E1: Local Anesthetics Flashcards
What are the two different classes of local anesthetics?
Esters or amides
Do esters or amides have a shorter duration of action?
Esters
Do esters or amides have increased systemic toxicity?
Esters
In general, the closer the pKA is to physiologic pH, the ** the concentration of the drug in the ** form
Higher
Non-ionized
What is the MOA of local anesthetics?
- Blocks Na+ channels and inhibits neuronal firing
- complete block results from the drug binding to more and more Na channels, which increases the threshold for excitation and impulse conduction slows. As more channels are blocked, the rate of the AP declines and complete block is achieved
What kind of channels do local anesthetics have high affinity for?
High affinity for channels in the activated (open) and inactivated states and low affinity for channels in the resting (Closed) state
- the block is more effective in rapidly firing axons than a resting axon
- extent of the block is voltage and time (firing) dependent
What is the effect of increased calcium on local anesthetics?
Increased calcium increases (hyperpolarizes) membrane potential, more channels are in the resting state, and the block is diminished
What is the effect of elevated potassium on local anesthetics?
Elevated K+ depolarizers the membrane, more channels are in the inactivated state, and the block is enhanced
Smaller and more lipophilic local anesthetics have a *** rate of interaction with the Na+ channel.
Faster
How do Local anesthetics cross the cell membrane?
- LAs are weak bases and at physiologic pH are predominately ionized.
- Binding in on the inner membrane and they need to be non-ionized to cross the membrane.
- Once they are inside, they become ionized again and binds to the Na+ channel
What is the relationship between the potency of an LA and the duration of action?
As the potency increases, the duration of action increases
Which LA has a short duration of action?
Procaine
Which LAs have long duration of action?
Tetracaine, bupivicaine, and ropivicaine
Duration of action of an LA is dependent upon what?
Time at the site of action
What factors affect systemic absorption of LA?
- Dosage
- site of injection
- drug tissue binding
- chemical properties of the drug
- local blood flow
- vasoconstricting agents
How are amides metabolized?
In the liver by CYP450s
How are esters metabolized?
Rapidly metabolized by butyrylcholinesterases in the plasma
What is a differential block?
When the block is not limited to the intended site, blocks noxious stimuli but also blocks motor nerves
What are the general side effects and toxicities of local anesthetics?
- Cardiovascular: Arrhythmias, vasodilation, and hypotension
- CNS: depression of cortical inhibitory pathways
- Allergic reactions
- Prolonged sensory and motor deficit following high doses
- Localized toxicity: Neural injury and transient neurological symptoms
What two local anesthetics cause the most cardiovascular effects?
Bupivicaine and cocaine
Which local anesthetic may cause methemoglobinemia?
Prilocaine and benzocaine
Which kind of local anesthetic is more likely to cause an allergic reaction? Why?
Esters
-PABA is a metabolite of esters and PABA may cause hypersensitivity
What is the use of Procaine?
Used for infiltration anesthesia and diagnostic nerve blocks
Is procaine and ester or amide?
Ester
What is the duration of action of procaine?
Short
Is tetracaine an ester or amide?
Ester
What is the onset and duration of action of tetracaine?
- Slow onset of action
- Long duration of action
- 16x more potent and more toxic than procaine
What is the use of tetracaine?
- preferred for ophthalmological use
- spinal anesthesia
Is Benzocaine an ester or amide?
Ester
What is the use of Benzocaine?
Used topically only to treat sunburns, minor burns, and pruritis in OTC preparations
Is cocaine and ester or amide?
Ester
What is the use of cocaine as a local anesthetic?
-Topical anesthesia of mucous membranes typically around the upper respiratory tract
What is the MOA of Cocaine?
Inhibits Na+ channels secondary to its effect on increasing DA in the CNA and periphery
What are the adverse effects of cocaine?
- CNA and cardiovascular
- use with caution in addicts or with other drugs that increase catecholamines
Is lidocaine an ester or amide?
Amide
What is the duration of action of lidocaine?
- Rapidly absorbed, intermediate duration of action
- rapid onset of anesthesia
What is the use of lidocaine?
- Preferred for infiltration blocks and epidural anesthesia
- No preferred for spinal blocks, risk of TNS
- Also used as an antiarrhythmic agent
Is prilocaine an ester or amide?
Amide
Which amide has the highest rate of clearance?
Prilocaine
What are the contraindications of prilocaine?
Cardiac or respiratory disease
Is bupivicaine an ester or amide?
Amide
What is the use of bupivicaine?
- Analgesia for post operative pain control
- spinal anesthesia, infiltration blocks, and epidural anesthesia (preferred as epidural during labor and childbirth)
Which amide has the greatest cardio toxicity?
Bupivicaine
Is Ropivacaine an ester or amide?
Amide
How is Ropivacine related to Bupivicaine?
Ropivacine is an S-enantiomer of bupivicaine
-Ropivacine is less lipid soluble and cleared more rapidly than bupivicaine
What is the use of ropivacaine?
- uses for peripheral and epidural blocks
- vasoconstricing effects at clinical doses
What kind of drugs are Mepivacaine and Etidocaine?
Amide type drugs
What is the duration of action of Mepivacaine?
Intermediate
What is the use of Mepivacaine?
- Preferred for peripheral nerve blocks
- Not used topically or in labor anesthesia
What is the duration of action of Etidocaine?
-Long duration of action
What is the use of Etidocaine?
-Inverse differential block, but may cause motor block before or without sensory block
What kind of drug is Articaine? What is the benefit of this?
- Amide type local anesthetic with an additional ester group which subjects it to metabolism by plasma esterases
- this decreases half life and potential for systemic toxicity
What is the use of articaine?
-Widespread use in dental medicine due to larger therapeutic window and low potential for systemic toxicity
What are the adverse effects of articaine?
-Rare, but may induce the development of persistent paresthesias
Is Dibucaine an ester or amide?
Amide type drug
What is the use of Dibucaine?
- Used as spinal anesthetic outside the US, still used as topical in the US
- Measure butyrylcholinesterase activity
What are the centrally acting muscle relaxants?
-Baclofen, Cyclobenzaprine, Diazepam, and Tizanidine
What are the direct acting muscle relaxants?
- Dantrolene
- Botulinum toxin
What is the MOA of Diazepam?
Acts on the GABAa receptor to facilitate GABA-mediated presynaptic inhibition in the spinal cord
What is the MOA of Baclofen?
-Agonist at GABAb receptors
-Stimulation opens K+ channels leading to
Hyperpolarization
-presynaptic inhibition of Ca+ influx decreases NT release
What are the side effects of Baclofen?
-drowsiness, weakness, increased seizure activity, respiratory depression may occur with intrathecal administration
What is the MOA of Tizanidine?
- Alpha2 receptor agonist
- produces both pre and post synaptic inhibition of spinal cord synaptic activity to decrease muscle spasticity
What are the side effects of Tizanidine?
- sedation, some hypotension
- dry mouth, weakness, falls in elderly
- hepatotoxic
What is the MOA of Dantrolene?
- Inhibits Ca+ release from th SR by blocking the ryanodine receptor 1 channel
- Interferes with excitation-contraction coupling of actin and myosin in the skeletal muscle fiber
What is the use of Dantrolene?
Used to treat neuroleptic malignant syndrome and malignant hyperthermia
What is the MOA of Botulinum toxin?
-Inhibits ACH release from nerve at NMJ
