General Anaesthetics and Local Anaesthetics (gaba, glycine, glutamate, cation)

1. General Anaesthesia
• General anaesthetics are the drugs that produce
reversible loss of all sensation & consciousness.
Classification:
1. Inhalational
A. Gas: N2O, Xenon
B. Liquids: Ether, Halothane, En/Iso/Des/Sevo-flurane
2. Intravenous
A. Inducing agents: Thiopentone sodium, Propofol,
Methohexitone, Etomidate
B. Slow acting
 Dissociative anesthesia: Ketamine
 Benzodiazepines: Diazepam, Lorazepam, Midazolam
 Opioid analgesics: Fentanyl

2. Induction, Maintenance & Recovery
• Induction is defined as the period of time from
administration of anaesthetic to the development of
effective surgical anaesthesia in the patient.
• Maintenance provides a sustained surgical anaesthesia.
• Recovery is the time from discontinuation of administration
of anaesthesia until consciousness and protective
physiologic reflexes are regained.
Balanced Anesthesia
• All components of anesthesia is achieved by using
combination (e.g: low dose opioids + volatile GA + N2O)
Minimum Alveolar Concentration (MAC)
• Lowest concentration of the inhalational anesthetic in
alveoli needed to produce immobility in response to painful
stimulus.

3. Stages of anaesthesia
1. Stage I—Analgesia: Loss of pain sensation results from
interference with sensory transmission. The patient progresses
from conscious and observes analgesia. Amnesia and reduced
awareness of pain occur as Stage II is approached.
2. Stage II—Excitement: The patient experiences delirium and
possibly combative behaviour. A rapid acting agent, such as
propofol, is given intravenously before inhalation anaesthesia is
administered.
3. Stage III—Surgical anaesthesia: There is gradual loss of muscle
tone and reflexes as the CNS is further depressed. Regular
respiration and relaxation of skeletal muscles with eventual loss
of spontaneous movement occur in this stage. This is the ideal
stage of anaesthesia for surgery. Continuous careful monitoring
is required to prevent undesired progression into Stage IV.
4. Stage IV—Medullary paralysis: Severe depression of the
respiratory and vasomotor centres occur during this stage.
Death can rapidly ensue unless measures are taken to maintain
circulation and respiration.

4. Mechanism of action of General Anaethetics
• Inhalational anaesthetics, barbiturates,
benzodiazepines & propofol potentiate the action of
inhibitory transmitter GABA to open Cl¯ channels.
• Action of glycine (another inhibitory transmitter
which also activates Cl¯ channels) in the spinal cord
and medulla is augmented by barbiturates, propofol
& many inhalational anaesthetics.
• Ketamine selectively inhibits the excitatory NMDA
type of glutamate receptor.
• Certain fluorinated anaesthetics and barbiturates
inhibit the neuronal cation channel gated by
nicotinic cholinergic receptor.

5. Inhalational Anaesthetics
Nitrous oxide (N2O)
• It is cheap & commonly used anaesthetic.
• It is low potency anaesthetic but good analgesic.
• It has fast onset & recovery.
• It is given as 70% N2O + 25-30% O2 + 0.2-2% other potent
anaesthetic (Halothane)
• It has little effect on respiration, heart & BP.
Uses: Maintain surgical anaesthesia, obstetric practice,
emergency management of injuries, refractory pain, etc
Adverse Effects: It interacts & degrades Vit B12.
Contraindications: Pneumothorax, air embolus, obstructive
middle ear, etc.

6. Halothane
• It is a volatile liquid with sweet odour, non-irritating &
non-explosive.
• It is potent anaesthetic but poor analgesic.
• It dilates bronchi so preferred in asthma patient.
• For induction 2-4% & for maintenance 0.5-1% is delivered
by using special vapouriser.
Adverse effects:
• Hepatitis
• Hyperthermia
• Hangover
• Shivering
Contraindication:
• Jaundice
• Raised CSF pressure

7. Intravenous anaesthetics
Inducing agents
• Produce anaesthesia within 20 sec.
• Reduce dose of other anaesthetics
• Supplemented with analgesics & muscle relaxant
Thiopentone sodium.
• It is ultrashort acting thiobarbiturate administered i.v.
• Single dose induces hypnosis & anaesthesia without analgesia
• When administerd i.v. it quickly enters CNS & depresses function
within minutes. Injected i.v. (3-5mg/kg) as 2.5% solution.
• Redistributed to skeletal muscles & adipose tissue serves as
reservoir.
Uses: Inducing agent, Control of convulsion, Protect from cerebral
ischemia
Adverse effects: Laryngospasm, shivering & delirium during recovery
Contraindications: Hypersensitivity to barbiturates, Hypotension

8. Propofol
• It is liquid employed as 1% emulsion.
• It has quick action used for both induction &
maintenance for surgical procedures lasting 1hr.
• Dose 2mg/kg bolus i.v. for induction & 100-200
µg/kg/min for maintenance.
• It decreases intracranial pressure.
• It is metabolized fast so quick recovery is
possible
• It is safe in pregnancy
• It is similar to Thiopentone sodium but is more
potent & has quicker action.

