2. ANESTHESIA: loss of sensation
General Anesthesia : Renders
the patient
1.amnesic
2.unconscious while causing
muscle relaxation
3.suppression of undesirable
reflexes
3. Anesthesia
In the “old days” the following were used for
anesthesia.
– Alcohol
– Ice for numbing
– Blow to the head
– Strangulation
7. Theories of anesthesia
• Anesthetic potency is closely correlated with
lipid solubility
• Postulated interaction with the lipid membrane
bilayer.
• Interaction with ligand-gated membrane ion
channels.
• Most anesthetics enhance the activity of
inhibitory GABA A-receptors
• Many inhibit activation of excitatory receptors,
such as glutamate and nicotinic acetylcholine
receptors.
8. Stages of Anesthetic Activity
• Stage I - Analgesia
– conscious but drowsy.
– responses to painful stimuli reduced
• Stage II - Excitement
– lose consciousness
– no longer responds to non-painful stimuli
– responds in a reflex fashion to painful stimuli
• Stage III - Surgical anesthesia
– movement ceases and respiration becomes regular
• Stage IV - Medullary paralysis
– respiration and vasomotor control cease
– death occurs
9. Properties of Ideal Inhalational
Anesthetics
• Rapid & pleasant anesthetic induction &
recovery
• Rapid changes in anesthetic depth
• Adequate relaxation of skeletal muscles
• Wide margin of safety
• Absence of toxic effects or other adverse
properties in normal doses
10. MOA
• Increase neuronal threshold for firing leading
to a decrease in neuronal activity
• Hyperpolarization of neurons via activation of
K+ currents
12. • MAC:
• -concentration of
anesthetic gas needed to
eliminate movement among 50%
of patients challenged by
standardized skin incision
13. • INVERSE of MAC is an index of
potency
• *the more lipid soluble,
the LOWER the concentration
needed to produce anesthesia
• The lower the MAC, the more
potent is the anesthetic
14. Highest to lowest MAC
• NO
• Ether
• Enflurane
• Isoflurane
• halothane
15. Solubility to blood
• Based on blood/gas partition coefficient
• Lowest to highest
• NO
• Isoflurane
• Enflurane
• halothane
17. Individual Inhalation Anesthetics
Nitrous oxide:
– low potency, therefore must be combined with
other agents
– rapid induction and recovery
– good analgesic, WEAK anesthetic properties
– risk of bone marrow depression with prolonged
administration.
– Laughing gas
– Can retard O2 uptake during recovery,thus 20% of
O2 is always needed
18. NO
• can cause diffusion hypoxia
• Least hepatotoxic
• safest
19. HALOTHANE
• Prototype
• Weak analgesic; POTENT anesthetic
• Usually co-administered w/ N2O, opioids, or
local anesthetics
• Metabolized to tissue-toxic hydrocarbons
(trifluroethanol) & bromide ion
21. Individual Inhalation Anesthetics
• Enflurane:
– halogenated anesthetic similar to halothane
– less metabolism than halothane; therefore, there is less
risk of toxicity
– faster induction and recovery than halothane (less
accumulation in fat)
– some risk of epilepsy-like seizures. Cns excitation
– Metabolized to flouride ion,excreted in the kidney
22. ISOFLURANE
• Does NOT induce cardiac arrhythmias and
does NOT sensitize the heart to
cathecolamines
• Stable molecule
24. Individual Inhalation Anesthetics
• Desflurane and sevoflurane
– similar to isoflurane
– have faster onset and recovery
– lack of respiratory irritation
– commonly used clinically
25. METHOXYFLURANE
• potent, high lipid solubility
• Used in child birth
• Disadvantages: Metabolized to flouride;
Respiratory and circulatory depression
26. HALOTHANE ENFLURANE ISOFLURANE NITROUS OXIDE
ARRHYTHMIA INCREASED
SENSITIVITY TO
CATHECHOLAMI
NES
INCREASED SLIGHT INC.
