An academic presentation on General Anesthetics, covering only the Pharmacological aspect of the drugs (ie the Pharmacokinetic and pharmacodynamic profile) available for general anesthesia. Topics not covered are different mechanisms of administering anesthesia and other basics of anesthesia.

2. OUTLINE
CONCLUSION
SUMMARY :DRUGS IN A NUTSHELL
INTAVENOUS ANESTHETICS
INHALATIONAL ANESTHETICS
CLASSIFICATION
INTRODUCTION
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
2

3. ABBREVIATIONS
• CBF- CEREBRAL BLOOD FLOW
• CMRO2- CEREBRAL METABOLIC RATE
• ICT- INTRA CRANIAL TENSION
• TV: TIDAL VOLUME
• RR: RESPIRATORY RATE
• MV= MINUTE VOLUME
• BZD: BENZODIAZEPINES
• DOA: DURATION OF ACTION
• PPB: PLASMA PROTEIN BINDING
• MAC: MINIMUM ALVEOLAR CONCENTRATION
• ABP: ARTERIAL BLOOD PRESSURE
• CO: CARDIAC OUTPUT
• NI: NON- INFLAMMABLE
• NE: NON- EXPLOSIVE
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
3

4. 1. INTRODUCTION:
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
4

5. DISCOVERIES:
HORACE
WELLS
JOSEPH
PRIESTLEY
WILLIAM T.G.
MORTON
EDMOND
EGER
RUPA BAI
FURDOONJI
OF
HYDERABAD
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
5

6. AGENTS BRINGING ABOUT LOSS OF ALL
MODALITIES NAMELY
• SENSATIONS E.G. PAIN
• AUTONOMIC REFLEXES
• SKELETAL MUSCLE RELAXATION
• AMNESIA
• REVERSIBLE LOSS OF CONSCIOUSNESS
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
6

7. GENERAL PRINCIPLES OF SURGICAL
ANESTHESIA:
• MINIMIZING POTENTIAL DIRECT/INDIRECT EFFECTS
OF GENERAL ANESTHETIC AGENTS AND TECHNIQUES
• SUSTAINING PHYSIOLOGICAL HOMEOSTASIS
• IMPROVING POST- OPERATIVE OUTCOME
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
7

8. PROPERTIES OF AN IDEAL ANAESTHETIC
PATIENT’S PERSPECTIVE
• NON-IRRITATING
• RAPID INDUCTION AND
RECOVERY
• PLEASANT WITH
MINIMUM N&V
SURGEON’S PERSPECTIVE
• ADEQUATE ANALGESIA/
IMMOBILITY/ REFLEX
SUPPRESSION
• NI&NE- CAUTERY
ANAESTHETIST’S
PERSPECTIVE
• EASY TO ADMINISTER/
CONTROL
• MINIMAL ORGAN
TOXICITY
• STABLE/ NON REACTIVE
TO TUBING/ SODA LIME
• WIDE MARGIN OF
SAFETY
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
8

9. CLASSIFICATION:
INHALATIONALAGENTS:
VOLATILE
LIQUIDS
DIETHYL ETHER
TCE
ETHYL
CHLORIDE
HALOTHANE
ISOFLURANE
DESFLURANE
ENFLURANE
SEVOFLURANE
GASES:
NITROUS
OXIDE
INTRA-VENOUS AGENTS:
ULTRA-SHORT ACTING:
THIOPENTAL SODIUM
METHOHEXITAL
PROPOFOL
BENZODIAZEPINES: MIDAZOLAM, DIAZEPAM
PHENCYCLIDINE: KETAMINE
OPIOID ANALGESICS:
MORPHINE, FENTANYL,
SUFENTANYL
MISCELLANEOUS:
ETOMIDATE,
DEXMEDETOMIDINE
11-03-2019
Topiwala National Medical
College, Mumbai
9

10. INHALATIONAL ANESTHETICS
11-03-2019TOPIWALA NATIONAL MEDICAL COLLEGE, MUMBAI10

11. GENERAL CONCEPTS
ALL ARE ETHERS EXCEPT N2O
AND HALOTHANE
STORED IN TIGHTLY SEALED
BOTTLES: VOLATILITY
REQUIREMENT DECREASED
WITH N2O AND OPIOIDS
DESFLURANE AND ISOFLURANE:
MINIMALLY METABOLIZED(99%
ELIMINATED UNCHANGED
FROM LUNGS )
PARTITION CO-EFFICIENT:
• BLOOD: GAS
• BRAIN: BLOOD
• FAT: BLOOD
LOW BLOOD:GAS PARTITION
CO-EFFICIENT CORRESPONDS
WITH LOW SOLUBILITY AND
IMPLIES FASTER INDUCTION
AND RECOVERY FROM
ANESTHESIA
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
11

