Chapter 15 - Local & General Anesthesia

Uses of Local Anesthesia

- topical

- inflitration

- field block or nerve block

Topical

applied to the skin or mucosa & penetrates 2-3 mm deep

Infiltration

injection into subcutaneous tissue to numb a local region & works primarily on nerve endings in the affected area

Field Block & Nerve Block

used to provide large area of anesthesia through injection proximal to site of concern

Epidural

- used for labor & some surgical procedures

- allows for catheter placement and repeat infusions

- most signifcant effects on nerve roots near infusion site

Spinal Anesthesia

- used for lower limb & pelvic surgery

- injection into subarachnoid space caudal to L2

- dependent on dose, can achieve full anesthesia of all distal structures

All local anesthetics are all ______

weak bases

Local Anesthetics become ionized as pH ____

decreases

Functional consequence of being weak bases

when you have infected/inflamed tissues (which are more acidic) a higher dose of drug is required in order to be affective

Chemical Classes

- esters

- amides

Esters

- less commonly used

- more easily broken down

- generally short duration

- higher risk of allergy

Amides

- medium to long acting

- inclueds drugs such as lidocain

- drug allergies lesss common

Duration of action is affected by ________

metabolism & the ability of the drug to stay at the site

More vacular tissue in the area of injection =

shorter action of the drug

How can you increase the drug availability at the site?

co-administer drug ith a vasoconstrictor

What must a molecule do to perform anesthetic action?

it must cross several membranes of the nerve sheath as well as plasma membrane of individual neuron

Onset, duration, & degree of anesthesia is influenced by:

- lipid solubility

- degree of ionization

- nerve bundle diameter

Lipid soluability

you want an anesthetic that is moderately lipid soluable beccause if it is too lipid soluable it will get stuck in the cell but if it is not lipid soluable at all it won't get into the cell

Degree of Ionization

if an anesthetic is ionized it will not cross the membrane

Nerve bundle diameter

you want to target smaller nerve bundle diameter because the drug can get to the axon faster & therefore act quicker

The ______ the fiber diameter the _____ likely it is to be sensitive to blockade

smaller; more

The _____ myelinated the fiber the _____ likely it is to be sensitive to blockade

less; more

Which type of fiber is least sensitive to blockade?

Type a (motor)

Which type of fiber is most sensitive to blockade?

Type C (sympathetic, pain)

Order of Nerve Function Loss

- 1. sympathetic

- 2. pain

- 3. cold

- 4. warm

- 5. touch

- 6. motor

Action Potential States

resting state (closed channel) -> activated state (open channel) -> inactivated state (closed channel due to block)

What do local anesthetics do to the voltage-gated Na+ channels?

block them, inhibiting action potential to be carried down the axon

Poorly Hydrophobic Local Anesthetic

the local anesthetic cannot get into the cell & therefore nothing hapens to the channel

Moderately Hydrophobic Local Anesthetic

the local anesthetic is able to diffuse from extracellular fluid, through the membrane, & into the cytosol of the cell in order to bind to intracellular portion of voltage-gated Na+ channel which blocks the channel, therefore blocking the action potential down the axon that causes pain signal

Extremely Hydrophobic Local Anesthetic

drug diffuses into the membrane but gets stuck

Which channel states have the highest affinity for local anesthetics?

open or inactivated conformations

Tonic Block

drug binds to closed channel without requiring it to open first; this channel opens infrequently & the drug diffuses away between action potentials

Phasic Block

drug binds to actively firing or frequently stimulated channel; # of channels bound to drug increases with each action potential

Functional Consequence of Phasic Block

more inhibition occurs in more active nerve fibers

Saltatory Conduction

the rapid propagation of action potentials along myelinated axons, where the electrical signal "jumps" from one uninsulated gap (the node of Ranvier) to the next

Critical Length Hypothesis

in order for saltatory conduction to be effective, the field of action of a local anesthetic must include at least 3 nodes of an axon

The bigger the axon, the _____ the myelin segment & the _____ nodes within a given field

longer;fewer

Smaller Axons Field =

5 nodes

Larger Axons Field =

2 nodes (you have to inject larger field to get proper affect)

Lidocaine

- standard local anesthetic with many uses

- medium duraction (1-2 hrs)

