PHARMACOLOGY OF

ANESTHESIA I

By:
Dr . Hesham Elhabashy , M.D.
Consultant Anesthesia & I.C.U.
habashy_h@hotmail.com
habashy_h@yahoo.com
.Theories of GA action -1
Inhalational Anesthetic -2
.Agents
.I.V. Anesthetic Agents -3
.Skeletal Muscle Relaxants-4
.Local Anesthetic Agents -5
.Opioids -6
.Others -7
 Definition of G.A.
Altered physiologic state in which, as a
result of reversible drug-induced
unconsciousness, noxious stimuli can
.neither be perceived nor recalled

Definition of G.A. Agent

It is that Drug which its primary effect is
.able to reversibly induce such a state
 Theories of GA action
There are many theories, but none of them completely
explain the mode of action of all anesthetics

:The most recent one is

Affection of Synaptic Transmission
Decrease Synaptic Transmission rather than Axonal Impulse
.conduction
;This occurs by
:A- Presynaptic Mechanisms
Activation of presynaptic K+ channels -1
.Transmitter same as presynaptic inhibition

Volatile agents & propofol (but not thiopental) -2

.glutamate
:B- Postsynaptic Mechanisms
.G.A. Depression of postsynaptic response

:In Summary
G.A. act mainly at synaptic transmission rather than
.axonal impulse conduction
 INHALATIONAL
ANESTHETIC AGENTS
Minimum Alveolar Concentration (MAC)
:Definition
It is the Minimum Alveolar Concentration of the
anesthetic at 1 atmosphere absolute that prevents
movement of 50% of the population to a standard
stimulus (e.g. surgical incision)
:Types of M.A.C
M.A.C as above -1
M.A.C awake -2
M.A.C 95% -3
M.A.C intubation -4
 .Factors Affecting M.A.C
Factors M.A.C Factors M.A.C
(CNS Excitation) (CNS Depression)

Hypothermia 42 C -1 Hyperthermia & Hypothermia-1

Young -2 Age : Elderly -2
Chronic Abuse -3 Alcohol : Acute Toxicity -3
Thyrotoxicosis -4 Myxoedema -4
Hypernatremia -5 Hyponatremia -5

:Drugs -6
Sympathomimetics e.g. cocaine, --
ephedrine(they symp. Activity)
Acute Amphetamine --
Cocaine -
:Drugs -6
Alpha 2 agonist e.g. methyl dopa, - -
reserpine, clonidine ( the symp.
Activity)
Chronic Amphetamine -
Local Anesth. (exp. Cocain)-
Others; N20, Barbiturates, -
Ketamine, Opioids,
Benzodiazepines
;Inhalational Anesthetic includes
N2O -1
Halothane -2
Ether -3
Methoxyfluran -4
Enflurane -5
Isoflurane -6
Desflurane -7
Sevoflurane -8
 Sevoflurane Desflurane N2O
Chemical
Structure
Non-flammable- Non-flammable- Non-flammable- Physical
Non-explosive- Non-explosive- Non-explosive- Properties
Colorless- Colorless- Colorless-
Pleasant odor- Pungent odor- Odorless(sweet odor)-
2% )7.3(6-9 105% MAC
rapid induction ,slower The most rapid
.recovery than Desf induction & recovery

Excretion &
Metabolism
Nephrotoxicity The main
Hepatotoxicity
route of excretion ofProlonged Exposureare the
all anesthetics Toxicity
Lung
Due to Fluoride & ( only 1 case reported) vit.B12 dependent--
compound A Metabolism occurs in the Liver by Cytochrme
:enzymes P-450 isoenzymes
causing
Peripheral Neuritis,
Myelo-neuropathy,
Megaloblastic Anemia,
Agranulocytosis, Bone
Marrow Aplasia
Teratogenic effect
 Sevoflurane Desflurane N2O Action

Good Anesthetic Good Anesthetic Good Analgesic CNS

Weak Analgesic Weak Analgesic Weak Anesthetic
Cer. VD CBF ICT Cer. VD CBF ICT Cer. VD CBF ICT
CMRO2

