Ketamine poonam

For Internal use onlyFor Internal use only 11

KETAMINEPresented by :

Dr. Poonam Mude

Guide:

Dr. Abhay Bodhey

Govt. Medical College

Department of Anesthesiology

http://en.wikipedia.org/wiki/Image:Ketamine-2D-skeletal.png

For Internal use only 2

Anesthetic agents


Anesthetic agents

Local anesthetics

Current inhaled general anesthetic agents

Current intravenous anesthetic agents (non-opioid)

Current intravenous opioid analgesic agents

Current muscle relaxants

Current intravenous reversal agents


Current Intravenous Anesthetic agents (non-opioid)

Barbiturates Thiopental Methohexital

Benzodiazepines Midazolam Lorazepam Diazepam

Propofol Etomidate Ketamine


Ketamine - Identification Data

IdentifiersCAS number: 6740-88-1 ATC code: N01AX03 N01AX14 PubChem: 3821 DrugBank: APRD00493

Chemical data Formula: C13H16ClNO Mol. Mass: 237.725 g/mol

Pharmacokinetic data Half life: 2.5-3 hours. Excretion: renal (>90%)

Arylcyclohexylamine

http://en.wikipedia.org/wiki/Image:Ketamine-2D-skeletal.png


Ketamine – Common Names

K

Ketanest

Ketaset

Ketalar

Special K

Vitamin K


Ketamine – Introduction

Phencyclidine derivative

Synthesized by Stevens in 1962

First used in humans by Domino and Corsen in 1965

2 Stereoisomers:S-(+) and R-(-)

S-(+)-isomer more potent with fewer side effects as it is preservative free

A drug with abuse potential so cautiously used


Physical And Chemical PropertiesPhysical And Chemical Properties Preservative- Benzethonium chloridePreservative- Benzethonium chloride

pH acidic (3.5-5.5)pH acidic (3.5-5.5)

Highly lipid soluble than thiopentone and is also Highly lipid soluble than thiopentone and is also water solublewater soluble

Stored at room temp.(15 to 30 degree C) Stored at room temp.(15 to 30 degree C)

Protected from light and heatProtected from light and heat

Not to be mixed with barbiturate in same Not to be mixed with barbiturate in same syringe as precipitate may formsyringe as precipitate may form


PharmacokineticsPharmacokinetics

Rapid onset of action within 30 to 60 sec.Rapid onset of action within 30 to 60 sec.

Relatively short duration of action; early Relatively short duration of action; early regain of consciousness after 15 to 20 regain of consciousness after 15 to 20 min.is because of redistributionmin.is because of redistribution

Elimination half time-2-3 hrElimination half time-2-3 hr

Volume of distribution 2.5-3.5 lit/kgVolume of distribution 2.5-3.5 lit/kg

Clearance is 16-18ml/kg/minClearance is 16-18ml/kg/min


PharmacokineticsPharmacokinetics

Not significantly bound to plasma proteins.Not significantly bound to plasma proteins.

Due to extreme lipid solubility initially Due to extreme lipid solubility initially distributed to brain.distributed to brain.

Total body clearance is approximately Total body clearance is approximately equal to liver blood flow,thus halothane equal to liver blood flow,thus halothane which decreases hepatic blood flow which decreases hepatic blood flow decreases clearance.decreases clearance.


MetabolismMetabolism Hepatic microsomal Hepatic microsomal

enzymes cytochrome P450 enzymes cytochrome P450 by N-demethylation to by N-demethylation to form norketamine which is form norketamine which is hydroxylated and hydroxylated and conjugated to water conjugated to water soluble glucuronide soluble glucuronide derivatives and excreted in derivatives and excreted in urine.urine.

Norketamine is active Norketamine is active metabolite, contributes to metabolite, contributes to prolonged effects prolonged effects (analgesia) with repeated (analgesia) with repeated doses or a continuous i.v. doses or a continuous i.v. infusion, may be a cause infusion, may be a cause of tolerance.of tolerance.


