General anaesthetics

General anaesthetics

• 1.
  General AnaestheticsGeneral Anaesthetics
• 2.
  General Anesthesia “Global butreversible depression of CNS function resulting in the loss of response to and perception of all external stimuli” Characteristics – Analgesia – Amnesia – Attenuation of sensory & autonomic responses – Muscle relaxation - Immobility – Unconsciousness (no response to external stimuli) History: ether/chloroform/N2O/cyclopropane/halothane
• 3.
  Pre-anaesthetic MedicationPre-anaesthetic Medication AimsAims –Relief of anxiety and apprehensionRelief of anxiety and apprehension – AmnesiaAmnesia – Supplement analgesiaSupplement analgesia – Decrease secretions and vagal stimulationDecrease secretions and vagal stimulation – Anti-emetic effect (peri & postoperative)Anti-emetic effect (peri & postoperative) – Decrease acidity-avoid aspiration of gastric contentsDecrease acidity-avoid aspiration of gastric contents – Reduce dose of gen. anestheticsReduce dose of gen. anesthetics Timing & Route of administration (30 m-1h prior, I/V)Timing & Route of administration (30 m-1h prior, I/V)
• 4.
  Sedative / Hypnotic/ AnxiolyticsSedative / Hypnotic / Anxiolytics – Benzodiazepines (diff DOAs)Benzodiazepines (diff DOAs) Diazepam (longest acting)Diazepam (longest acting) LorazepamLorazepam (0.05mg/kg) MidazolamMidazolam (0.07mg/kg) – BarbituratesBarbiturates (100-200mg) SecobarbitalSecobarbital PentobarbitalPentobarbital CharacteristicsCharacteristics 1. relieve anxiety / relax pt.1. relieve anxiety / relax pt. 2. sedate pt.2. sedate pt. 3. provide amnesia3. provide amnesia Pre-anaesthetic MedicationPre-anaesthetic Medication
• 5.
  Opioid AnalgesicsOpioid Analgesics(10-20mg) – Morphine (IV)Morphine (IV) – Pethidine (IV)Pethidine (IV) – Fentanyl (transdermal patch) +Fentanyl (transdermal patch) + congenerscongeners Characteristics (delayed awakening,Characteristics (delayed awakening, constipation, asthma, urine retention,constipation, asthma, urine retention, excessive hypotension—morphine)excessive hypotension—morphine) H2 Rec. blockers / PPIs (emergencies-dec. gastric secr.-dec. aspiration pneumonia) −− Cimetidine & Ranitidine (150 mg)
• 6.
  AntiemeticsAntiemetics – MetoclopramideMetoclopramide (10-20mgIM) – AntihistaminesAntihistamines (25-50mg) – Phenothiazines (Promethazine)Phenothiazines (Promethazine) – 5HT5HT33 Receptor BlockersReceptor Blockers OndansetronOndansetron TropisetronTropisetron GranisetronGranisetron CharacteristicsCharacteristics – Used in cancer chemotherapy ptsUsed in cancer chemotherapy pts
• 7.
  Anticholinergics:Anticholinergics: 1. decrease secretions1.decrease secretions 2. inhibit vagal stimulation2. inhibit vagal stimulation – AtropineAtropine (0.4-0.6mg IV) – Hyoscine (crosses BBB)Hyoscine (crosses BBB) – Glycopyrronium (doesn’t cross BBB)Glycopyrronium (doesn’t cross BBB)
• 8.
  Anti HistaminesAnti Histamines ─Diphenhydramine ─Dimenhydrinate Characteristics(anti-emetics, sedatives,Characteristics (anti-emetics, sedatives, anxiolytics & anti-cholinergics)anxiolytics & anti-cholinergics) Used in combinations according to:Used in combinations according to: 1. patient’s requirement1. patient’s requirement 2. patient’s clinical status2. patient’s clinical status 3. type of operation3. type of operation 4. duration of operation4. duration of operation
• 9.
  Classification of GeneralAnaestheticsClassification of General Anaesthetics Inhalational Anaesthetics Volatile Liquids Halothane, Isoflurane, Sevoflurane, Methoxyflurane, Desflurane, Enflurane, Ethyl chloride, Trichloroethylene, Chloroform Gases Nitrous Oxide, Cyclopropane
• 10.
  Intravenous Anaesthetics Ultra ShortActing Barbiturates Thiopentone Sodium Methohexital Phencyclidine Derivatives Ketamine Steroids Althesin Eugenol Derivatives Propanidid Alkyl Phenols Propofol Etomidate Neurolept anaesthesia (used in psychiatry) Droperidol + Fentanyl + Nitrous oxide
• 11.
  Stages ofStages ofGeneral AnesthesiaGeneral Anesthesia GGuedel’s Signs – with Ether (not newer agents) Stage-I Stage Of Analgesia (no pain, drowsy, reflexes intact, no amnesia, HR/BP normal, pupil size normal) Stage-II Stage Of Excitement-most dangerous (excited, delirious, RR inc., jerky movements – injury, rapid eye movements, vagal stimulation -cardiac arrest, catecholamines - arrhythmias) Stage-III Stage Of Surgical Anesthesia – Plane-I : pupils constricted, inc. regular resp., muscles relax, corneal/conjunctival reflexes lost
• 12.
  Stages ofStages ofGeneral AnesthesiaGeneral Anesthesia – Plane-II : pupils dilate, dec. regular resp., eye- balls fixed, dec. muscle tone, abdominothoracic resp., no light reflex – Plane-III : thoracic resp. ceases, pupils dilated, muscles relaxed, laryngeal/pharyngeal reflexes dec. – surgery performed in this plane – Plane-IV : abdominal resp. ceases, all reflexes lost – warning sign Stage-IV Stage Of Medullary Paralysis (CVS & resp. centers suppr – CVS collapse + Resp. failure) Monitoring by anesthetist
• 13.
  Inhalational AnestheticsInhalational Anesthetics Modeof Delivery – Open Drop method - Ether – Anaesthetic machines assisted methods Open System – accurate Closed System – sodalime - Trichloroethylene Semiclosed System
• 14.
  Depth of anesthesiaDepthof anesthesia – PotencyPotency Dose-response characteristicsDose-response characteristics MACMAC – definition– definition - example- example** -- Partial Pressure (PP) in brainPartial Pressure (PP) in brain Inhalational AnestheticsInhalational Anesthetics
• 15.
  Pathway for GeneralAnestheticsPathway for General Anesthetics INDUCTION RECOVERY
• 16.
  PharmacokineticsPharmacokinetics Administration, Uptake, distribution& eliminationAdministration, Uptake, distribution & elimination Induction & RecoveryInduction & Recovery****** – Rate of change of PPRate of change of PP FACTORSFACTORS Related to drugRelated to drug – Concentration in inspired airConcentration in inspired air Fick’s lawFick’s law – SolubilitySolubility In blood – Blood:gas partition coefficientIn blood – Blood:gas partition coefficient**** - Inverse relation with induction- Inverse relation with induction In tissues – Tissue:blood partition coefficientIn tissues – Tissue:blood partition coefficient** - Arteriovenous conc gradient- Arteriovenous conc gradient
• 17.
  Related to bodyRelatedto body – Pulmonary ventilationPulmonary ventilation Rate & depthRate & depth Hyperventilation / Resp depessionHyperventilation / Resp depession – Pulmonary blood flow / perfusionPulmonary blood flow / perfusion ShockShock – Alveolar exchangeAlveolar exchange Pul vent / perfusionPul vent / perfusion Lung diseaseLung disease – Cerebral blood flowCerebral blood flow COCO22
• 18.
  AnaestheticAnaesthetic Blood: GasBlood:Gas PartitionPartition CoefficientCoefficient MinimalMinimal Alveolar ConcAlveolar Conc (MAC) %(MAC) % Metaboli-Metaboli- smsm CommentsComments Nitrous OxideNitrous Oxide 0.470.47 >100>100 NoneNone Incomplete anesthetic rapidIncomplete anesthetic rapid onset & recoveryonset & recovery DesfluraneDesflurane 0.420.42 6-76-7 <0.05%<0.05% Low volatility; poorLow volatility; poor induction agent; rapidinduction agent; rapid recoveryrecovery SevofluraneSevoflurane 0.690.69 2.02.0 2-5%2-5% Rapid onset & recovery;Rapid onset & recovery; unstable in soda-limeunstable in soda-lime IsofluraneIsoflurane 1.1401.140 1.401.40 <2%<2% Medium rate of onset andMedium rate of onset and recoveryrecovery EnfluraneEnflurane 1.801.80 0.750.75 >8%>8% Medium rate of onset &Medium rate of onset & recoveryrecovery HalothaneHalothane 2.302.30 0.750.75 >40%>40% Medium rate of onset andMedium rate of onset and recoveryrecovery MethoxyfluraneMethoxyflurane 1212 0.160.16 >70 %>70 % Slow onset & recoverySlow onset & recovery PROPERTIES OF INHALED ANESTHETICS
• 19.
