Local Anesthetics Flashcards
what is the chemical structure of local anesthetics ?
- lipophilic group (aromatic ring)
- am intermediate chain (ester or amide)
- a hydrophilic group (secondary or tertiary amine)
- except benzocaine
what are the ester linked anesthetics?
cocaine
procaine (Novocain)
chloroprocaine
tetracaine (Pontocaine)
proparacaine
benzocaine
what are the amide linked anesthetics?
Lidocaine (Xylocaine)
Mepivacaine (Carbocaine, Isocaine)
Bupivacaine (Marcaine)
Ropivacaine (Naropin)
Cinchocaine
Articaine
Prilocaine (Citanest)
Dibucaine
Etidocaine
what are the ether linked anesthetics?
Pramoxine
Phenacaine
what are the ether linked anesthetics primarily used for?
Pramoxine: topicals
Phenacaine: used in ophthalmology
what is the ketone/ether anesthetic and what is it used for?
Dyclonine (topical)
what is the effect of pH on local anesthetic in normal tissue?
In normal tissue (pH 7.4):
- anesthetic molecules remain in their non-ionized form, which is required for better nerve penetration
- Once inside, the intracellular environment is slightly more acidic, shifting more of the drug into the ionized (active) form to block Na⁺ channels
what is the effect of pH on local anesthetic in infected tissue?
In inflamed or infected tissue (pH < 7.4, acidic environment):
- More anesthetic exists in the ionized (charged) form outside the nerve.
- Less of the drug can cross the nerve membrane, reducing anesthetic effectiveness.
Solution: Use a higher dose or add bicarbonate to alkalinize the solution and increase the fraction of non-ionized anesthetic.
what effects do the HCl Salt formulations and carbonated solutions have on local anesthetics?
- HCl salt formulations are more stable but have a slower onset due to low pH and repeated injections lower local pH further, causing progressive loss of effectiveness (tachyphylaxis)
- carbonated solutions cause intracellular pH to decrease (localized acidosis) which allows more anesthetic molecules to become ionized inducing stronger and faster nerve blockade
what is the reason for adding Vasoconstrictors to local anesthetics?
- to reduce systemic absorption (lower toxicity)
- decrease regional blood flow (less carried away)
- prolong the duration
- enhance the intensity of the nerve block
two common vasoconstrictors used?
- Epinephrine (most common, typically 1:50,000 or 1:100,000 dilutions)
- Phenylephrine (used primarily in nasal preparations)
how are ester local anesthetics metabolized?
- metabolized by butyrylcholinesterase (BChE), also known as pseudocholinesterase, which is found in the bloodstream (shorter duration of action)
- some are metabolized into p-Amino Benzoic Acid (PABA)
which local anesthetics are metabolized into p-Amino Benzoic Acid (PABA)?
Procaine
chloroprocaine
tetracaine
benzocaine
how are amide local anesthetics metabolized?
undergo hepatic metabolism (liver metabolism) via cytochrome P450 (CYP) enzymes which leads to a longer duration of action
how would liver disease and reduced hepatic blood flow affect local anesthetic metabolism?
- liver disease reduces enzyme activity, slowing metabolism and increasing toxicity risk.
- conditions that reduce hepatic blood flow (heart failure, hypotension) slow drug clearance, prolonging anesthetic effects
excretion of local anesthetics
after metabolism they are converted into more water-soluble metabolites that are then excreted by the kidneys in the urine
how does acidification of the urine decrease the renal absorption?
more acidic urine causes anesthetic metabolites exist in their ionized (charged) form (4°N) that are less likely to be reabsorbed by renal tubules, meaning more drug is excreted in the urine and accelerates drug clearance from the body
what is the MOA of local anesthetics?
bind to a site near the intracellular end of voltage-gated Na⁺ channels, preventing sodium influx and stopping the propagation of action potentials
- Voltage-Dependent Block: LAs have a higher affinity for Na⁺ channels when the membrane is depolarized (i.e., the inside of the neuron is more positive).
- Time-Dependent Block: LAs are more effective on rapidly firing neurons, as these neurons cycle more frequently between open and inactivated states.
what are the dose-dependent effects of local anesthetics from low to high dose?
- low dose: increases the action potential threshold
- moderate dose: decreases the rate of rise and the amplitude of the action potential
- higher dose: slowing the impulse conduction
- very high dose: abolishes the inability to generate an action potential
how is the effectiveness of local anesthetics influenced by molecular size and lipid solubility?
the smaller and more lipophilic (more potent) the molecule the faster the rate of interaction
which anesthetics are more lipid soluble and have longer effects?
Tetracaine, bupivacaine, ropivacaine
explain what differential nerve block means
Certain types of nerves are more sensitive to LAs than others, which explains why pain sensation is lost before motor function
what are the factors that influence differential nerve block?
- size: smaller diameter nerve fibers are blocked first
- myelination: among fibers of the same size, myelinated fibers are blocked more easily than unmyelinated fibers
- frequency and duration of depolarization: LAs bind better to Na⁺ channels that are frequently opening and closing
- location in nerve bundle: outer fibers are affected first
what are the effects of local anesthetics on cardiac cell membrane?
