Claro M. Isidro md

Loss of consciousness Analgesia Adequate muscle relaxation

Analgesia•Loss of sensation to pain

General Anesthetics• Reversible loss of consciousness• Loss of CNS activity

Local Anesthetics• No loss of consciousness• Reversible loss of pain sensation

INHALATIONAL ANESTHETICS

INTRAVENOUS ANESTHETICS

Stage I: Analgesia Stage II: Excitement/ Delirium Stage III:Surgical Anesthesia

› Plane I: reg. breathing loss of eye movement

› Plane II initiation of IC muscle paralysis

› Plane III: completion ICM paralysis› Plane IV: diaphragmatic paralysis

Stage IV:Medullary Paralysis

Pharmacokinetics: tension (partial pressure) in the brain

depth tension in this tissues rate of

induction and recovery

Flow of anesthetic during induction:Anesthesia Lungs Arterial Brain &

machine blood tissues

GENERAL ANESTHETICS:

Pharmacokinetics: absorption (uptake) distribution metabolism elimination lungs

Principal objective:To achieve a constant and optimal brain partial pressure of the inhaled anesthetic

GENERAL ANESTHETICS:

• 2 PHASES:2 PHASES:

– Pulmonary PhasePulmonary Phase

– Circulatory PhaseCirculatory Phase

GENERAL ANESTHETICS: UPTAKEGENERAL ANESTHETICS: UPTAKE

Pulmonary Phase Concentration of the anesthetic

agent in the inspired gas

Pulmonary ventilation

Transfer of anesthetic gases from alveoli to blood• solubility of the agent• rate of pulmonary blood flow• partial pressure in the alveoli

and mixed venous blood

GENERAL ANESTHETICS: UPTAKEGENERAL ANESTHETICS: UPTAKE

GENERAL ANESTHETICS: SOLUBILITYPartition Partition

CoefficientCoefficientBlood:GasBlood:Gas Brain:BloodBrain:Blood

SolubleSolubleMethoxyfluraneMethoxyflurane 1212 22IntermediateIntermediateHalothaneHalothane 2.42.4 1.91.9EnfluraneEnflurane 1.91.9 1.51.5IsofluraneIsoflurane 1.41.4 1.61.6Poorly solublePoorly solubleNitrous OxideNitrous Oxide 0.460.46 1.11.1DesfluraneDesflurane 0.420.42 1.31.3SevofluraneSevoflurane 0.590.59 1.71.7

Pulmonary Phase Concentration of the anesthetic

agent in the inspired gas

Pulmonary ventilation

Transfer of anesthetic gases from alveoli to blood• solubility of the agent• rate of pulmonary blood flow• partial pressure in the alveoli

and mixed venous blood

GENERAL ANESTHETICS: UPTAKEGENERAL ANESTHETICS: UPTAKE

GENERAL ANESTHETICS: UPTAKEGENERAL ANESTHETICS: UPTAKE• Circulatory or Distribution Phase

SolubilitySolubility tissue:blood solubility coefficienttissue:blood solubility coefficient

Tissue Blood FlowTissue Blood Flow Vessel-Rich group – 75% of COVessel-Rich group – 75% of CO Muscle Group – 3%Muscle Group – 3% Fatty Group – 2%Fatty Group – 2% Vessel-Poor group - <1%Vessel-Poor group - <1%

Partial Pressure of Gas in Arterial Partial Pressure of Gas in Arterial Blood and TissuesBlood and Tissues

RECOVERY and EMERGENCEFactors affecting rate of Elimination

SOLUBILITY IN BLOOD & TISSUE BLOOD FLOW

Flow of anesthetic during elimination:Tissue/ Blood Lungs AnesthesiaBrain Machine

GENERAL ANESTHETICS:GENERAL ANESTHETICS:

Rapid & pleasant induction & recovery Rapid changes in depth of anesthesia Adequate relaxation of smooth muscle Wide margin of safety Absence of toxic effect

