Local and General Anesthetics

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3/14/2012

ANESTHETICS

Major Classes of Anesthetic Agents
Local – Are injected at the operative site to block nerve conduction General – Are given either as inhaled or intravenous agents – Primarily have CNS effects

I. II.

LOCAL ANESTHETICS GENERAL ANESTHETICS

Local Anesthesia
• Is the condition that results when sensory transmission from a local area of the body to the CNS is blocked

Local Anesthetics
Esters Long-acting – Tetracaine Short-acting – Procaine (Novocain) – Chloroprocaine (Nesacaine) Surface-acting – Cocaine – Benzocaine (Cetacaine) Amides Long-acting – Bupivacaine (Marcaine) – Ropivacaine – Mepivacaine (Polocaine/Carbocaine) – Etidocaine (Duranest) – Prilocaine Medium-acting – Lidocaine (Xylocaine)

Mechanism of Action of Local Anesthetics
Blockade of voltage-dependent sodium channels on the neuronal membrane

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Mechanism of Action of Local Anesthetics
Blockade of voltage-dependent sodium channels on the neuronal membrane

Vasoconstrictors added to Local Anesthetics
Epinephrine (1:2000,000 or 5 ug/ml)
– Increased uptake of the local anesthetic – Higher anesthetic concentration near nerve fibers (increased local anesthetic concentration in the vicinity of sensory nerves – Increased duration action: prolongation conduction blockade by about 50% longer

Epinephrine
– Reduced systemic absorption by about 33% (advantage: absorption rate more likely to match metabolic rate resulting in less local anesthetic systemic toxicity)
Increased cardiac irritability which may cause an increased risk of cardiac arrhythmias Increased possibility of hypertensive response in susceptible patients

Dextran
Low-molecular-weight When added to local anesthetic solutions result in increased peripheral nerve block anesthesia duration

Factors Influencing the Effectiveness of EPI on local anesthesia
Lipophilicity – more lipophilic local anesthetics will tend on their own to associate strongly with tissues such as Mepivacaine (Carbocaine) and Etidocaine (Duranest) than with Lidocaine (Xylocaine), which is less lipophilic

Factors Influencing the Effectiveness of EPI on local anesthesia
Level of sensory blockade needed for spinal or epidural anesthesia Duration of lower extremity sensory anesthesia extended by epinephrine or phenylephrine (Neo-Synephrine) which is not observed for abdominal region anesthesia

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Clinical Uses of Local anesthetics
To abolish painful stimulation prior to surgical, dental (tooth extraction), or obstetric (delivery) procedures. Commonly found as ingredients in many OTC preparations for sunburns, insect bites, and hemorrhoids

Common Side Effects of Anesthetics

How does metabolism of the ester and amide anesthetics differ?
Esters – More rapidly metabolized by blood and tissue esterases, which gives them shorter half-lives Amides – Are metabolized by hepatic microsomal enzymes, which results in a longer half-life

GENERAL ANESTHETICS
- Are CNS depressants which abolish pain by inhibiting the function of the CNS through an unknown mechanism

PROPERTIES OF GENERAL ANESTHESIA
All sensation (hearing, sight, touch, smell and pain) is ABSENT Primarily used to prevent the reaction to painful stimuli associated with surgery All of the major areas of the CNS are suppressed except the medullary centers which regulate the vital organs

SIGNS AND STAGES OF ANESTHESIA
STAGE 1 – ANALGESIA The cerebral cortex is gradually inhibited Euphoria, giddiness, and loss of consciousness STAGE 2 – DELIRIUM AND EXCITEMENT Affects the thalamus Increase sympathetic tone, increase BP and heart rate; irregular respirations

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SIGNS AND STAGES OF ANESTHESIA
STAGE 3 – SURGICAL ANESTHESIA Plane 1 – Sleep, normal BP and respiration Plane 2 – dilated pupils; loss of corneal reflex Plane 3 – skeletal muscle relaxation Plane 4 – paralysis of the diaphragm STAGE 4 – MEDULLARY PARALYSIS Respiratory paralysis leading to circulatory collapse and death * Clinical signs associated with each stage may vary with
the agent used

INDUCTION OF ANESTHESIA
– Is the time required to take the patient from consciousness to stage 3.

