anesthetics.ppt

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ANESTHETICSDr.Shadi- SarahroodiPharm.D & PhD

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General AnestheticsSigns and Stages of Anesthesia (Somewhat

related to the response from Diethyl Ether):

1. Stage I Analgesia

2. Stage IIExcitement

3. Stage IIISurgical anesthesia

4. Stage IVMedullary paralysis


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Patient Factors in Selection

of AnesthesiaLiver and kidney

Respiratory systemCardiovascular systemNervous system

Pregnancy


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Summary of anesthetics


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MOA

modulating ligand-gatedion channels

activating GABAchannels(hyperpolarizing cells)blocking excitatoryreceptors (like NMDA-glutamate receptors).


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Inhalation Anesthetics

Modern inhalation anesthetics are nonflammable,nonexplosive

nitrous oxidehalothane, desflurane, enflurane, isoflurane,sevoflurane, and methoxyflurane (easily vaporized

liquid halo-genated hydrocarbons)


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Inhalation Anesthetics

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


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MAC (minimal alveolar concentration)

concentration of anesthetic agent that renders50% of patients immobile during surgerythis is measured as the percentage of theagent in inspired air MAC is a direct measure of the potency of adruginfluenced by theage and physiologic stateof the patient and by thepresence of other pharmacologic agents


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blood:gas partition

coefficientsolubility of the agent in bloodand is a measure of how quickly the inhalationanesthetic will equilibrate between lungs andblood and ultimately the target site in the brainlow blood:gas coefficient (e.g., desflurane)equilibrate quicklylower the blood:gas coefficient faster the induction and the faster the recovery


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speed of induction of

anesthetic effectsSolubilityInspired gas partial pressure- high partialpressure in the lungs rapid achievementof anesthetic levels in the bloodVentilation ratePulmonary blood flow high pulmonary bloodflows onset of anesthesia is reduced.


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Alveolar Blood

Concentration


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Anesthetic Blood: Gas PartitionCoefficient

Minimum Alveolar Concentration (%)*

Metabolism

Nitrous oxide 0.47 >100 None

Desflurane 0.42 6.5 70% (fluoride)


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ELIMINATION

redistribution of the drugfrom the brain to thebloodand elimination of the drugthrough the

lungs.


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desflurane, sevoflurane low bloodsolubility shorter recovery


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EFFECTS OF INHALED

ANESTHETICS CNS effects:decrease brain metabolic rate.reduce vascular resistance increasecerebral blood flow.High concentrations of enfluranemay causespike-and-wave activityand muscle twitching,nitrous oxide has low anesthetic potency (ie, ahigh MAC), it exerts markedanalgesic andamnestic actions.


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EFFECTS OF INHALED

ANESTHETICS Cardiovascular effectsdecrease arterial blood pressure moderatelyEnflurane and halothane: myocardialdepressantsisoflurane, desflurane, and sevoflurane:peripheral vasodilationNitrous oxide: less likely to lower bloodpressure


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EFFECTS OF INHALED

ANESTHETICS Respiratory effects:dose-dependent decrease in tidal volume andminute ventilation increase in arterialCO2 tensionBronchodilation except desflurane(pulmonaryirritant).


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Toxicities

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

Methoxyflurane, enflurane and sevoflurane:Fluoride release renal insufficiencynitrous oxide: megaloblastic anemia

anesthetics + neuromuscular blockers(Susceptible patients):malignant hyperthermia

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

Dantrolene


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Intravenous Anesthetics

B ARBITURATES: Thiopental and methohexitalBENZODIAZEPINES: MidazolamKETAMINE OPIOIDS: Morphine and fentanylPROPOFOL ETOMIDATE


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BARBITURATES

high lipid solubility rapid entry into the brainsurgical anesthesia in one circulation time

(< 1 min).short surgical procedureshepatic metabolismrespiratory and circulatory depressantsdepress cerebral blood flowdecrease intracranial pressure.


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Redistribution of

Thiopental


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BENZODIAZEPINES

The onset of its CNS effects isslower than thatof thiopental

flumazenil, accelerates recovery frommidazolam and other benzodiazcpines.


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KETAMINE

dissociative anesthesiapatient remains consciousmarked catatonia, analgesia, and amnesia.phencyclidine (PCP)cardiovascular stimulantincrease in intracranial pressure.disorientation, excitation, and hallucinations

occur during recovery


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OPIOIDS

Morphine and fentanylIntravenous opioids :chest wall rigidityRespiratory depressionNeuroleptanesthesia (state of analgesia and amnesia): fentanylis used with droperidol and nitrous oxide. Alfentanil and remifentanil(NEW)


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PROPOFOL

Rapid as the intravenous barbituratesantiemeticprolonged sedationmarked hypotension during induction of anesthesiaTotal body clearance isgreater than hepaticblood flow, suggesting elimination includesother mechanisms in addition to metabolism byliver enzymes.


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ETOMIDATE

rapid inductionminimal change in cardiac functionminimal change in respiratory ratenot analgesiccause pain and myoclonus on injection andnausea postoperativelyProlonged administration may cause adrenalsuppression.


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