Transcript drugs used for anesthesia, muscle relaxation - Suny

DRUGS USED FOR
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)
• Procaine is the prototype drug of the local
anesthetics. It has the lowest potency
(except for Benzocaine).
• It is used for nerve block, epidural and
spinal anesthesia. Novocaine is generally
not used in dentistry anymore.
b. benzocaine
• Topical use only
• benzocaine (Solarcaine, Orajel, Lanacaine
etc)
• It is used for minor mouth conditions (i.e
teething, canker sores) sore throat,
sunburn, and other minor skin conditions
c. cocaine
• Cocaine is 2 times as potent as procaine.
It is used for ear, nose and throat
procedures.
d. tetracaine(Pontocaine)
• Used for:
• spinal anesthesia requiring 2 to 3 hours of
anesthesia
• surface anesthesia of the eye, nose and
throat.
• It is 16 times as potent as procaine.
3. Amide local anesthetics
• Commonly used local anesthetics
containing the amide functional group are
bupivacaine, lidocaine, mepivacaine, and
ropivacaine.
a. bupivacaine(Marcaine) and
levobupivacaine (Chirocaine)
• These are used in infiltration and epidural
anesthesia. They are 16 times more
potent than procaine.
• Generally, they are more cardiotoxic than
the other long acting local anesthetics.
b. lidocaine
• Used topically for minor dermatological
procedures (i.e skin tag removal)
• It is 4 times more potent than procaine and
has replaced procaine in the area of dental
anesthesia.
c. mepivacaine (Carbocaine)
• This local anesthetic is used for dental
procedures, surgical procedures and
during labor and delivery.
d. ropivacaine (Naropin)
• This is used for surgical procedures,
including caesarian sections. Although it is
similar pharmacologically to bupivacaine, it
is less cardiotoxic.
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4. Adverse effects
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a. Low concentration dosages:
dizziness
sleepiness
restlessness
• b. Higher concentration dosages:
• muscular twitching
• seizures
• and hypotension (except for cocaine,
which can result in vasoconstriction and
hypertension, as well as cardiac
arrhythmias).
B. General anesthesia
1. general information
• General anesthesia provides rapid and
complete loss of sensation.
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It is characterized by:
total analgesia (no pain)
unconsciousness deeper than sleep
loss of memory
complete muscle relaxation.
• Although similar to sleep there are
profound differences:
• There is the loss of the “fight or flight
response”, which is not lost during sleep.
• General anesthetics stop most nervous
activity in the brain, sleep only stops
activity in very specific areas, and
increases activity in other areas.
• It is the ultimate “altered state”, like
flipping a switch to temporarily turn off the
nervous system.
• In the past decade it has become apparent
that the GABA receptor-chloride channel is
the target of many general anesthetics
(inhaled anesthetics, BZ’s, barbiturates,
propofol).
• The GABA receptor complex consists of
alpha, beta, and gamma subunits
surrounding and controlling a central
chloride ion channel.
• All anesthetics bind at sites in the α and β
subunits, which are removed from the
GABA binding site.
• The binding of GABA (gamma
aminobutyric acid) to its receptor causes
an opening of the chloride ion channel.
• The increase of chloride ion leads to a
hyperpolarization of the cell.
• For IV benzodiazepine anesthetics and the
inhalation anesthetics, binding to the
GABA receptor complex, concurrent with
GABA binding, results in a greater
duration of chloride channel opening.
• This increases the entry of chloride ion
into the cell. The increased
hyperpolarization reduces neural
excitability by making it more difficult for
the cell to depolarize.
• This means that a much larger than
normal stimulus is required to reach the
threshhold potential and generate an
action potential.
• IV barbiturate binding to the GABA
receptor complex also increases the
duration of GABA-activated chloride
channel opening.
• In addition, higher concentrations of
barbiturates may directly activate chloride
channel opening even in the absence of
GABA, leading to "barbiturate anesthesia”.
• In addition to their actions on these
chloride channels, general anesthetics
also decrease the duration of opening of
various cation channels (K1+, Ca2+).
• This enhances the hyperpolarization of the
membrane.
• General anesthesia usually requires more
than one drug. Multiple medications are
used to rapidly cause unconsciousness
and muscle relaxation and to maintain
deep anesthesia.