- block cardiac sodium channels
- depress cardiac pacemaker activity, excitability,
and conduction - Some are anti-arrhythmic agents cause arrhythmia at high concentrations.
what are the toxins that act on Na+ channels and how do they affect them?
- tetrdotoxin and saixitoxin block channels at extracellular surface
- batrachotoxin, aconitine and scorpion venoms bind to receptors within the channel prolonging its activation
clinical pharmacology of local anesthetics
- provide temporary but complete anesthesia of localized area of the body
- topical use
- injection into the vicinity of peripheral nerve endings and major nerve trunks
- widely used in dentistry for dental procedures
what are the topical anesthetics and what are they used for?
Dibucaine: use on skin
Dyclonine: found in sucrets (throat lozenge), some forms of Cepacol (sore throat sprays) and Tanac (for cold sores)
Pramoxine: hemorrhoid creams, wipes, and anti-itch medications (nepsporin plus)
Cinchocaine: in hemorrhoid creams and wipes
Benzocaine: only topically, applied directly to wounds and ulcerated surfaces
what anesthesias are used for the cornea and conjunctiva?
Proparacaine and tetracaine
what are the Anesthesia used for mucous membranes of the nose, mouth, throat, tracheobronchial tree, esophagus, and genitourinary tract for procedures and for cosmetic surgery?
Tetracaine and lidocaine
- Lidocaine combined with epinephrine is most widely used.
list the anesthetics suitable for injection
Articaine
Lidocaine
Chloroprocaine
Mepivacaine
Prilocaine
Ropivacaine
Procaine
Tetracaine
what are the short, intermediate and long acting local anesthetics?
short: procaine, chloroprocaine
intermediate: lidocaine, mepivacaine, prilocaine
long: tetracaine, bupivacaine, ropivacaine
what type of local anesthetics should be used in pregnant people and children?
short/intermediate acting drugs with a vasoconstrictor
*pregnant people require lower doses and are more susceptible to toxicity
what anesthetic should NOT be used in pregnant people?
bupivacaine
when and where should spinal anesthetics be administered?
- in surgery or obstetrics
- injected within the epidural or subarachnoid spaces surrounding the spinal cord
what does the sympathetic block during spinal anesthesia reduce?
peripheral vasospasms
what are the drug interactions for ALL local anesthetics ?
**CNS depressants, such as alcohol, opioids, benzodiazepines, antidepressants, antipsychotics, and antihistamines, the effects add up, leading to:
- Drowsiness and confusion
- Dizziness and impaired coordination
- Respiratory depression (slowed breathing)
***antiarrhythmic drugs can cause increased cardiac depression
what are the drug interactions for amide linked local anesthetics?
- Beta blockers reduce hepatic blood flow, thus reduce metabolism of amides
- Cimetidine decreases hepatic metabolism of amides
what are the drug interactions for ester linked local anesthetics?
- ester anticholinesterases drugs reduce metabolism of esters
- ester anesthetics inhibit sulfonamide action
Use lowest dose possible
Avoid injection into blood vessels.
what are the dose dependent side effects and toxicity on the CNS
- Early Signs (Low Doses): numbness around the mouth and tongue, metallic taste
- Progression with Increasing Dose: Auditory disturbances (tinnitus), visual disturbances, sleepiness, light-headedness, restlessness, paresthesias (tingling, burning, pricking sensations
- High Doses (Severe Toxicity): seizures (convulsions), CNS depression, Respiratory failure, coma, Death in extreme overdose
how do you prevent convulsions?
pre-medicate with a benzodiazepine
if large doses are needed
what do you do if a seizure occurs?
treat with
- benzodiazepines (i.v. diazepam) or
barbiturates (i.v. thiopental).
- N-M blockers (i.v.succinylcholine) for muscle manifestation.
- prevent low oxygen levels (hypoxemia) and acid buildup (acidosis) in the body
what are the dose dependent side effects and toxicity on the Cardiovascular system?
- depress cardiac pacemaker activity, excitability, and conduction
- depress the strength of cardiac contraction
- cause arteriolar dilatation -> hypotension
- Large doses: cardiovascular collapse and death.
why would you use ropivacaine (levobupivacaine) over Bupivacaine?
Bupivacaine is more cardio-toxic than others
why does Lidocaine have a better safety profile?
CNS toxicity (seizures, dizziness) occurs before significant heart effects making it easier to recognize and manage toxicity before the heart is affected
what local anesthetics can cause allergic reactions?
ester type local anesthetics are converted to p-
aminobenzoic acid derivatives, which may
elicit allergic reaction
why is Prilocanine rarely given at doses high than 10 mg/kg?
it can cause methemoglobinemia due to accumulation of o-toluidine, a metabolite
* can be converted back to normal hemoglobin using reducing agents
what are the dose dependent side effects and toxicity on the PNS?
- At high concentrations, all are toxic
- Prolonged sensory and motor deficits following
spinal anesthesia with large doses of chloroprocaine or lidocaine
what is the MOA of cocaine?
blocks the re-uptake of norepinephrine,
epinephrine, dopamine, serotonin
