10-09 L4 Local anesthetic drugs Flashcards
Name the three kinetic phases for sodium channel.
- -Open (active),
- Closed (inactive),
- Closed (resting)
Alterations of sodium channel function occur where?
LA’s block sodium channels at sites near the intracellular side of the channel.
Blocking of sodium channel function is dependent on what two factors?
And what phase do they act on, on the 3 phases?
- Time and voltage dependent
- LA’s are greater in rapidly firing axons compared to resting fibers
What is (are) the most potent sodium blockers?
Tetrototoxin (it will kill you!)
What are the advantages of local anesethetics?
- They are spontaneous
- predictable
- completely reversible
Differential block
Different nerve fibers have different sensitivities to LA block.
What are the characteristics that nerve fibers affect sensitivity to LA block
- **Fiber diameter: ** thinner fibers more sensitive to block than thicker fibers
- Firing frequency: rapidly/repetitively firing fibers more sensitive than resting fibers
- Fiber position in nerve bundle: Outer fibers more sensitive to block than inner fibers.
What are the most susptible nerve fibers to LA?
Type A-Delta and Type C
What are LA composed of:
- a lipiophilic group (an aromatic ring)
- an intermediate chain (an ester or amide)
- an ionizable group (a tertiary amine: this group is hydrophilic)
List the 4 Ester drugs and their time duration.
-
Short:
- Procaine (Novocain)
- Chloroprocaine (Nesacaine)
- Cocaine
-
Long:
- Tetracaine (Pontocaine)
List the 5 different amides and theri duration time.
- **Intermediate: **
- Lidocaine (Xylocaine)
- Mepivacaine (Carbocaine)
- Prilocaine (Citanest)
- **Long: **
- Bupivacaine (Marcaine)
- Ropivacaine (Naropin)
How are Ester type of LA metabolized in the plasma?
Plasma cholinesterases
How are Amide linkage LA hydrolyzed? what are the two components that hydrolyzation is dependent on?
- they are hydrolyzed by hepatic cytochrome P450 isoenzymes
- depenedent on blood flow to the liver and liver fuction
What are the 5 physiochemical properties of LA? (M-CLIP)
- Molecular Weight
- Chirality
- Lipid solubility
- Ionization
- Protein binding
What is the correlation of the pKa and the pH of the LA penetrating the lipid membrane?
- Lower the pKa the less the % ionized
- thus the more LA molecule can diffuse across the lipid membrane to bind to the intracellular NA channel binding site.
- the higher the pKa the more the % ionized
- thus the less LA molecule can diffuse across the lipid membrane to bind to the intracellular NA channel binding site.
What is the only achiral LA?
Lidocaine
Which of the following is more potent between S (+) and R (-) isomers?
- S(+) isomer (levobupivacaine) is more potent than R (-) isomer (bupivacaine)
What is used to counteract vasodilitory effects?
Epinephrine
What are topical creams used for?
-Starting iv’s -dental procedures
What are infiltrations used for?
Suturing laceration, plastic surgery
What are Intravenous (Bier Block) used for?
Hand and wrist surgery
What are peripheral nerve block used for?
Extremity surgery
Epidural anesthesia is used for what?
- C-section
- Lower extremity surgery
- post-operative analgesia.
Who uses spinal anesthesia and why?
- Urology,
- gynecology,
- lower extremity surgery
because they are cheap.
What does Epinerphrine as an additive do?
- (vasoconstrictor)
- decreases systemic absorption
- increases duration.
What does sodium bicarbonate as an additive do?
- increases pH,
- increases proportion of LA in the uncharged form
- increased lipid solubility and speed of the onset of the block.
What does local acidiosis do?
- It decreases diffusion
- (more LA is in the charged form)
- produce tachyphaylaxis.
What does pregnancy do in terms of LA?
It increases the likelihood of LA toxicity.
What is important about the highly protein bound LA’s being adminsitered to a pregnant patient?
- Highly bound LA’s (bupivacaine; ropivacaine) poorly cross the placenta at normal concentrations,
- making them suitable for epidural analgeaisa for labor
Why is Chloroprocaine a good choice for anesthesia for emergent delievery?
- Chloroprocaine has a rapid onset
- rapidly metabolized (reducing the likelihood for fetal toxicity).
Neuropathic pain states characterized by rapid repetitive firing of sensory nerve fibers can be treated by what two LA’s?
IV (lidocaine) and Oral (mexiletine)
Local Anesthetics can lead to cardiovascular toxicity by four ways what are they?
- Blockage of autonomic nerves
- (hypotension, bradycardia),
- Direct myocardial depression,
- cardiac arrhythmias
What is used to treat severe cardiotoxicity?
Lipid rescue
What are the two allergic reactions to LA’s?
- angioneurotic edema
- Anaphylaxis (most commonly p-aminobenzoic acid, an ester type metabolite)
Allergy to amide-types is extremely rare
What is the cause of Methemoglobinemia?
- caused by prilocaine or benzocaine overdosage -o-toluidine:
- a metabolite of prilocaine, oxidizes hemoglobin to methemoglobin,
pt may appear cyanotic, SpO2 85% regardless of PaO2
What would you use to treat a pt that walks in with cyanotic lips, and a SpO2 85%?
-pt has methemoglobinemia treat pt with methylene blue 1-2 mg/kg IV
Which drug has high surface local anesthetic activity and i_ntrinsic vasoconstrictor actions that reduce bleeing_ in the mucous membranes?
- Cocaine!
How does cocaine cause intrinsic vasoconstricor activity?
- blocks the reuptake of noreepinephrine released from sympathetic nerve endings.
- side note: cocaine has a signifciante surface local anesthetic activity
- favored for head neck and pharyngeal surgery.
What is the side effects of Bupivacaine?
- cardiovascular collapse
- marked drop in blood pressure
- arrhythmia
Prilocaine is relatively contraindiated in pt’s with cardiovascular or pulmonary disease because of?
- Can cause decompenstion through formation of O-Toluidine
- O-toluidine converts hemoglobin to methemoglobine
- pts. appear cyantoic
- blood= chocolate-colored
- high plasma leves of methemoglobin have resulted in decompensation in patients with cardiac or pulmonary disease.
- O-toluidine converts hemoglobin to methemoglobine