• IV agents are usually administered first
because they act within a few seconds.
• After the patient loses consciousness,
inhaled agents are used to maintain the
anesthesia.
• This approach allows the dose of
inhalation anesthetic to be lower so that
the procedure is safer for the patient
• General anesthesia occurs in distinct
steps or stages:
Stage 1
• Loss of pain, loss of general sensation, but
the patient may be awake
Stage 2
• Excitement and hyperactivity
• The patient may try to resist, their
heartbeat and breathing may become
irregular and blood pressure can increase.
• The anesthesiologist will try to quickly
move through stage 2. Often an IV agent
will be given to calm the patient during this
stage.
Stage 3
• Called surgical anesthesia
• Skeletal muscles become relaxed,
cardiovascular and breathing activities
stabilize
• Eye movements slow down and the
patient becomes very still. This is the
stage when surgery begins and remains
until the procedure ends.
Stage 4, or overdose
• This is marked by hypotension or
circulatory failure. Death may result if the
patient cannot be revived quickly.
2. Inhaled general anesthetics
These agents are nonflammable,
nonexplosive gases or volatile liquids.
• One of their major advantages is that the
depth of anesthesia may be very quickly
changed by altering the concentration of
the agent.
• The median alveolar concentration (MAC)
is a term used to determine the potency of
various inhalation anesthetics.
• It is the median effective dose (ED50) of
the anesthetic, and is expressed as the %
of the gas in the mixture necessary to
achieve an anesthetic effect.
• The smaller the MAC, the more lipid
soluble is the anesthetic, and the lower
the concentration of the anesthetic needed
to produce anesthesia. Therefore, the
more potent is the anesthetic.
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Anesthetic MAC value, in %
Isoflurane
1.2
Sevoflurane
2.0
Desflurane
6.0
Nitrous oxide
100
• All of the inhalation anesthetics (except
nitrous oxide) are respiratory depressants.
• Isoflurane is more depressant than
desflurane and sevoflurane
• All 3 increase the resting partial pressure
of CO2 in arterial blood (PaCO2), increase
the apneic threshold, and decrease the
ventilator response to hypoxia.
• These effects can be mitigated by
mechanically assisting ventilation.
a. Nitrous oxide (laughing gas)
• This is the only gas used routinely for
anesthesia.
• It is not very soluble in blood and tissues,
which enables it to move in and out of the
body very rapidly
• Used for dental procedures and brief
obstetrical and surgical procedures
• See Youtube video from the Pink Panther
Strikes again (Google video Peter Sellers;
Clouseau, Dentist)
• It may also be used together with other
general anesthetics.
• Nitrous oxide in higher doses has been
found to depress the heart.
3. Volatile anesthetics
• These are liquid at room temperature,
converted into a vapor and inhaled
• The most commonly administered liquid
volatile agents in the U.S. are:
• desflurane (Suprane)
• Sevoflurane (Ultane)
• Isoflurane (Forane)
a. desflurane
• 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 patient’s 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)
• This is the prototype drug of the BZ’s
• It is water-insoluble, so IV use requires a
nonaqueous vehicle which can cause local
irritation/pain
b. midazolam (Versed)
• Midazolam is water soluble, so drug of
choice for IV administration
• It has a more rapid onset and more rapid
elimination than the other BZ’s.
• In addition, midazolam is the most potent
amnestic
c. lorazepam (Ativan)
• It is water-insoluble, so IV use requires a
nonaqueous vehicle which can cause local
irritation/pain
• It is a less potent amnestic than
midazolam, but a more potent amnestic
than diazepam.
2. Barbiturates
• The 3 main drugs used in this category are
thiopental, thiamylal, and methohexital.
• Their hypnotic activity is due to side chains
at position 5 (especially if one of them is
branched).
• There is a more rapid onset and shorter
duration of action if there is a sulfur
instead of oxygen atom at position 2 (so,
thiamylal and thiopental have more rapid
onset and shorter duration of action than
methohexital).
• None of these drugs provides analgesia or
significant muscle relaxation.
