LOCAL ANESTHETICS LECTURE NOTES

CASE: ANESTHETICS:
LM, a 26 y.o. male who works in the school canteen, sustained a - Grouped by the nature of the linker region. Procaine is a
lacerated wound on his R middle finger while slicing vegetables. He prototypic ester-type local anesthetic;
was brought to the ER and was scheduled for suturing of the wound. - esters - hydrolyzed by plasma esterases - short duration of
What could be given to facilitate suturing of the wound? action
- Local infiltration of local anesthetic – digital block using - Lidocaine is a prototypic amide-type local anesthetic -- more
Lidocaine - 1 ampule = 100mg resistant to clearance and have longer durations of action.
- Maximum dose of lidocaine =
- Mechanism of action of local anesthetics: 2 TYPES OF LOCAL ANESTHETICS
o Blocks sodium channel AMIDES ESTERS
o Effect: analgesia Bupivacaine Benzocaine
Levobupivacaine Chloroprocaine
LOCAL ANESTHETICS: Etidocaine Cocaine
- Local anesthetics provide anesthesia and analgesia by blocking Lidocaine Procaine
the transmission of pain sensation along nerve fibers Mepivacaine Tetracaine
- KEY TARGET: VOLTAGE-GATED SODIUM CHANNEL Prilocaine
o Binding is INTRACELLLULAR and is mediated by hydrophobic Ropivacaine
interactions Emla
- The degree of blockade depends on both DRUG - Lidocaine + prilocaine
CONCENTRATION and VOLUME - For warts
- Efficacy for clinical use of local anesthetic may be increased by
addition of: Mechanism of action
o Epinephrine, opioids, and alpha2- adrenergic agonists - Blocks conduction by decreasing or preventing sodium
- The rate of local anesthetic system absorption depends on the permeability
site of injection, the dose, the drug’s intrinsic pharmacologic - No propagation of action potential → nerve conduction fails
properties, and the addition of vasoactive agents - The degree of block depends on how the nerve has been
o Do not add vasoactive agents on areas w/ end arteries stimulated and on its resting membrane potential
o Ex. Tip of the nose, penis - ↑ frequency of stimulation and more positive membrane
potential cause a greater degree of anesthetic block
COCAINE - Gains access to its binding site w/in the pore only when the
- Coca shrub (Erythroxylon coca) channel is in the open state
- Albert niemann: 1st isolated in 1860, numbing of tongue
- Sigmund Freud: cocaine’s physiological actions DIFFERENTIAL SENSITIVITY OF NERVE FIBERS
- Carl Koller: topical anesthetic for ophthalmological surgery 1884
- Halstead: infiltration and conduction block anesthesia

MOTOR
DEEP function
TOUCH Pressure •myelina
TEMP •myelina ted
•Myelina
PAIN ted ted •alpha-
•myelina alpha
ted •A- •A-beta
•unmyeli fiber
nated •A-delta gamma
fiibers fibers
•C fibers

PROLONGATION OF ACTION BY VASOCONTRICTORS

EPINEPHRINE – vasoconstrictor
2 roles:
1. Decreases the rate of absorption, it localizes the
anesthetic at the desired site
2. Allow the rate at w/c it is destroyed in the body to keep
pace w/ the rate at which it is absorbed into the circulation
- Reduces systemic toxicity

Sympathomimetic amines
- ↑ consumption of o2 + vasoconstriction = hypoxia, local tissue
damage

Contraindication:
- Regions w/ limited collateral circulation
o Could produce irreversible tissue damage, tissue necrosis,
** Hydrophobic (aromatic) moiety (black), a linker region (orange), gangrene
and a substituted amine (hydrophilic region, in red).

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LOCAL ANESTHETICS LECTURE NOTES
CASE: o Neonate: deficiency in plasma proteins
FS, a 32 y.o. female, was diagnosed w/ multinodular goiter 1 year ▪ Susceptible to toxicity
ago. She was scheduled for thyroidectomy. During the operation, o Reduced cardiac output
the ENT surgeon infiltrated lidocaine + epinephrine in the incision ▪ Slows delivery of the amide compounds to the liver,
site. reducing their metabolism and prolonging their plasma
half-lives
What is the purpose of the local anesthetic?
- To reduce post-op pain LOCAL ANESTHETICS
Why was epinephrine added to the local anesthetic? COCAINE
- To prolong the action of local anesthetic - Toxicity and Potential for abuse decreases its clinical use
- To have a better operating view (field) → less bleeding - Inhibits catecholamine (NE) uptake
o Sensitization to catecholamines, vasoconstriction, mydriasis
UNDERSIRED EFFECTS OF LOCAL ANESTHETICS - Inhibit DA uptake → euphoria
AG, a 36 y.o. male, was inadvertently given BUPIVACAINE (a local - Used primarily for topical anesthesia of the upper respiratory
anesthetic for spinal/epidural anesthesia) INTRAVENOUSLY. After a tract
few minutes, he was noted to have difficulty of breathing and o Anesthesia, shrinking of the mucosa
became unconscious. ECG showed ventricular tachycardia
LIDOCAINE
What were the clinical manifestations noted after inadvertent giving - Transdermal patch – relief of pain for postherpetic neuralgia
of BUPIVACAINE IV? - Oral patch – dental procedures
- Difficulty of breathing - EMLA – lidocaine + prilocaine
- Loss of consciousness - Lido + tetracaine – topical analgesics
- Vtach
Explain the condition of the patient BUPIVACAINE
- More cardiotoxic
CENTRAL NERVOUS SYSTEM EFFECTS:
- Blocks cardiac sodium channel during systole but dissociates
Restlessness →tremor →clonic convulsion →depression→ death more slowly during diastole
- Usually goes before cardiovascular - Cardiac toxicity difficult to treat
o Enhanced by coexisting acidosis, hypercarbia and hypoxemia
CARDIOVASCULAR
MYOCARDIUM: ARTICAINE
- ↓ in electrical excitability, conduction rate and force of - amide + ester
contraction - Dental and periodontal procedures
- Seen only after high systemic concentrations are attained and - 1-6 mins (rapid onset)
effects on the cns are produced - Duration of action ~1hr
- BUPIVACANE – vtach and fibrillation
o Inadvertent IV admin CHLOROPROCAINE
o Cardiotoxic - Rapid onset and short duration of action
- Reduced acute toxicity due to its rapid metabolism
SMOOTH MUSCLE - ↑ incidence of back pain – tetany of paraspinous muscle
- GIT – depress contractions in the intestines o Calcium binding by EDTA
- VASCULAR and BRONCHIAL smooth muscle – relaxarion
- SYMPATHETIC NS – paralysis MEPIVACAINE
- UTERINE MUSCLE - ↑ resting tone, ↓ contraction - Amide
- INTRAPARTUM – uterine contractions not depressed - More toxic to neonate – not for obstetrical anesthesia
- Ion trapping - ↓ pH of neonatal blood
NMJ and GANGLIONIC RESPONSE – block nicotinic ach receptors
HYPERSENSITIVITY PRILOCAINE
- RARE
- amide
- allergic dermatitis, asthma
- Methemoglobinemia at 8mg/kg
o Metabolism of the aromatic ring to o-toluidine
METABOLISM OF LOCAL ANESTHETICS
ESTERS
ROPIVACAINE
- BENZOCAINE, CHOLORPROCAINE, COCAINE, PROCAINE,
- Less toxic than bupivacaine
TETRACAINE
- Used in delivery
o Hydrolyzed by Plasma cholinesterase
PROCAINE
AMIDES
- 1st synthetic local anesthetic
- Lidocaine, prilocaine, bupivacaine, ropivacaine
- ester
o Hepatic CYPs → N-dealkylation → hydrolysis
- hydrolyzed in vivo to produce para-aminobenzoic acid
- PRILOCANE
o inhibits the action of sulfonamides
o Initially Hydrolysis → o-toluidine metabolite
▪ Can precipitate methemoglobinemia
TETRACAINE
- Extensively bound to a1-ACID GLYCOPROTEIN
- Long action
o ↑ a1-ACID GP – cancer, surgery, trauma, MI, smoking, and
uremia
o ↓ a1- acid gp – oral contraceptives
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LOCAL ANESTHETICS LECTURE NOTES
LOCAL ANESTHETICS TO ANESTHESIZE MUCOUS MEMBRANE AND - Duration increased by epinephrine
SKIN o Epinephrine-containing solutions should not be injected into
- Effective in the symptomatic relief of anal and genital pruritus, tissues supplies by end arteries
poison ivy rashes, and numerous other acute and chronic ▪ Fingers and toes, ears, nose, and penis
dermatoses o Vasoconstriction→ gangrene
- DIBUCAINE, DYCLONINE HCL, PRAMOXINE HCL
FIELD BLOCK ANESTHESIA
ANESTHETICS OF LOW SOLUBILITY - Subcutaneous injection in order to anesthetize the region distal
- Less toxicity – less absorbed to injection
- Apply directly to wounds and ulcerated surfaces, where they - Scalp, ant abdominal wall, upper and lower ex
remain localized for long periods of time - Anesthesia of proximal portion of volar surface of forearm →
o Sustained anesthetic action extensive anesthesia starting at 2-3cm distal to the site of
- Benzocaine – can cause methemoglobinemia injection
- Local anesthetic – never intended to be directly injected to the
LOCAL ANESTHETICS RESTRICTED TO OPHTHALMOLOGICAL USE nerve → painful and would cause nerve damage
- COCAINE – 1st LA used in ophthalmology o You bathe the nerve only
o Disadvantage: mydriasis, corneal sloughing o Anesthetic agent is deposited as close to the nerve as
- PROPARACAINE – used in patients sensitive to esters possible
- TETRACAINE - When local anesthetic is deposited at peripheral nerve, it
- Long term administration diffuses from the outer surface toward the core along a
o retarded healing, pitting, and sloughing of the corneal concentration gradient
epithelium
o predisposition of eye to inadvertent injury Determinants of onset of sensory anesthesia following injection
- For a given concentration, local anesthetics with lower pKa
BIOLOGICAL TOXINS values tend to have a more rapid onset of action because more
GC, a 40 y.o. male, was rushed to the emergency room after eating drug is uncharged at neutral pH.
shellfish. He is experiencing difficulty in breathing. There has been
advisory in the news on the presence of red tide. INTRAVENOUS REGIONAL ANESTHESIA (BIER’S BLOCK)
- Extremity is exsanguinated w/ a ESMARCH (elastic) bandage,
What are the differential diagnosis? and a proximally located tourniquet is inflated to 100-150 mmHg
- Toxin – saxitoxin causing respiratory paralysis above the systolic BP
- r/o: asthma attack - Bandage is removes, and the local anesthetic is injection into a
previously cannulated vein
explain the manifestation of the patient in relation to presence of o Lidocaine w/o epinephrine
shell toxin - Used for: surgery of the forearm and hand, foot and distal leg
- Blocks Na channel
- Effect: paralysis of respiratory muscles SPINAL ANESTHESIA
- Injection of la into the subarachnoid space
MECHANISM OF ACTION: - Spinal cord ends at L1 (above L2)
- Blocks SODIUM channel → no action potential - Sympathetic blockade
- Channels in cardiac myocytes and dorsal root ganglion are o Vasodilation (venous>arterial), hypotension
resistant - at high levels of spinal blockade, the cardiac accelerator fibers,
o Only in skeletal muscles, therefore the paralysis of w/c exit the SC at T1-T4, will be blocked →bradycardia
respiratory muscles - decrease of BP to ~30% of resting values: warrants treatment
o No effect on the heart unlike bupivacaine o O2 fluid infusion (500-100mL)
- TETRODOTOXIN o Manipulation of px position
o puffer fish (fugu), newts of Salamandridae, Costa Rican Frog o Administration of vasoactive drug (ephedrine,
Atelopus phenylnephrine)
- SAXITOXIN – clams and shellfish – red tide - Peritoneum block
- If the patient survives shellfish poisoning for 24 hours, the o T4 block
prognosis is good o There is 2 segment regression per hour

