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INTRVENOUS INDUCTION AGENTS

DR.KEERTHI REKHA DEPT. OF ANAESTHESIOLOGY

Overview
• • • • • • • Classification Mechanisms of action Pharmacological principles Individual agent overviews Pharmacokinetics Induction characteristics Organ effects

CLASSIFICATION OF IV INDUCTION AGENTS RAPID ACTINGBarbiturates- thiopental, methohexitone  Propofol  Etomidate SLOW ACTING Ketamine- Dissociative anaesthesia  Benzodiazapines

NMDA receptor antagonism.influx => hyperpolarisation Propofol & Barbiturates – acts on GABAA receptor Barbiturates-GABA mimetic Benzodiazepines -GABA facilitator Etomidate.How do they work? • • • • • • • Major inhibitory neuro-transmitter in the CNS = GABA Active GABA receptor => Cl. • These lead to sedative & hypnotic effects .GABA facilitator Ketamine .

Distribution & Elimination .

Single-injection Kinetics .

SINGLE INJECTION ELIMINATION KINETICS • ELIMINATION HALF TIME • ELIMINATION HALF LIFE .

Context-sensitive Half-Time • Time necessary for plasma drug concentration to decrease by 50% after discontinuing a continous infusion of a specific duration. .

Pharmacodynamics • Increasing dose => sedation => hypnosis • All iv anaesthetics affect other organ systems – Potential for respiratory depression – Potential for CVS depression – Potential for altered CBF/ICP • Hypovolaemia => severe haemodynamic effects seen due to decreased blood pool .

5[methyl.butyl]2 thiobarbiturate.introduced by lundy & waters in 1935 • Derived from Barbituric acid-cyclic compound obtained by combinatin of urea& malonic acid • Precipitates with acidic drugs e.Thiopental Thiobarbiturate.5 ethyl.g. NMBs • Extravascular injection => pain + tissue injury • Intra-arterial injection => crystals + ischaemia • Chemical structure. .

pentobarbitone -80% excreted through kidney .desulphuration -ring cleveage to form urea -products are thiobarbituricacid.• Metabolism.in liver -side chain oxidation -hydroxylation.

• USESInduction and maintainance. .Bronchial asthma Myxoedema pts Hepatic or Renal diseases. Cerebral protection in trauma pts. Anticonvulsant. • CONTRAINDICATIONS• ABSOLUTE.Porphyria. • RELATIVE.

Bronchospasm .COMPLICATIONS• LOCAL -Thrombophlebitis.Laryngeal spasm . • GENERAL . -Arterial spasm.

Management of intra-arterial injection of Thiopental Stop injection but leave needle or cannula in place Dilute with immediate injection of saline Give intra-arterial LA + vasodilator Lidocaine 50mg (5 ml of 1% solution) Phenoxybenzamine (a blocker) 0.5 mg bolus or 50-200 mg/minute infusion Consider systemic papaverine 40-80 mg Consider sympathetic blockade (stellate ganglion or brachial plexus block) Start iv heparin infusion Consider intra-arterial hydrocortisone Postpone non-urgent surgery Liaise with vascular surgeon .

lower in elderly Wake-up due to redistribution.2% lecithin (egg yolk phosphatide .In liver –conjugation to sulphate& glucuronide • Also ring hydroxylation. 2.Propofol • CHEMICAL STRUCTURE -2.? allergen) • METABOLISM. not metabolism .6-diisopropylphenol Emulsion with 10% soybean oil.4-hydroxy propofol • .25% glycerol and 1. Induction dose higher in childrn.

-Antiemetic[10-15 mg i.USES -Day care surgeries -Significant vasodilatation -Pressor response is less than thiopentone. .v] -Suppresses laryngeal reflexes -sedation in icu -Antipruritic effects[10mg iv] .

-Pain on injection -Hypotensive episodes -Tendency for apnoea -Propofol infusion syndrome .COMPLICATIONS- -allergic respose-to emulsifying agent.

C chain • FEATURESMetabolic acidosis Multiple organ failure Hepato megaly Rhabdomyolysis Hyperkalemia. impaired E. PROPOFOL INFUSION SYNDROME .• Caused by propofol in critically ill pediatric pts or on long term infusion [>48 hrs] or at high doses[>5mg/kg/hr] MECHANISM. triglycerides.Inc.

Etomidate • CHEMICAL STRUCTURE-Imidazole derivative. short half-life . D(+) isomer • Poorly soluble in H2O => 35%propylene glycol used • METABOLISM • Metabolised by ester hydrolysis • Wake-up due to redistribution Minimal haemodynamic effects.

• High incidence of PONV (35-40%) • May activate seizure foci. myoclonus in 50% • Adrenocortical suppression • Dose-dependent 11 b-hydroxylase inhibition • Lasts 4-12 hrs after single dose (much longer in critically ill) .