12. ISOFLURANE
HIGHLY VOLATILE
LIQUID- STORED IN
TIGHTLY SEALED
BOTTLES
NEITHER
INFLAMMABLE NOR
EXPLOSIVE
ODOR IS PUNGENT:
NOT SUITABLE FOR
INDUCTION
INDUCTION DOSE:
1.5- 3% IN < 10 MINS
MAINTENANCE: 1-2%
>99% ELIMINATED
UNCHANGED FROM
LUNGS
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
12

13. ORGAN EFFECTS:
CNS:
• DILATES CEREBRAL
VASCULATURE
CBF
• DOSE DEPENDENT
DECREASE IN CMRO2
CVS:
• CONCENTRATION
DEPENDENT
DECREASE IN ABP
VASODILATATION
• CO IS MAINTAINED
• POTENT
VASODILATOR OF :
• SKIN
• MUSCLE
• CORONARIES
RS
• CONC. DEPENDENT
RESP. DEPRESSION
• BRONCHODILATORY
EFFECT BUT AIRWAY
IRRITANT
• VENTILLATORY
RESPONSE TO
HYPOXIA /
HYPERCAPNIA
OTHER SYSTEM
• MUSCLES: SKELETAL
MUSCLE RELAXANT
• POTENTIATES
NON/DE- POLARIZING
SMRs
• NOT USED IN VAGINAL
DELIVERIES
• LIVER/ KIDNEY/ GIT:
• DUE TO DECLINE IN
SBP DECREASED
PERFUSION TO THESE
ORGANS
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
13

14. SEVOFLURANE
CLEAR, COLORLESS,
VOLATILE STORED IN
TIGHTLY SEALED BOTTLES
NI AND NE
EXOTHERMIC REACTION
WITH DRY CO2 
AIRWAY BURNS +
SPONTANEOUS IGNITION +
EXPLOSION AND FIRE
CLINICAL USE: WIDELY
USED ON OUTPATIENT
CASES
IDEAL INDUCING AGENT:
• PLEASANT SMELL
• RAPID ONSET
• NON- IRRITANT
REPLACED HALOTHANE IN
ALL AGE GROUPS
LOW SOLUBILITYRAPID
INDUCTION AND
RECOVERY
METABOLISM:
5% BY HEPATIC CYP2E1HFIP
& INORGANIC F-
WITH SODA LIME
COMPOUND A
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
14

15. ORGAN EFFECTS
CNS:
• DILATES CEREBRAL
VASCULATURE
CBF
• DOSE DEPENDENT
DECREASE IN CMRO2
• DELIRIUM REPORTED
AS EMERGENT
REACTION IN
CHILDREN
CVS:
• CONC. DEPENDENT
SYSTEMIC BLOOD
PRESSURE DUE TO
LOWERED PVR
• CO
• NO TACHYCARDIA
PREFERED IN IHD
RS:
• CONC. DEPENDENT
TIDAL VOLUME,
RR OVERALL
MV
• MOST EFFECTIVE
CLINICAL
BRONCHODILATOR
OTHER SYSTEM
• MKS:
• SKELTAL .M.R.
• KIDNEY:
• NEPHROTOXIC
METABOLITE
COMPOUND A
• LIVER AND GIT:
• NO ADVERSE EFFECT
REPORTED
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
15

16. DESFLURANE
HIGHLY VOLATILE(VAPOR PRESSURE= 669 MM HG) STORED IN TIGHTLY SEALED BOTTLES
NI & NE
NEEDS SPECIALLY HEATED VAPORIZER FOR FLOW
CLINICAL USE:
• CAN BE USED ON OUTPATIENT BASIS
• AIRWAY IRRITANTCOUGH/SALIVATION/BRONCHOSPASM USED FOR MAINTENANCE
• @ DOSE: 6-8% = 1 MAC
• LOW BLOOD: GAS PARTITION COEFFIECCIENT:  FAST RECOVERY FROM EFFECT
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
16