CLINICAL USES OF LOCAL ANESTHETICS COMPLICATIONS OF SPINAL ANESTHESIA

TOPICAL ANESTHESIA - Neurological deficits (rare) – foreign substances (s/a
- TETRACAINE, LIDOCAINE, COCAINE disinfectants or talc) into the subarachnoid space, infection,
- EMLA (Eutectic Mixtures of Local Anesthetics) hematoma, or direct mechanical trauma
o Lidocaine (2.5%)/Prilocaine (2.5%) – EMLA - Contraindicated in px w/ pre-existing disease of the spinal cord
o Lidocaine (7%)/Tetracaine (7%) - PLIAGIS - Postdural puncture headache (PDPH)
- Shrinking of mucus membranes ↓ operative bleeding while o Upright position causes pain or headache
improving surgical visualization o Tx: conservative bed rest, analgesics, epidural blood patch
- Local anesthetics are absorbed rapidly into the circulation
following topical application to mucus membranes or denuded EPIDURAL ANESTHESIA
skin - Injection of LA into the epidural space
- Site of action: SPINAL NERVE ROOTS
INFILTRATION ANESTHESIA - Requires ↑ dose than spinal anesthesia
- Direct injection to tissue w/o taking into consideration the - The level of sympathetic block is close to the level of sensory
course of cutaneous nerves – skin to deeper structures block
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LOCAL ANESTHETICS LECTURE NOTES

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