General Anaesthetics and Local Anaesthetics

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: Inhalational Gas: N 2 O, Xenon Liquids: Ether, Halothane, En/ Iso /Des/ Sevo-flurane Intravenous Inducing agents: Thiopentone sodium, Propofol , Methohexitone , Etomidate 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 + N 2 O) Minimum A lveolar 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 (N 2 O) It is cheap & commonly used anaesthetic . It is low potency anaesthetic but good analgesic. It has fast onset & recovery. It is given as 70% N 2 O + 25-30% O 2 + 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 B 12 . 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

11. 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.

12. 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.

13. 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

14. 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

15. 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

16. 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)

17. 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

18. 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

19. 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

20. 5. Epidural anaesthesia L A 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 THANK YOU