‫بسم ال الرحمن الرحيم‬

General Anesthetics

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 General Anesthetics
• Introduction
• Anesthesia includes:
• Analgesia, amnesia, loss of consciousness, inhibition of
reflexes & muscle relaxation
• Ideal anesthetic should:
• Induce anesthesia smoothly, rapidly & for enough time
• Allow prompt recovery & be safe (no adverse effects)
• No single agent possesses all these qualities
• Anesthesiology involves use of suitable combinations
of inhaled & intravenous anesthetics
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 Signs & stages f anesthesia
• Classical signs & stages of anesthesia (Guedel’s signs)
• Based on use of ether, has slow onset & gradual recovery
• I- Stage of analgesia: loss of pain sensations & amnesia
• II- Stage f excitement: excitement, delerium, struggle, retching,
vomiting & irregular respiration
• III- Stage of surgical anesthesia: starts with regular respiration
& ends with loss of spontaneous respiration
• Divided into 4 planes described upon: pupil size, ocular
movements & eye reflexes. Reflect depth of anesthesia
• Suitable signs: loss of eyelash reflex & regular respiration
• IV- Stage of medullary depression: depression of vasomotor &
respiratory centers
• Important to monitor vital signs (pulse, BP, respiration)
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 Mechanism of action
• Inhaled anesthetics, barbiturates & benzodiazepines facilitate
GABA-A receptor Cl- channels & inhibit synaptic transmission
• Inhaled anesthetics also open K-channels & block strychnine
sensitive glycine receptors
• Ketamine antagonizes excitatory effect of glutamic acid on
NMDA (N-Methyl-D-Aspartate) receptors
• Neurophysiological basis of stages of anesthesia
• Substantia gelatinosa neurons in dorsal horn of spinal cord are
affected first (analgesia of stage-I)
• Blockade of small inhibitory neurons (Golgi type-II), explains
excitement of stage-II
• Inhibition of reticular activating system occurs in stage-III
• Last to inhibit are respiratory & vasomotor centers (stage IV) 4
 Inhaled Anesthetics
• Gas:
Nitrous oxide
• Volatile liquids:
Halothane , methoxyflurane, enflurane,
isoflurane, desflurane & sevoflurane

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 Inhaled Anesthetics (Cont.)
• Pharmacokinetics:
• Governs availability of anesthetic agent in brain, includes:
• Uptake, distribution & elimination : which depend upon:
• Solubility of anesthetic agent:(blood : gas partition coefficient)
• More soluble in blood (methoxyflurane), B/G PC 12, slow to
diffuse to & from brain. Slow onset & gradual recovery
• Less soluble in blood (nitrous oxide), B/GPC 0.47, easily diffuses
to & from brain. Rapid onset & recovery
• Anesthetic concentration in inspired air:
• Rapid onset with high concentration & vice versa
• Pulmonary ventilation & pulmonary blood flow:
• ↑ respiration speeds induction of anesthesia, ↑ blood flow slows it
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 Minimum Alveolar Anesthetic Concentration
(MAC)
• MAC measures relative potency of anesthetic agents
• Defined as concentration of anesthetic agent (% of
alveolar gas mixture or its partial pressure) that results
in immobility in 50% of patients exposed to a noxious
stimulus (e.g. surgical incision)
• Partial pressure of inhaled anesthetic in lung (alveoli)
equals that in brain, so measures its potency in brain
• Lower the MAC, more potent the anesthetic agent

