Local Anesthetics Flashcards
Properties of Ideal local anesthetics
1) Short onset, long duration of action
2) Minimal absorption/distribution
3) Act predictably and reversibly without causing tissue damage
4) Large safety margin
Aromatic Ring determines ______
lipophilicity, potency
Aromatic Ring duration of action is influenced by
protein binding (high affinity for protein binding increase duration of action). Also decreases availability of free drug in blood to reduce potential for toxicity
Intermediate linkage determines____
class of drug (amino ester or amino amide). this determines route of metabolism, toxic potential, potential for allergic reaction
Esters are metabolized by _____ and have longer or shorter half lives compared to amino amides.
How are they excreted?
1) plasma esterases (plasma cholinesterase)
2) shorter half life
Water soluble metabolites excreted in urine
What part of esters causes allergic reactions in some people?
esters are derivatives of PABA
Amides are metabolized in ____. What would decrease metabolism/increase toxicity?
How are metabolites cleared?
1) liver
2) decreased hepatic function (cirrhosis) or hepatic blood flow (congestive heart failure)
3) renal clearance
cocaine, procaine, benzocaine and tetracaine are all ____
esters (contain only ONE “i”)
lidocaine, mepivicaine, bupivicaine, prilocaine, ropivicaine, dibucaine are all ___
amides (all contain at least TWO “i’s”)
Terminal amine (hydrophilic portion) correlates with ____ and is determined by ____ and ____.
1) onset of action
2) pKa of local anesthetic
3) pH of local environment
Which form of the terminal amine is able to diffuse through cell membrane and which form of the terminal amine is actually active once in the cell?
1) diffuse through membrane = unionized form
2) active in cell = ionized form
The higher the pKa of the local anesthetic the (higher or lower?) the concentration of unionized (diffusable) drug at physiologic pH, the (faster or slower?) the onset
1) LOWER
2) SLOWER
Acidic pH of local environment (ex: abscess) favors which form of drug? Is onset faster or prolonged?
Shifts equation to the LEFT, ionized form favored, less able to cross membrane, slower onset of block
Basic pH of local environment (ex: c-section) favors which form of drug? Is onset faster or prolonged?
Shifts equation to the RIGHT, unionized form favored, more able to cross membrane, faster onset.
Mechanism of action of local anesthetics
ionized form of drug (the active form) blocks the intracellular portion of the inactivated voltage gated sodium channel to slow recovery and prevent propagation of action
Onset of block depends on what 3 things?
1) size of nerve fiber (small diameter–>penetrates faster)
2) degree of myelination (myelinated nerve only needs to be blocked at nodes of ranvier so blocked more quickly)
3) firing frequency (faster firing–>more inactive channels available)
How are nerve fascicles blocked?
From outside in (proximal to distal progression) ie elbows to fingers
Order of neuron types blocked first to last
B>C>A delta>A gamma>A beta>A alpha
Order of systems blockaded from first to last
sympathetic tone, temperature, pain, light touch, motor
Absorption is determined by what 3 factors?
1) site of injection (highly vascular–>fast absorption)
2) presence of vasoconstrictors (epinephrine for ex) will decrease absorption–>inc neuronal uptake–>prolong duration of action–>limit toxic side effects (works best with short acting drugs)
3) local anesthetic agent (highly tissue bound–> more slowly absorbed)
Distribution of a drug determined by what 2 factors?
1) tissue perfusion (highly perfused organs get initial uptake, like brain/lung/liver/heart)
2) tissue/blood partition coefficient (strong plasma protein binding retains anesthetic in blood while high lipid solubility facilities tissue uptake)
What are the 3 types of systemic toxicity experienced with anesthetic drugs?
1) CNS toxicity
2) Cardiovascular toxicity
3) methemoglobinemia
What are the signs of early CNS toxicity?
CNS excitation (excitatory neurons function unopposed) causing decreased inhibition (talkativeness), sensory disturbances (perioral numbness, metallic taste in mouth), restlessness, tremor, tinnitus
What are signs of late CNS toxicity and how do you tx?
CNS depression ((lethargy, hypotension, bradycardia, decreased respiratory rate, seizures). Tx by protecting airway, stoping seizure activity with benzodiazepines
What are signs of cardiovascular toxicity and how do you tx?
reduction in cardiac conductivity, excitability, contractility (Na/K+block), indirect vasodilation and bradycardia, arrhythmias, hypotension, QRS widening (early sign). Tx with ACLS, Intralipid
What is the tx for Methemoglobinemia?
methylene blue
What are 2 types of local toxicity experienced with anesthetics?
1) transient neurologic symptoms (often worse than surgical pain; linked to Lidocaine; doesn’t include sensory loss, motor weakness or loss of bladder/bowel); lidocaine fallen out of favor as spinal anesthetic
2) neuronal injury (most feared complication, mechanism poorly understood)
True allergy to local anesthetics is rare (apart from PABA). What is actually happening w/patients who claim they are allergic to local anesthetics?
Psychogenically mediated vagal response (syncope, bradycardia, hypotension) or direct effects from epinephrine additive (tachycardia, palpitations)