17. ORGAN EFFECTS
CNS
• CEREBROVASCULAR
RESISTENCE CMRO2
• BURST SUPPRESSION OF EEG AT 2
MAC  CMRO2 LOWEREB BY 50%
• AT NORMOCAPNIA/
NORMOTENSION CBF AND
• ICT
• VASOCONSTRICTIVE RESPONSE TO
HYPOCAPNIA PRESERVED
• RISE IN ICP PREVENTED BY
HYPERVENTILATION
CVS
• SBP PVR
• CO MAINTAINED
• DESFLURANE INDUCED
SYMPATHETIC NERVOUS SYSTEM
STIMULATION
RS
• CONC. DEPENDENT DECREASE IN TV,
• RR PRESERVED MV
• BRONCHODILATOR
• AIRWAY IRRITANT NOT A
PRIMARY INDUCING AGENT
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
17

18. ENFLURANE
CLEAR, COLORLESS
VOLATILE LIQUID WITH
MILD SWEET ODOR
NI & NE
CLINICAL USE:
• INDUCTION DOSE: 2-4.5% IN
O2
• TIME OF INDUCTION: < 10 MIN
• MAINTENANCE DOSE: 0.5 – 3%
DOSE REQUIREMENT
DECREASED WITH USE OF
N20 + O2
HIGH BLOOD: GAS
PARTITION CO-
EFFICIENT SLOW
INDUCTION & RECOVERY
HEPATIC
METABOLISM BY
CYP2E1 F - 2-8%
DRUG-DRUG
INTERACTION: WITH
ISONIAZIDE ENHANCED
METABOLISM F-
(TOXIC LEVEL)
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
18

19. ORGAN EFFECTS
CNS:
• CEREBRAL
VASODILATOR
ICP
• PROCONVULSANT
CVS:
• ARTERIAL BP DUE
TO VASODILATION
& DECREASED
MYOCARDIAL
CONTRACTILITY
• HR: UNAFFECTED
RS:
• BRONCHODILATOR
• RAPID SHALLOW
BREATHING
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
19

20. HALOTHANE
LIGHT SENSITIVE
STORED IN AMBER
COLOR BOTTLES
NI & NE
USE IS RESTRICTED BY:
HALOTHANE HEPATITIS
• FULMINANT HEPATIC
NECROSIS
• I;10,OOO CASES
• FATALITY: 50% OF AFFECTED
HALOTHANE HEPATITIS:
SIGNS AND SYMPTOMS:
• FEVER
• ANOREXIA
• N&V
• RASH
• PERIPHERAL EOSINOPHILIA
ETIOPATHOGENESIS:
IMMUNE RESPONSE AGAINST A METABOLITE
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
20

21. NITROUS OXIDE
WEAK ANESTHETIC(WEAK
MUSCLE RELAXATION) WITH
SIGNIFICANT ANALGESIA
N20 DECREASES METHIONINE
SYNTHASE
ACTIVITYMEGALOBLASTIC
ANEMIA
50% N20 X 12
HRSMEGALOBLASTIC
ANALGESIA AT 20% CONC.
MEDIATED THROUGH:
• OPIOIDERGIC NEURON IN PAG MATTER
• ADRENERGIC NEURON IN LOCUS
CERULEUS
SURGICAL ANESTHESIA NEEDS
HYPERBARIC CONDITION
DENTAL USE: 50% N20
PROVIDES GOOD ANALGESIA
AND MILD SEDATION
• >80% CONC. N20 CANNOT BE USED
O2 AVAILABILITY
• THERFORE USED AS AN ADJUNCT
SECOND GAS EFFECT AND
DIFFUSIONAL HYPOXIA
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
21

22. SUMMARY
ISOFLURANE SEVOFLURANE DESFLURANE ENFLURANE HALOTHANE NITROUS
OXIDE
• MAINTENANCE OF
ANESTHESIA
• COMMONLY USED
INHALATIONAL
ANESTHETIC
• PREFERRED AGENT
FOR ANESTHETIC
INDUCTION
• USED FOR
OUTPATIENT
ANESTHESIA
(NOT IRRITATING
AIRWAY; INDUCTION
AND RECOVERY ARE
RAPID)
• USED FOR
OUTPATIENT
SURGERY
(RAPID ONSET,
RAPID
RECOVERY)
• MAINTENANCE
OF ANESTHESIA
• MAINTENANCE OF
ANESTHESIA
• WEAK
ANESTHETIC
AGENT USED FOR
ITS SIGNIFICANT
ANALGESIC
EFFECTS
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
23