  AnaestheticAnaesthetic Blood: GasBlood:Gas PartitionPartition CoefficientCoefficient Brain: BloodBrain: Blood PartitionPartition CoefficientCoefficient MetaboMetabo l-isml-ism CommentsComments Nitrous OxideNitrous Oxide 0.470.47 1.11.1 NoneNone Rapid onset & recoveryRapid onset & recovery DesfluraneDesflurane 0.420.42 1.31.3 <0.05%<0.05% Low volatility; poorLow volatility; poor induction agent; rapidinduction agent; rapid recoveryrecovery SevofluraneSevoflurane 0.690.69 1.71.7 2-5%2-5% Rapid onset & recovery;Rapid onset & recovery; unstable in soda-limeunstable in soda-lime IsofluraneIsoflurane 1.1401.140 2.62.6 <2%<2% Medium rate of onset andMedium rate of onset and recoveryrecovery EnfluraneEnflurane 1.801.80 1.41.4 >8%>8% Medium rate of onset &Medium rate of onset & recoveryrecovery HalothaneHalothane 2.302.30 2.92.9 >40%>40% Medium rate of onset andMedium rate of onset and recoveryrecovery MethoxyfluraneMethoxyflurane 1212 2.02.0 >70 %>70 % Slow onset & recoverySlow onset & recovery PROPERTIES OF INHALED ANAESTHETICS
• 20.
  Elimination Recovery Depends on –Routes Lung Hepatic Metabolism** – Concentration in lungs – Variable tissue concentration – Duration of exposure Second gas effect : Nitrous oxideSecond gas effect : Nitrous oxide Diffusion hypoxia : Nitrous oxideDiffusion hypoxia : Nitrous oxide Clearance & Metabolism
• 21.
  Mechanism of Actionof GeneralMechanism of Action of General AnestheticsAnesthetics Old Theories – Unitary Theory – Meyer-Overton Theory – Pauling’s Theory – Ferguson’s Theory – Mullen’s Theory Newer Concepts – Specific Targets – Differential Sensitivity of Neurons- Stages
• 22.
  Newer Mechanisms – MolecularActions Channels & Receptors –Different binding sites –GABAA receptor-chloride channels Inhalational agents, barbiturates, propofol, etomidate –Glycine receptor-chloride channels Inhalational agents, barbiturates, propofol
• 23.
  –Glutamate receptor-NMDA channels Ketamine,nitrous oxide, cyclopropane –K+ channels (TREK) – Hyperpolarization Inhalational agents, nitrous oxide, cyclopropane –Nicotinic receptor-activated cation channels Inhalational agents Neurotransmitters –Acetylcholine –Endorphin
• 24.
  HalothaneHalothane Chemical and PhysicalPropertiesChemical and Physical Properties – 2-bromo-2-chloro-1,1,1-trifluoroethane2-bromo-2-chloro-1,1,1-trifluoroethane – VolatileVolatile // odourlessodourless // colourlesscolourless – Non-irritantNon-irritant // non-explosivenon-explosive // non-inflammablenon-inflammable – Light-sensitiveLight-sensitive // corrosivecorrosive // interaction - rubberinteraction - rubber PharmacokineticsPharmacokinetics – MAC -MAC - 0.750.75 – B:G part. coef. -B:G part. coef. - 2.32.3 – Medium rate of onset & recoveryMedium rate of onset & recovery – Metabolism – trifluoroacetic acidMetabolism – trifluoroacetic acid - trifluoroacetylchloride- trifluoroacetylchloride – Clearance (hepatic)Clearance (hepatic)
• 25.
