General Anesthetics

Learning objectives

Explain the purpose of application of GAs

Classify the GAs & the typical drugs

Identify the mechanism of action of GAs

Analyze the characteristic ADR of GAs

At the end of this class, you are able to:

Definition

The drugs induce the state of general anesthesia, which create a reversible condition of comfort, quiescence, and physiological stability before, during, and after a surgical procedure.

Why we use general anesthetics?

Analgesia

Skeletal muscle relaxation

Sedation and reduction of anxiety

Lack of awareness and amnesia

Suppression of troublesome reflexes

Pre-anesthetics Preanesthetic medications – drugs given generally

prior to anesthesia (may be given during or after, as well) in order to:

① Decrease anxiety

② Sedation

③ Provide amnesia

④ Relieve pre-and post-operative pain

⑤ Inhibit secretion

⑥ Antiemetic

Preanesthetic AgentsDrug Classification Generic Name

Desired Effect

Benzodiazepines DiazepamMidazolam

Reduce anxiety, Sedation, Amnesia, “Conscious sedation”

Antihistamines Hydroxyzine Sedation

Opioid analgesics MorphineMeperidineFentanylRemifentanil

Sedation to decrease tension, anxiety, and provide analgesia

Phenothiazines Promethazine Sedation, antihistaminic, antiemetic, decreased motor activity

Anticholinergics AtropineGlycopyrollate

Inhibit secretion, bradycardia, vomiting, and laryngospasms

GI Drugs OndansetronRanitidineMetoclopramide

Antiemetic

Decrease gastric acidity

Decrease stomach contents

Inhaled • Nitrous oxide• Desflurane • Halothane• Isoflurane• sevoflurane

Classifications of GAs

Intravenous • Barbiturates• Benzodiazepines• Dexmedetomidine• Etomidate• Ketamine• Opioids• Propofol

Theories of Anesthetic Action

No single theory adequately explains how anesthetics exert their pharmacological effects. Physical theories

Based on physico-chemical properties of anesthetics, e.g., lipid solubility.

Theories of ActionReceptor theories

Anesthetics exert their effects by direct interactions with proteins (membrane receptors or ion channels).

Most anesthetics increase the sensitivity of the Ɣ-aminobutyric acid (GABA) and glycine receptors to GABA and glycine respectively.

Anesthetics also generally inhibit the activity of excitatory transmitters acetylcholine (Nicotinic) and serotonin.

Ketamine and nitrous oxide inhibit glutamate activity via its antagonism of the action of the excitatory neurotransmitter glutamic acid on the N-methyl-D-aspartate(NMDA)

Thus neurons are hyperpolarized.

Inhalation Anesthetic Agents

General pharmacological effects CNS – dose dependent depression of all portions

of CNS. Order of sensitivity (most to least) is Reticular Arousal System(RAS) and cortex → hippocampus → basal ganglia → cerebellum → spinal cord → medulla (irregularly descending anesthesia)

Autonomic nervous systemInhibition of sympatheticsStimulation of parasympatheticsNausea and vomiting

Inhalation Anesthetic Agents General pharmacological effects

CardiovascularDose related negative inotropic effect ↓ BP Arrhythmias Sensitization to circulating catecholamines

Respiration Dose dependent depression of medullary respiratory

center

Inhalation Anesthetic Agents

General pharmacological effects Hypothermia

Altered thermoregulatory control and reduced metabolic rate

MiscellaneousDecrease lower esophageal sphincter tonePost-operative cognitive dysfunction

Inhalation Anesthetic Agents Anesthetic gases – only one is Nitrous Oxide Volatile liquids

Halothane (Fluothane) : Malignant hyperthermia; Halothane hepatitis

Isoflurane (Forane) – commonly used anesthetic for adults

Enflurane (Ethrane) – like isoflurane, except increased risk of seizures. Rarely used

Desflurane (Suprane) – similar to isoflurane except for more rapid emergence, and more irritating to airway

Sevoflurane (Ultane) – similar to desflurane except not irritating to airway

Anesthetic Agents Intravenous agents

Barbiturates – sodium thiopentalPropofol (Diprivan) – similar to thiopental except

that it can be used for longer periods of anesthesiaDissociative – ketamineBenzodiazepines – diazepam, midazolamEtomidate (Amidate)Dexmedetomidine (Precedex)

Properties of Intravenous Anesthetic Agents

Drug Speed of Induction and Recovery

Main Unwanted Effects

Notes

Thiopental Fast (accumulation occurs, giving slow recovery) Hangover

Cardiovascular and respiratory depression

laryngospasm

Used as induction agent declining. Decreases cerebral blood flow and O2 consumption.

Etomidate Fast onset, fairly fast recovery Excitatory effects during induction and recovery, including seizures

Adrenocortical suppression

Less cardiovascular and respiratory depression than with thiopental, Causes pain at injection site

Propofol Fast onset, very fast recovery Cardiovascular and respiratory depression.

Pain at injection site.

Most common induction agent. Rapidly metabolized; possible to use as continuous infusion.

Ketamine Slow onset, after-effects common during recovery

Psychotomimetic effects following recovery, Postoperative nausea, vomiting and salivation

Produces good analgesia and amnesia

Midazolam Slower than other agents Memory loss, specifically short-term antegrade amnesia

Little respiratory or cardiovascular depression

Anesthetic Antagonists

Naloxone (Narcan) and nalmefene (Revex)

Flumazenil (Romazicon)

Usmle questions A 20-year-old male patient scheduled for hernia surgery was

anesthetized with halothane and nitrous oxide, tubocurarine was provided for skeletal muscle relaxation. The patient rapidly developed tachycardia and became hypertensive. Generalized skeletal muscle rigidity was accompanied by marked hyperthermia. Laboratory values revealed hyperkalemia and acidosis. This unusual complication of anesthesia is lost likely caused by:

A. acetylcholine release from somatic nerve endings at skeletal muscle

B. activation of brain dopamine receptors by halothane

C. block of autonomic ganglia by tubocurarine

D. pheochromocytoma

E release of calcium form the sarcoplasmic reticulum

The patient should be treated immediately with

A. Atropine B. Baclofen C. Dantrolene D. Edrophonium E. Flumazenial