diprivan)
From DI-isoPRopyl IV ANesthetic
chemical name: 2,6-diisopropylphenol
Propofol is a sedative/hypnotic that can be
used for induction or maintenance of
general anesthesia.
It is also used for sedating intubated,
mechanically ventilated patients.
Analgesic effect is poor and addition of an
analgesic to the anesthetic regimen is
necessary for surgery.
Advantages:
Rapid induction and recovery times
It can be given for prolonged periods
without resulting in prolonged recovery
Disadvantages:
apnea
bradycardia and hypotension.
Propofols abuse as a recreational drug (it
produces euphoria) has been seen, in
some anesthesiologists who have access
to the drug.
In addition, Michael Jacksons death in
June 2009 has been attributed to a
cocktail of propofol and other drugs
Jacksons cardiologist, Dr. Conrad Murray
had been administering to Jackson 50 mg
of propofol IV, nightly for 6 weeks for his
insomnia.
Fearing that Jackson was forming an
addiction to the anesthetic, he attempted
to wean him by lowering the dose to 25
milligrams and adding the sedatives
lorazepam and midazolam.
According to the MSNBC news service, the sequence of
drugs given, on the day of his death were:
1:30 a.m. 10 mg tablet of diazepam
2 a.m. 2 mg, IV of lorazepam
3 a.m. 2 mg, IV of midazolam
5 a.m. 2 mg, IV of lorazepam
7:30 a.m. 2 mg, IV of midazolam
10:40 a.m. 25 mg, IV of propofol diluted with
lidocaine
10:50 a.m. Dr leaves Jacksons room; returns
minutes later to him not breathing. Administers 0.2
mg of flumazenil (a BZ antagonist)
D. Neuromuscular blocking drugs
These drugs are used during surgery
(especially intra-abdominal and intra-
thoracic), and to aid intubation for surgical
and diagnostic procedures (endoscopy).
Previously, adequate muscle relaxation
was only possible with deep anesthesia
(which leads to CNS depressant effects).
Contraction of skeletal muscles is
voluntarily controlled by impulses that
originate in the CNS.
Impulses from the brain are conducted
through the spinal cord to the somatic
motor neutrons.
Somatic motor neurons eventually connect
with skeletal muscle fibers forming a
neuromuscular junction (NMJ).
The neuronal endings of the somatic
motor fibers contain the neurotransmitter
acetylcholine (ACH).
When ACH is released into the
neuromuscular synapses, it binds to
receptors known as nicotinic-II (NII)
receptors.
Neuromuscular blockers inhibit skeletal
muscle contraction by interfering with the
NII receptors.
There are 2 types of neuromuscular
blockers:
nondepolarizing
depolarizing
1. Nondepolarizing blockers
These bind to the receptors but do not
stimulate the receptors. They are
structurally similar to ACH and function as
a competitive inhibitor.
By binding to the nicotinic receptor, they
prevent ACH from binding and inhibit
muscular contraction.
They do not cause the sodium channels in
the membrane to open, therefore no
depolarization of the receptor occurs.
Remember, the resting membrane
potential (on the inside of the cell
membrane) is typically 70mV, with closed
sodium channels. Any shift from the
resting potential toward 0mV is called a
depolarization.
After I.V. injection, there is generally, a
rapid onset of effects: