Anesthetic course

1. ANESTHETICS
By; Monas Kitessa
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By; Monas k.

2. • Anesthesia
• The state of depressed CNS activity
• The condition of loss of responsiveness to sensory stimulation:
pain, touch, temp, taste, ..
• Muscle relaxation
• State of insensibility
• Anesthetics
• Agents that depress CNS or consciousness
• Two types of anesthetics
• General anesthetics
• Local anesthetics
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By; Monas k.

3. 1. Local Anesthetics
• Regional anesthetics
• Drugs that suppress pain by blocking impulse conduction
along axons
• Block only neurons located near the site of anesthetic
administration
• Blockade of sensory transmission to brain from localized area
• Produce loss of pain sensation
• Without the loss of total consciousness/ general depression of
CNS
• Much low risk vs. general ones
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By; Monas k.

4.  Mechanism of Action
• Block specialized sodium channels in axonal membrane
• Stop axonal conduction
• Propagation of an AP requires mov’t of Na+ from outside axon to
inside
• It is charged drug that bind to open form of Na+ channel from
cytoplasmic side of neuronal membrane
• Onset and duration of action is affected by
• Tissue pH, pKa of drug, concentration & lipid solubility of the drug.
• But a number of highly polar toxins (tetrodotoxin & saxitoxin)
block Na+ channel from outer surface of neuronal membrane
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By; Monas k.

5.  Pharmacological effects
• Small, non-myelinated neurons mediating pain are much
more susceptible than large, myelinated fibres mediating
motor functions
 Functional consequences of Na+ channel blockade
• Nerves: decrease or abolition of conduction
• Vascular smooth muscle: vasodilatation
• Heart: decreased excitability (reduced pacemaker activity,
prolongation of effective refractory period)
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By; Monas k.

6.  Anesthetic-induced vasodilatation can be counteracted
• By concomitant administration of a
vasoconstrictor (Epi):
1. Prolongation of anaesthetic action
2. Decreased risk of toxicity
3. Decrease in bleeding from surgical
manipulations
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By; Monas k.

7.  Clinical uses (techniques of LA)
 Topical application
• For surface analgesia on skin & mucous
membranes
• To relieve skin pain, itching & soreness
• Lidocaine, tetracaine, and cocaine
 Injection application
1. Infiltration anesthesia
• Immediate area around of operation
• Lidocaine & bupivacaine
2. Nerve block anesthesia
• Dental & minor surgery
• Around the nerve supplying surgical field
• Lidocaine, mepivacaine or bupivacaine
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By; Monas k.

8. 3. Field anesthesia
• To anesthetize the extremities
• Into a distal vein of an arm or leg
• Lidocaine without vasoconstrictor
4. Epidural anesthesia
• Into the epidural space (within the spinal column)
• Lidocaine and bupivacaine
5. Spinal (Subarachnoid) anesthesia
• Major surgery (abdomen) or childbirth
• Into the subarachnoid space
• Bupivacaine, lidocaine, and tetracaine
• Hypotension
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By; Monas k.

9.  Adverse effects
1. CNS
• Excitation, convulsion, depression
2. CVS
• Bradycardia, heart block, reduced contractile force, and even
cardiac arrest & hypotension
3. Allergic reactions
• From allergic dermatitis to anaphylaxis
• Common with ester-type anesthetics
• Cross-allergy: all of them yeild PABA, allergy mediating cpd
4. Prolong labor
• Depress uterine contractility and maternal expulsion effort
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By; Monas k.

10. 2. General Anesthetics
• Drugs that produce unconsciousness and a lack of
responsiveness to all painful stimuli
• A reversible loss of total consciousness
• All sensations are lost
• Used for surgical procedure
• render the patient unaware / unresponsive to the painful stimuli
• An ideal anesthetic would produce
• Unconsciousness
• Amnesia
• Analgesia
• Muscle relaxation
• Brief & pleasant induction
N.B: No single agent provide all these desirable effects—adjuncts to
anesthesia is needed 10
By; Monas k.