Ketamine • CHEMICAL STRUCTURE-Phencyclidine derivative • Racemic mixture: S-isomer fewer adverse effects • METABOLISM.high hepatic clearence n-demethylation.hydroxylation .

-IV ketamine for labour analgesia.USES.10mg bolus and then 0. .Significant analgesia at sub-anaesthetic doses -Bronchodilatation -Preserves larengeal & pharyngeal reflexes -Choice in shock.5mg/min.

• SIDE EFFECTS-Secretions -Vomiting -Epileptogenic -Hypertension and tachycardia -Vivid dreams -Hallucinations .

lorazepam • Midazolam has imidazole ring • Ring protonated => water soluble at acid Ph • In body.Benzodiazepines • IV prep: midazolam. diazepam. ring unprotonated => lipid soluble • At pH 4 only 9% of MDZ rings are open (75% at pH 2) .

• Bind specific site between a + g subunits of GABAA receptor METABOLISM-IN LIVER -hydroxylation -conjugation with glucuronic acid • USES – induction and sedative agent -sedative supplement in regional blocks -sedative in icu pts -Anticonvulsant -Total intravenous anaesthesia [midazolam+propofol+fentanyl] .

• Avoided in pregnancy • Avoided in acute narrow angle glaucoma • Avoided with cemitidine and ranitidine • Overdose is treated with FLUMAZENIL .• SIDE EFFECTS.may cause respiratory depression.

7-2.7-1.8-1.5-3.9-5.3 2.2 2-10 3.8-1.5 2.7 0.5 0.5 6.5-4.2-0.Single dose pharmacokinetics Drug Redistribution T1/2 (min) Protein binding % VdSS l/kg Clearance ml/kg/min Elimination T1/2 (hrs) Thiopental Methohexital Propofol 2-4 5-6 2-4 85 85 98 2.7 0.8 18-25 12-17 1.5 2.6 20-50 11-22 2.1-1.3 11 20-30 11 4 4-23 Midazolam Diazepam Lorazepam Etomidate Ketamine 7-15 10-15 3-10 2-4 11-16 94 98 98 75 12 1.3 2-4 .4-11 0.

3-0.5 <30 <30 15-45 5-10 5-10 5-10 + ++ + 0/+ + ++ + ++ 0/- -- Midazolam Diazepam Lorazepam Etomidate Ketamine 0.6 0.03-0.Induction Characteristics Drug Induction dose (mg/kg) Onset (secs) Duration (mins) Excitation Injection pain Heart rate BP Thiopental Methohexital Propofol 3-6 1-3 1.2-0.2-0.4 0.06 0.3 1-2 30-90 45-90 60-120 15-45 45-60 10-30 15-30 60-120 3-12 10-20 0 0 0 +++ + 0 +/+++ ++ +++ 0 0 0 0 0 ++ 0/0/0/0 ++ .5-2.

CNS effects of IV anaesthetics Drug CMRO2 CBF CPP ICP Anticonvulsant Thiopental Methohexital Propofol Etomidate Benzodiazepines Ketamine ----+ ----+ ++ + + + 0 + ---+ Yes No Yes No Yes No CMRO2 = cerebral metabolic rate for oxygen CBF = cerebral blood flow CPP = cerebral perfusion pressure ICP = intracranial pressure .

CVS Effects of IV Anaesthetics Drug MAP HR CO Contractility SVR Venous dilatation Thiopental Methohexital Propofol Etomidate Diazepam Midazolam Ketamine -0 0/0/++ + ++ 0 + + ++ 0 0 0/+ 0 0 0 + + + -0 -/0 -/0 + ++ + ++ 0 + + 0 .

RS Effects of IV Anaesthetics Drug Ventilation Respiratory rate CO2 response Hypoxia response Propofol -----/--- Thiopental -- - -- Ketamine Unchanged Unchanged Unchanged ? Midazolam Unchanged Unchanged - - Etomidate - - - .

Propofol SBP Decrease 0/Decrease Decrease Decrease Thiopental Decrease Increase Decrease Decrease Ketamine Increase Increase Increase Unchanged Etomidate Decrease Decrease Decrease Unchanged CVS Heart rate SVR Ventilation RESP Resp rate CO2 response CBF CMRO2 Decrease Decrease Decrease Decrease Decrease Yes? No No Decrease Decrease Decrease Decrease Decrease Yes No No Unchanged Unchanged Unchanged/Increa se Unchanged/increa se Unchanged/Increa se Unclear No Yes Unchanged Unchanged Unchanged Unchanged/Decre ase Unchanged CNS ICP Anticonvulsant Anxiolysis Analgesia Yes? No? .

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