CARDIAC
OUTPUT
DECREASED DEC BUT
RECOVERS
DECREASED
BP DECREASED DEC BUT
RECOVERS
DECREASED
RESPI REFLEX INHIBITED INHIBITED
HEPATOTOXICITY HIGH RISK SOME RISK
27. Intravenous Anesthetics
• Thiopental
– barbiturate with very high lipid solubility
– GABA- mimetic
– rapid action because of rapid transfer across blood-brain
barrier
– short duration (about 5 minutes) because of
redistribution, mainly to muscle
– Potent anesthetic, weak analgesic effect
– Little muscle relaxation
– Laryngospasm,not for asthma pt,not w/ porphyria
29. Intravenous Anesthetics
• Etomidate
- potent non barbiturate , hypnotic,
no analgesic
–similar to thiopental but more quickly
metabolized
–less risk of cardiovascular depression
31. Intravenous Anesthetic Agents
• Ketamine
– analogue of phencyclidine, w/ similar properties
(psychotic reactions)
– effect on NMDA-type glutamate receptors
– onset of effect is relatively slow (2-5 minutes)
– produces “dissociative” anesthesia, in which patient may
remain conscious and insensitive to pain
– can increase intracranial pressure
– Causes cardiovascular stimulation but not respiratory
depression
32. Intravenous Anesthetics
• Propofol
– rapidly metabolized
– very rapid recovery; no cumulative effect
– useful for day-case surgery
– causes more respiratory and cardiovascular
depression than barbiturates
– Lowers intracranial pressure
33. propofol (Diprivan)
• Used for maintenance of anesthesia,
sedation, or treatment of agitation
• Has antiemetic properties
– Drowsiness
– Respiratory depression
– Motor restlessness
– Increased blood pressure
34. fentanyl
• Dosage Forms
– IV (Sublimaze)
– patch (Duragesic)
– lozenge (Actiq) for children
• Used extensively for open-heart
surgery due to lack of cardiac
depression
35. Summary of Intravenous Anesthetics
DrugDrug
Speed of induction andSpeed of induction and
recoveryrecovery
Main unwanted effectsMain unwanted effects NotesNotes
ThiopentalThiopental Fast (cumulation occurs,Fast (cumulation occurs,
giving slow recovery)giving slow recovery)
Cardiovascular andCardiovascular and
respiratory depressionrespiratory depression
Widely used as inductionWidely used as induction
agent for routineagent for routine
purposespurposes
HangoverHangover
etomidateetomidate Fast onset, fairly fastFast onset, fairly fast
recoveryrecovery
Excitatory effects duringExcitatory effects during
induction and recoveryinduction and recovery
Less cardiovascular andLess cardiovascular and
respiratory depressionrespiratory depression
than with thiopentalthan with thiopental
AdrenocorticalAdrenocortical
suppressionsuppression
Causes pain at injectionCauses pain at injection
sitesite
propofolpropofol Fast onset, very fastFast onset, very fast
recoveryrecovery
Cardiovascular andCardiovascular and
respiratory depressionrespiratory depression
Rapidly metabolizedRapidly metabolized
Possible to use asPossible to use as
continuous infusioncontinuous infusion
Causes pain at injectionCauses pain at injection
sitesite
KetamineKetamine Slow onset, after-effectsSlow onset, after-effects
common during recoverycommon during recovery
Psychotomimetic effectsPsychotomimetic effects
following recoveryfollowing recovery
Produces good analgesiaProduces good analgesia
and amnesiaand amnesia
Postoperative nausea,Postoperative nausea,
vomiting and salivationvomiting and salivation
MidazolamMidazolam Slower than other agentsSlower than other agents
Little respiratory orLittle respiratory or
cardiovascularcardiovascular
37. • . Local anesthesia
• - MOA: blocks sodium channels in nerves
• - provides analgesia without loss of
consciousness
38. Local Anesthesia
Variety of Dosage Forms
– Topical
– Superficial injection (infiltration)
– Nerve block
– IV
– Epidural
– Spinal
39. • Administration:
• Topical, injected into nerves, epidural or
subarachnoid space (spinal)
• Notes:
• Reduced pH, as in inflamed tissues reduces
effectiveness (cationic form predominates)
• Co-administered with vasoconstrictor epinephrine
(1:100,000)
