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ANESTHETICANESTHETICSS

Dr.Shadi- SarahroodiDr.Shadi- SarahroodiPharm.D & PhDPharm.D & PhDPUBLISHED BYPUBLISHED BY

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General AnestheticsGeneral AnestheticsSigns and Stages of Anesthesia Signs and Stages of Anesthesia

(Somewhat related to the response (Somewhat related to the response from Diethyl Ether):from Diethyl Ether):

1.1. Stage I—AnalgesiaStage I—Analgesia

2.2. Stage II—ExcitementStage II—Excitement

3.3. Stage III—Surgical anesthesiaStage III—Surgical anesthesia

4.4. Stage IV—Medullary paralysisStage IV—Medullary paralysis


Patient Factors in Patient Factors in Selection of Selection of AnesthesiaAnesthesia

Liver and kidneyLiver and kidney Respiratory systemRespiratory system Cardiovascular systemCardiovascular system Nervous systemNervous system PregnancyPregnancy


Summary of Summary of anestheticsanesthetics


MOAMOA

modulating ligand-gated modulating ligand-gated ion channels ion channels

activating GABA activating GABA channels channels (hyperpolarizing cells) (hyperpolarizing cells)

blocking excitatory blocking excitatory receptors (like NMDA-receptors (like NMDA-glutamate receptors). glutamate receptors).


Inhalation AnestheticsInhalation Anesthetics

Modern inhalation anesthetics are nonflammable, Modern inhalation anesthetics are nonflammable, nonexplosivenonexplosive

nitrous oxide nitrous oxide halothane, desflurane, enflurane, isoflurane, halothane, desflurane, enflurane, isoflurane,

sevoflurane, and methoxyflurane (easily vaporized sevoflurane, and methoxyflurane (easily vaporized liquid halo-genated hydrocarbonsliquid halo-genated hydrocarbons))


Inhalation AnestheticsInhalation Anesthetics

ether [which is highly flammable]ether [which is highly flammable] chloroform [which has toxic properties] chloroform [which has toxic properties] are no longer used as general anestheticsare no longer used as general anesthetics


important conceptsimportant concepts

minimal alveolar concentration (MAC) minimal alveolar concentration (MAC) blood:gas partition coefficientblood:gas partition coefficient


MACMAC(minimal alveolar concentration)(minimal alveolar concentration)

concentration of anesthetic agent that renders concentration of anesthetic agent that renders 50% of patients immobile during surgery50% of patients immobile during surgery

this is measured as the percentage of the agent this is measured as the percentage of the agent in inspired airin inspired air

MAC is a direct measure of the potency of a drugMAC is a direct measure of the potency of a drug influenced by the influenced by the ageage and and physiologic state physiologic state of the of the

patient and by the patient and by the presence of other presence of other pharmacologic agentspharmacologic agents


blood:gas partition blood:gas partition coefficientcoefficient

solubility of the agent in blood solubility of the agent in blood and is a measure of how quickly the inhalation and is a measure of how quickly the inhalation

anesthetic will equilibrate between lungs and anesthetic will equilibrate between lungs and blood and ultimately the target site in the brainblood and ultimately the target site in the brain

low blood:gas coefficient (e.g., desflurane) low blood:gas coefficient (e.g., desflurane) equilibrate quicklyequilibrate quickly

lower the blood:gas coefficientlower the blood:gas coefficient faster the faster the induction and the faster the recoveryinduction and the faster the recovery


speed of induction of speed of induction of anesthetic effectsanesthetic effects

SolubilitySolubility Inspired gas partial pressure-Inspired gas partial pressure-high partial high partial

pressurepressure in the lungs in the lungs rapid rapid achievement achievement of anesthetic levels in the bloodof anesthetic levels in the blood

Ventilation rateVentilation rate Pulmonary blood flowPulmonary blood flow——high pulmonary blood high pulmonary blood

flowsflows onset of anesthesia is reduced.onset of anesthesia is reduced.


Alveolar Blood Alveolar Blood ConcentrationConcentration


Anesthetic Blood: Gas Partition Coefficient

Minimum Alveolar Concentration (%)*

Metabolism

Nitrous oxide 0.47 >100 None

Desflurane 0.42 6.5 <0.1%

Sevoflurane 0.69 2.0 2-5% (fluoride)

Isoflurane 1.40 1.4 <2%

Enflurane 1.80 1.7 8%

Halothane 2.30 0.75 >40%

Methoxyflurane

12 0.16 >70% (fluoride)


ELIMINATIONELIMINATION

redistribution of the drug redistribution of the drug from the brain to the from the brain to the bloodblood and elimination of the drug and elimination of the drug through the through the lungs.lungs.


desflurane, sevofluranedesflurane, sevoflurane low blood low blood solubilitysolubility shorter recoveryshorter recovery


EFFECTS OF INHALED EFFECTS OF INHALED ANESTHETICSANESTHETICS

CNS effects: CNS effects: decrease brain metabolic rate. decrease brain metabolic rate. reduce vascular resistance reduce vascular resistance increase cerebral increase cerebral

blood flow. blood flow. High concentrations of High concentrations of enfluraneenflurane may cause may cause spike-and-spike-and-

wave activity wave activity and muscle twitching, and muscle twitching, nitrous oxide has low anesthetic potency (ie, a high nitrous oxide has low anesthetic potency (ie, a high

MAC), it exerts marked MAC), it exerts marked analgesicanalgesic and and amnesticamnestic actions.actions.