SiteSite and Mechanism of action and Mechanism of action Acts at thalamoneocortical projectionActs at thalamoneocortical projection

Inhibits cortex(unconsciousness) and thalamus Inhibits cortex(unconsciousness) and thalamus (analgesia) and stimulates limbic system (analgesia) and stimulates limbic system (emergence reaction and hallucinations)(emergence reaction and hallucinations)

Blocks polysynaptic reflexes in spinal cord and Blocks polysynaptic reflexes in spinal cord and inhibiting excitatory neurotransmitter effects in inhibiting excitatory neurotransmitter effects in selected areas of brainselected areas of brain

NMDA receptor (n-methyl-d-aspartate, a subtype NMDA receptor (n-methyl-d-aspartate, a subtype of glutamate receptor which is excitatory of glutamate receptor which is excitatory neurotransmitter) antagonist ,decreases neurotransmitter) antagonist ,decreases presynaptic release of glutamate and potentiates presynaptic release of glutamate and potentiates effects of inhibitory neurotransmitter gamma-effects of inhibitory neurotransmitter gamma-amino-butyric acidamino-butyric acid


Site and Mechanism of actionSite and Mechanism of action

Analgesic effect is due to descending inhibitory Analgesic effect is due to descending inhibitory monoaminergic pain pathways and direct monoaminergic pain pathways and direct inhibition of cytokines in blood, also ketamine inhibition of cytokines in blood, also ketamine suppresses neutrophil production of inflammatory suppresses neutrophil production of inflammatory mediators and improves blood flowmediators and improves blood flow

Antagonist effect at muscarinic receptorsAntagonist effect at muscarinic receptors

Interacts with voltage gated sodium channels, Interacts with voltage gated sodium channels, sharing a binding site with local anaesthetics.sharing a binding site with local anaesthetics.


Systemic effectsSystemic effects

CNSCNS ‘‘’’Dissociative anaesthesiaDissociative anaesthesia’’-’’- A state which dissociates individual from A state which dissociates individual from

himself and surroundings-i.e.cataleptic state-himself and surroundings-i.e.cataleptic state-eyes open with slow nystagmic gaze, non eyes open with slow nystagmic gaze, non communicative although awake, hypertonic and communicative although awake, hypertonic and purposeful skeletal muscle movements in purposeful skeletal muscle movements in absence of surgical stimuli. pt.is amnesic and absence of surgical stimuli. pt.is amnesic and analgesia is intense.evidence on EEG of analgesia is intense.evidence on EEG of dissociation between thalamocortical and limbic dissociation between thalamocortical and limbic systems.systems.


Systemic effectsSystemic effectsCNSCNS

Profound analgesia-somatic more than visceral-Profound analgesia-somatic more than visceral-due to activity in thalamic and limbic system due to activity in thalamic and limbic system which are responsible for interpretation of which are responsible for interpretation of painful signals, potent cerebral vasodilator, painful signals, potent cerebral vasodilator, causes postoperative analgesia so reduces causes postoperative analgesia so reduces opiate requirement.opiate requirement.

Corneal, cough, swallow reflexes may be Corneal, cough, swallow reflexes may be present but should not be assumed to be present but should not be assumed to be protectiveprotective


Systemic effectsSystemic effectsCNS-CNS- Increases brain OIncreases brain O22 consumption and metabolic consumption and metabolic

rate, ICT is highly raisedrate, ICT is highly raised Psychedelic effects during awakening from Psychedelic effects during awakening from

anaesthesia called emergence reactions due to anaesthesia called emergence reactions due to depression of inferior colliculus and medial depression of inferior colliculus and medial geniculate nucleus. geniculate nucleus.

Incidence-10-30%Incidence-10-30% Hallucinations-mainly auditory.30-40%Hallucinations-mainly auditory.30-40% Benzodiazepines, opioids, barbiturates given with Benzodiazepines, opioids, barbiturates given with

ketamine decreases hallucinations and ketamine decreases hallucinations and emergence reactionsemergence reactions


Systemic effectsSystemic effectsCVSCVS Stimulates central sympathetic system-Stimulates central sympathetic system-

tachycardia, hypertension, increase C.O.tachycardia, hypertension, increase C.O.

In debilitated patients catecholamines In debilitated patients catecholamines depleted so direct myocardial depressant depleted so direct myocardial depressant effect.effect.

Benzodiazepines and NBenzodiazepines and N22O attenuate O attenuate responseresponse


Respiratory SystemRespiratory System

Potent bronchodilatorPotent bronchodilator Respiratory depression in child if Respiratory depression in child if

given in bolus dosesgiven in bolus doses Increases salivary and Increases salivary and

tracheobronchial secretions, so tracheobronchial secretions, so use of atropine or glycopyrollate use of atropine or glycopyrollate is necessary is necessary


EYEEYEIncreases intraocular tension, dilates pupil, nystagmusIncreases intraocular tension, dilates pupil, nystagmus

GITGITIncreases intragastric pressureIncreases intragastric pressure

MUSCULAR SYSTEMMUSCULAR SYSTEMIncreases muscle toneIncreases muscle tone

HEPATIC AND RENAL SYSTEMHEPATIC AND RENAL SYSTEMNo significant effectNo significant effect