11.  Phases of general anesthesia
1. Phase I: Induction
• Depends on how fast effective conc. of the anesthetic drug
reach the brain
• Adult—IV anesthetics (propofol—30-40sec unconsc.)
• Children—non pungent inhalation GA(halothane/sevoflurane)
2. Phase II: Maintenance of anesthesia
• Volatile anesthetics + opioids (fentanyl)
3. Phase III: Recovery
• Reverse of induction—how fast drug diffuse out of brain
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By; Monas k.

12.  Stages of anesthesia
• A single agent may produce four distinct stages
• Stage I- Analgesia
• Loss of sensibility to pain
• Mild CNS depression
• Suitable for surgical procedure not requiring muscle relaxation
• Stage II- delirium or disinhibition
• Excitement, combative behavior – dangerous state
• Increase involuntary activity and hypersecretion
• Managed by anticholinergics
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By; Monas k.

13. • Stage III- Surgical anesthesia
• General loss of spinal reflexes and muscle tone
• Most surgical operations are performed at this stage
• Stage IV- Medullary paralysis
• Respiratory and vasomotor control ceases
• Death rapidly ensue unless measure is taken to maintain
circulation and respiratory system
• Manifestation of overdose
• Generally not desirable
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By; Monas k.

14.  Two classes of general anesthetics
1. Inhalation anesthetics
• For maintenance
2. Injectable (IV) anesthetics
• For induction
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By; Monas k.

15. 1. Inhalation Anesthetics
• Given by inhalation
• For maintenance of anesthesia
• Advantage of controlling the depth of anesthesia.
• Metabolism is very minimal
• Excreted by exhalation
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By; Monas k.

16.  Molecular mechanism of action
• UNKNOWN!!
• Postulations
• Nonspecific interactions with lipid components
of neuronal cell membrane
 Suppress axonal conduction & synaptic transmission
• Current data, by:
• Enhancing transmission at inhibitory synapses &
• Depressing transmission at excitatory synapses
• All except nitrous oxide enhance activation of
receptors for GABA
• Allosteric modulations
• But nitrous oxide block-NMDA actions
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By; Monas k.

17. • Pharmacokinetics
• Uptake
 Determined by conc in inspired air
 Pulmonary ventilation
 Solubility in blood
 Pulmonary blood flow
• Distribution
 Determined by regional blood flow
 Brain, liver, kidney, heart---skin & skeletal muscles---fat, bone, ligaments
& cartilage
• Elimination
• Redistribution [brain—blood—air]
• Metabolism- toxic metabolites
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By; Monas k.

18.  Adverse effects
1. Respiratory & cardiac depression
• Mechanical support for ventilation
2. Sensitization of the heart to catecholamines
• Halothane
• Dysrhythmias
• Due to release of endogenous catecholamines- pain
3. Malignant hyperthermia
• All inhalation anesthetics except nitrous oxide
• Genetic predisposition
• Muscle rigidity & excessive elevation of body temp, 43 0C
• Increased risk with Succinylcholine
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By; Monas k.

19. 4. Aspiration of gastric contents
• Due to blockade of aspiration reflexes
• Bronchospasm & pneumonia
• Rx- endotracheal tube
5. Hepatotoxicity
6. Toxicity to operating room personnel
• Headache, reduced alertness, and spontaneous abortion
• Rx- ventilation
 Drug interactions
• Analgesics
• CNS depressants
• CNS stimulants
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By; Monas k.

20.  Classification of inhalation anesthetics
a. Gases
 Nitrous oxide
b. Volatile liquids
• Fluorinated halogenated hydrocarbons
 Halothane
 Enflurane
 Isoflurane
 Desflurane
 Sevoflurane
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By; Monas k.