EFFECTS OF INHALED EFFECTS OF INHALED ANESTHETICSANESTHETICS Cardiovascular effectsCardiovascular effects decrease arterial blood pressure moderatelydecrease arterial blood pressure moderately Enflurane and halothane: myocardial Enflurane and halothane: myocardial

depressants depressants isoflurane, desflurane, and sevoflurane: isoflurane, desflurane, and sevoflurane:

peripheral vasodilation peripheral vasodilation Nitrous oxide: less likely to lower blood pressureNitrous oxide: less likely to lower blood pressure


EFFECTS OF INHALED EFFECTS OF INHALED ANESTHETICSANESTHETICS Respiratory effects:Respiratory effects: dose-dependent decrease in tidal volume and dose-dependent decrease in tidal volume and

minute ventilationminute ventilation increase in arterial increase in arterial COCO22 tension tension

Bronchodilation except desflurane(pulmonary Bronchodilation except desflurane(pulmonary irritant). irritant).


ToxicitiesToxicities

Halothane: Postoperative hepatitis (rarely)Halothane: Postoperative hepatitis (rarely)(formation of reactive metabolites that cause direct toxicity or initiate immune-mediated responses.)(formation of reactive metabolites that cause direct toxicity or initiate immune-mediated responses.)

Methoxyflurane, enflurane and sevoflurane: Methoxyflurane, enflurane and sevoflurane: Fluoride releaseFluoride release renal insuffi ciency renal insuffi ciency

nitrous oxide: megaloblastic anemianitrous oxide: megaloblastic anemia anesthetics + neuromuscular blockers anesthetics + neuromuscular blockers (Susceptible patients)(Susceptible patients): :

malignant hyperthermia malignant hyperthermia mutations in the gene loci corresponding to the ryanodine receptor (RyRl)mutations in the gene loci corresponding to the ryanodine receptor (RyRl)

Dantrolene


Intravenous Intravenous Anesthetics Anesthetics BARBITURATES: Thiopental and methohexital BARBITURATES: Thiopental and methohexital BENZODIAZEPINES: Midazolam BENZODIAZEPINES: Midazolam KETAMINEKETAMINE OPIOIDS: Morphine and fentanyl OPIOIDS: Morphine and fentanyl PROPOFOLPROPOFOL ETOMIDATEETOMIDATE


BARBITURATESBARBITURATES

high lipid solubilityhigh lipid solubility rapid entry into the brain rapid entry into the brain surgical anesthesia in one circulation time (< 1 surgical anesthesia in one circulation time (< 1 min). min).

short surgical proceduresshort surgical procedures hepatic metabolismhepatic metabolism respiratory and circulatory depressantsrespiratory and circulatory depressants depress cerebral blood flowdepress cerebral blood flow decrease intracranial pressure.decrease intracranial pressure.


Redistribution of Redistribution of ThiopentalThiopental


BENZODIAZEPINESBENZODIAZEPINES

The The onsetonset of its CNS effects is of its CNS effects is slower than that slower than that of thiopentalof thiopental

flumazenil, accelerates recovery from flumazenil, accelerates recovery from midazolam and other benzodiazcpines.midazolam and other benzodiazcpines.


KETAMINEKETAMINE

dissociative anesthesiadissociative anesthesia patient remains conscious patient remains conscious marked catatonia, analgesia, and amnesia. marked catatonia, analgesia, and amnesia. phencyclidine (PCP)phencyclidine (PCP) cardiovascular stimulantcardiovascular stimulant increase in intracranial pressure. increase in intracranial pressure. disorientation, excitation, and hallucinations occur disorientation, excitation, and hallucinations occur

during recoveryduring recovery


OPIOIDSOPIOIDS

Morphine and fentanyl Morphine and fentanyl Intravenous opioids :chest wall rigidityIntravenous opioids :chest wall rigidity Respiratory depression Respiratory depression Neuroleptanesthesia Neuroleptanesthesia ((state of analgesia and amnesia):state of analgesia and amnesia): fentanyl fentanyl

is used with droperidol and nitrous oxide.is used with droperidol and nitrous oxide. Alfentanil and remifentanilAlfentanil and remifentanil (NEW) (NEW)


PROPOFOLPROPOFOL

RapidRapid as the intravenous barbiturates as the intravenous barbiturates antiemeticantiemetic prolonged sedation prolonged sedation marked hypotension during induction of anesthesiamarked hypotension during induction of anesthesia Total body clearance is Total body clearance is greater than hepatic greater than hepatic blood blood

flow, suggesting elimination includes flow, suggesting elimination includes other other mechanisms mechanisms in addition to metabolism by in addition to metabolism by liver liver enzymes.enzymes.


ETOMIDATEETOMIDATE

rapid induction rapid induction minimal change in cardiac function minimal change in cardiac function minimal change in respiratory rate minimal change in respiratory rate not analgesicnot analgesic cause pain and myoclonus on injection and cause pain and myoclonus on injection and

nausea postoperativelynausea postoperatively Prolonged administration may cause adrenal Prolonged administration may cause adrenal

suppression.suppression.


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www.medicalppt.blogspot.com for more lectures anesthetics dr.shadi- sarahroodi pharm.d & phd...

Documents

brainlow blood

cerebral blood flow

gas coefficientfaster

low anesthetic potency

high mac

gaba channels

excitatory receptors

recoveryspeed of induction