PLATELETSPLATELETSInhibits platelet aggregationInhibits platelet aggregation

Systemic EffectsSystemic Effects


DRUG INTERACTIONSDRUG INTERACTIONS

Theophylline & Ketamine predisposes to seizures Theophylline & Ketamine predisposes to seizures

Non-depolarising neuromuscular blocking agents Non-depolarising neuromuscular blocking agents are potentiatedare potentiated

Propranolol unmask direct myocardial depressant Propranolol unmask direct myocardial depressant effect of Ketamineeffect of Ketamine

It produces myocardial depression with volatile It produces myocardial depression with volatile anesthetics[VA] like halothane as VA depresses anesthetics[VA] like halothane as VA depresses sympathetic outflow from CNSsympathetic outflow from CNS

Lithium prolongs the duration of action of Ketamine Lithium prolongs the duration of action of Ketamine


DOSESDOSES

INTRAVENOUSINTRAVENOUSINTRAMUSCULARINTRAMUSCULAR ORAL ORAL NASALNASALRECTALRECTAL EPIDURAL- Preservative – free solutionEPIDURAL- Preservative – free solution

Sedation and analgesiaSedation and analgesia -0.2-0.8 mg/kg i.v over 2-3 min-0.2-0.8 mg/kg i.v over 2-3 min 2-4 mg/kg i.m.2-4 mg/kg i.m.

Preemptive/Preventive analgesiaPreemptive/Preventive analgesia 0.15-0.25 mg/kg i.v.0.15-0.25 mg/kg i.v. Oral-3 to 10 mg/kgOral-3 to 10 mg/kg Interaction with propofol is additive, dose of each is reduced to Interaction with propofol is additive, dose of each is reduced to

halfhalf


DOSESDOSES

Maintenance of GAMaintenance of GA 0.5-1 mg/kg i.v.prn with 50% N0.5-1 mg/kg i.v.prn with 50% N22O in OO in O22

15-45 microgm/kg /min i.v. with 50 to 70% N15-45 microgm/kg /min i.v. with 50 to 70% N22O O in O2in O2

30-90 microgm/kg/min i.v without N30-90 microgm/kg/min i.v without N2200

Induction of GAInduction of GA 0.5 to 2 mg/kg i.v.0.5 to 2 mg/kg i.v. 4 to 6mg/kg i.m.4 to 6mg/kg i.m.


USESUSES

Induction and maintenance of AnaesthesiaInduction and maintenance of Anaesthesia Poor risk patients [ASA Class IV] with RS Poor risk patients [ASA Class IV] with RS

& CVS system disorders (excluding IHD & & CVS system disorders (excluding IHD & CAD) CAD)

Inducing agent of choice in shock Inducing agent of choice in shock Inducing agent of choice in AsthmaInducing agent of choice in Asthma Cardiac tamponade, restrictive pericarditis Cardiac tamponade, restrictive pericarditis

as it preserves HR and Rt. Atrial pressure as it preserves HR and Rt. Atrial pressure through it’s sympathetic stimulating through it’s sympathetic stimulating effects.effects.


USESUSES Congential heart disease like Rt to Lt shunts Congential heart disease like Rt to Lt shunts

[TOF] , as by causing hypertension increases [TOF] , as by causing hypertension increases afterload and decreases shunt fraction.afterload and decreases shunt fraction.

Malignant hyperthermia. Malignant hyperthermia.

In known depression, improved postoperative In known depression, improved postoperative depressive state. depressive state.

As an analgesic in low doses after thoracic As an analgesic in low doses after thoracic surgery.surgery.

Epidural/Caudal administration [0.5-1 mg/Kg].Epidural/Caudal administration [0.5-1 mg/Kg].


USESUSESSEDATIONSEDATION In pediatric patients for cardiac catheterization, In pediatric patients for cardiac catheterization,

radiation therapy, radiological studies, dressing radiation therapy, radiological studies, dressing changes [Subanesthetic dose <= 1mg/Kg I.V.] , changes [Subanesthetic dose <= 1mg/Kg I.V.] , dental workdental work

Cautious use in cardiac catheterization with Cautious use in cardiac catheterization with elevated pulmonary vascular resistance elevated pulmonary vascular resistance


USESUSESOther UsesOther Uses For Supplementation of regional anesthesia For Supplementation of regional anesthesia

Ketamine [0.5 mg/KG IV], combined with Ketamine [0.5 mg/KG IV], combined with diazepam [0.15 mg/KG IV] diazepam [0.15 mg/KG IV]

Combined with Nitrous oxide and propofol for Combined with Nitrous oxide and propofol for supplementation of local anesthesiasupplementation of local anesthesia