Bupivacaine

- longer duraction of action

- can be used when vasoconstrictor is contraindicated

- often used for spinal & epidural anesthesia

Cocaine

- use is rare

- has both anesthetic & vasoconstrictive properties

- mostly replaced with vasoconstrictor/anesthetic combinations

What is the vasoconstrictor used in local anesthesia?

epinephrine

Advantages of Epinephrine

- improve duraction of anesthesia by keeping drug near infiltration site

- less drug reaches systemic circulation

- reduce bleeding

- prevent vasodilation caused by anesthetic

What condition should you use epinephrine with caution?

cardiovascular disease (use lowest dose necessary & avoid inuection into artery)

What areas should you avoid injecting epinephrine?

areas with poor circulation such as fingers, nose, penis, & toes in order to prevent ischemic necrosis

Drug Interactions with Epinephrine

- monoamine oxidase inhibitors & sympathomimetics

- alpha blockers

Monoamine Oxidase Inhibitors

increase risk of systemic toxicity because monoamine breaks down epinephrine

Alpha Blockers

will reduce effect of vasocontrictor because it blocks receptor that epinephrine is trying to activate

Adverse effects of local anesthetics

- allergic reactions

- psychogenic

- methemoglobinemia

PABA (para-aminobenzoic acid)

metabolite of most ester anesthetics & is the most common allergen

Physiological Reactions

most common adverse effects of local anesthetics including vasovagal syncope related to needle & hyperventilation/other anxiety-related symptoms

Methemoglobinemia

rare complication more commonly seen in infants that is likely increased by genetic predisposition or drug interaction

Systemic Toxicity

this can occur due to injection into a vessel or too much drug used, but is rare with proper use of anesthetics

Central Nervous System Effects

- initial CNS excitation (talkativeness, lightheadedness, tinnitus, etc.)

- later/high dose toxicity (CNS depression/coma & possible death)

Cardiovascular Effects

- suppression of cardiac conduction leading to cardiac arrest in severe cases

- hypotension due to decreased peripheral resistance

Goals of General Anesthesia

- loss of consciousness

- amnesia

- analgesia

- muscle relaxation

- suppression of reflexes

Stage I

- analgesia

- amnesia

- euphoria

Stage II

- excitement

- delirium

- combative behavior

Stage III

- surgical anesthesia

- unconsciousness

- regular respiration

- decreasing eye movement

Stage IV

- medullary depression

- respiratory arrest

- cardiac depression & arrest

- no eye movement

Minimum alveolar concentration (MAC)

the concentration of an inhaled anesthetic gas in the lungs required to prevent skeletal muscle movement in 50% of patients in response to a standard surgical incision

What does the minimum alveolar concentration act as?

standard for comparing the potency of different volatile anesthetics

General anesthetics have a _______ dose response & ______ therapeutic index

steep;narrow

Meyer-Overton Rule

lipid solubility is directly proportional to potency

Isoflurane

inhaled (volatile) anesthetic used for induction and maintenance of general anesthesia

Balanced anesthesia

the practice of combining multiple drugs for anesthesic affects because no single drug provides all necessary effects at a tolerable dose

Malignant Hyperthermia

a hereditary condition of widespread muscle contraction/rigidity that causes uncontrolled heat production when susceptible people receive certain anesthetic drugs

What drug do we use to treat malignant hyperthermia?

dantrolene

Dantrolene

blocks Ca2+ release from ryanodine receptor/sarcoplasmic reticulum to prevent the contraction/rigidity that causes heat products

Conscious Sedation

drugs used to sedate patient & produce analgesia; patient is awake but may have reduced awarenesss & amnesia after procedure

What types of drugs are used for conscious sedation?

- benzodiazepines

- IV anesthetic

- opioids

Propofol

- IV anesthetic

- short acting; rapid recovery

- stimulates GABA signaling

- causes sedation

- no analgesia

Fentanyl

- opioid

- short duration of action (60-80 min)

- causes analgesia & sedation

Midazolam

- benzodiazepine

- works as a positive allosteric modulator at GABA receptor, increases inhibitory neurotransmission

- causes anxiolysis, amnesia, mild sedation

- no analgesia