23. N20/ DES-/SEVO-FLURANE RAPID ONSET AND RECOVERY
HALOTHANE/ ISO-/EN-FLURANE MEDIUM ONSET AND RECOVERY
ALL ARE CARDIO-DEPRESSANT: HALOTHANE/ENFLURANE>>ISO-/SEVO-/DES-FLURANE
ISO-/SEVO-/DES- FLURANE PR/ PRELOAD/ AFTERLOAD PRESERVE CO BETTER CHOICE IN
PATIENTS WITH IMPAIRED MYOCARDIAL FUNCTION
ISO-/DES- FLURANE PUNGENT ODOR NOT SUITABLE FOR BRONCHO-REACTIVE PATIENTS
HALOTHANE SENSITIZES MYOCARDIUM TO CATECHOLAMINES
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
24

24. INTRAVENOUS ANESTHETICS
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
25

25. PROPOFOL AND FOSPROPOFOL
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
26

26. PROPOFOL
• CHEMICAL NAME: 2,6 DI-ISO PROPYL-PHENOL
• CONTEXT SENSITIVE T1/2 BRIEF PROMPT RECOVERY EVEN AFTER CONTINUOUS INFUSION
• 10 MINUTES AFTER 3 HOURS INFUSION
• 30 MINUTES AFTER 8 HOURS INFUSION
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
27
DRUG INDUCTION
DOSE
(MG/KGIV)
DURATION OF
ACTION
(MINUTES)
VOLUME OF
DISTRIBUTION
(L/KG)
DISTRIBUTIO
N
T1/2
(MINUTES)
PROTEIN
BINDING
(%)
CLEARANCE
(ML/KG/MIN
)
ELIMINATON
T1/2
(HR)
PROPOFOL 1-2.5 3-8 2-10 2-4 97 20-30 4-23

27. CONTEXT SENSITIVE T1/2:
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
28

28. PROPERTIES OF PROPOFOL
CHEMICAL NAME: 2,6 DI-
ISOPROPYL PHENOL
EMULSION: 10%
SOYABEAN OIL + 2.25% OF
GLYCEROL + 1.2%
LECITHIN(PURIFIED EGG
PHOSPHATIDE)
MILKY WHITE,
VISCOUS
PH = 7
0.05 MG/DL DINA EDTA + 0.25
MG/ML SODIUM METABISULPHITE
ADDED AS ANTI- BACTERIAL IN
THE US.
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
29

29. ORGAN EFFECTS
CNS
• MOA: GABAA + GLYCINE GATED CL-
CHANNEL NEURONAL
HYPERPOLARIZATION
• GENERAL SUPPRESION OF CNS BUT
OCCASIONAL EXCITATION
EPISODES
• PARADOXICAL EFFECT OF PROPOFOL
• HYPNOSIS WITHOUT ANALGESIA
• CBF CMRO 2 ICT IOT
• SUITABLE FOR CEREBRAL ISCHEMIA
PATIENTS
• HAS ANTICONVULSIVE EFFECTS
WITH BURST SUPPRESSION OF EEG
CVS
• DOSE DEPENDENT
BPPROFOUND ARTERIOLAR +
VENO DILATATION
• PRELOAD AFTERLOAD
MYOCARDIAL SUPPRESSION
• EFFECT EXAGGERATED IN :
• ELDERLY
• RAPID INJECTION
• INTRAVASCULAR FLUID VOLUME
• BARORECEPTOR REFLEX- BLUNTED
• IN HEALTHY – BRADYCARDIA +
ASYSTOLE
RS
• TV + RR = MV
• RESPIRATORY EFFECTS ARE
SLIGHTLY GREATER THAN
THIOPENTAL
• LESS BRONCHOSPASM SUITABLE
IN ASTHMATICS
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
30

30. OTHER EFFECTS:
a)PROPOFOL
INFUSION
SYNDROME
b)ANTI-EMETIC
EFFECTS
PAINFUL INJECTIONS
i) PREMEDICATE WITH
OPIODS
ii) USE LARGE
VEINS
iii) DILUTE
PROPOFOL
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
31