  Pharmacological EffectsPharmacological Effects –CVSCVS ↓↓BP / HRBP / HR Myocardial sensitization to catecholaminesMyocardial sensitization to catecholamines Atropine / beta-blockersAtropine / beta-blockers Redistribution of blood flowRedistribution of blood flow – Respiratory systemRespiratory system ↑↑ RR, ↓ Tidal vol., dec. ventilatory response to CO2RR, ↓ Tidal vol., dec. ventilatory response to CO2 Inc. PaCOInc. PaCO2,2, raised apneic thresholdraised apneic threshold Bronchodilator – larnygeal/pharyngeal reflexesBronchodilator – larnygeal/pharyngeal reflexes abolishedabolished – CNSCNS inc CBF & dec CMRinc CBF & dec CMR If CBF inc.—ICP inc.If CBF inc.—ICP inc. EEG:initial activation-low dose, slowing-high doseEEG:initial activation-low dose, slowing-high dose
• 26.
  – Kidneys (dec.GFR & RBF), -GITKidneys (dec. GFR & RBF), -GIT – Liver (dec. portal bl. flow, raised LFTs)Liver (dec. portal bl. flow, raised LFTs) – Skeletal muscles (relaxation, inc. curare eff)Skeletal muscles (relaxation, inc. curare eff) – UterusUterus (conc. dependant relaxation)(conc. dependant relaxation) UseUse – Maintenance anesthesia – 0.5-1%Maintenance anesthesia – 0.5-1% – Induction of anesthesia – 2-4%Induction of anesthesia – 2-4% – Used in childrenUsed in children – Low costLow cost Adverse effectsAdverse effects – Halothane shake/shivering during recoveryHalothane shake/shivering during recovery – CVS / Resp. sys depressionCVS / Resp. sys depression – Chronic toxicity - not carcinogenic/mutagenicChronic toxicity - not carcinogenic/mutagenic
• 27.
  – HepatitisHepatitis Pathophysiology: immuneresponsePathophysiology: immune response against triflouroacetylated proteinsagainst triflouroacetylated proteins Predisposing factors: elderly, obese,Predisposing factors: elderly, obese, females, electrolyte imbalance, enzymefemales, electrolyte imbalance, enzyme inducers, halothane exposureinducers, halothane exposure Clinical S/S: nausea, vomiting, lethargy,Clinical S/S: nausea, vomiting, lethargy, fever, rash, gen. weakness (days later)fever, rash, gen. weakness (days later) Biochemical tests: eosinophilia, LFTsBiochemical tests: eosinophilia, LFTs deranged, autoantibodies,deranged, autoantibodies, triflouroacetylated proteinstriflouroacetylated proteins Treatment: liver transplant in severe casesTreatment: liver transplant in severe cases – Malignant HyperthermiaMalignant Hyperthermia (seen with halothane & succinylcholine)(seen with halothane & succinylcholine)
• 28.
  Pathophysiology:Pathophysiology: autosomal dominant geneticdiseaseautosomal dominant genetic disease –Ryanodine Rec (RyR1) gene mutationRyanodine Rec (RyR1) gene mutation –L-type CaL-type Ca+2+2 channels gene mutationchannels gene mutation Clinical S/S: hyperthermia, hypertension,Clinical S/S: hyperthermia, hypertension, hypercapnia, hyperkalemia, inc. HR,hypercapnia, hyperkalemia, inc. HR, metabolic acidosis, muscle rigiditymetabolic acidosis, muscle rigidity Biochemical tests: acidosis, hyperkalemia,Biochemical tests: acidosis, hyperkalemia, deranged electrolytes, inc. free cytosolicderanged electrolytes, inc. free cytosolic Ca conc. in skeletal muscle cells (in vitroCa conc. in skeletal muscle cells (in vitro caffeine - halothane contracture test)caffeine - halothane contracture test) Treatment :Treatment : Dantrolene (reduces Ca release from SR)Dantrolene (reduces Ca release from SR) Symptomatic Rx for feverSymptomatic Rx for fever Restoration of electrolyte & acid-Restoration of electrolyte & acid-
• 29.
