Local Anesthetics

Local anesthetics (LAs) block __________ channels to inhibit pain transmission.

voltage-gated sodium (Na⁺)

They prevent the neuron from reaching __________, which stops action potential propagation.

depolarization

The local anesthetic must be in the __________ form to cross the membrane and enter the neuron.

unionized

Once inside, the drug becomes __________ and binds to the sodium channel from the cytoplasmic side.

ionized

Esters contain a __________ linkage, while amides contain a __________ linkage.

–COO–; –CONH–

__________ local anesthetics are more stable and longer-acting due to hydrolysis resistance.

amide

__________ are hydrolyzed more rapidly by plasma esterases.

esters

Esters tend to form __________, a metabolite that can cause allergic reactions.

para-aminobenzoic acid (PABA)

Benzocaine is an __________ with a very low pKa, making it mostly __________ at physiological pH.

ester, unionized

Because of its low water solubility, benzocaine is used __________.

topically

Benzocaine can cause __________ due to aromatic amine oxidation.

methemoglobinemia

Procaine is an ester with an added __________ group, improving water solubility.

ionizable amine

Procaine is hydrolyzed to PABA and has a __________ duration of action.

short

Lidocaine is an __________ local anesthetic with a longer duration and better solubility.

amide

A common use for lidocaine is in __________ procedures.

dental and minor surgical

The basic SAR for local anesthetics includes three parts:
→ __________ ring, __________ chain, __________ amine

aromatic; intermediate (ester/amide); hydrophilic

The aromatic ring increases __________ and enhances potency.

lipophilicity

Electron-donating groups on the aromatic ring (e.g., –NH₂, –OCH₃) tend to __________ potency.

increase

A branched or bulky intermediate chain hinders __________ and increases duration.

hydrolysis

A tertiary amine at the hydrophilic end allows for __________ formation.

salt

Ester LAs are metabolized by __________ in the blood.

plasma esterases

Amide LAs are metabolized in the liver by __________ enzymes.

CYP450

One toxic metabolite of lidocaine is __________, which can contribute to methemoglobinemia.

2,6-dimethylanilinea

Methemoglobinemia is caused by oxidation of Fe²⁺ to __________ in hemoglobin.

Fe³⁺

Symptoms of methemoglobinemia include cyanosis and poor oxygen delivery, even with normal __________ levels.

oxygen saturation (SpO₂)

Combining LAs with __________ prolongs duration by causing vasoconstriction.

epinephrine

Excessive vasoconstriction from EPI can lead to __________ if used in end-artery areas.

tissue necrosis

Local anesthetics should be avoided in areas like __________ and __________ due to poor blood flow.

fingers; toes (also acceptable: ears, nose)

Risk factors for methemoglobinemia include age under __________, anemia, G6PD deficiency, and prolonged use.

2 years

__________ is an ester local anesthetic that’s 10–50× more potent than procaine.

Tetracaine

__________ is a long-acting amide anesthetic with high cardiotoxicity risk.

Bupivacaine

__________ is a dental amide anesthetic that contains sodium metabisulfite, which may trigger allergies.

Articaine

__________ is a topical ester anesthetic with low solubility and is not injectable.

Benzocaine

__________ is an amide anesthetic commonly used with rapid onset and short duration.

Mepivacaine

Amides tend to have longer action due to their __________ to hydrolysis.

resistance

LAs with lower pKa values have a __________ onset of action.

faster

LAs with higher lipid solubility have __________ potency and longer duration.

greater

EPI increases local anesthetic duration by activating __________ receptors.

alpha-1 adrenergic

Allergic reactions from ester LAs may cross-react with __________ antibiotics due to PABA similarity.

sulfa