31. CLINICAL USES
INDUCTION OF ANESTHESIA
• DOSE: 1-2.5 MG/KG IV
• INCREASED REQUIREMENT IN CHILDREN: 2.5- 3.5 MG/KG (RAPID CLEARANCE AND LARGE CENTRAL
VOLUME)
• DECREASED REQUIREMENT IN – ELDERLY/ LOW CARDIAC RESERVE/ PREMEDICATION WITH BZD AND
OPIOIDS
BALANCED ANESTHESIA
ONLY IV AGENTS:
• INFUSION RATE: 100- 200 UGM/KG/MIN(DESIRED LEVEL- 3-8 UGM/L)
• ICU SETTINGS: INFUSION RATE: 25-75 UGM/KG/MIN(DESIRED LEVEL 1-2 UGM/ML)
DOSE FOR POST-OP N&V: 10-20 MG IV BOLUS OR INFUSION @ 10 UGM/KG/MIN
SEDATING DOSE: 20- 50% OF GA
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
32

32. FOSPROPOFOL
WATER SOLUBLE PO4 ESTER PRODRUG OF PROPOFOL
FOSPRPOPOFOL PROPOFOL + PO4 + HCHO
PHYSICAL PROPERTIES:
STERILE, AQUEOUS, COLORLESS, CLEAR SOLUTION
DOSE : 6.5 MG/KG IV BOLUS 1.6 MG/KG IV IF NEEDED
25% DOSE REDUCTION IN:
• >65 YEARS
• ASA GRADE 3/4
• DOA: 45 MINUTES
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
33
Alkaline phosphatase
Endothelial cells

33. 5-
MORIBUND
PATIENT
WHO IS NOT
EXPECTED
TO SURVIVE
4- SEVERE
SYSTEMIC
DISEASE
THAT IS A
THREAT TO
LIFE
3- SEVERE
SYSTEMIC
DISEASE
2- WITH
MILD
SYSTEMIC
DISEASE
1- NORMAL
HEALTHY
PATIENT
ASA GRADES:
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
34

34. BARBITURATES
THIOPENTAL/ METHOHEXITAL AND THIAMYL
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
35

35. THIOPENTAL
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
36
Drug Induction
dose
(mg/kg IV)
Duration of
action
(minutes)
Volume of
distribution
(l/kg)
Distribution
t1/2
(minutes)
Protein
binding
(%)
Clearance
(ml/kg/min)
Eliminaton
t1/2
(hr)
Thiopental 3-5 5-10 2.5 2-4 83 3.4 11
FIRST ANESTHETIC
TO BE USED
INTRAVENOUSLY
DOSE :3-5 MG/KG
IV
PH FOR STATBILITY:
10 – 11
ONSET OF ACTION:
< 30 SEC

36. ORGAN EFFECTS
CNS
• DOSE DEPENDENT CNS
DEPRESSION
• NO ANALGESIA DECREASES
PAIN THRESH HOLD
HYPERALGESIA
• POTENT VASOCONSTRICTOR:
• CBF CMRO2 ICT
• BURST SUPPRESSION OF EEG
CVS
• SYSTEMIC BP DUE TO:
•PERIPHERAL VASODILATION
•-VE IONOTROPIC EFFECT
• EXAGGERATED EFFECTS IN:
• CAD
• CARDIAC TAMPONADE
• CARDIOMYOPATHY
• HYPOVOLEMIA
• VALVULAR DISEASE
RS
• DEPRESSANT:
• RR + TV = MV
• LUNG RESPONSE TO
HYPERCAPNEA/ HYPOXIA
CENTRAL EFFECT
• SUPPRESSION OF LARYNGEAL
+ COUGH REFLEX LESS
MARKED
• LARYNGOSPASM +
BRONCHOSPASM
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
37

37. BENZODIAZEPINES
MIDAZOLAM/ LORAZEPAM/ DIAZEPAM
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
38

38. MIDAZOLAM
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
39
Drug Induction
dose
(mg/kg IV)
Duration of
action
(minutes)
Volume of
distribution
(l/kg)
Distribution
t1/2
(minutes)
Protein
binding
(%)
Clearance
(ml/kg/min)
Eliminaton
t1/2
(hr)
Midazolam 0.1-0.3 15-20 1.1-1.7 7-15 94 6.4-11 1.7-2.6
MIDAZOLAM AND LORAZEPAM ARE COMMONLY USED WHEREAS DIAZEPAM IS SELDOM USED
SHORT CONTEXT SENSITIVE T1/2: SUITABLE FOR CONTINUOUS IV INFUSION
SUCCESSIVE IV DOSES OF MIDAZOLAM NEEDS TO BE SPACED