  HALOTHANE ADVANTAGESADVANTAGES DISADVANTAGESDISADVANTAGES POTENT NOTAN ANALGESIC LESS IRRITANT VARIABLE MUSCLE RELAXATION INDUCTION SMOOTH AND RAPID SENSITIZES HEART TO CATECHOLAMINES QUICK RECOVERY HYPOTENSION NON – INFLAMMABLE BRADYCARDIA COMPATIBLE WITH SODA LIME HEPATITIS BRONCHODILATOR RESPIRATORY DEPRESSION UTERINE RELAXANT SHIVERING DURING RECOVERY
• 30.
  ADVANTAGESADVANTAGES DISADVANTAGESDISADVANTAGES LESS INCIDENCEOF POST- OPERATIVE NAUSEA/VOMITING MALIGNANT HYPERPYREXIA DOES NOT CAUSE LARYNGOSPASM ENZYME INDUCER EASIER ENDOTRACHEAL INTUBATION DUE TO RELAXATION OF MASSETER MUSCLES CORRODES METALS COST-EFFECTIVE REACTS WITH RUBBER EQUIPMENTS
• 31.
  ENFLURANE Chemically it ishalogenated ether Non inflammable Non irritant Clear, colorless liquid with sweet odor Blood : Gas coefficient 1.80 MAC : 0.75 Metabolism 8% Stable with soda lime Medium rate of onset & recovery
• 32.
  ENFLURANE Pharmacological actions: CVS Resp System CNS RenalSystem Better Muscle Relaxant Produces convulsions and involuntary movements during induction or recovery Liver damage is rare Not recommended in children & epileptics USE:
• 33.
  ISOFLURANE Volatile liquid Non inflammable B:Gpartition coefficient; 1.4 MAC : 1.4 Metabolism: 2% Costly Medium rate of onset & recovery Pharmacological Actions
• 34.
  ISOFLURANE Most widely usedvolatile anesthetic. Resemble Halothane Except: Less incidence of hypotension Less sensitization of heart to Catecholamines Less toxic Powerful Coronary vasodilator, may cause coronary steal phenomenon No pro-convulsive properties Not cost effective Irritant, resp depression USE: Maintenance of anesthesia
• 35.
  DESFLURANE Volatile halogenated compound TEC6, an apparatus required for vapourization Non inflammable, Non explosive Pungent smell (not for induction, but maintenance) B:G partition coefficient: 0.42 MAC: 6-7 Metabolism: 0.05% Rapid induction & rapid recovery (low B:G coeff) Pharmacological actions
• 36.
  DESFLURANE Newer drug Chemically similarto Isoflurane Faster induction and recovery due to lower solubility in blood ,so preferred for use in day case surgery No significant metabolism Less potent due to high MAC about 6 % Concentration used for induction is 10 %.It can cause respiratory irritation leading to coughing, salivation and bronchospasm USE: Maintenance and ideal for outdoor procedures
• 37.
  SEVOFLURANE Clear, colourless, volatileliquid Non inflammable, non irritant, pleasant smell B:G 0.69 MAC: 2 Metabolism: 2-5% ( Nephrotoxic) Rapid induction & recovery (low B:G coeff)
• 38.
  SEVOFLURANE CVS Resp System CNS Renal System Lesstoxic Can cause malignant hyperthermia USE: Outpatient anesthesia & induction
• 39.
  METHOXYFLURANE Properties Same asHalothane Except: Good muscle relaxation Good analgesic effect Slow induction & recovery Cause severe renal damage Not used any more
• 40.
  DesfluraneDesflurane – Rapid onset& recoveryRapid onset & recovery – Pungent / irritantPungent / irritant – Low volatilityLow volatility SevofluraneSevoflurane – Rapid onset & recoveryRapid onset & recovery – NephrotoxicNephrotoxic Compound A - COCompound A - CO22 absorbent (soda lime)absorbent (soda lime) - met. by beta-lyase (renal)- met. by beta-lyase (renal) Hepatic – free inorganic FlHepatic – free inorganic Fl-- producedproduced
• 41.
