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An unpleasant sensory and emotional experience associated with actual or potential tissue damage

Pain

The relatively objective characteristic of pain, including its location, duration and intensity

thermal v Mechanical v Chemical

Sensory Component

The aspects of pain associated with past experiences, fear, suffereing, anxiety and cultural difference

Motivational/Affective components

A drug that is used to decrease the sensation of pain

Analgesic

A drug that is used to abolish all sensation (blocking nociception is the primary goal)

Anesthetic

A drug causing a loss of sensation, whose action is limited to a specific area of the body, depending on which nerve was blocked and what area it innervates

Local anesthetic

An anesthetic agent whose action includes the entire body and all sensations

General anesthetic

Allodynia vs hyperalgesia

Allodynia: Pain caused by a stimulus that is normally innocuous (non-painful)

Hyperalgesia: Exaggerated pain response to a stimulus that is normally painful

sensitization of peripheral nociceptors in an area of tissue damage or due to the presence of algesic chemcials (bradykinin, substance P, etc)

Primary hyperalgesia

Increased pain response in the absence of local causes. Due to changes in the central nervous system (spinal cord and or higher centers) that result in a sensitization of nociceptors (eg referred pain and convergence)

Secondary hyperalgesia

Reffered pain and convergence

Nociceptors innervating deep structures often synapse with the same central neurons as the nociceptors from the superficial structures (they converge on the same neurons in the CNS)

A nociceptor is a peripheral neuron which is specialized to convey noxious (painful stimuli)

____ and ____ fibers

Adelta and C

- mechanical (pinch)

- Chemical (jalapeno peppers)

- Thermal

Anatomy:

Trigeminal nerve

Trigeminal ganglion

Pars oralis

Neurons:

- A-beta mechanoreceptors

- A-delta C

- Schwann cells/myelination

fyi

Impulse conduction

Resting membrane potential

Depolarization

Threshold stimulus

Refractory period

.

Immediately following an action potential, the neuron is unresponsive for a very brief period

absolute refractory period

This is followed by a period of time when a larger-than-normal depolarization is required to initiate a potential

relative refractory period

Two classes of LAs depending on their intermediate chain

Esters and amides

Esters and amides are ___ bases

weak

Equilibrium in solution based on _____ of LA and ____ of solution (H/H equation)

pka

Some LA disrupt the ____ ____

lipid bilayer

Mechanism of Action

Both uncharged and charged forms are required for action

.

Less _______ (RN) LA will exist in an acidic environment

uncharged

When there is an acidic environment, this means that far fewer molecules can enter the axon, so the resulting blockade of AP's (numbness) will be ____ and possibly _____

poor inadequate

This is often a problem when treating areas with infection - inflammed tissue has a lower acidity

lower pka = more ____ onset of the LA

rapid

Faster onset of LA when pKa closest to ______ pH

physiologic (7.4)

More particles become de-ionized to diffuse through nerve sheath at _______ pH

physiological

Increased lipid solubility of the LA leads to increased _____

potency

When the LA has increased lipid solubility it has ____ ability to penetrate lipid membrane of nerves

increased

Pharmacokinetics

Uptake: Some diffusion into surrounding tissue occurs

Distribution: Distributed throughout the body and can pass the BBB and placenta

uptake of LA has some diffusion into ____ ____ occurs

surrounding tissues

diffusion of LA is distributed throughout the____ and can pass the ____ and _____

body

BBB

placenta

Ideal properties of LA

Reversible

Non-irritating

Rapid onset

Sufficient duration

Low systemic toxicity

Non-addicting

Effective at all sites

Stable in solution

History of LA

Cocaine in 1860s - topical and injection

Procaine developed in 1905

lidocaine synthesized in 1943

Articaine in 1969 - approved by FDA in 2000

Uses of LA

Topical anesthesia

Dental procedures

Minor surgical procedures

Spinal anesthesia

Epidural anesthesia

Useful for irregular heart rate

Ester LA are hydrolyzed in plasma by enzyme plasma __________-

pseudocholinesterase

Procaine (ester LA) is broken down into _____

PABA

Atypical pseudocholinesterase

ester LA is excreted into the ____

urine

Amides LA are metabolized in the ___

liver

amides are excreted in the _____-

urine

Methemoglobinemia

Some LAs can trigger methemoglobinemia

- prilocaine, articaine, and benzocaine

Altered state of hemoglobin

- Heme iron oxidized from Fe2+ to Fe 3+

- Ferric heme does not bind O2

- Remaining ferrous hemes in the tetramer have increased O2 affinity

Some LAs can trigger methemoglobinemia

methemoglobinemia

Altered state of hemoglobin

which LA can result in methemoglobinemia

prilocaine, articaine, and benzocaine

what happens in methemoglobinemia

Altered state of hemoglobin

- Heme iron oxidized from Fe2+ to Fe 3+

Ferric heme does not bind O2

Remaining ferrous hemes in the tetramer have increased ___ affinity

O2

Systemic actions of LAs

CNS

CVS

Minimize systemic actions HOW DO WE DO THAT EVEN

- Avoid intravascular injections

- Use vasoconstrictors

- Know and avoid maximum doses

CNS

Initially, ______ signs predominate but CNS ______ is the ultimate outcome

excitatory

depression

CNS side effects of LA

slurred Speech, Muscle tremors and twitches

Numbness, dizziness, drowsiness

The ____ is directly affected by LAs

heart

LA casues _____ electrical excitability, conduction rate, contraction force and eventual circulatory collapse occur with toxic doses

decreased

LAs also directly dilate _____ ______, adding to the hypotension

peripheral vasculature

Systemic toxicity

Avoid intravascular injections by aspirating the syringe

Add vasoconstrictors to slow absorption of LA into bloodstream

Know and avoid the maximum dosage

Avoid intravascular injections by ______ the syringe

aspirating

to avoid toxicity add ______ to slow absorption of LA into bloodstream

vasoconstrictors

Know and avoid the ____ ______

maximum dosage

Ideal properties

Reversible

Non-irritating

Rapid onset

Sufficient duration

Low systemic toxicity

non-addicting

Effective at all sites

Stable in solution

Summary: What is pain

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. It has both sensory component (location, intensity, duration) and a motivational/affective component influences by emotions, past experiences, and culture

Summary: How does the structure of the nerve fiber contribute to conduction

Nerve fibers differ in diameter and myelination, which affects conduction speed. Larger, myelinated fibers (a-beta, a-delta) conduct impulses much faster than smaller unmyelinated C fibers

Summary: How is the impulse conducted

Impulse conduction occurs through changes in membrane potential, including depolarization once a threshold is reached. This propagates along the neuron as an action potential, followed by a refractory period before another signal can occur

Summary: What Ions are involved and at what points

Na are primarily responsible for depolarization as they enter the neuron through voltage-gated channels. Potassium ions (K) help restore the resting membrane potential during repolarization

Summary: What is the refractory period

The refractory period is the time after an action potential when a neuron cannot or is less likely to fire another impulse

Summary: What is the MOA of LA

Local anesthetics block Na channels in nerve membranes, preventing depolarization and stopping nerve impulse transmission. Both charged and uncharged forms are needed, and effectiveness is reduced in acidic environments

Summary: What are ideal properties for a local anesthetic

An ideal local anesthetic is reversible, non-irritating, and has rapid onset with sufficient duration. It should also have low toxicity, be stable, non-addicting, adn effective at all sites