39. ORGAN EFFECTS
CNS
• ISOELECTRIC EEG NOT
REACHED CEILING
EFFECT
• CBF CMRO2 
LESS EXTENT
• POTENT ANTI-
CONVULSANT EFFECT
SO USEFUL IN:
• STATUS EPILEPTICUS
• LA INDUCED SEIZURES
• NO NEUROPROTECTIVE
EFFECT
CVS
• FALL IN SBP
PERIPHERAL
VASODILATION
RS
• MINIMAL RESPIRATORY
DEPRESSION
• CLINICAL USES:
• RAPID INDUCTION
• DOSE:
• 1-2 MG IV AS PRE-
ANESTHETIC
• 0.1 – O.3 MG/KG IV AS
GENERAL ANESTHETIC
• DOA: 20 MINS
OTHER EFFECTS
• PAIN +
THROMBOPHLEBITIS
MOSTLY SEEN WITH
DIAZEPAM DUE TO POOR
SOLUBILTY
• ANTI- DOTE:
FLUMAZENIL 8-15
UGM/KG IV
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
40

40. ETOMIDATE
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
41
Drugs Induction
dose
(mg/kg IV)
Duration of
action
(minutes)
Volume of
distribution
(l/kg)
Distribution
t1/2
(minutes)
Protein
binding
(%)
Clearance
(ml/kg/min)
Eliminaton
t1/2
(hr)
Etomidate 0.2-0.3 3-8 2.5-4.5 2-4 77 18-25 2.9-5.3
CARBOXYLATED
IMIDAZOLE
D -ISOMER 
MORE ACTIVE
MINIMUM HEMODYNAMIC
EFFECT RESERVED FOR
PATIENTS WITH
HYPOTENSION/
MYOCARDIAL ISCHEMIA
DOSE LIMITING
ENDOCRINE
EFFECTS
POORLY WATER
SOLUBLE 2
MG/ML IN 35%
PROPYLENE GLYCOL

41. ORGAN EFFECTS
CNS
• EFFECT COMPARABLE
TO THIOPENTAL
• NO NEUROPROTECTION
• POTENT CEREBRAL
VASOCONSTRICTOR
• CBF CMRO2
• PROCONVULSANT
• MYOCLONUS > 50%
TIMES  PRE-
MEDICATE WITH BZD/
OPIATES
CVS
• MODEST FALL IN
BP
• MINIMUM EFFECT
ON HR/ CO/
CARDIAC
CONTRACTILITY
• EFFECTS
EXAGGERATED
WITH
INHALATIONAL
ANESTHETICS
AND OPIOIDS
RS
• LESS
PRONOUNCED
EFFECTS NO
HISTAMINE
RELEASE
ENDOCRINE
• ADRENO-
CORTICAL
SUPPRESSION
• DOSE DEPENDENT
INHIBITION OF
11B
HYDROXYLASE(TI
LL 4-8 HOURS OF
LAST DOSE)
• METHOXY
CARBONYL
ETOMIDATE
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
42

42. KETAMINE
Drugs Induction
dose
(mg/kg IV)
Duration of
action
(minutes)
Volume of
distribution
(l/kg)
Distribution
t1/2
(minutes)
Protein
binding
(%)
Clearance
(ml/kg/min)
Eliminaton
t1/2
(hr)
Ketamine 1-2 5-10 3.1 11-16 12 12-17 2-4
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
43
• PHENCYCLIDINE DERIVATIVE: ARYL CYCLO HEXYLAMINE
• PARTIALLY WATER SOLUBLE + HIGHLY LIPID SOLUBLE
• S+VE MORE ACTIVE THAN R-VE
• MOA: NMDA INHIBITION
• LOW DOSE KETAMINE= OF POTENTIAL USE IN DEPRESSION
• PK PECULIARITY:
a) ONLY IV DRUG WITH LOW PPB
b) HIGHLY LIPID SOLUBLE = RAPID ONSET
c) ACTION TERMINATED BY REDISTRIBUTION
METABOLISM N- DEMETHYLAATION
LIVER
CYP 450
NOR- KETAMINE
WATER SOLUBLE
METABOLITES
CONJUGATION
HYDROXYLATION