  EnfluraneEnflurane – Slow induction& recoverySlow induction & recovery – Potential nephrotoxic – beta-lyasePotential nephrotoxic – beta-lyase – Seizure-like activity (self limited)Seizure-like activity (self limited) IsofluraneIsoflurane – Rapid onset & recoveryRapid onset & recovery – Coronary circulation (vasodilation)Coronary circulation (vasodilation) – Pungent (not used for induction, butPungent (not used for induction, but maintenance)maintenance) MethoxyfluraneMethoxyflurane – Nephrotoxic – met. by beta-lyaseNephrotoxic – met. by beta-lyase - >30% hepatic met. - Fl- >30% hepatic met. - Fl-- – No longer usedNo longer used
• 42.
  Ethyl chloride – Explosive,kept under pressure (low boiling point) – Use – local anesthetic – cooling effect - cryosurgery Trichloroethylene – Analgesia > Anesthesia – Interacts with Soda lime – toxic metabolite Chloroform (animal studies) – Causes breath holding – Hepatotoxic – CVS depressant
• 43.
  CyclopropaneCyclopropane Potent GA Non-irritant /explosive / flammable (cautery couldn’t be used) Severe CV collapse - Cyclopropane shock Rx : small amount of CO2 administered
• 44.
  Nitrous OxideNitrous Oxide Chemicaland Physical PropertiesChemical and Physical Properties – Inorganic gas (N2O) – Odourless / colourless / heavier than air – Non-explosive / non-inflammable / supports combustion – Laughing gas: euphoria-small amounts, abused in past PharmacokineticsPharmacokinetics – MAC - 105 – B:G part. coef. – 0.47 at 37 C – Rapid induction & recovery – Not metabolized (99.9% exhaled unchanged)
• 45.
  Pharmacological Effects – CVS/ Respiratory system (depends on other agents) – CNS (inc. CBF – inc. ICP) – GIT / Muscles Uses – Analgesia (40%) – Sedation (30-80%) – Anesthesia – less potency - adjuvant - second gas effect - short surgical procedures (dental extraction, postoperative pain, painful dressings, fracture manipulation, child birth)
• 46.
  Adverse effectsAdverse effects –Diffusional hypoxia / anoxia – Vitamin B12 deficiency (inhibits methionine synthetase, req. for vitamin B12 synthesis) Megaloblastic anemia Peripheral neuropathy – Replaces N2 in air-containing cavities (obstructed middle ear, air embolus, pneumothorax) enlarges it – Effect of NO2 & O2 in same cylinder (1st insufficient anesthesia – later-on hypoxia)
• 47.
  ADVANTAGES Non-inflammable Non-irritating Very PotentAnalgesic: 30 – 40 % Analgesia 65 – 70 % Loss of consciousness 80 % plane one of Surgical Anesthesia Non-explosive, however supports combustion. Rapid induction and recovery. Use in procedures of short durations (tooth extraction, obstetrical analgesia, cleaning and debridement of wounds).
• 48.
  Induction and maintenanceof anesthesia I/V Thiopentone-Gas-Oxygen-Halothane technique Safe, no organ toxicity (Resp, CVS, Renal or Hepatic)  the dose of GA when combined   adverse effects,  complications  recovery period from anaesthesia
• 49.
  DISADVANTAGES Not a potentanesthetic & muscle relaxant Violent excitement Carbon dioxide accumulation and hypoxia  cardiac irregularities during anesthesia
• 50.
  DISADVANTAGES Specialized apparatus tocontrol its administration Adm for more than 7hrs  Bone marrow depression ( leucopenia, anemia) Prolonged adm  Peripheral neuropathy & Megaloblastic anemia due to interference with B12metabolism, Abortion, peripheral Neuropathy Second gas effect leading to transient hypoxia Diffusion hypoxia
• 51.
