Anesthetics & Muscle Relaxants

Chemical Classes of Local Anesthetics

esters and amides

Local Anesthetics

sensory transmission from a local area of the body to the CNS is blocked by decreasing conduction along nerve fibers

Local Anesthetic MOA

at non-toxic concentrations, medications block voltage gated Na+ channels of excitable membranes from inside the neuron

Local Anesthetic Actions

transient and reversible loss of sensation in a circumscribed region of the body without loss of consciousness

AVOIDS large physical perturbations

What charge must a drug have to diffuse across the membranes to bind to receptors?

UNcharged

If a drug is charged, how does it block sodium channel receptors?

binds to sodium gated channel on the inside to block it

How do pH changes affect drug actions?

allow or permit membrane permeability

How do you know if you have given too much of a dose of local anesthetic?

systemic effects occur

Potency of local anesthetics correlate with?

lipid solubility (ability to cross lipophilic membrane)

Potency of local anesthetics inversely correlate with?

molecular size (larger = will not cross as easy)

Which characteristics allow a local anesthetic to have faster effects?

lipophilic, smaller

Less water soluble local anesthetics will have ___ durations of action and be ___ potent.

longer; more

ex: bupivacaine, tetracaine [longer acting drugs]

More water soluble local anesthetics will have ___ durations of action and be ___ potent.

shorter; less

ex: lidocaine, procaine [more short acting drugs]

Ester Anesthetics

more likely to cause hypersensitivity (allergic reactions)

Ester Anesthetics end in?

-caine

Examples of Ester Anesthetics

• Procaine (short)
• Tetracaine (long)
• Benzocaine (surface)
• Cocaine (surface)

Amide Anesthetics

more likely to cause systemic effects at other tissues

Examples of Amide Anesthetics

• Lidocaine (medium)
• Bupivacaine (Long)

Which nerve fibers are blocked first?

smaller diameter

(sympathetic postganglionic, dorsal root, type B, type C)

T/F: Myelinated nerves are blocked before unmyelinated nerves of the same size.

TRUE (she says this anyways)

Fibers with ____ conduction are blocked first.

low -- pain fibers

(sensory fibers blocked first and motor fibers are blocked last_

Which type of firing frequency fibers get blocked first?

fast firing -- pain fibers

Which pH of tissues are more difficult to anesthetize?

lower pH -- infected tissues

decreases lipid soluble form of the drug

What effect does hyperkalemia have on nerve fiber blockades?

enhances the effect of local anesthetics due to depolarizing the membrane further

What effects do hypercalcemia have on nerve fiber blockades?

partially antagonizes the action of local anesthetics by hyperpolarizing the membrane and favoring the rested state of the Na+ channel

Why do you not want local anesthetics to affect alpha fibers?

do not want to block movement, just pain

Which fibers will recover first from the local anesthetic?

alpha motor neurons and pressure neurons (beta)

What is an adverse effect of local anesthetics to a sympathetic nerve fiber?

may cause local systemic effects

Local Anesthetic Effect on Cardiac Cells

can cause depression of cardiac frequency, conduction, automaticity, and contractility

ESPECIALLY with a history of cardiac issues

Which anesthetics are sometimes used as antiarrhythmic agents?

lidocaine

Local Anesthetic Adverse Effects

• Bupivacaine can lead to lethal arrythmias in high doses with cardiac issues

• Block sympathetic nerve fibers causing peripheral vasodilation

• Cocaine can block reuptake of NTs in the brain

Which local anesthetic does NOT cause peripheral vasodilation?

cocaine

(vasoconstrictor)

Absorption of local anesthetics depends on?

1. Physiochemical properties of the drug
2. Use of a vasoconstrictor
3. Site of injection

What can accelerate the onset of local anesthesia?

addition of sodium bicarbonate to the solution, making the pH increase to neutral

When would it be beneficial to add a sodium bicarbonate solution to local anesthetics?

cases of infection (lower pH) where the tissues are more difficult to anesthetize

Local anesthetics area administered with a?

vasoconstrictor

(ex: epinephrine)

Which locations in the body should you not administer local anesthetic + vasoconstrictor?

anatomic regions with limited circulation

ex: earlobes, fingers, toes, nose, penis

Injecting a local anesthetic without a vasoconstrictor can cause what adverse effects?

hypoxia, tissue necrosis, gangrene

Where do amide LAs distribute to?

highly perfused organs (heart, kidneys)

Where do ester LAs distribute to?

metabolized by plasma esterase and do not get distributed much at all

After amides are distributed, how are they transformed?

metabolized by P450 in the liver

Drugs inhibiting P450 will work to _ anesthetic effect.

increase

Local Anesthetic Routes of Administration

• Topical
• Infiltration
• Transdermal
• Peripheral Nerve Block

Topical Administration

direct application LA to mucous membranes or damaged skin

Uses for Topical Administration

minor surface irritation/injury or minor surgical procedure

Cons to Topical Administration

risk of systemic toxicity when used in high concentrations in large surface areas

Examples of Topical LAs

benzocaine, lidocaine

Infiltration Administration

direct injection into selective tissue; allowed to diffuse to sensory nerve endings within that tissue

Uses for Infiltration Administration

suturing of lacerated skin, dentistry, etc.

superficial to include only the skin or deeper structures

What happens when you add epinephrine to infiltration LAs?

duration of infiltration is doubled

Why does epinephrine doubling infiltration duration matter?

caution in tissues supplied by end arteries

may cause intense vasoconstriction and gangrene

Transdermal Administration

application directly to the skin for the drug to be absorbed into the underlying tissues/deeply

What may enhance transdermal administration?

iontophoresis or phonophoresis

Transdermal Administration Uses

painful subcutaneous structures (tendons, bursae, etc.)

