Local Anesthetics Flashcards
Analgesics
Specific inhibitors of pain pathways
Anesthestics
Non-specific inhibitors of peripheral sensory including pain, motor, and autonomic pathways
Local anesthetics
Inhibit conduction of action potentials in all afferent and efferent nerve fibers
Local anesthetics- pharmacology
Hydrophobic, weak bases either ester or amide linked
Local anesthetics- kinetics
Diffuse to site of action after administration also taken up into systemic circulation.
Local anesthetics-distribution
In the blood bind to alpha-1-acid glycoprotein and albumin. Hydrophobic agent has greater binding affinity (bound drug is no longer effective)
Less hydrophobic has greater plasma concentration and vice versa.
Ester linked metabolism/elimination
Procaine, tertracaine, and cocaine
Metabolized locally by tissue and plasma esterases (psuedocholinesterase_.
Short DOA and minute metabolism
Eliminated via the kidneys
Amide linked metabolism/elimination
Lidocaine, prilocaine, bupivicaine, articaine
Primarily P450 in the liver, although in the lungs as well
Metabolites eliminated via kidney
Longer DOA
Tonic inhibiton
Occurs when the time b/w action potentials is long compared to the time of dissociation of the local anesthetic from the Na channel.
Phase inhibition
Not enough time b/w action potentials. Action potential conduction increasingly inhibited at higher frequencies of impulses.
Procaine
Ester based
Short-acting low hydrophobicity, low potency
Rapidly metabolized in plasma by cholineresterases
Sulfa drugs decrease effectiveness
Tetracaine
Ester based
Long-acting, highly potent due to high hydrophobicity
Metabolized by cholinesterase in plasma but slower effect than with procaine as released gradually from tissues to blood stream
Used as spinal and topical anesthesia.
Cocaine
Only naturally occurring ester based local
Medium potency and DOA
inhibits catechlamine uptake peripherally and centrally (vasoconstriction and euphoria- cardiac toxicity)
Used as ophthalmic and topical anesthesia
Lidocaine and Prilocaine
Amide based
Moderate hydrophobicity, large fraction of drug is in neutral form at physiologic pH= rapid onset, med DOA, and moderate potency
Metabolism by live by P450
Used for peripheral nerve blocks, epidural, spinal, and topical anesthesia.
Toxicities- CNS depression and cardiotoxicity
Prilocaine
vasoconstricive
Lidocaine
antiarrhythmic
Bupivicaine
Amide based
long DOA and highly hydrophobic (high potency)
Metabolized by live P450
R and S enatiomer
Cardiac toxicity due to blocking Na channels in cardiac myocytes during systole but is slow to dissociate during diastole.
Articaine
Amide based
Exhibits an ester group making it act differently
Partially metabolized in the plasma by cholinesterase and in the liver by P450
Administration- topical
applied to skin or mucous membranes, short term relief, absorbed rapidly into circulation,
Ex- TAC, EMLA, and lidocaine patch
Administration- infiltration
Used to number area of skin of mucosal surface via an injection. Kept at acidic pH to help absorption
Ex- lidocaine, procaine, bupivicaine
Administration- peripheral nerve block
Injected percutaneous
Administration- central nerve block
Drug delivered near spinal cord (epidural or intrathecal) Bupivicaine used in labor, ropivicaine and levobupivicaine due to not having cadiotoxicity
Administration- intravenous regional
Beir’s block occasionally used in arm and hand surgery
Toxicities
Hypersensitivity rxn- rare usually have sulfa drug allergy
Local irritation due to local application
CNS- extreme excitement followed by depression
Cardiac- effects on Na, K, and Ca channels lead to potential toxicity
Peripheral vasculature and bronchial smooth muscle- initial constriction followed by dilation.