• Like most of the “older” drugs, barbiturates
have a worse toxicological profile than the
benzodiazepines
• They all may cause coughing,
laryngospasm, bronchospasm, or apnea.
a. Thiopental
• Thiopental, the
flagship of the
barbiturate anesthetic
group, has been a
standard anesthetic
induction agent for
more than 60 years
and is the drug in this
category, to which all
others are compared.
b. Thiamylal
c. Methohexitol
• Thiamylal is not significantly different from
thiopental in potency, incidence of
laryngospasm, respiratory depression,
cardiotoxicity or recovery time.
3. Opioids
• The terms opioid and opiate are often
used interchangeably, but have different
meanings.
• An opiate is derived from the juice of the
opium poppy, Papaver Somniferum,
which is commonly called ‘White Poppy’
and ‘Herb of Joy’.
• An opioid is a compound, either synthetic,
or a natural product which has morphinelike effects.
• Opioids produce moderate sedation and
profound analgesia. They exert their
effects by binding with opioid receptors in
the central nervous system.
• There are 3 major opioid receptors
classified, functionally, as μ (mu), κ
(kappa), and δ (delta).
• There is pharmacological evidence for
subtypes of each receptor in addition to
other, less well-known opioid receptors,
epsilon (ε ), zeta (ζ ), iota (ι ) and lambda
(λ).
• There is a common general structure
found in all opioid receptors embedded in
plasma membranes. They are, usually,
linked to a G protein.
• Once the receptors are bound, a portion of
the G protein is activated, allowing it to
diffuse within the plasma membrane.
• The G protein moves laterally within the
membrane until it reaches its target, an ion
channel.
• The ion channels are involved with either a
reduction of Ca2+ influx or an increase in
K1+ efflux.
• Either of these results in hyperpolarization
(becoming more negative) which impairs
the firing of neurons and neurotransmitter
release.
• Opioids may be used to supplement
anesthesia when other anesthetic drugs
don’t adequately control pain reactions.
• They may be used as induction agents or
as the primary drug for the maintenance of
anesthesia when hemodynamic stability is
essential
• The high doses required to produce
unconsciousness do not depress the
myocardium, nor do they cause a
significant reduction in blood pressure.
• Doses must be at least 10 times the dose
used for control of pain in ambulatory
patients, thus this is referred to as high
dose opioid.
• Opioids depress respiration by inhibiting
the responsiveness of the medullary
respiratory center to PCO2 and alter the
rhythm of breathing.
• Consequently, it is necessary to assist
ventilation.
• Since respiratory depression may extend
into the post-operative period as a result of
drug accumulation in the tissues, the use
of opioids whose clearances are slow
remain most appropriate for patients who
are expected to require p.o. ventilatory
care.
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The opioids most commonly used are
fentanyl (Sublimaze)
sufentanil citrate (Sufenta)
alfentanil (Alfenta)
remifentanil (Ultiva)
a. fentanyl (Sublimaze)
• One of the most
frequently used
because of how
quickly it produces
analgesia
• Fentanyl is a potent synthetic opioid
agonist with between 50-100 times the
analgesic potency of morphine.
• Fentanyl is used to aid induction and
maintenance of general anesthesia and to
supplement regional and spinal
anesthesia.
• Fentanyl is preferred to morphine in
anesthesia due to its ability to maintain
cardiac stability.
• Fentanyl may be administered alone or in
combination with inhalation anesthetics,
local anesthetics, or benzodiazepines.
b. sufentanil citrate (Sufenta)
• 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 it’s ester linkages
are susceptible to hydrolysis by esterases
in tissues and RBC’s.
• 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.
• Propofol’s abuse as a recreational drug (it
produces euphoria) has been seen, in
some anesthesiologists who have access
to the drug.
• In addition, Michael Jackson’s death in
June 2009 has been attributed to a
“cocktail” of propofol and other drugs
• Jackson’s 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 Jackson’s 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 intrathoracic), 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:
1st: Fine muscles affected (those of eyes &
fingers)
• 2nd: limbs, neck & trunk
• 3rd: intercostal muscles
• 4th: diaphragm
• Recovery is in the reverse order
a. Tubocurarine
• This is the prototype of the nondepolarizing neuromuscular blockers. It is
found in curare, which derives from the
South American plant genus Strychnos.
