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1. General Anaesthetics & Skeletal
muscle relaxants
Dr. Karun Kumar
Senior Lecturer
Dept. of Pharmacology

2. General anaesthetics
• Drugs which produce reversible loss of all sensation
and consciousness
• The cardinal features of general anaesthesia are:
1. Loss of all sensation, especially pain
2. Sleep (unconsciousness) and amnesia
3. Immobility and muscle relaxation
4. Abolition of somatic and autonomic reflexes

3. • In dental practice, GA is admin. By a qualified
anaesthetist & not by the dental surgeon himself
• Minimal alveolar concentration (MAC)  Lowest
concentration of the anaesthetic in pulmonary
alveoli needed to produce immobility in response to
a painful stimulus (surgical incision) in 50%
individuals.
• Greater the MAC, lesser is the potency
• Methoxyflurane is most potent

4. Stages of anaesthesia
1. Stage of analgesia  Starts from beginning of
anaesthetic inhalation and lasts upto the loss of
consciousness. Pain is progressively abolished.
Though some minor operations can be carried out
during this stage, it is rather difficult to maintain—
use is limited to short procedures.

5. 2. Stage of delirium  From loss of consciousness to
beginning of regular respiration. Apparent excitement
is seen—patient may shout, struggle and hold his
breath; muscle tone increases, jaws are tightly closed,
breathing is jerky; vomiting, involuntary micturition or
defecation may occur. This stage is inconspicuous in
modern anaesthesia.

6. 3. Surgical anaesthesia  Extends from onset of
regular respiration to cessation of spontaneous
breathing. Most dental/surg. procedures are carried
out
4. Medullary paralysis  Cessation of breathing to
failure of circulation and death. It is never attempted.

7. Stages of
anaesthesia

8. Properties of an ideal anaesthetic
1. For the patient  It should be pleasant,
nonirritating, should not cause nausea or vomiting.
• Induction and recovery should be fast with no after
effects.
2. For the surgeon  It should provide adequate
analgesia, immobility and muscle relaxation. It should
be noninflammable and nonexplosive so that cautery
may be used.

9. 3. For the anaesthetist
1. Its administration should be easy, controllable and
versatile.
2. Margin of safety should be wide—no fall in BP.
3. Heart, liver and other organs should not be
affected.
4. It should be potent so that low concentrations are
needed and oxygenation of the patient does not
suffer.
5. Rapid adjustments in depth of anaesthesia should
be possible.
6. It should be cheap, stable and easily stored.
7. It should not react with rubber tubing or soda lime.

11. Classification

13. Mechanism of action

14. Mechanism of action
• Inhaled anaesth., barbs., BZDs, Etomidate & Propofol
facilitate GABA mediated inhibition at GABAA
receptor sites & thereby ↑ Cl- flux through its
channel
• N2O & Ketamine inhibit the excitatory NMDA type of
glutamate receptor which gates mainly Ca2+ channels
in the neurons

15. Nitrous oxide (N2O)
• Colourless, odourless, heavier than air,
noninflammable gas supplied under pressure in steel
cylinders
• It is nonirritating, but low potency anaesthetic;
unconsciousness cannot be produced in all
individuals
• Nitrous oxide is a good analgesic but weak muscle
relaxant
• 2nd gas eff. & diffusion hypoxia only with N2O

16. • Neuromuscular blockers are mostly required
• Onset of action is quick and smooth (but
thiopentone is often used for induction), recovery is
rapid, because of its low blood solubility
• Post-anaesthetic nausea is not marked
• A mixture of 70% N2O + 25–30% O2 + 0.2–2%
another potent anaesthetic is employed for most
surgical procedures

17. • 2nd gas eff.  Seen when another inhal. agent (like
Halothane) is admin. along with N2O. Due to
generation of -ve pressure 2nd gas is also taken in
from the cylinder
• Diffusion hypoxia  It occurs when supply of N2O is
stopped while recovery from anesthesia. It can be
prevented by 100% O2 inhalation. Oxygen is given
during the last few minutes of anaesthesia and in the
early post anaesthetic period

18. Halothane
• Volatile liquid with sweet odour, nonirritant and
noninflammable
• Solubility in blood is intermediate—induction is
reasonably quick and pleasant
• It is a potent anaesthetic—precise control of
administered concentration is essential
• For induction 2–4% and for maintenance 0.5–1% is
delivered by the use of a special vaporizer
• It is not a good analgesic or muscle relaxant, but it
potentiates competitive neuromuscular blockers

19. • Halothane causes direct depression of myocardial
contractility by reducing intracellular Ca2+
concentration
• Pharyngeal and laryngeal reflexes are abolished early
and coughing is suppressed while bronchi dilate. As
such, Halothane is preferred for asthmatics
• It inhibits intestinal and uterine contractions
• Hepatitis occurs in rare susceptible individuals
especially after repeated use

