Pharmacology of Anesthesia 1

8/8/2019 Pharmacology of Anesthesia 1

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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 AxonalImpulse conduction.



This occurs by;

Presynaptic Mechanisms:- A

1- Activation of presynaptic K+ channelsTransmitter same as presynaptic inhibition.

2- Volatile agents & propofol (but not thiopental) glutamate.

Postsynaptic Mechanisms:-B

G.A. Depression of postsynaptic response.

Summary:In

G.A. act mainly at synaptic transmission rather thanaxonal impulse conduction.



M inimum Alveolar Concentration ( M AC)

Definition:

It is the Minimum Alveolar Concentration of theanesthetic at 1 atmosphere absolute that preventsmovement of 50% of the population to a standard

stimulus (e.g. surgical incision)

Types of M. A.C:1- M.A.C as above2- M.A.C awake 3- M.A.C 95%

4- M.A.C intubation



F actors Affecting M. A.C .

F actors M. A.C (CNS Excitation)

F actors M. A.C (CNS Depression)

1- Hypothermia 42 C1-Hyperthermia & Hypothermia

2- Young2- Age : Elderly

3- Chronic Abuse 3- Alcohol : Acute Toxicity

4- Thyrotoxicosis4- Myxoedema

5- Hypernatremia5- Hyponatremia

6- Drugs:-- Sympathomimetics e.g. cocaine,

ephedrine(they symp. Activity)-- Acute Amphetamine

- Cocaine

6- Drugs:-- Alpha 2 agonist e.g. methyl dopa,

reserpine, clonidine ( the symp. Activity)

-Chronic Amphetamine-Local Anesth. (exp. Cocain)- Others; N20, Barbiturates,Ketamine, Opioids,

Benzodiazepines



I nhalational Anesthetic includes;

1- N2O2- Halothane

3- Ether

4- Methoxyfluran

5- Enflurane

6- Isoflurane7- Desflurane

8- Sevoflurane



SevofluraneDesfluraneN2O

ChemicalStructure

-Non-flammable-Non-explosive-Colorless-Pleasant odor

-Non-flammable-Non-explosive-Colorless-Pungent odor

-Non-flammable-Non-explosive-Colorless-Odorless(sweet odor)

PhysicalProperties

2%rapid induction ,slower

recovery than Desf.

6-9(7.3)The most rapid

induction & recovery

105%MA C

Excretion &Metabolism

Nephrotoxicity

Due to Fluoride &compound A

Hepatotoxicity

( only 1 case reported)

Prolonged Exposure

--vit.B12 dependentenzymes causing:Peripheral Neuritis,Myelo-neuropathy,Megaloblastic Anemia, Agranulocytosis, Bone

Marrow AplasiaTeratogenic effect

Toxicity

The main route of excretion of all anesthetics are the Lung

Metabolism occurs in the Liver by Cytochrme P-450 isoenzymes



SevofluraneDesfluraneN2O Action

Good Anesthetic Weak Analgesic

Cer. VD CBF ICT

Good Anesthetic Weak Analgesic

Cer. VD CBF ICT

Good Analgesic Weak Anesthetic

Cer. VD CBF ICTCMRO2

CNS

Same ;but the least effect onRespiration

Irritant to Resp.(coughing,breath-holding&secretions), RR & Vt

Bronchodilator, DepressesHypoxic Drive

Not irritantRR & Vt

Depresses Hypoxic

Drive

Resp.

- Dep. Myoca. Contra.- SVR, ABlP, C VD

- Dep. Myoca. Contra.- SVR, ABlP, HR,C VD

- Dep. Myoca. Contra.- P.V C P.VR - Arrhythmias

C VS

Moderately RelaxesStrongly RelaxesNo MR Neurmuscular

Renal

Hepatic

RBF GFR UOP

H.B.F. H.B.F.



SevofluraneDesfluraneN2O

Potentiates NDMR Potentiates NDMR Air Embolism

Acute int. obstru.PneumothoraxTymp. Memb. Graf.PHTN

Contraindication

Inhal ati nal nesthetic icit :H epat t icit .- 1

. N ephr t icit- 2

Abs r bents. 2 Inter acti n with O- 3



P harmacokinetic of I .V. Anesthetics :

- A bsorption

- Distribution

- Metabolism (Biotransformation)

- Excretion



I .V. Anesthetics include :1- Thiopentone Sodium

2- Methohexitone Sodium

3- Propofol

4- Etomidate

5- KetamineOther i.v. agents used in anesthesia:

- Benzodiazepines

- Opioids- Neuroleptic Agents



KetamineEtomidatePropofolThiopentone

Sodium

Lipid Soluble WaterSoluble

PhysicalProperties

IV: 1-2mg/kg

IM: 5-10mg/kgOr: 5-10mg/kg

IV :0.2-0.3

mg/kg

IV: 1.5-2.5 mg/kg

IVI :10mg/kg/hr 1st 10m8mg/kg/hr 2nd 10m6mg/kg/hr

IV: 3-5 mg/kg

Rectal : 30-44mg/kg

Dose

Metabolism

Excretion

Lipid Soluble

LIVER URINE



KetaminePropofolThiopentone SodiumPh.Action

Mech. of Action:Dissociativ Aneth.(dissociates thalamus

from cortex.Blocks NMDA Rs.- Clinically..- CNS (+)-EEG changes.- CMR

- PONV - ++ Excitatory Ph.

Mech. of Action: As Thiopentone ; but- Not Anticonvulsant

- Excitatory Ph.

Mech. of Action:Depresses RF in B.stemby GABA

unconscious.- CNS depresses- Anticonvulsant- CMR - No PONV - No Excitatory Ph.

CNS

1- Resp.(--)1- Resp.(--)1- Resp.(--)2- Bronchospasm3- Laryngeal spasm

Resp.

1- ABP2- HR 3- CO +ve inotropic

1- ABP2- HR 3- CO maintained

1- ABP2- HR 3- CO maintained

C VS

N-M



KetaminePropofolThiopentone Sodium

1- Crosses Placenta2- IOP3- Salivation

1- RBF2-HBF3- Cortisol

1- RBF2- HBF3- IOP

Others

1-CNSExcitatory Ph. +ICP ++PONV 2- C VS ABP++

3- Salivation

1- Resp.(--)2-CNS(Excitatory Ph. +)3- C VS (--)4- During Injection5- Allergic Reaction

1- CNS (Drowsiness)2- Res.(--)3- C VS (--)4- During Injection5- Allergic Reaction

AdverseEffects

......................................Indicat-ion

1- Airway O struction1- Airway O struction

2- Hypersensitivity 3- Long ter sedationin children in ICU

1- Airway O struction

2- Hypersensitivity 3- Porphyria

Contrai-

ndication

T I V A



THANK YOU

Pharmacology of Anesthesia 1

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