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 Adverse effects of inhaled anesthetics
• CVS:
• Most inhaled anesthetics lower blood pressure by:
decrease in cardiac output &/or vasodilatation
• Desflurane can ↑ heart rate & BP (sympathetic stimulation)
• BLOOD:
• Megaloblastic anemia with NO2
• RESP:
• Inhaled anesthetics (except NO2 ) depress respiration & ↑ PaCO2
• Also depress muco-ciliary function in respiratory tract
• Desflurane & enflurane irritate airway (problem in induction)
 Adverse effects of inhaled anesthetics (Cont.)
• BRAIN:
• Inhaled anesthetics ↑ cerebral blood flow & ↑ ICP
• NO2 causes lesser ↑ in ICP
• LIVER:
• Volatile anesthetics ↓ hepatic blood flow
• Halothane can cause liver toxicity
• URO-GENITAL:
• All inhaled anesthetics ↓ GFR & effective renal plasma flow
(↑ renal vascular resistance)
• ↑ risk of abortion in pregnancy
 Adverse effects of inhaled anesthetics (Cont.)
• Malignant hyperthermia:
• An autosomal dominant genetic disorder of Sk. muscle
• Can occur with inhaled anesthetics & succinylcholine
• Biochemical abnormality is ↑ Ca release in muscles
• Consists of: tachycardia , hypertension, hyperthermia,
muscle rigidity, hyperkalemia & acidosis
• Dantrolene is specific antidote & ↓ Ca release from
sarcoplamic reticulum of muscle
• Carcinogenecity: ↑ risk of cancer in operation room
personel
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 Uses of inhaled anesthetics
• Used in combination with IV anesthetic agents in
regimens of balanced anesthesia
• Volatile anesthetics relax uterine smooth muscle &
used for intrauterine fetal manipulation & manual
extraction of retained placenta during delivery
• Volatile anesthetics relax smooth muscle of bronchi
& used in status asthmaticus
• NO2 is potent analgesic & used as obstetric analgesic

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 Intravenous anesthetics
• Short acting barbiturates: Thiopental, Methohexital
• Commonly used IV for induction of anesthesia
• Highly lipid soluble, rapidly cross blood brain barrier
• Bolus IV Inj. induces anesthesia in < 1 minute
• Effect terminates in 5-10 minutes due to redistribution
to muscle & fat
• Then slowly metabolized in liver & eliminated
• Adverse effects:
• Can cause cardiovascular & respiratory depression
• ↑ acute intermittent porphyria, as induces ALA synthase
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 Intravenous anesthetics (Cont.)
• Benzodiazepines: Diazepam, lorazepam, medazolam
• Used as pre-medication for sedative & amnesic effects
& given before induction of anesthesia
• Compared with barbiturates produce slow onset of
central nervous & respiratory depressant effects
• Cause delayed recovery, which is not desirable
• However, high anterograde amnesia is useful
• Flumazenil (specific antagonist) can be used to enhance
recovery from excessive sedation from benzodiazepines
• Medazolam is relatively rapid acting with shorter t-1/2

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 Intravenous anesthetics (Cont.)
• Opioids:
• Fentanyl, sufentanyl, alfentanyl & ramifentanyl
• Use :
• For pre-medication (analgesic effect), for induction &
as IV anesthetic agent for cardiac risk patients
• Adverse effects:
• Chest wall rigidity & respiratory impairment
• Naloxone (specific antagonist) can be used to ↑ recovery
• Ramifentanyl is shortest acting due to rapid metabolism
by estrases in blood (not plasma cholinestrase)
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 Intravenous anesthetics (Cont.)
• Propofol:
• Used for induction & maintenance of anesthesia, as a
component of balanced anesthesia
• Rapid onset. Rapid & pleasant recovery (rapidly
metabolized by glucuronide & sulfate conjugation)
• Less post-operative nausea & vomiting (anti-emetic)
• Adverse effects:
• Acidosis in children with respiratory infection
• Can cause hypotension & respiratory depression
• Muscle hypotonus & tremors
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 Intravenous anesthetics (Cont.)
• Ketamine:
• Produce dissociative anesthesia: amnesia, analgesia &
catatonia, with or without actual loss of consciousness
• Causes ↑ in HR, BP & CO (from 2-4 min to 10-20 min)
• Stimulates central sympathetic system & inhibits reuptake
of nor-adrenaline
• Useful anesthetic for cadiogenic & septic shock patients
• Also useful for painful procedures (dressing of burns)
• Adverse effects:
• Post-operative disorientation, sensory & perceptual
illusions & vivid dreams (give diazepam before ketamine)
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