43. REDISTRIBUTION:
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
44

44. ORGAN EFFECTS
CNS
• CEREBRAL VASODILATOR
• CBF CMRO2 ICT
• MINIMUM CHANGE IN
CEREBRAL METABOLISM
• INCOMPLETE AMNESIA
• POTENTIAL MYOCLONIC
ACTIVITY
• CI: INTRACRANIAL PATHOLOGY
CVS
• SYSTEMIC BP DUE TO CENTRAL
SYMPATHETIC DISCHARGE
• HR CO INDIRECT
INHIBITION OF CENTRAL/
PERIPHERAL CATECHOLAMINE
REUPTAKE
• CARDIAC WORKLOAD
MYOCARDIAL O2
CONSUMPTION
• BUT PARADOXICAL DIRECT
MYOCARDIAC DEPRESSANT
EFFECTS
RS
• NO SIGNIFICANT DEPRESSION
• TRANSIENT HYPOVENTILATION
+ APNEA AFTER LARGE DOSE
RAPIDLY INJECTED
• BRONCHO- RELAXATION
EFFECT SAFE IN HYPERACTIVE
AIRWAY DISEASE
• BLUNTING OF REFLEX RESPONSE
TO HYPERCAPNIA LESS
MARKED
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
45

45. TO BE USED CAUTIOUSLY IN CHILDREN
SALIVATION  LARYNGOSPASM
USEFUL IN MR AND UNCO-OPERATIVE
CHILDREN
INDUCTION DOSE:
• IV- 1-2 MG/KG
• IM- 4-6 MG/KG
GA MAINTENANCE: 15- 45 UGM/KG/MIN +
50% N2O
• IF USED ALONE: 30 – 90 UGM/KG/MIN
OTHER USES
SUB- ANALGESIC DOSE: 3-5
UGM/KG IV INFUSION
• TO LIMIT/ RESERVE OPIOID
TOLERANCE AS AN ADJUNCT
• OPIOID INDUCED
HYPERALGESIA
AS AN ADJUNCT IN
REGIONAL
ANESTHESIA:
0.2-0.8 MG/ KG IV
NEURAXIAL
ANESTHESIA IN
CESARIAN DELIVERY
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
46

46. DEXMEDETOMIDINE
HIGHLY SELECTIVE
ALPHA 2 ADRENERGIC
AGONIST
IMIDAZOLE
DERIVATIVE
ACTIVE S-
ENANTIOMER
OF
MEDETOMIDINE
HEPATIC METABOLISM:
N- DEMETHYLATION +
HYDROXYLATION +
CONJUGATION
CONTEXT
SENSITIVE T1/2
:
10 MIN
INFUSION4 MIN
AND 8 HOUR
INFUSION  250
MIN
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
47
Drugs Induction
dose
(mg/kg IV)
Duration of
action
(minutes)
Volume of
distribution
(l/kg)
Distribution
t1/2
(minutes)
Protein
binding
(%)
Clearance
(ml/kg/min)
Eliminaton
t1/2
(hr)
Dexmedeto
midine
NA NA 2-3 6 94 10-30 2-3

47. ORGAN EFFECTS
CNS
• ACTIVATES ALPHA 2
RECEPTORS:
• LOCUS
CERULEUSHYPNOSIS
(INHIBITORY INFLUENCE)
• SPINAL CORD ANALGESIA
• PHYSIOLOGICAL DEEP
SLEEP (VLPO MEDIATED
INHIBITION)
• CBF BUT ICT AND
CMRO2 UNCHANGED
CVS
• HR PVR = SBP
• ON BOLUS INJECTION
SBP DUE TO PERIPHERAL
ALPHA 2 ACTIVATION
• ASYSTOLE/ HEART BLOCK /
BRADYCARDIA
UNOPPOSED VAGAL
STIMULATION
RS
• MILD TYPE UPPER AIRWAY
OBSTRUCTION
CLINICAL USES
• SHORT TERM SEDATION FOR
PT. ON VENTILLATION IN ICU
SETTING
• AS AN ADJUNCT TO GA /
SEDATION
• LOADING DOSE: 0.5
UGM/KG OVER 15
MIN0.2- 0.7 UGM/KG/HR
MAINTENANCE
• ALL EMERGENT REACTIONS
MITIGATED WITH
COMBINED USE OF OPIOIDS
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
48