  NITROUS OXIDE ADVANTAGESADVANTAGES DISADVANTAGESDISADVANTAGES STRONGANALGESICSTRONG ANALGESIC LESS POTENTLESS POTENT RAPID INDUCTIONRAPID INDUCTION TRANSPORTATION DIFFICULTTRANSPORTATION DIFFICULT RECOVERY RARELYRECOVERY RARELY EXCEEDS 1-4 MINEXCEEDS 1-4 MIN SPECIAL EQUIPMENT FORSPECIAL EQUIPMENT FOR ADMINISTRATIONADMINISTRATION NON IRRITANTNON IRRITANT PENETERATES INTO CAVITIESPENETERATES INTO CAVITIES NAUSSEA / VOMITINGNAUSSEA / VOMITING UNCOMMONUNCOMMON COCO22 ACCUMULATION ANDACCUMULATION AND HYPOXIA ON PROLONGEDHYPOXIA ON PROLONGED ADMINISTRATIONADMINISTRATION LITTLE EFFECTS ONLITTLE EFFECTS ON CIRCULATION,CIRCULATION, RESPIRATION, LIVER,RESPIRATION, LIVER, KIDNEYKIDNEY MEGALOBLASTIC ANEMIA ONMEGALOBLASTIC ANEMIA ON PROLONGED ADMINISTRATIONPROLONGED ADMINISTRATION POOR MUSCLE RELAXANTPOOR MUSCLE RELAXANT COST EFFECTIVECOST EFFECTIVE DIFFUSIONAL ANOXIADIFFUSIONAL ANOXIA
• 52.
  Intravenous AnestheticsIntravenous Anesthetics BarbituratesBarbiturates –Thiopental / Thiopentone Sodium Induction / Onset Narrow therapeutic index. Ph is 7-10 Administered rapidly by I/V line Onset of action 60sec DOA 5-10min α t1/2 3min (distr. t ½, resp. for DOA) β t1/2 12hrs (elimination t ½, drowsiness) PPB 85%
• 53.
  Pharmacological Effects –CNS (dec.CMRO2 & CBF) – CVS depressant (dec. CO & BP) – Resp. sys depressant –GIT –Poor analgesia / muscle relaxation –Renal system
• 54.
  UsesUses –Induction –Dental procedures –Endoscopy –Circumcision –Orthopedic procedures –Changingpainful dressings – Head injuries –Psychoanalysis (truth drug) Adverse effects – laryngospasm, shivering & restlessness (recovery) injection site pain, Inadvertent injection – Acute porphyria, hypotension, apnea, resp depression, hyperalgesia, local necrosis, thrombophlebitis, gangrene
• 55.
  ADVANTAGES DISADVANTAGES RAPID ANDPLEASANT INDUCTION INSIGNIFICANT ANALGESIC ACTION EASY ADMINISTRATION VERY SHORT DURATION OF ACTION NON EXPLOSIVE REPEATED DOSES ACCUMULATE LESS INCIDENCE OF NAUSEA / VOMITING CAN NOT BE USED ALONE AS AN ANESTHETIC NON IRRITANT COUGHING, HICUP, LARYNGOSPASM, BRONCHOSPASM MAY DEVELOP DURING INDUCTION QUIET RESPIRATION MUSCLE RELAXATION IS NOT ADEQUATE THIOPENTONE (CONTD)
• 56.
  ADVANTAGES DISADVANTAGES NO SENSITIZATIONOF HEART TO CATECHOLAMINES PHARYNGEAL/ LARYNGEAL REFLEXES ARE NOT ABLOLISHED RAPID RECOVERY IN OVER DOSAGE DEPRESSION OF VMC, MYOCARDIUM AND RESPIRATION NO EXCITEMENT DURING INDUCTION REGURGITATION DUE TO RELAXATION OF GASTROESOPHAGEAL SPHINCTER INJECTION MAY CAUSE NECROSIS, THROMBOPHLEBITIS, NERVE DAMAGE, VASOSPASM ON INTRA – ARTERIAL INJECTION
• 57.
  EtomidateEtomidate Carboxylated imidazole Pharmacokinetics – Rapidonset / recovery – T1/2: distributive : 2-4 min eliminative : 2.9-5.3 h – Metabolism (Liver) – Excretion (78% renal, 22% biliary) Pharmacological Effects -- little or no effects on CVS / Resp. sys -- CNS (dec. CMRO2 & CBF) -- no analgesia
• 58.
  EtomidateEtomidate Use – Poor cardiovascularreserve (old pts, IHD, cardiomyopathy) Adverse effects – Injection site pain (Rx : lignocaine) – Nausea, vomiting, restlessness, tremors – Steroidogenesis inhibition esp. cortisol,by inhibiting 11B hydroxylation. This effect is transient if given for short period but hypotension, electrolyte imbalance & oliguria can occur on long use
• 59.
