Katzung Chapter 26: Local anesthetics

Local anesthesia

-complete loss of sensation (analgesia) in a limited region of the body

-Reversibly block impulse conduction along nerve axons and other excitable membranes

-Used to block pain sensation or sympathetic vasoconstrictor impulses

-Other physiological effects -Muscle paralysis

-Suppression of somatic or visceral reflexes

-Recovery is spontaneous, predictable and without residual effects

Local anesthesia chemistry

-lipophilic group, intermediate chain and a ionizable hydrophilic group (usually a tertiary amine)

Local anesthesia absorption

-local injection

-Anesthetics more lipid soluble generally more potent, have longer duration of action and take longer to achieve effect

-Important factors

+Site of injection

+Highly perfused tissue absorption is more rapid w/ higher blood levels

-Highly perfused organs- brain, liver, kidney and heart

-Presence of vasoconstricting substances

+Decrease systemic absorption and therefore reduce toxic effects

+Higher local concentration of drug from enhanced local uptake of anesthetic

+Epinephrine stimulates alpha 2 receptors in spinal cord during spinal anesthesia and may produce analgesic effect

Local anesthetics - metabolism + excretion

-converted in liver or plasma to more water-soluble metabolites and excreted by kidneys

Local anesthetics - MOA

-Blockade of VgNaC

-Bind to intracellular portion of channels

+higher affinity for activated and inactivated than resting channels

-Elevated extracellular Ca favors resting state of Na channel

-Elevated extracellular K increases effects of local anesthetics

-higher and higher concentrations result in blockade of more and more Na channels

-Recovery from drug-induced block is 10-1000 times slower than recovery of sodium channels from normal inactivation.

-Bind to numerous other channels, enzymes and receptors

biological toxins - LA

-act as sodium channel agonists and prevent inactivation of the channel

Marine toxins - LA

-bind to extracellular surface of sodium channels and block channel activity

LA - Structure characteristics

-smaller, lipophilic agents have faster rates of interaction w/ channel and higher potency

-More water soluble- lidocaine, and mepivacaine

-Less water soluble- tetracaine, ropivacaine and bupivacaine

Local anesthetics - action on nerves

-Greater action on small diameter nerve fibers

-Myelinated nerves blocked before unmyelinated

-High frequency fibers blocked more efficiently

-In large mixed nerve trunks fibers on circumference affected first

Local anesthetics - routes of administration

-Surface anesthesia
-Topical injection
-Injection near peripheral nerve endings and major nerve trunks
-Epidural injections
-Subarachnoid injections

Orderly evolution of nerve block - LA

-First- sympathetic transmission
2. Temperature
3. Pain
4. Light touch
-Last- Motor block

Local anesthetics - duration

-Short-acting- chloroprocaine

-Intermediate-acting- lidocaine, mepivacaine and prilocaine

-Long-acting- tetracaine, bupivacaine, and ropivacaine

-Vasoconstrictors can prolong the duration of action

-Carbon dioxide can accelerate the onset

LA CNS toxicity

-Local causes:
sedation, lightheadedness, visual and auditory disturbances, restlessness, nystagmus and muscle twitching, tonic-clonic seizures

LA CV toxicity

-Local causes:

act on cardiac sodium channels and depress pacemaker activity, excitability and conduction

LA neurotoxicity

-Local effects from direct contact
i. Conduction failure
ii. Membrane damage
iii. Enzyme leakage
iv. Cytoskeletal disruption
v. Accumulation of intracellular calcium
vi. Disruption of axonal transport
vii. Growth cone collapse
viii. Apoptosis

LA transient neurologic symptoms (TNS)

-Transient pain of dysesthesia- can be quite severe

-Linked to spinal anesthesia w/ lidocaine

-Can occur at modest doses in up to 1/3 of patients

-Risk w/ other local anesthetics varies considerably

Articaine

Local anesthetic
-Enhanced lipophilicity and tissue penetration
-Short half-life
-Toxicity- persistent paresthesia - rare

Benzocaine

Local anesthetic
-Pronounced lipophilicity
-Topical anesthesia
-Toxicity- methhemoglobinemia

Bupivacaine

Local anesthetic
-Peripheral anesthesia and analgesia for postop pain and labor analgesia
-Long duration of action not suitable for outpatient or ambulatory surgery
-Toxicity- cardiotoxic (high volumes)

Chloroprocaine

Local anesthetic
-Short duration of action
-Little or no risk for TNS
-Epidural anesthesia or peripheral nerve block in a short procedure

Cocaine

Local anesthetic
-Limited to topical anesthesia for ear, nose and throat procedures
-Intense vasoconstriction limits bleeding

Lidocaine

Local anesthetic
-intermediate duration anesthetic

Mepivacaine

Local anesthetic
-Vasoconstrictor producing longer duration of action
-Major nerve blocks
-Toxicity- slowly metabolized by the fetus

Prilocaine

Local anesthetic
-Highest clearance and reduced risk of systemic toxicity
-Toxicity- methhemoglobinemia

Ropivacaine

Local anesthetic
-High-volume peripheral nerve blocks
-Epidural infusions to control labor and postoperative pain
-Low perceived cardiotoxicity

EMLA

Local anesthetic
-Lidocaine and prilocaine topical mixture
-Penetrates keratinized skin and produces numbness