48. ANAESTHESIA IN MENTALLY RETARDED AND
ASTHMATICS:
FOR MR CASES:
• KETAMINE USEFUL OPTION
• METHOHEXITAL: PER
RECTALLY20-30 MG/KG
FOR ASTHMATICS:
• KETAMINE
• PROPOFOL
• SEVOFLURANE: CLINICALLY
MOST EFFECTIVE BRONCHO-
DILATOR
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
49

49. SUMMARY
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
50

50. Drugs Induction
dose
(mg/kg IV)
Duration of
action
(minutes)
Volume of
distribution
(l/kg)
Distribution
t1/2
(minutes)
Protein
binding
(%)
Clearance
(ml/kg/min)
Eliminaton
t1/2
(hr)
Dexmedetomidine NA NA 2-3 6 94 10-30 2-3
Diazepam 0.3-0.6 15-30 0.7-1.7 - 98 0.2-0.5 20-50
Etomidate 0.2-0.3 3-8 2.5-4.5 2-4 77 18-25 2.9-5.3
Ketamine 1-2 5-10 3.1 11-16 12 12-17 2-4
Lorazepam 0.03-0.1 60-120 0.8-1.3 3-10 98 0.8-1.8 11-22
Methohexital 1-1.5 4-7 2.2 5-6 73 11 4
Midazolam 0.1-0.3 15-20 1.1-1.7 7-15 94 6.4-11 1.7-2.6
Propofol 1-2.5 3-8 2-10 2-4 97 20-30 4-23
Thiopental 3-5 5-10 2.5 2-4 83 3.4 11
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
51

51. ALL ARE
CEREBRAL
VASOCONSTRICT
ORS EXCEPT
KETAMINE
CVS EFFECTS:
• HR, PVR,
SYSTEMIC
BLOOD PRESSURE
MOST CAUSE
RESPIRATORY
DEPRESSION
EXCEPT: BZD,
ETOMIDATE,
KETAMINE
DRUGS WITH
HIGH VOLUME OF
DISTRIBUTION
AND RAPID
CLEARANCE:
CONTINUOUS IV
INFUSION CAN BE
GIVEN
LARGE VD WITH
SLOW
ELIMINATION:
LONG LASTING
EFFECTS
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
52

52. CONCLUSION
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
53

53. INHALATIONAL ANESTHETICS ARE AGENTS WITH NARROW THERAPEUTIC INDEX HENCE NEEDS TO USED TOO CAUTIOUSLY.
SEVOFLURANE TURNS FLAMMABLE IN PRESENCE OF DRY CO2 , HENCE FLOW NEED TO BE REGULATED WELL WITH MEASURES
OF EXTINGUISHING THE FIRE IN CASE OF MISHAP.
HALOTHANE BEING HIGHLY HEPATOTOXIC IS STILL BEING USED IN DEVELOPING COUNTRIES WHICH REQUIRES A VIGILANT
WITHDRAWAL OF THE AGENT AT SUCH CENTRES.
INTRAVENOUS AGENTS SHARE COMMON PROPERTIES WITH CERTAIN EXCEPTIONS AND THEIR USE NECESSITATES CAREFUL
MONITORING OF THE VITALS AND CERTAIN AGENTS ARE BEST SUITED FOR CERTAIN CONDITIONS LIKE USE OF KETAMINE,
ETOMIDATE IN BRONCHIAL ASTHMATIC PATIENTS.
DISCOVERY OF ANESTHETIC AGENTS REVOLUTIONIZED PATIENT TREATMENT ESPECIALLY REQUIRING SURGICAL
INTERVENTION, WITH RADIOLOGICAL UTILITY AS WELL. HOWEVER LOOKING AT ITS ABILITY OF BEING FATAL WITH MINISCULE
CHANGE IN CONCENTRATION WARRANTS ITS THOROUGH STRICT USE AND ONLY BY QUALIFIED PROFESSIONALS.
11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
54

54. 11-03-2019
TOPIWALA NATIONAL MEDICAL
COLLEGE, MUMBAI
55