  Advantages Minimum CVS Depression MinimumRespiratory Depression Larger margin of safety Very rapid induction within seconds Rapid recovery within 3-5 minutes
• 60.
  Disadvantages No analgesic effect Postoperative Nausea & vomiting Pain during injection Myoclonus / involuntary movements during induction Adrenocortical Suppression (with prolonged use)
• 61.
  PropofolPropofol Chemistry: 2,6 Diisopropylphenol Formulations –Conventional (oily)/ Ampofol / Fospropofol (water-soluble prodrug) Pharmacokinetics – Onset (10-15 s) / recovery /Dose 1.5 -2.5 mg/kg – T ½ : distributive : 2-4 min eliminative : 4-23 hrs – Metabolism / Excretion (Liver)
• 62.
  PropofolPropofol Pharmacological Effects – CVS& Resp. sys depression – CNS (dec. CMRO2 & CBF) – Poor analgesia / muscle relaxation
• 63.
  UsesUses – Induction &maintenance – Ambulatory surgery (outpatient surgery) – Sedation (less dose, endoscopy, ventilator pts) – Dexmedetomidine * Adverse effectsAdverse effects – CVS / resp. sys depression – Injection site pain (propofol + lignocaine) – Apnea, laryngospasm, myoclonus, tremors Children with resp. inf.– acidosis (long use) - neurological effects on withdrawal
• 64.
  Advantages Rapid Induction Very rapidrecovery as Compared to Thiopental, without any significant hangover effect Post operative nausea and vomiting is uncommon as has antiemetic actions. No cumulative effect.
• 65.
  Disadvantages Very expensive Apnoea canoccur CVS depression Pain at site of injection Clinical infections
• 66.
  KetamineKetamine Phencyclidine congener (racemicmixture of S & R) Pharmacological Effects – CNS Blocks NMDA receptors (prevents glutamate binding) Psychoactive drug—abused as hallucinogenic Inc.CBF, CMRO2 & ICP (avoid in head injury) – Stimulates CVS – sympathetic stimulation + NE reuptake block (peak: 2-4 min, normal: 10-20 min) – Respiratory – doesn’t abolish reflexes, bronchodilation– sympathetic stimulation + direct eff.
• 67.
  Pharmacokinetics Highly lipophilic ,rapidly distributed in highly vascular organs, potent, crosses BBB rapidly Route I/V, I/M, Oral, Rectal αt1/2 15 min βt1/2 3 hrs Onset of effect 2 – 5 min DOA 5-10min Metabolism
• 68.
  Uses Induction smooth butrecovery unpleasant – Dissociative anesthesia: analgesia, catatonia, amnesia, hypnosis, unresponsive to painful stimuli, sometimes involuntary limb movements – Analgesia: short procedures – Old age (poor CV reserves) / children – Topical use (arthritic pains) – Hemodynamic stability (cardiogenic/septic shock) – Asthma / COPD (bronchdilation) Adverse effects – CVS: cardiostimulatory—avoid in IHD – Emergence delirium: hallucinations (Rx: BZs)
• 69.
  KETAMINE Advantages Disadvantages Effective byboth I/V & I/M INJ No Muscle Relaxation Anesthesia is accompanied by profound analgesia Tends to raise intraocular, Intracranial BP and heart rate Does not produce Vomiting Hypotension, Bronchospasm Cannot be used for surgery on Larynx, Pharynx & Bronchi Less respiratory complications due to less impairment of Pharyngeal/ Laryngeal reflexes Poor in relieving visceral pain Useful for poor risk geriatric pts and in unstable pts Emergence phenomena Used in low doses as outpatient anesthesia
• 70.
  NEUROLEPT ANESTHESIA  Itis a method of IV anesthesia which combines the use of a neuroleptic drug with a narcotic analgesic drug.  Administration of such a combination produces a state which differs from the classical general anesthesia in that the subject is conscious and is able to cooperate during the operative procedure.
• 71.
  The most commoncombination is that of Droperidol (neuroleptic) and Fentanyl (opioid analgesic) Fentanyl - 0.5-1 mg & Droperidol 2.5 -5mg/ml Prep: INNOVAR Injection NEUROLEPT ANALGESIA