20. • A genetically determined reaction malignant
hyperthermia occurs rarely
• Many susceptible subjects have an abnormal RyR1
(Ryanodine receptor) calcium channel at the SR of
skeletal muscles
• This channel is triggered by Halothane to release
massive amounts of Ca2+ intracellularly causing
persistent muscle contraction and increased heat
production
• Rapid external cooling, bicarbonate infusion, 100%
O2 inhalation and i.v. Dantrolene are used to treat
malignant hyperthermia

21. Isoflurane
• Routinely used; produces rapid induction and
recovery, and is administered through a special
vaporizer; 1.5–3% induces anaesthesia in 7–10 min,
and 1–2% is used for maintenance
• Does not sensitize the heart to adrenergic
arrhythmias
• Postanaesthetic nausea and vomiting is low
• Advantages  Better adjustment of depth of
anaesthesia and low toxicity

22. Thiopentone sodium
• Ultrashort acting thiobarbiturate
• Injected i.v. (3–5 mg/kg) as a 2.5% solution, it
produces unconsciousness in 15–20 sec.
• Poor analgesic  Painful procedures should not be
carried out under its influence unless an opioid or
N2O has been given
• A/E  Laryngospasm occurs generally when
respiratory secretions or other irritants are present,
or when intubation is attempted while anaesthesia is
light

23. Propofol
• Has superseded thiopentone as an i.v. anaesthetic,
both for induction as well as maintenance.
• Unconsciousness occurs in 15–45 sec and lasts 5–10
min.
• It lacks airway irritancy and is not likely to induce
bronchospasm  preferred in asthmatics
• It is particularly suited for outpatient surgery,
because residual impairment is less marked and
shorter-lasting
• Incidence of postoperative nausea and vomiting is
low; patient acceptability is very good

24. Ketamine
• Induces a so called ‘dissociative anaesthesia’
characterized by profound analgesia, immobility,
amnesia with light sleep
• The patient appears to be conscious, i.e. opens his
eyes, makes swallowing movements and his muscles
are stiff, but he is unable to process sensory stimuli
and does not react to them. Thus, the patient
appears to be dissociated from his body and
surroundings
• The primary site of action is in the cortex and
subcortical areas

25. • Mechanism of action  It acts by blocking action of
glutamate (an excitatory amino acid) at NMDA receptor
• Ketamine has been used for
1. Operations on the head and neck
2. In patients who have bled
3. In asthmatics (relieves bronchospasm)
4. For short operations
5. Burn dressing
6. Combined with diazepam, it has found use in
angiographies, cardiac catheterization and trauma
surgery.
• C/I  HTN, in ischaemic heart disease (increases cardiac
work)

26. Fentanyl
• Highly lipophilic, short acting (30–50 min) potent
opioid analgesic related to pethidine given i.v. at the
beginning of painful surgical procedures
• Reflex effects of painful stimuli are abolished
• Frequently used to supplement anaesthetics in
balanced anaesthesia
• Combined with BZDs, it can obviate the need for
inhaled anaesthetics for diagnostic, endoscopic,
angiographic and other minor procedures in poor
risk patients, as well as for burn dressing

27. • Anaesthetic awareness with dreadful recall is a risk
• Nausea, vomiting and itching often occurs during
recovery
• The opioid antagonist naloxone can be used to
counteract persisting respiratory depression and
mental clouding
• Also employed as adjunct to spinal and nerve block
anaesthesia, and to relieve postoperative pain
• MOA  It acts as an agonist on μ opioid receptor

28. Remifentanil
• Faster acting congener of Fentanyl with a shorter and
more predictable duration of action
• After i.v. inj., produces analgesia in 1-2 mins. which
fades in 10-15 mins.
• Plasma t1/2 is 10-15 mins.
• Used to provide strong & titratable analgesia to cover
short & painful procedures
• MOA  It acts as an agonist on μ opioid receptor

29. Conscious sedation
• A monitored state of altered consciousness that can
be employed (supplemented with local anaesthesia),
to carryout diagnostic/short therapeutic/dental
procedures in apprehensive subjects or medically
compromised patients, in place of general
anaesthesia
• It allows the operative procedure to be performed
with minimal physiologic and psychologic stress

30. • In conscious sedation, drugs are used to produce a
state of CNS depression (but not unconsciousness)
enabling surg. procedure to be carried out while
maintaining communication with the patient, who at
the same time responds to commands and is able to
maintain a patent airway
• The difference between conscious sedation and
anaesthesia is one of degree
• The protective airway and other reflexes are not lost,
making it safer