GASEOUS ANESTHETIC: NITROUS OXIDE CYCLOPROPANE

VOLATILE ANESTHETIC:A. HalogenatedA. Halogenated B. Non B. Non

HalogenatedHalogenated1. 1. HalothaneHalothane 1. Ether1. Ether2. Enflurane2. Enflurane 2.2. Chloroform Chloroform3.3. Isoflurane Isoflurane 4. Methoxyflurane4. Methoxyflurane5. Sevoflurane5. Sevoflurane6.6. Desflurane Desflurane

2 bromo-111 triflouroethane is a non ether derivative ( an ethane) vapor is pleasant to smell and non-irritating can cause a dose dependent reduction of arterial

blood pressure due to: 1.  Direct depression of the myocardium 2. The normal baroreceptor mediated tachycardia

in response to hypotension is obtunded sensitizes the myocardium to catecholamines

leading to cardiac arrhythmia’s causes a dose related reduction in the ventilatory

response to carbon dioxide produce adequate muscle relaxation has no toxic effect on the kidneys

Repeatedadministration over a short period of time has been implicated to produce halothane hepatitis

another dreaded complication is malignant hyperthermia, which is characterized by the following:

1. Rapid rise in body temperature 2. massive increase in oxygen consumption 3. increase production of carbon dioxide Cardiotoxic, Hepatotoxic but not Nephrotoxic

2 chloro-112 trifluroethyl difluromethyl ether an halogenated ether derivative produce mild stimulation of salivation and bronchial cause dose dependent myocardial depression

similar to that of halothane sensitizes the myocardium to the effect of

catcholamines , no unusual effect on the GIT muscle relaxation is greater than that of halothane contraindicated in patient with seizure disorder

because it cause CNS irritability in high doses the free fluoride radical a metabolite of enflurane

has been implicated to its renal toxicity so it is contraindicated in patient with renal disorder

Cadiotoxic, Nephrotoxic but not Hepatotoxic

1 chloro-222 trifluroethyl difluromethyl ether an halogenated ether derivative the chemical and physical properties are similar to

those of its isomer enflurane does not sensitize the myocardium to the effect of

cathecholamines cerebral blood flow is increased while the cerebral

metabolism is reduced produce adequate muscle relaxation less nephrotoxic than enflurane less hepatotoxic than halothane agent of choice for cardiac surgery non Cardiotoxic, non Hepatotoxic, non Nephrotoxic Least vicerotoxic

2,2dichloro- 1,1 difluroethyl methyl ether it is clear, colorless liquid with sweet fruity odor non flammable and non explosive in air most potent of the inhalational anesthetic induction of anesthesia is slow due to its high

solubility coefficient respiratory and cardiovascular depression is

generally similar to that of halothane sensitize the myocardium to the effects of

catecholamines nephrotoxicity and hepatotoxicity are the major

disadvantage most toxic of the inhalational anesthetic Cardiotoxic, Hepatotoxic, and Nephrotoxic

a fluorinated methyl ethyl ether that differ from isoflurane only by substitution of a fluoride atom from chlorine

can produce a dose related decrease in blood pressure and cardiac output

non Cardiotoxic, non Hepatotoxic, non Nephrotoxic

Sevoflurane also a fluorinated methyl ethyl ether not irritating to the airways cardivascular effect is similar to isoflurane

Ether first anesthetic discovered seldom use today because of its flammability

and explosive property

Chloroform no longer use today because of liver toxicity non explosive and non flammable has rapid induction and recovery

Nitrous Oxide sweet smelling, non irritating, colorless gas the only inorganic gas in common use possessing

anesthetic properties potent analgesic but a weak anesthetic in the

sense that it does not produce adequate muscular relaxation

ventilatory drive is not affected little or no cardiovascular effectCyclopropane explosive and flammable property

GASEOUS ANESTHETIC: NITROUS OXIDE CYCLOPROPANE

VOLATILE ANESTHETIC:A. HalogenatedA. Halogenated B. Non B. Non

HalogenatedHalogenated1. 1. HalothaneHalothane 1. Ether1. Ether2. Enflurane2. Enflurane 2.2. Chloroform Chloroform3.3. Isoflurane Isoflurane 4. Methoxyflurane4. Methoxyflurane5. Sevoflurane5. Sevoflurane6.6. Desflurane Desflurane

BARBITURATES the most commonly use barbiturates is the ultra short acting

thiopental following a single IV anesthetic dose of thiopental

unconsciousness occur after 10-20 seconds and returns in 20-30 minutes

poor analgesic and may even increase the sensitivity to pain (hyperalgesia) when administered in inadequate amounts.