9. Ketamine
• Causes dissociative anaesthesia (sensory loss, analgesia,
amnesia)
• Fast onset of action & recovery. Dose 1-2mg/kg i.v. or
3-5mg/kg i.m.
• Children tolerate better
• Causes sympathetic stimulation , increase intracranial
pressure
• Preferred in asthmatic & hypotensive patients
• Good for repeated use
Uses: dressing of burns, radiotherapy, marrow sampling, minor
orthopedic procedure, short duration surgery
Adverse effects: hallucination, rise in BP, increased salivation
Contraindications: HTN, IHD

10. Benzodiazepines
• Pre-anaesthetic medication
• Used for inducing, maintaining & supplementing
anaesthesia
Opioids
• Fentanyl is short acting potent opioid related to
Pethidine
• Used for neuroleptic analgesia(intense analgesia)
during endoscopies, angiographies, burn-dressings
Adverse effects: Nausea, Vomiting, Muscle dystonia

12. Pre-anaesthetic medications
• Medicines used before anaesthesia to make it
more pleasant & safe. They are given for:
Relief of anxiety & apprehension
Amnesia
Potentiate & supplement analgesic action
Decrease secretion & vagal stimulation
Antiemetic effect
Decrease acidity & volume of gastric juice
e.g: opioids, sedative anti-anxiety drugs,
anticholinergics, antacids, antiemetics, etc.

13. LOCAL ANAESTHESIA (LA)
• Local anaesthetics are the drugs that blocks the
generation & conduction of nerve impulse without
affecting consciousness.
• The generation & transmission of nociception
(pain) can be prevented by blocking voltage gated
Na+ channel in afferent neuron.
• They can act on any part of the nervous system &
on every type of nerve.
• Advantages of LA over GA: Unaltered
consciousness, function of vital organ is
unaffected, safe for patients, useful for minor &
major operations.

15. Classification:
Injectable
• Low potency, short duration: Procaine,
Chloroprocaine
• Intermediate potency & duration: Lignocaine
(Lidocaine), Prilocaine
• High potency, long duration: Bupivacaine,
Ropivacaine, Tetracaine
Surface Anaesthetic
• Soluble: Cocaine, Lidocaine, Tetracaine
• Insoluble: Benzocaine, Oxethazaine

16. Chemistry
• Local anaesthetics are weak bases with ampiphilic
(lipohilic & hydrophilic) property linked through
ester/amide linkage.
• Ester linked: cocaine, procaine
• Amide linked: lignocaine, bupivacaine
Combination of LA with Vasoconstrictor (Adr)(1:50000-1:200000)
Advantages Disadvantages
 Prolong duration of action
 Reduce systemic toxicity
 Provides more bloodless field
 Delays wound healing
 Painful injection & chances of
necrosis
 Increased BP & arrythmia

17. Systemic action of LA
CNS
• Stimulation followed by depression
• Cocaine causes CNS stimulation
CVS
• Cardiac depressant
• Tend to fall BP except cocaine
Blood vessels
• Vasodilation leading to fall in BP
Others
• Ganglionic blockade, neuromuscular blockade
Adverse Effects
• Occurs due to escape of local anesthetics to systemic circulation
• CNS: lightheadness, dizziness, auditory & visual disturbance,
confusion
• CVS: myocardial depression & vasodilation, occasional
hypersensitivity

18. Lignocaine
• Versatile LA used for surface application &
injection.
• Has fast onset of action (within 3 min)
• Causes vasodilation in injected area
Uses: Surface application, infiltration, nerve block,
spinal & intravenous regional block anaesthesia.
Also used as antiarrhythemic drug.
Adverse effects: drowsiness, dysphoria & altered
taste. Overdose may cause convulsion, coma &
respiratory arrest.
Dose: 2-4% gel (Xylocaine gel), 100mg/ml spray, 1-
2% injection (with or without adrenaline)

19. Bupivacaine
• Potent & long acting LA.
• Causes more sensory block than motor block.
Uses: infiltration, nerve block, epidural & spinal
anaesthesia. Popular in obstetrics & postoperative
pain relief.
Adverse effect: cardiotoxic
Dose: 0.25-0.5% injection
Ropivacaine
• It is a congener of bupivacaine but less cardiotoxic

20. Uses & Techniques of LA
1. Topical anaesthesia
• LA is directly applied to the skin & mucous membrane of
nose, mouth, throat, tracheo-bronchial tree, esophagus
& genitourinary tract
• Only superficial layer is anaesthesised
2. Infiltration anaesthesia
• LA is injected directly into the tissue
• Motor function is not affected
• Used for minor operations: incision, hydrocele, hernia
3. Conduction block
• Field block: s.c. injection, all nerves coming to a field are
blocked
• Nerve block: injection around nerve trunk or plexuses

21. 4. Spinal anaesthesia
• LA is injected in subarachnoid space betweenL2-3 or L3-4
• Acts on nerve roots in caudaequina
• Lower abdomen & hind limb are anaesthesised & paralysed.
• Level of anaesthesia depends on volume & speed of
injection & posture of patient.
• Bupivacaine(0.5-0.75%), lidocaine(1.5-5%), tetracaine(0.25-
0.5%) is commonly used.
Uses: operation on lower limbs, pelvis, lower abdomen,
prostatectomy, fracture setting, obstetric procedures,
caesarean section
Adverse effects: headache, nausea, vomiting, septic
meningitis, hypotension, respiratory paralysis & cauda
equina syndrome
Contraindication: hypotension & hypovolemia, mentally ill
patient, infant & children

24. 5. Epidural anaesthesia
• LA is injected in the epidural space that acts on nerve
roots
• It can be thoracic, lumbar or caudal depending on site
of injection
• Lidocaine 1-2% & Bupivacaine 0.25-0.5% are used.
• Epidural catheter allows continuous or repeated
administration
• Lesser complications
6. Intravenous regional anaesthesia
• LA is injected in veins
• 0.5% lidocaine is injected i.v.
• Used for upper limb & orthopedic procedures
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