L20- Local Anesthetics Flashcards
describe the intended goals / actions of local anesthetics
- block nerve conduction: sensory impulses (PNS) to CNS
- high doses may abolish sensation and motor control
-no LOC
describe the general structure of local anesthetics
- lipophilic group (aromatic ring)
- *Intermediate group- Ester (1 I in names) or Amide (2 Is in names)
- ionizable group (tertiary amine)
(esters/amides) are more prone to hydrolysis, therefore they have (2) in terms of drug actions
Esters –> shorter half-life
Local Anesthetics are commonly weak (acids/bases) with a pKa of (2). At physiological pH, 7.4, anesthetics will be in (cat/an)-ionic form.
1- weak bases
2- pKa: 8.0-9.0
3- cationic
describe the function of the uncharged form and ionized form of local anesthetics
Uncharged: penetration of biological membranes (to diffuse into cells / neurons
Ionic: active form that binds intracellular receptors
local anesthetics preparations usually also contain (1) to assist the action of the anesthetic through (2) mechanism having (3) effects on anesthetics
1- epinephrine
2- vasoconstriction (keep drug in local area longer)
3- neuronal uptake is enhanced —- systemic toxic effects are reduced
a (1) is not added to local anesthetic preparations in areas with end artery supply, like (2) locations because of fear of losing (2) due to (3) processes
1- vasoconstrictors
2- fingers, toes, ears, nose, retina, penis,
3- delayed wound healing, tissue edema, necrosis
(1) is a local anesthetic that constricts blood vessels by potentiating the action of (2), and therefore preventing the absorption of (1) itself
1- cocaine (ester)
2- NE
compare ester-linked and amide-linked anesthetics in terms of metabolism
Esters: shorter half-lives
- more prone to hydrolysis
- metabolized by tissue and plasma cholinesterases (pseudocholinesterase)
Amides: longer half-lives
-degraded by liver – microsomal cytochrome P450 system
describe the MOA of local anesthetics, simply
- lipophilic form crosses neuronal membrane
- switched to ionic form
- binds to receptors (intracellular) near V-gated Na channels
- blocks V-gated Na channels
- prevents / abolishes APs
Local Anesthetics, pharmacology:
- potency correlates to (1)
- speed of onset of action correlates to (2)
- duration of action correlates to (3)
- toxicity correlates to (4)
1, 3, 4- liposolubility
2- pKa (closer to body pH –> faster the onset — more in ionic form)
list the common ester local anesthetics
(Note- 1 I in name)
- cocaine
- benzocaine
- procaine, chloroprocaine
-tetracaine
list the common amide local anesthetics
(Note- 2 Is in name)
- lidocaine
- prilocaine
- mepivacaine
- bupivacaine
- ropivacaine
- etidocaine
list the short-acting local anesthetics
procaine, chloroprocaines (esters)
list the intermediate-acting local anesthetics
lidocaine, mepivacaine, prilocaine (amides)
list the long-acting local anesthetics
- tetracaine (esters)
- bupivacaine, etidocaine, ropivacaine (amides)
list the CNS AEs of local anesthetics
- initial response
- secondary response
1st) CNS stimulation => restlessness, tremor, clonic convulsions (toxic rxn to excess levels)
2nd) respiratory depression –> death
CNS AEs of local anesthetics are treated prophylactically with….
benzodiazepine –> to prevent seizures
the main PNS AE for local anesthetics is….
toxicity to nerve tissue at high concentrations (destruction)
Local anesthetics may cause CVS toxicity due to its (1) action affecting the heart and possibly leading to (2) and or (3).
1- blockade of Na channels
2- [cardiac depression of pacemaker activity, excitability, and conduction] –> arrhythmia
3- [dec contractility] –> arterial dilatation + hypotension
______ is the only local anesthetic that may cause vasoconstriction, hypertension, and cardiac arrhythmias
cocaine:
- vasoconstriction / HTN due to NE potentiation
- arrhythmia due to Na channel blockade
______ is the most cardiotoxic local anesthetics
bupivacaine
list the systemic AEs of local anesthetics as plasma concentrations inc
(from lowest concentration to highest) drowsiness paresthesia in mouth/tongue tinnitus, auditory hallucinations muscular spasms seizures coma respiratory arrest cardiac arrest
Prilocaine may lead to accumulation of its metabolite (1) which is responsible for causing (2), treated with (3)
(at large doses)
1- o-toluidine
2- converts Hb –> methemoglobin (–> hypoxia)
3- methylene blue
Ester type local anesthetics are converted to (1) metabolite which can cause (2) in a small portion of the population.
1- PABA (p-aminobenzoic acid derivatives)
2- allergic reaction
Note- amides very rarely ever cause allergic reactions – no conversion into PABA
______ is the main contraindication / drug interaction to avoid with use of ester type local anesthetics (procaine mainly)
Sulfonamides:
- Procaine –> PABA (p-aminobenzoic acid derivatives)
- inhibits actions of Sulfas (used as antibiotic)
