1. HINDU COLLEGE
PG COURSE

2. General Anesthesia Sleep induction Loss of pain responses Amnesia
Skeletal muscle relaxation
Loss of reflexes

3. General Anesthesia Stages of Anesthesia Stage I Stage II Stage III
Analgesia
Stage II
Disinhibition
Stage III
Surgical anesthesia
Stage IV
Medullary depression

4. Types of anesthetics
I. Inhalation anesthetics II. Intravenous anesthetics III. Local anesthetics

5. I. Inhalation anesthetics
Mechanisms of Action
Activate K+ channels
Block Na+ channels
Disrupt membrane lipids
In general, all general anesthetics increase the cellular threshold for firing, thus decreasing neuronal activity.

6. I. Inhalation anesthetics
Ether (diethyl ether)
Spontaneously explosive
Irritant to respiratory tract
High incidence of nausea and vomiting during induction and post-surgical emergence

7. I. Inhalation anesthetics
Nitrous Oxide
Rapid onset
Good analgesia
Used for short procedures and in combination with other anesthetics
Supplied in blue cylinders

8. I. Inhalation anesthetics
Halothane (Fluothane)
Volatile liquid
Narrow margin of safety
Less analgesia and muscle relaxation
Hepatotoxic
Reduced cardiac output leads to decrease in mean arterial pressure
Increased sensitization of myocardium to catecholamines

9. I. Inhalation anesthetics
Enflurane (Ethrane)
Similar to Halothane
Less toxicities
Isoflurane (Forane)
Volatile liquid
Decrease mean arterial pressure resulting from a decrease in systemic vascular resistance

10. I. Inhalation anesthetics
Pharmacokinetics
The concentration of a gas in a mixture of gases is proportional to the partial pressure
Inverse relationship between blood:gas solubility and rate of induction
Nitrous oxide
(low solubility)
Alveoli
Blood
Brain
Halothane
(high solubility)

11. I. Inhalation anesthetics
Pharmacokinetics
Increase in inspired anesthetic concentration will increase rate of induction
Direct relationship between ventilation rate and induction rate
Inverse relationship between blood flow to lungs and rate of onset
MAC=minimum concentration in alveoli needed to eliminate pain response in 50% of patients
Elimination
Redistribution from brain to blood to air
Anesthetics that are relatively insoluble in blood and brain are eliminated faster

12. I. Inhalation anesthetics
Side Effects
Reduce metabolic rate of the brain
Decrease cerebral vascular resistance thus increasing cerebral blood flow = increase in intracranial pressure
Malignant Hyperthermia
Rare, genetically susceptible
Tachycardia, hypertension, hyperkalemia, muscle rigidity, and hyperthermia
Due to massive release of Ca++
Treat with dantrolene (Dantrium), lower elevated temperature, and restore electrolyte imbalance

13. II. Intravenous anesthetics
Ketamine (Ketaject, Ketalar)
Block glutamate receptors
Dissociative anesthesia:
Catatonia, analgesia, and amnesia without loss of consciousness
Post-op emergence phenomena:
disorientation, sensory and perceptual illusions, vivid dreams
Cardiac stimulant

14. II. Intravenous anesthetics
Etomidate (Amidate)
Non-barbiturate
Rapid onset
Minimal cardiovascular and respiratory toxicities
High incidence of nausea and vomiting

15. II. Intravenous anesthetics
Propofol (Diprivan)
Mechanism similar to ethanol
Rapid onset and recovery
Mild hypotension
Antiemetic activity
Short-acting barbiturates
Thiopental (Pentothal)
Benzodiazepines
Midazolam (Versed)

16. III. Local anesthetics
Blockade of sensory transmission to brain from a localized area
Blockade of voltage-sensitive Na+ channels
Use-dependent block
Administer to site of action
Decrease spread and metabolism by co-administering with a1-adrenergic receptor agonist (exception….cocaine) O C H 2 5 H N C O C H C H N 2 2 2 C H 2 5
Procaine

17. Structure-Activity Relationships
III. Local anesthetics
Structure-Activity Relationships
Benzoic acid derivatives (Esters)
Aniline derivatives (Amides)

18. Structure-Activity Relationships
III. Local anesthetics
Structure-Activity Relationships H 2 N C O 5
Procaine (Novocain)
Lidocaine (Xylocaine, etc.)

19. Structure-Activity Relationships
III. Local anesthetics
Structure-Activity Relationships
Direct correlation between lipid solubility AND potency as well as rate of onset
Local anesthetics are weak bases (pKa’s ~ )
Why are local anesthetics less effective in infected tissues?

20. See Katzung, Page 220 Activation gate (m gate) is voltage-dependent
Open channel allows access to drug binding site (R) from cytoplasm
Inactivation gate (h gate) causes channel to be refractory
With inactivaton gate closed, drug can access channel through the membrane
Closing of the channel (m gate) is distinct from inactivation and blocks access to drug binding site
Thus, local anesthetics bind preferentially to the open/inactivated state

21. III. Local anesthetics Drug Duration of Action Esters Cocaine Medium
Procaine (Novocain)
Short
Tetracaine (Pontocaine)
Long
Benzocaine
Topical use only
Amides
Lidocaine (Xylocaine)
Medium
Mepivacaine (Carbocaine, Isocaine)
Medium
Bupivacaine (Marcaine)
Long

22. III. Local anesthetics Techniques of administration
Topical: benzocaine, lidocaine, tetracaine
Infiltration: lidocaine, procaine, bupivacaine
Nerve block: lidocaine, mepivacaine
Spinal: bupivacaine, tetracaine
Epidural: bupivacaine
Caudal: lidocaine, bupivacaine

23. III. Local anesthetics Toxicities:
CNS-sedation, restlessness, nystagmus, convulsions
Cardiovascular- cardiac block, arrhythmias, vasodilation (except cocaine)
Allergic reactions-more common with esters

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