In outpatients premedication with midazolam, In outpatients premedication with midazolam, concurrent propofol and intermittent Ketamine concurrent propofol and intermittent Ketamine [for analgesia] in does < 3 mg/KG for [for analgesia] in does < 3 mg/KG for debridement, skin grafting patients debridement, skin grafting patients

Preferred agents for patients with full stomach Preferred agents for patients with full stomach Remote places and in inexperience hand as it Remote places and in inexperience hand as it

does not depress respiration and heart does not depress respiration and heart


USESUSES

Other UsesOther Uses Reversal of Opioid tolerance Reversal of Opioid tolerance In restless leg syndrome by inhibiting In restless leg syndrome by inhibiting

neuroinflammation in spinal cordneuroinflammation in spinal cord Safe in porphyria patientsSafe in porphyria patients Used in veterinary medicine because of anesthetic Used in veterinary medicine because of anesthetic

and analgesic effectsand analgesic effects With Opioid useful for cancer pain With Opioid useful for cancer pain In small does [0.1 – 0.5 mg/KG/hr] as a local In small does [0.1 – 0.5 mg/KG/hr] as a local

anesthetic for treatment of neuropathic pain anesthetic for treatment of neuropathic pain


ContraindicationsContraindications

In raised ICT and intracranial mass lesions In raised ICT and intracranial mass lesions Patients with open eye injury Patients with open eye injury Ischemic heart disease and vascular aneurysms Ischemic heart disease and vascular aneurysms Psychiatric disease like schizophrenia or a history Psychiatric disease like schizophrenia or a history

of adverse reaction to ketamine of adverse reaction to ketamine Due to preservative chlorobutanol, which is Due to preservative chlorobutanol, which is

neurotoxic SAB route is C/Ineurotoxic SAB route is C/I Abruptio placentae and cord prolapse, not to be Abruptio placentae and cord prolapse, not to be

used with ergometrine as it increase uterine tone used with ergometrine as it increase uterine tone and intrauterine pressure in both pregnant and and intrauterine pressure in both pregnant and non pregnant uterus non pregnant uterus

Hyperthyroidism Hyperthyroidism


Comparison between Thiopentone Comparison between Thiopentone and Ketamineand Ketamine

ThiopentoneThiopentone BarbiturateBarbiturate

Poor analgesicPoor analgesic Weak muscle Weak muscle

relaxantrelaxant Alkaline solution Alkaline solution

pH 10.5pH 10.5 Powder for Powder for

reconstitutionreconstitution

KetamineKetamine Phencyclidine Phencyclidine

derivativederivative Good analgesicGood analgesic Increases muscle Increases muscle

tonetone Acidic solution pH Acidic solution pH

3.5 to 5.53.5 to 5.5 Solution for Solution for

reconstitutionreconstitution


Continued…Continued… Lipid solubleLipid soluble

Highly bound to Highly bound to plasma proteinsplasma proteins

Depressed respirationDepressed respiration BronchoconstrictorBronchoconstrictor Metabolism affected Metabolism affected

by hepatic enzyme by hepatic enzyme activityactivity

GABA A receptor GABA A receptor inhibitorinhibitor

Acts on RASActs on RAS

Highly lipid soluble Highly lipid soluble than thiopentonethan thiopentone

Least bound to plasma Least bound to plasma proteinsproteins

Stimulates respirationStimulates respiration BronchodilatorBronchodilator Metabolism affected Metabolism affected

by hepatic blood flowby hepatic blood flow

NMDA receptor NMDA receptor inhibitorinhibitor

Acts on neocortical Acts on neocortical projectionprojection


Continued…Continued…

Depresses sympathetic Depresses sympathetic nervous systemnervous system

Decreases BP, ICT, IOTDecreases BP, ICT, IOT Decreases CMRO2Decreases CMRO2 Cerebral vasoconstrictor Cerebral vasoconstrictor Precipitates porphyriaPrecipitates porphyria Induction tested by loss Induction tested by loss

of corneal and eyelid of corneal and eyelid reflexreflex

Used in status Used in status epilepticusepilepticus

Stimulates central Stimulates central sympathetic systemsympathetic system

Increases BP, ICT, IOTIncreases BP, ICT, IOT Increases CMRO2Increases CMRO2 Cerebral vasodilatorCerebral vasodilator Safe in porphyriaSafe in porphyria Induction tested by pupil Induction tested by pupil

dilation, fixation and dilation, fixation and nystagmusnystagmus

Used in status Used in status asthmaticusasthmaticus

Ketamine poonam

Documents

Transcript of Ketamine poonam