; Same Irritant to Resp. Not irritant .Resp

but the least effect on (coughing,breath-holding RR & Vt
Respiration &secretions), RR & Vt Depresses Hypoxic
Bronchodilator, Depresses Drive
Hypoxic Drive
.Dep. Myoca. Contra - .Dep. Myoca. Contra - .Dep. Myoca. Contra - CVS
SVR, ABlP, CVD - SVR, ABlP, HR,CVD - P.VC P.VR -
Arrhythmias -
Moderately Relaxes Strongly Relaxes No MR Neurmu
scular
Renal
Hepatic

RBF GFR UOP

.H.B.F .H.B.F
 Sevoflurane Desflurane N2O

Potentiates NDMR Potentiates NDMR Air Embolism Contraindication

.Acute int. obstru
Pneumothorax
.Tymp. Memb. Graf
PHTN

:Inhalational Anesthetic Toxicity

.Hepatotoxicity -1
.Nephrotoxicity -2
.Interaction with CO2 Absorbents -3
 I.V. ANESTHETIC AGENTS
: Pharmacokinetic of I.V. Anesthetics
Absorption -
Distribution -
Metabolism (Biotransformation) -
Excretion -
: I.V. Anesthetics include
Thiopentone Sodium -1
Methohexitone Sodium -2
Propofol -3
Etomidate -4
Ketamine -5
:Other i.v. agents used in anesthesia
Benzodiazepines -
Opioids -
Neuroleptic Agents -
 Ketamine Etomidate Propofol Thiopentone
Sodium

Lipid Soluble Water Physical

Lipid
Soluble Soluble Properties

IV: 1-2mg/kg IV :0.2-0.3 IV: 1.5-2.5 mg/kg IV: 3-5 mg/kg Dose
IM: 5-10mg/kg mg/kg : IVI Rectal : 30-44
Or: 5-10mg/kg 10mg/kg/hr 1 10m
st mg/kg
8mg/kg/hr 2nd 10m
6mg/kg/hr

Metabolism

LIVER Excretion

URINE
 Ketamine Propofol Thiopentone Sodium Ph.Action
:Mech. of Action :Mech. of Action :Mech. of Action CNS
.Dissociativ Aneth As Thiopentone ; but Depresses RF in B.stem
dissociates thalamus( Not Anticonvulsant - by GABA
.from cortex .Excitatory Ph - .unconscious
.Blocks NMDA Rs CNS depresses -
..…………Clinically - Anticonvulsant -
)+( CNS - CMR -
.EEG changes- No PONV -
CMR - .No Excitatory Ph -
PONV -
.Excitatory Ph ++ -

)--(.Resp -1 )--(.Resp -1 )--(.Resp -1 .Resp

Bronchospasm -2
Laryngeal spasm -3

ABP -1 ABP -1 ABP -1 CVS

HR -2 HR -2 HR -2
CO +ve inotropic -3 CO maintained -3 CO maintained -3

N-M
 Ketamine Propofol Thiopentone Sodium
Crosses Placenta -1 RBF -1 RBF -1 Others
IOP -2 HBF-2 HBF -2
Salivation -3 Cortisol -3 IOP -3

CNS-1 )--(.Resp -1 CNS (Drowsiness) -1 Adverse

+ .Excitatory Ph CNS(Excitatory Ph. +)-2 )--(.Res -2 Effects
++ ICP )--( CVS -3 )--( CVS -3
PONV ……During Injection -4 ………During Injection -4
++CVS ABP -2 Allergic Reaction -5 Allergic Reaction -5
Salivation -3
.…………………… .................................... .………………………… Indicat-
ion
Airway Obstruction -1 Airway Obstruction -1 Airway Obstruction -1 Contrai-
Hypersensitivity -2 Hypersensitivity -2 ndication
Long term sedation -3 Porphyria -3
in children in ICU

TIVA
THANK
YOU