31. • However, by itself, conscious sedation is not able to
suppress the pain of dental procedure, LA must be
injected in addition
• Drugs used for conscious sedation are:
1. Diazepam
2. Propofol
3. Nitrous oxide
4. Fentanyl

32. Complications of GA
A. During anaesthesia
1. Respiratory depression and hypercarbia
2. Salivation, respiratory secretions. This is less
problematic now as nonirritant anaesthetics are
mostly used
3. Cardiac arrhythmias, asystole
4. Fall in BP
5. Aspiration of gastric contents: acid pneumonitis
6. Laryngospasm and asphyxia

33. 7. Awareness  Dreadful perception and recall of
events during surgery. This may occur due to use of
light anaesthesia + analgesics and muscle relaxants.
8. Delirium, convulsions and other excitatory effects are
generally seen with i.v. anaesthetics; especially if
phenothiazines or hyoscine have been given in
premedication. These are suppressed by opioids.
9. Fire and explosion  Rare now due to use of non-
inflammable anaesthetics.

34. B. After anaesthesia
1. Nausea and vomiting
2. Persisting sedation: impaired psychomotor function
3. Pneumonia, atelectasis.
4. Organ toxicities: liver, kidney damage
5. Nerve palsies—due to faulty positioning
6. Emergence delirium
7. Cognitive defects: prolonged excess cognitive
decline has been observed in some patients,
especially the elderly

35. Drug interactions
1. Patients on antihypertensives given GA  BP ↓↓
2. Neuroleptics, opioids, clonidine & MAOIs potentiate
3. Halothane sensitizes the heart to Adr.
4. If a patient on corticosteroids is to be
anaesthetized, 100 mg hydrocortisone given
intraoperatively because anaesthesia is a stressful
state—can precipitate adrenal insufficiency and
cardiovascular collapse
5. Switch over to plain insulin if patient is on OHA

36. Skeletal Muscle Relaxants
• Drugs that act peripherally at neuromuscular
junction/muscle fiber itself or centrally in the
cerebrospinal axis to reduce muscle tone and/or
cause paralysis
• The neuromuscular blocking agents are used
primarily in conjunction with general anaesthetics to
provide muscle relaxation for surgery, while centrally
acting muscle relaxants are used mainly for painful
muscle spasms and spastic neurological conditions

37. Peripherally acting MRs
I. Neuromuscular blocking agents
A. Nondepolarizing (Competitive) blockers
1. Long acting  d-Tubocurarine, Pancuronium,
Doxacurium, Pipecuronium
2. Intermediate acting  Vecuronium, Atracurium,
Cisatracurium, Rocuronium, Rapacuronium
3. Short acting: Mivacurium
B. Depolarizing blockers  Succinylcholine (SCh)
Decamethonium
II. Directly acting agents  Dantrolene sodium, Quinine

39. MOA of Nondepolarizing (Competitive)
blockers
1. The site of action of both competitive and
depolarizing blockers is the end plate of skeletal
muscle fibers
2. At low doses  Competitively block ACh at the
nicotinic receptors
3. At high doses  Block the ion channels of the
motor endplate

41. MOA of Depolarizing agents
• Depolarizing blocking agents work by depolarizing
the plasma membrane of the muscle fiber, similar to
the action of ACh
• However, these agents are more resistant to
degradation by Acetylcholinesterase (AChE) and can
thus more persistently depolarize the muscle fibers
• Succinylcholine attaches to the nicotinic receptor and
acts like ACh to depolarize the junction

42. • The depolarizing agent first causes the opening of
the sodium channel associated with the nicotinic
receptors, which results in depolarization of the
receptor (Phase I)
• This leads to a transient twitching of the muscle
(fasciculations)
• A fasciculation, or muscle twitch, is a small, local,
involuntary muscle contraction and relaxation which
may be visible under the skin

44. • Continued binding of the depolarizing agent renders
the receptor incapable of transmitting further
impulses
• With time, continuous depolarization gives way to
gradual repolarization as the sodium channel closes
or is blocked
• This causes a resistance to depolarization (Phase II)
and flaccid paralysis

46. Actions
1. Skeletal muscles  Intravenous injection of
nondepolarizing blockers rapidly produces muscle
weakness followed by flaccid paralysis
• Small fast response muscles (fingers, extraocular) are
affected first; paralysis spreads to hands, feet—arm,
leg, neck, face—trunk—intercostal muscles—finally
diaphragm: respiration stops
• Recovery occurs in the reverse sequence;
diaphragmatic contractions resume first

47. 2. Autonomic ganglia  Cholinergic receptors in
autonomic ganglia are nicotinic NN ,competitive
neuromuscular blockers produce some degree of
ganglionic blockade; d-TC has the maximum propensity
in this regard, while the newer drugs (Vecuronium, etc.)
are practically devoid of it
• SCh may cause ganglionic stimulation by its agonistic
action on nicotinic receptors

