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1.Absorption (uptake) from alveoli into pulmonary capillary blood. 2.Distribution in the body 3.Metabolism 4.Elimination (lungs)
is to achieve a constant and optimal brain partial pressure of inhaled anesthetic PA Pa Pbr PA is an indirect measurement of anesthetic partial pressure at brain.
1.Transfer of inhaled anestetic from machine to alveoli 2.Transfer from alveoli to arterial blood 3.Transfer from arterial blood to brain
concentration (Fi) -Fresh gas flow rate, -volume of breathing system, -absorption by machine or breathing circuit.
Uptake
Uptake by pulmonary circulation = b/g
C(AV)Q b/g = blood gas partition coefficient C(AV)= difference of concentration of anesthetic between alveolar and venous blood Q = Cardiac output
of FA and alveolar partial pressure of anesthetic slower the rate of induction (Concentration of a gas partial pressure)
A. Solubility in blood B. Alveolar blood flow C. Partial pressure difference between alveolar gas and venous blood
are taken up by blood less avidly has faster rate of induction than soluble agents like halothane.
gas in each of two phases at equilibrium (equal partial pressures) b /g = 0.47 for nitrous oxide.
Partition coefficients of volatile Agent N 2O Halot hane Isoflurane Desflurane Sevofluran e anesthetics at 37oC Blood/Gas Brain/Blood Fat /Blood 0.47 2.4 1.4 0.42 0.65 1.1 2.9 2.6 1.3 1.7 2.3 60 45 27 48
Higher b/g induction is prolonged. Blood/gas solubility is increased by post prandial lipidemia
and is decreased by anaemia.
cardiac output anesthetic uptake slower induction Effect of cardiac output is more pronounced for more blood
soluble anesthetic
Halothane may create a positive feed back loop. Cerebral blood flow: It is maintained even in shock up to
moribund stage (BP<40 mmHg) and takes a greater proportion of cardiac output, increasing the effect of inhaled anesthetic.
(c) Partial pressure difference between alveolar gas and venous blood
tissue is determined by (1) Tissue solubility of agent, (2) Tissue blood flow, (3) Partial pressure difference between arterial blood and tissues
their
Tissue can be divided into 4 groups based on solubility's and blood flow.
endocrine organ) (moderate solubility and small volumes), first to take up appreciable amount of anesthetic and first to fill.
halothane) will create a negative feed back protective effect. This effect is lost in mechanical ventilation.
Concentration effect
concentration of inhaled anesthetic in a smaller lung volume due to uptake of all gases in lung.
1.7%second gas O
2
31.7%
80% sec g
N2O
66.7%
N2O
40% 0.4%
O N2O
7.6 32%
Reflect the ability of high volume uptake of one gas (first gas) to accelerate the rate of increase of alveolar partial pressure of a second concurrently administered 'Companion gas' (Second gas) Factors affecting arterial concentration (Fa)
pressure are assumed to be equal, but in reality arterial partial pressure are consistently less than alveolar due to venous admixture, alveolar, dead space, ventilation perfusion mismatching.
Elimination comprises :
-Biotransformation: accounts for minimal decrease in rate of decline of alveolar partial pressure. More important for soluble anesthetic, cytochrome P-450 group of isozymes (CYP2E1) appears to important for some volatile anesthetic. Ex. it accounts for halothane faster elimination than isoflurance. -Transcutaneous loss. -Exhalation: The most important route for elimination is alveolar factors that speed induction also favour recovery that is elimination of rebreathing, high fresh gas flow, low anaesthetic circuit volume, high cerebral blood flow, increased ventilation.
Clinical application
Factors that increased the speed of
induction - Greater inhaled concentration - Hyperventilation - Poor circulation to nonvital organs- shock, dehydration old age, wasting of body tissue - High gas flow system Factors that decrease speed of induction - Respiratory obstruction, laryngospasm, bronchial secretions, lug disease. - Respiratory depression due to premedication iv induction agent inhalational agent itself. - Increased circulation to non vital organs: in anxiety, thyrotoxicosis, obesity, robust subjects.
concentration at 1 atm that prevents skeletal muscle movement in response to a supramaximal painful stimulus (surgical incision) in 50% of patients. Immobility measured by MAC is medicated principally by effects on spinal cord only. MAC mirrors brain partial pressure, allows comparison of patency, standard for experimental evaluation.
Ag e n t
N 2O
M AC%
V a p or p r e ssur e ( m m H g a t 2 0 oC)
MAC are roughly additive for CNS depression. CVS effect may not be equivalent at same MAC. MAC is equivalent to median effect dose. Roughly 1.3 MAC of any volatile anesthetic has been found prevent movement in about 95% of patients (ED95)
Variable
HYPOTHERMIA HYPERTHERMIA YOUNG AGE ELDERLY ACUTE ALCOHOL INTOX CHRONIC ALCOHOL ABUSE ANAEMIA HEMATOCRIT <10% Pao2 < 40 mmHg PaCO2 > 95 mmHg THYROID DISEASE B.P. MAP < 40 mmHg HYPERCALCEMIA HYPERNATREMIA HYPONATREMIA PREGNANCY I.V. ANESTH. DRUGS
Effect on MAC
decrease decrease increase decrease decrease increase decrease decrease decrease no change decrease decrease increase decrease decrease decrease
Com m ent s
increase if > 42 0 C
Among the most striking is 6% decrease in MAC per decade of age MAC is relatively unaffected by species, sex or duration of anesthesia 150 Estimated MAC = -------------------------------------oil gas partition coefficient
Theories of anesthetic action General anesthesia: loss of consciousness, analgesia, amnesia, muscle relaxation. Variety of substances capable of producing general anesthesia. Various agents probably prevalence anesthesia by different methods (agent specific theory)
Mechanism of immobility: - due to action on spinal cord. Drug induced depression of excitation and enhancement of inhibition. Excitatory alpha amino 3AMPA and NMDA receptors and inhibitory. GABA and glycine receptors involved, Na ion channel also important Ionotropic and metabotrapic receptors Ionctropic (ligand gated ion channels) neurestransmitter GABA receptors. Metabotropic receptors Neutrotransmitter acetyl choline activation of G protein lead to second messenger pathway. Glumatate (NMDA, AMPA and kainate receptors) Glutamate is principal excitatory neurotransmitter and - important role in immobility
unconsciousness Inhaled anesthetics must act through specific interactions with target
molecule (presumably protein) in CNS
Unconsciousness results from action at higher centre. Correlation between ability to hyperpolarize neurons and anesthetic
potency.
certainly ct by binding directly to proteins rather than by pertubing lipid bilayers. Stereoselectively suggest existence of specific binding sites on membrane protein. Ex. levoisomer of isoflurane is more potent. There is accumulating evidence the GABA and glycine receptors provide molecular binding sites for inhaled anesthetics.
volume hypothesis) Unitary hypothesis All inhalational agents share a common mechanism of action at molecular level.
(critical concentration) in crucial hydrophobic sites such as lipid cell membrane, there is distortion of channel necessary foreign flux, likewise changes in lipid matrix produced by dissolved anesthetic molecules could alter the function of protein in cell membrane.
Evidence against theory include: Effect on lipid bilayers are implausibly small and can
produced by temperature change of 1oC Not all lipid soluble drugs are anesthetic infact, some
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