INHALATION AGENTS 2013/05/28 1
2013/05/28 Isn t it romantic? 2
Administration 3
Physics Critical temperature Vapour vs. Gas Vapour pressure Blood Gas Partition Coefficient BGPC MAC 2013/05/28 4
Critical temperature Substance in gaseous phase Forced back into fluid phase If pressure in container increases Except!!!!!!!!!!!!!!!!!!!! 2013/05/28 5
Critical temperature If substance in gaseous phase exist Above a specific critical temperature NO in pressure will force phase change! Will stay a gas 6
Critical temperature 7
Critical temperature 8
Definition of a vapour/gas Vapour Gaseous phase below critical temperature Gas Gaseous phase above critical temperature 9
Application of Tcrit. Oxygen = T crit. of -119ºC Quantity in cylinder measured by pressure gauge Nitrous oxide = T crit. of 36,5ºC Revert to fluid phase in cylinder Quantity in cylinder by weight! Is a VAPOUR not a gas! 2013/05/28 10
Vapour pressure 2013/05/28 11
Vapour pressure: implications 2013/05/28 12
INHALATION AGENTS IDEAL INHALATION AGENT Stable (heat, light, metal, soda lime) No preservative Long shelf life Non-flammable, explosive in air, O 2, N 2 O Non-irritating to airways Atmospherically friendly Cheap to synthesize 2013/05/28 13
INHALATION AGENTS IDEAL INHALATION AGENT Low MAC Low blood-gas coefficient Not metabolised Non-toxic to any organ No cardiovascular effects No respiratory effects Analgesic 2013/05/28 14
INHALATION AGENTS IDEAL INHALATION AGENT Reversible CNS effects No epileptogenic activity No drug interaction No effect on pregnant uterus or foetus 2013/05/28 15
INHALATION AGENTS RATE OF UPTAKE IN BLOOD DEPENDS ON: Solubility in blood Cardiac output Concentration administered Alveolar ventilation 2013/05/28 16
INHALATION AGENTS F i FA BGPC What makes the patient sleep? C.O. LUNGS PLASMA BRAIN 2013/05/28 17
INHALATION AGENTS 18
Solubility of vapour in blood 19
Solubility of vapours in blood 2013/05/28 20
INHALATION AGENTS BLOOD-GAS PARTITION COEFFICIENT Solubility of vapour in blood: The higher the BGPC the more soluble The higher the BGPC the slower the action The higher the BGPC the slower the recovery and the opposite is also true 2013/05/28 21
INHALATION AGENTS Bus vs motorcycle 2013/05/28 22
INHALATION AGENTS MINIMUM ALVEOLAR CONCENTRATION: MAC 50 Alveolar [vapour] when 50% of people will lie still upon skin incision (and 50% will move!) Indication of potency! 2013/05/28 23
INHALATION AGENTS VAPOUR BGPC MAC Desflurane 0,42 6% N 2 O 0,47 104% Sevoflurane 0,6 2% Isoflurane 1,4 1,15% Enflurane 1,8 1,68% Halothane 2,3 0,77% 2013/05/28 24
INHALATION AGENTS MAC Chronic C 2 H 5 OH Hyperthyroidism Hyperthermia Small children Drug dependency Narcotic misuse Cardiac output MAC Acute C 2 H 5 OH Analgesics Sedatives / Opiates Hypothyroidism Hypothermia Geriatrics Cardiac output 2013/05/28 25
INHALATION AGENTS HALOGENATED HYDROCARBONS Halothane ETHERS Enflurane Isoflurane Sevoflurane Desflurane Diethylether GASSES N 2 O / Xenon 2013/05/28 26
N 2 O N 2 O 0,47 104% Colourless, odourless, non-flammable Colour code = blue Critical temperature = 36,5 o C Vapour pressure = 5500kPa Weigh cylinder to determine content Below 36,5 o C VAPOUR!! (don t tell anyone!) 2013/05/28 27
N 2 O N 2 O 0,47 104% - 2 nd gas effect - Diffusion hypoxia 2013/05/28 28
N 2 O N 2 O 0,47 104% - Expand air filled cavities - Bone marrow suppression - Teratogenic - PVR - Myocardial contractility 2013/05/28 29