Not irritating to the respiratory tract Cerebral blood flow and cerebral metabolic rate are reduced Produce a dose related depression of respiration and circulation Agent of choice for induction of anesthesia in patient with

increased intracranial pressure and hypertension Contraindicated in patient with acute intermittent porphyria

and hypotension

INTRAVENOUS ANESTHETICSINTRAVENOUS ANESTHETICS

first introduced for the treatment of anxiety rapidly absorbed from the GIT after oral

administration hypnosis and unconsciousness may be produced

with large doses cause amnesia in 50% of patients

characteristically Anterograde type may cause moderate depression of circulation

and respiration they are not analgesic and it is necessary to

combine several drugs to achieve surgical levels of anesthesia

Ketamine HCl used for induction of dissociative anesthesia a sensation of dissociation is noticed within 15

seconds and unconsciousness becomes apparent within another 30 seconds and lasts for some 40 minutes

intense analgesia and amnesia are established rapidly

muscular relaxation is poor cardiovascular and respiratory system are stable drug of choice for induction of anesthesia in

children and hypotensive patients contraindicated in patients with hypertension

because it increase sympathetic activity can cause increase intraocular pressure contraindicated in patient with glaucoma

2,6 Diisoprophylpenol produces anesthesia at a rate similar to

that of barbiturates cause marked decrease in systemic blood

pressure during induction post operative vomiting is less common

and may have anti-emetic property hypersensitivity is less common

should not be irritating to tissues should not cause permanent damage

to nerves have low systemic toxicity must be effective should have rapid onset but long

duration of action

MOA: block nerve conduction

Structure:› aromatic group (Hydrophobic lipophilic)› amide group (hydrophilic)

tertiary amine or secondary amine› intermediate chain

Ester or Amide

LOCAL ANESTHETICSLOCAL ANESTHETICS

CH2-CH3

NH2 O-O-CH2-CH2-N

O CH2-CH3

Aromatic grp Alkyl Amide grpLipophilic chain Hydrophilic

METABOLISM:

Ester plasma and liver esterases metabolite: PABA

Amide liver

EXCRETION: kidneys

LOCAL ANESTHETICSLOCAL ANESTHETICS

ROUTES OF ADMINISTRATION:

1. Topical2. Local Infiltration3. Nerve Block4. Spinal or Intrathecal injection5. Epidural 6. Caudal

LOCAL ANESTHETICSLOCAL ANESTHETICS

LOCAL ANESTHETICSLOCAL ANESTHETICS

ESTERS:ESTERS:

1.1. CocaineCocaine2.2. ProcaineProcaine3.3. ChloroprocaineChloroprocaine4.4. TetracaineTetracaine

AMIDES:AMIDES:

1.1. LidocaineLidocaine2.2. BupivacaineBupivacaine3.3. MepivacaineMepivacaine4.4. DibucaineDibucaine5.5. PrilocainePrilocaine6.6. EtidocaineEtidocaine

May also be classified into

a. Short acting – cocaine, procaineb. Intermediate acting – lidocaine,

mepivacaine, dibucaine, prilocainec. Long acting – tetracaine, bupivacaine,

etidocaine

1. Hepatotoxic agent a. Isoflurane2. Nephrotoxic agent b. Barbiturate3. Cardiotoxic agent c. Enflurane4. Thiopental d. Halothane5. Flammable agent e. Ether

a. Amide LA b. Esther LA6. Lidocaine7. Tetracaine8. Cocaine9. Bupivacaine10. Etidocaine