Patches are topical or transdermal?

topical

Peripheral Nerve Block

LA is injected near peripheral nerve trunks or plexuses

Peripheral Nerve MOA

affects the area innervated by the nerve

Peripheral Nerve Block Uses

surgery, dentistry, analgesia

Peripheral Nerve Block Examples

brachial plexus, cervical, femoral

Femoral Nerve Block

blocks more sensitive sensory nerves vs. motor nerves BUT quadriceps weakness may occur

Why might a femoral nerve block be dangerous?

• quadriceps weakness leads to falls
• hypotension
• muscle weakness

Pros of Peripheral Nerve Blocks

decreases the need for opioids

Which anesthetics are used for peripheral nerve blocks?

most local anesthetics

can add a vasoconstrictor

Central Nerve Blocks

spinal and epidural

Spinal Nerve Blocks

drugs injected into the subarachnoid space to mix with the CSF (more systemic)

Spinal Nerve Blocks MOA

produces dense anesthesia of all peripheral nerves distal to the point of injection

Spinal Nerve Block Uses

hip replacements, C-sections, etc.

Spinal Nerve Block Examples

• lidocaine
• tetracaine
• bupivacaine

Risks of Spinal Nerve Blocks

• Bradycardia and hypotension (sympathetic block)

• Respiratory depression (phrenic block)

• Postoperative urinary retention (blocking autonomic pelvic outflow)

• Spinal headache

Spinal Headache

need to lie flat and cannot stand or sit up without a headache

Mechanism of Spinal Headache

continued loss of CSF after intrathecal injection results in pressure differences when a patient is vertical but not lying down

causes severe headache when standing or sitting

Continuous Lidocaine Infusion (Catheter)

alterations in proprioception, touch, temp, and muscle weakness

What are continuous lidocaine infusions used for?

transient neurological syndrome (TNS) or neuronal injury

Transient Neurologic Syndrome (TNS)

pain and abnormal sensations without motor weakness

Epidural

produces segmental anesthesia of the dorsal nerve roots

only bathes the peripheral area of the region of injection

Epidural MOA

LA drug is injected into the epidural space surrounding the dura mater

does NOT enter the CSF

Cons of Epidural

larger volume of anesthetic is injected and takes longer for onset of analgesia than a spinal block

Epidural Uses

pain relief during childbirth, adjunct to general anesthetics, treatment of back pain, and post operative analgesia

Bier's Block

IV regional anesthesia used for short surgical procedures involving the UE and LE

< 60 minutes

Adverse Effects of Local Anesthetics in the CNS

• Light headedness
• Dizziness
• Restlessness
• Tinnitus
• Tremor
• Visual disturbances

At high blood concentrations, what can local anesthetics cause?

• Nystagmus
• Shivering
• Tonic-clonic seizures
• Respiratory depression
• Coma
• Death

What is an adverse effect of lidocaine and procaine?

sedation and sleep

How are adverse CNS effects of local anesthetics treated?

• Maintenance of airway
• Assisted ventilation
• IV diazepam for seizures
• Succinylcholine to suppress muscles

Dose Response of Sodium Channel Blockade in Non-Target Tissues

• Tongue numbness
• Lightheadedness
• Visual and auditory disturbances
• Twitching
• LOC
• Seizures
• Coma
• Respiratory arrest
• Cardiac arrest

How can local anesthetics affect the cardiovascular system?

• Hypotension
• Cardiac arrythmias
• Methemoglobinemia
• Hypersensitivity and allergic effects

How do local anesthetics cause hypotension?

arteriolar dilation and decreased cardiac contractility

Which local anesthetic is most likely to cause cardiac arrythmias?

bupivacaine

How do local anesthetics cause CV issues?

blocking cardiac sodium channels and depressing pacemaker activity

Methemoglobinemia

oxidative stress to hemoglobin; Hb has decreased oxygen carrying capacity

cyanosis occurs

Which local anesthetics cause hematologic effects?

benzocaine, lidocaine, and tetracaine

Why do only certain local anesthetics have hematologic effects?

they have an active metabolite

What type of allergic effects can local anesthetics cause?

rare rash, edema, and anaphylaxis

Which local anesthetics cause hypersensitivity and allergic reactions?

ester-type (benzocaine, procaine, tetracaine)

get metabolized to a specific chemical derivative

Which deficiency will cause you to undergo oxidative stress by certain medicines and foods?

NADPH deficiency (genetic)

What is NADPH responsible for?

converted methemoglobin to hemoglobin

A NADPH deficiency would appear as what in patients?

methemoglobinemia

Local Anesthetic Drug Interactions

• Sulfonamides
• Bactrim
• Chronic Alcohol
• Chronic NSAIDs

LAs vs. Sulfonamides

large doses of LAs diminish the antimicrobial effect of sulfonamides via antagonism

Rehab Relevance for LAs -- Intrathecal Administration

• Sedation, nystagmus, and restlessness may occur
• Increases risk of falls
• Decreases cognitive function
• May need to alert physician
• Reschedule until plasma levels decrease

Rehab Relevance for LAs -- Spinal Anesthesia w/Lidocaine

dysesthesia (abnormal sensations) can occur but needs to be correctly identified and reported