48. 3. Histamine release  d-TC releases histamine from
mast cells resulting in hypotension, flushing,
bronchospasm and increased respiratory secretions
4. C.V.S.  d-TC produces significant fall in BP. This is
due to—
(a) Ganglionic blockade
(b) Histamine release
(c) Reduced venous return—a result of paralysis of
limb and respiratory muscles

49. 5. G.I.T.  The ganglion blocking activity of competitive
blockers may enhance postoperative paralytic ileus
after abdominal operations
6. C.N.S.  All neuromuscular blockers are quaternary
compounds—do not cross BBB  no CNS effects

50. SCh apnoea
• SCh is rapidly hydrolysed by plasma
pseudocholinesterase to succinylmonocholine and
then succinic acid + choline (action lasts 5–8 mins.)
• Some patients have genetically determined
abnormality (low affinity for SCh) or deficiency of
pseudocholinesterase
• In them, SCh causes prolonged phase II blockade
resulting in muscle paralysis and apnoea lasting 4–6 h
• The prolonged apnoea can be tided over only by
mechanical ventilation

51. Interactions
1. Thiopentone sod. and SCh solutions should not be
mixed in the same syringe—react chemically
2. GA potentiate competitive blockers
3. Anticholinesterases reverse the action of
competitive blockers (Neostigmine)
4. Antibiotics  Aminoglycosides, Tetracyclines
5. Calcium channel blockers  Verapamil
6. Diuretics may produce hypokalemia which
enhances competitive block

52. Toxicity
1. Respiratory paralysis and prolonged apnoea is the
most important problem
2. Flushing is common with d-TC (due to histamine
release), can occasionally occur with atracurium
and mivacurium
3. Fall in BP and CV collapse can occur, especially in
hypovolemic patients

53. 4. Cardiac arrhythmias and even arrest have occurred,
especially with SCh
5. Precipitation of asthma by histamine releasing
neuromuscular blockers
6. Postoperative muscle soreness and myalgia may be
complained after SCh

54. Uses
1. Adjuvants to general anaesthesia
• Valuable in abdominal and thoracic surgery
• In dentistry, they may be needed for setting of
madibular fractures
• Vecuronium and Rocuronium  Most frequently
selected nondepolarizing blockers
• SCh is employed for brief procedures, e.g.
endotracheal intubation, laryngoscopy,
bronchoscopy, esophagoscopy, reduction of
fractures, dislocations, and to treat laryngospasm

56. 2. Assisted ventilation in critically ill patients in ICUs
facilitated by continuous infusion of competitive
neuromuscular blocker which reduces the chest wall
resistance to inflation
• Vecuronium is generally selected
3. Convulsions and trauma from ECT can be avoided by
the use of MRs
4. Severe cases of tetanus and status epilepticus, may
be paralyzed by a neuromuscular blocker and
maintained on intermittent positive pressure
respiration

57. Centrally acting MRs
• Drugs which reduce skeletal muscle tone by a
selective action in the cerebrospinal axis, without
altering consciousness
• They selectively depress spinal and supraspinal
polysynaptic reflexes involved in the regulation of
muscle tone without significantly affecting
monosynaptically mediated stretch reflex
• All centrally acting muscle relaxants do have some
sedative property

58. Classification
1. Mephenesin congeners  Carisoprodol,
Chlorzoxazone, Chlormezanone, Methocarbamol
2. Benzodiazepines  Diazepam and others
3. GABA mimetic  Baclofen, Thiocolchicoside
4. Central α2 agonist  Tizanidine

59. Uses
1. Acute muscle spasms  Overstretching of a muscle,
sprain, tearing of ligaments and tendons,
dislocation, fibrositis, bursitis, rheumatic disorders,
etc. cause painful spasm of muscles
• The mephenesin-like and BZD muscle relaxants,
combined with analgesics, are commonly used
• They may help to relieve trismus occuring after a
dental procedure
• Efficacy is not impressive

60. 2. Torticollis, lumbago, backache, neuralgias respond in
the same way as acute muscle spasms
3. Anxiety and tension  Increased tone of muscles &
bruxism. BZD group
4. Spastic neurological diseases  Hemiplegia,
paraplegia, spinal injuries, multiple sclerosis and
cerebral palsy are benefited by Baclofen, Diazepam,
Tizanidine and Dantrolene

63. 5. Tetanus  Most commonly diazepam is infused i.v.
6. Electroconvulsive therapy ECT  Diazepam
decreases the intensity of convulsions
7. Orthopedic manipulations  Performed under the
influence of Diazepam or Methocarbamol given i.v.