21. • Nitrous oxide- laughing gas
• Safest inhalational anesthetic
• No toxic effect on the heart, liver and kidney
• Postoperative NV
• Caution about hypoxia, megaloplastic anemia
• Weak anesthetic but a good analgesic
• Supplement the analgesic effects of the primary anesthetic
• Used alone—but only for analgesia, not anesthesia
• Dentistry
• Delivery
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By; Monas k.

22. • Halothane
• Potent anesthetic but weak analgesic
• Co-administered with N2O, opioids, LAs
• Pleasant induction +M
• GABA-A potentiation
• Commonly used in children, not hepatotoxic in pediatrics,
pleasant odor
• Catecholamine sensitization of the heart
• Dilates bronchus – preferred in asthmatics
• Relax both s.muscle & uterine
• Hypotension, respiratory depression, dysrhythmias, hepatitis and
malignant hyperthermia
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By; Monas k.

23. • Isoflurane
• Similar properties as halothane
• Commonly used with oxygen or nitrous oxide
• Not sensitize the heart to catecholamines
• Irritate the respiratory system
• Respiratory depression & hypotension
• No hepatic or renal toxicity, myocardial depression
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By; Monas k.

24. • Desflurane
• Delivered through special vaporizer
• Popular anesthetic for day care surgery
• For maintenance
• Irritates the air passages producing cough &
laryngospasm
• Sevoflurane
• Fast induction and maintenance
• Pleasant and acceptable due to lack of pungency
• Not cause air way irritancy
• Concerns about nephrotoxicity
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By; Monas k.

25. 2. Parenteral (IV) Anesthetics
• Used alone or to supplement the effects of inhalations
• Used for induction of anesthesia
• Rapid onset of action
• Recovery is mainly by redistribution
• Also reduce the amount of inhalation anesthetic for
maintenance
• Two benefits
1. Reduction of inhalation anesthetic dosage
2. Produce effects not produced by inhalations alone
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By; Monas k.

26. 1. Short-acting barbiturates, thiobarbiturates
• Thiopental
• Methohexital
• Unconsciousness
• For induction of anesthesia
2. Short-acting benzodiazepines
• Unconsciousness and amnesia
• Diazepam
• Lorazepam
• Midazola
3. Propofol
• IV sedative-hypnotic
• For induction & maintenance of anesthesia
• Need addition of opioids
• Replaced thiopental
• Produce euphoria
• No postaenesthetic NV
• Respiratory depression & hypotension
• GABA-A potentiation 26
By; Monas k.

27. 4. Etomidate
• Potent hypnotic agent
• Used for induction of surgical anesthesia
• Lack analgesic activity
• Less cardiovascular effects
• Usually only used for pts with angina, CV dysfunction such as shock
• GABA-A potentiation
5. Ketamine
• Good analgesia
• Pt is unconscious & does not feel pain but appears to be awake
• Provide Sedation, immobility, analgesia, and amnesia
• Activate sympathetic outflow—increase CO
• Used when circulatory depression is undesirable
• Not used in HTN pts
• Unpleasant psychologic reactions
 Hallucinations, disturbing dreams, and delirium
• Blocks NMDA receptors 27
By; Monas k.

28.  Preanesthetic medications (adjuvant agents)
• To complement the beneficial effects & counteract their
adverse effects
• Used before or after anesthesia
1. Sedative-hypnotics
• To relieve anxiety & promote amnesia
• Midazolam, secobarbital, thiopental, diazepam
2. Antihistamines
• To prevent allergic reactions
• Antihistamines (diphenhydramine)
3. Antiemetics
• Ondansetron, promethazine, droperidol
• To prevent nausea and vomiting
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By; Monas k.

29. 4. Opioid analgesics
• To provide analgesia, pre- & postoperative pain
• Also suppress cough
• Morphine, fentanyl, sufentanil
5. Anticholinergics
• To prevent bradycardia and secretion
• Atropine, scopolamine
6. Neuromuscular blockers
• Facilitate intubation and s.muscle relaxation
• Succinylcholine, pancuronium
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By; Monas k.

30. Have a nice time!
By; Monas k. 30