MAINTENANCE OF ANESTHESIA
– Is the ability to safely keep the patient in stage 3

THEORIES OF GENERAL ANESTHESIA
BIOCHEMICAL HYPOTHESIS
– Decrease cellular function by decreasing ATP production

TYPES OF ANESTHETICS
I. INHALATIONAL ANESTHETICS VOLATILE LIQUIDS HALOTHANE ISOFLURANE DIETHYL ETHER GASEOUS NITROUS OXIDE

HYDRATE THEORY
– Anesthetic molecules form gas hydrates or structured water which inhibit brain function

IONIC PORE THEORY
– Blockade of ionic channel by interaction of anesthetic molecule with the membrane

II. INTRAVENOUS ANESTHETICS
BARBITURATES METHOHEXITAL THIAMYLAL THIOPENTAL BENZODIAZEPINES DIAZEPAM LORAZEPAM MIDAZOLAM ETOMIDATE OPIOIDS FENTANYL MORPHINE DROPERIDOL AND FENTANYL CITRATE (Innovar) NEUROLEPTANESTHESIA KETAMINE – DISSOCIATIVE ANESTHETIC PROPOFOL

PHYSIOLOGICAL EFFECTS OF GENERAL ANESTHETICS
CNS EFFECTS All nervous tissues are depressed Voluntary (motor) and involuntary (autonomic) systems are inhibited Respiratory function is depressed Some cause pituitary secretion of ADH resulting to post operative urinary retention CARDIOVASCULAR EFFECTS Myocardium and BP are depressed Increase heart rate due to vagal inhibition

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PHYSIOLOGICAL EFFECTS OF GENERAL ANESTHETICS
RESPIRATORY SYSTEM Inhaled anesthetics irritate the mucosal lining of the respiratory tract Increase mucous secretion, coughing and spasm of the larynx SKELETAL MUSCLES Causes relaxation due to depression of pyramidal system and spinal reflexes Some causes relaxation by inhibiting the neuromuscular function

PHYSIOLOGICAL EFFECTS OF GENERAL ANESTHETICS
GI TRACT Nausea and vomiting (occurs during recovery) Decrease intestinal motility (post operative constipation) LIVER Halothane (high risk), Enflurane and chloroform cause liver toxicity

INHALATIONAL ANESTHETICS
Primarily used for the maintenance of anesthesia Produce all stages of anesthesia except Nitrous oxide Excreted through the lungs Depth of anesthesia can be rapidly altered by changing the concentration and providing hyperventilation Don’t cause respiratory depression

Advantages and Disadvantages of Inhalational anesthetics
Anesthetic ADVANTAGES
NITROUS OXIDE Good analgesia Rapid recovery Safe, non irritating

DISADVANTAGES
No muscle relaxation Must be used with other anesthetics for surgical anesthesia

HALOTHANE

Best agent in pediatric Lowers blood pressure patients Reduces renal and hepatic Bronchial smooth muscle blood flow relaxation; good for patients Hepatic toxicity with asthma Arrhythmias Good muscle relaxation Rapid recovery Does not raise intracranial pressure No sensitization of heart to Epinephrine

ISOFLURANE

INTRAVENOUS ANESTHETICS
IV Anesthetics Thiopental Advantages Rapid onset Potent anesthesia Disadvantages Poor analgesia Little muscle relaxation Laryngospasm

INTRAVENOUS ANESTHETICS
BARBITURATES Produce residual CNS depression, mental disorientation and nausea May cause laryngospasm/bronchospasm Accumulate in adipose tissue BENZODIAZEPINES Midazolam and Lorazepam are more potent than diazepam Facilitate amnesia while causing sedation

Ketamine Fentanyl Propofol

Good analgesia Good analgesia Rapid onset Lowers intracranial pressure Poor analgesia

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INTRAVENOUS ANESTHETICS
ETOMIDATE Hypnotic Lacks analgesic property Can cause uncontrolled skeletal muscle activity OPIOIDS Morphine + Nitrous oxide provide good anesthesia for cardiac surgery Are not good amnesics Can cause hypotension, respiratory depression and muscle rigidity as well as post op. nausea and vomiting

INTRAVENOUS ANESTHETICS
KETAMINE Produces dissociative anesthesia ( patient appears awake but is unconscious and does not feel pain) Provides sedation, amnesia and immobility Increase BP and cardiac output Vivid dreams and hallucinations occur during recovery period Employed mainly in children and young adults

INTRAVENOUS ANESTHETICS
FENTANYL CITRATE AND DROPERIDOL (Innovar) Narcotic analgesic + neuroleptic = neuroleptanalgesia Produces neurolepthanesthesia (provides excellent analgesia while the patient remains conscious) Can cause extrapyramidal muscle movements

INTRAVENOUS ANESTHETICS
PROPOFOL Sedative-hypnotic used in the induction or maintenance of anesthesia Supplementation with narcotics for analgesia is required Depress CNS, decrease BP without depressing the myocardium Decreases intracranial pressure

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