• It has a slow onset (>5 min) and a long
duration of action (1-2 hours), and it is not
commonly used any more.
b. Pancuronium bromide
(Pavulon)
• Full muscle paralysis for major surgery is
achieved in about 2–4 minutes, recovery is
about 2-3 hours
• It is also found as one of the components
in lethal injections. Amnesty International
has objected to this use stating that it "may
mask the condemned prisoner's suffering
during the execution”.
• Pancuronium bromide was one of the
compounds used by Efren Saldivar, the
"Angel of Death”.
• He was a serial killer who murdered
patients while working as a respiratory
therapist.
• He was employed by the Glendale
Adventist Medical Center, working the
night shift, when there were fewer staff on
duty.
• The police, in searching for evidence
strong enough to obtain a court conviction,
exhumed the remains of 20 patients who
had died during the time Saldivar was on
duty.
• They were specifically looking for
unusually high levels of Pavulon in the
cadaver, as this drug remains identifiable
for many months.
• 6 of the 20 cadavers had evidence of a
lethal concentration of Pancuronium
bromide.
• In 2002, Saldivar pleaded guilty to six
counts of murder and received six
consecutive life sentences without the
possibility of parole.
c. Atracurium besylate
(Tracrium)
• and its isomer cisatricurium besylate
(Nimbex)
• They are widely used and have an
intermediate duration (recovery is 95%
complete one hour after injection).
• However, a breakdown product of
atracurium, laudanosine may accumulate
due to very slow hepatic metabolism and
upon crossing into the brain may cause
seizures
• Cisatracurium has less laudanosine
formed and less histamine released than
atracurium.
• Federal regulators have cited St. Margaret
Mercy Healthcare Centers in Indiana for
dispensing Tracrium to Hammond Fire
Department Capt. Michael Magdziarz in
January 2002.
• Magdziarz had underwent a successful
bypass surgery and was recovering. His
surgeon had ordered a penicillin to fight
infection. Instead, the nurse administered
Tracrium.
• He became restless, complained of
shortness of breath, stopped breathing
and suffered cardiac arrest.
d. Vecuronium
bromide(Norcuron)
• This has a shorter duration of action than
pancuronium (recovery is 95% complete
45 minutes to one hour after injection).
• Its lack of significant cardiovascular effects
and lack of dependence on good kidney
function for elimination provide
advantages over other neuromuscular
blocking agents.
• Overall, the extent of adverse effects on
the nondepolarizing neuromuscular
blockers depends on the specific agent.
• The older drugs (i.e. tubocurarine,
pancuronium) tend to have more
cardiovascular actions (blood pressure
and heart rate changes) as well as
histamine release, and more difficulty with
their controlled reversal.
• The newer drugs (i.e. vercuronium) tend to
have minimal to no cardiac effects, slight
to no histamine release, and an easier
reversal.
2. Depolarizing
• Depolarizing agents are also structurally
similar to acetylcholine and function as
competitive inhibitors.
• However, when they bind to the nicotinic
receptor, they cause the sodium channels
in the membrane to open, leading to
depolarization of the receptor.
• These sodium channels only open briefly
and cannot be opened again until the
membrane is repolarized.
• Depolarizing neuromuscular blockers act
as persistent agonists at nicotine
receptors, but unlike acetylcholine, their
relatively slower degradation rate results in
paralysis.
• Generation of an action potential requires
a rapid change (increase) of membrane
potential from a negative state.
• As these drugs are eventually cleared and
receptors become unoccupied, they revert
to the original active state.
• Succinycholine is the only drug in this
class that is used by anesthesia providers
today.
• The duration of action of succinylcholine is
very short, because it is metabolized in the
body very quickly by an enzyme called
plasma cholinesterase.
• This short duration of action makes
succinylcholine a useful drug in situations
where muscle relaxation is needed for only
a short time such as to facilitate intubation.
• Side effects of succinycholine include:
• fasciculations (small muscle movements
caused when the drug binds to receptors)
•
• myalgias (muscle soreness which may be
the result of the fasciculations)
• cardiac rhythm disturbances
• increases in ocular and gastric pressure,
• hyperkalemia in at-risk patients
• malignant hyperthermia: a dramatic
increase in body temperature, acidosis,
electrolyte imbalance and shock
• The syndrome is though to be due to a
reduction in the reuptake of calcium, which
is necessary for termination of muscle
contraction. Consequently, muscle
contraction is sustained.