HALOTHANE Halothane 2,3 0,77% Cerebral blood flow intracranial pressure ICP 2013/05/28 30
Cardiac effects HALOTHANE Halothane 2,3 0,77% Decreased myocardial contractility Ca ++ antagonist SVR remains normal Sensitizes myocardium for catecholamines Suppresses conduction (whole conduction system) Bradycardia Re-entry phenomena 2013/05/28 31
HALOTHANE Halothane 2,3 0,77% Respiratory system Bronchodilator Hypoventilation 2013/05/28 32
HALOTHANE Liver 20% metabolised by liver Halothane hepatitis: Immunologic reaction Toxic reductive metabolites Tri-fluoro acetic acid (TFA) Ischaemic conditions Rare 1:35000 but mortality risk 90% 2013/05/28 33
HALOTHANE Halothane hepatitis predisposing factors: Female Middle age Obesity Multiple administrations Enzyme induction Glutathione (fasting) 2013/05/28 34
Relatively rapid induction and recovery Relatively low BGPC. Hepatitis Smells OK CVS Halothane RESP HR CO BP Dysrhythmias Conduction Catecholamine sensitivity VO 2 Secretions Breathing Bronchodilation 35
ENFLURANE 2013/05/28 36
ENFLURANE Enflurane 1,8 1,68% Irritating to the awake airway Less dysrhythmogenic than Halothane 2% metabolised by liver Increased ICP by increased CSF production and reabsorption Epileptogenic changes on EEG (with CO 2 ) BP more due to vasodilation (less CO) Potentiate skeletal muscle relaxants 2013/05/28 37
Smells Bad X Rapid Induction Low BGPC EXPENSIVE EEG EnfluranE Breathing CVS RESP No dysrhyhtmias BP less than Halo Finorg Bronchodilator 2013/05/28 38
ISOFLURANE Isoflurane 1,4 1,15% CNS Maintains autoregulation up to 1 MAC Non-epileptogenic CSF production & CSF absorption Least CBF Least ICP Most ideal for neuro-anaesthesia 2013/05/28 39
ISOFLURANE CVS Potent vasodilator Mild tachycardia? Less myocardial suppression compared to halothane Coronary steal? (steal-prone anatomy) Not dysrhythmogenic 2013/05/28 40
ISOFLURANE Irritating to the awake airway Potent muscle relaxant 0,2% metabolised by the liver 2013/05/28 41
BGPC=1.4 PUNGENT EXPENSIVE Isoflurane CVS Vasodilatation Coronary STEAL 2013/05/28 42 BP Bronchodilator Drug of choice: NEURO LIVER
SEVOFLURANE Sevoflurane 0,6 2% Non-irritating to the airways (SMELLS NICE!) Ideal agent for inhalation induction (second choice is Halothane) CNS = same as isoflurane CVS = small drop in BP = not dysrhythmogenic 2013/05/28 43
SEVOFLURANE Sevoflurane 0,6 2% 2-5% metabolised by the liver Hexa-fluoro-isopropanol hepatotoxic Inorganic fluoride Decomposes 6% per hour in soda lime at 22 o C 2013/05/28 44
SEVOFLURANE Sevoflurane 0,6 2% SEVOFLURANE Desiccated soda lime BREAKDOWN COMPOUND A 2013/05/28 45
SEVOFLURANE Sevoflurane 0,6 2% COMPOUND A β-lyase Nephrotoxic substance 2013/05/28 46
BGPC=0.6 Fast onset Fast emergence Pleasant smell VERY EXPENSIVE Sevoflurane CVS Vasodilatation BP NO STEAL Drug of choice: NEURO Gas induction Renal Compound A 47
DESFLURANE Desflurane 0,42 6% BGPC = 0,42 High vapour pressure (681mmHg at 20 o C) New technology vapouriser Tachycardia for few minutes Produces CO in desiccated soda lime (so does enflurane, isoflurane) 2013/05/28 48
DIETHYLETHER BGPC = 12 Respiratory depression precedes cardiovascular depression Good analgesic Highly flammable Nausea and vomiting Secretions 2013/05/28 49
BGPC=0.42 Rapid onset Rapid emergence VERY PUNGENT VERY EXPENSIVE Desflurane CVS Vasodilatation BP Sympathetic response RESP irritant Drug of choice: LIVER Short cases 50
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