E1- Local Anesthetics and Muscle Relaxants Flashcards
Do esters or amids typically have shorter duration of action and increased systemic toxicity?
Esters
LAs are weak acids/bases?
At physiologic pH, LA are predominantly ionized/nonionized?
Weak bases (pKa 7.5-9) Ionized
Which form of LAs crosses the cell membrane?
Non-ionized
Which form of LAs binds to the intracellular binding site of the Na+ channel?
Ionized
What LA is an exception to the ionization rules?
Benzocaine (pka 3.5)- always in the non-ionized form; topical application only
What is the secondary pathway for LAs?
Hydrophobic pathway: non-ionized enters the cell membrane and becomes ionized within the membrane; the ionized form then binds to the Na+ channel
The closer the pka is to physiological pH (7.4), the higher the concentration in the ____ form.
Faster/slower membrane transport?
Faster/slower onset of action
Non-ionized
Faster membrane transport
Faster onset of action
Does infection/inflammation lead to faster/slower onset of action?
Slower onset (need more drug) -Lower pH --> higher concentration in the ionized form --> membrane transport decreases
Does bicarbinate lead to faster/slower onset of action?
Faster onset
Higher pH –> higher concentration in the non-ionized form –> membrane transport increases
What is the MOA of LAs?
Block Na+ channels and inhibit neuronal firing
LAs have high affinity for what type of channels?
LAs have low affinity for what type of channels?
High affinity- active (open) and inactivated states
Low affinity- resting state (closed)
What is the effect on elevated Ca2+ on LAs?
Hyperpolarize membrane; more channels in resting state –> block is diminished
What is the effect on elevated K+ on LAs?
Depolarize membrane; more channels in inactivated state –> block is enhanced
Which LA has a short duration of action?
Procaine
Which LAs have an intermediate duration of action?
Cocaine
Mepivacaine
Lidocaine
Which LAs have a long duration of action?
Tetracaine
Bupivacaine
Ropivacaine
What is the effect of Epinephrine on LAs?
Vasoconstricting agent
- Decreases diffusion of drug
- Prolongs duration of action
- Decreases systemic absorption
- Decreases risk of systemic toxicity
Should Amides or Esters be avoided in pts with hepatic disease? Why?
Amides
Metabolized in the liver by CYP450s
How are Esters metabolized?
Rapidly metabolized by butyrylchoinesterases in the plasma
What LA preferentially blocks sensory neurons?
Bupivacaine
What AMIDE preferentially blocks motor neurons? (inverse differential block)
Etidocaine
How does anatomic arrangement affect anesthetic action?
Effect hits proximal fibers and proceeds to more distal fibers within nerve bundle
How does nerve diameter affect anesthetic action?
Smaller diameter fibers are more sensitive
How does degree of nerve myelination affect anesthetic action?
Myelinated fibers are less sensitive than unmyelinated fibers
How does nerve conduction velocity affect anesthetic action?
The faster the conduction velocity, the less sensitive the fiber (motor fibers are less sensitive than pain fibers)
What is the order of sensitivity of nerves?
Sympathetic > sensory (pain) > touch > motor
What are cardiovascular SE of LAs? (3)
Arrhythmias
Vasodilation
Hypotension
What are CNS SE of LAs? (7)
Sedation Visual/auditory disturbances Circumoral numbness Nystagmus Muscle twitching Convulsions Death
What metabolite of ESTERs may cause hypersensitivity?
PABA
What AMIDE has the greatest cardiac toxicity?
Bupivacaine
What LAs may cause methemoglobinemia?
How is it revered?
Prilocaine and Benzocaine
Methylene blue
What LA can cause transient neurological symptoms?
Lidocaine for spinal anesthesia
What are the ester drugs? (4)
Procaine
Tetracaine
Benzocaine
Cocaine
What is procaine used for? (2)
Infiltration anesthesia
Diagnostic nerve blocks
Is Tetracaine or Procaine more potent and toxic?
Tatracaine
What are the uses of Tetracaine?
Ophthalmological use Spinal anesthesia (combined with 10% dextrose/solution is denser than CSF- Hyperbaric)
How is Benzocaine administered?
Topical only
What is Benzocaine used for?
Sunburns, minor burns, pruritus
What are the uses of cocaine?
Mucous membranes typically around the upper respiratory tract Reduce bleeding (dental)
What are the uses of lidocaine (amide)?
Preferred for infiltration blocks and epidural anesthesia
NOT spinal blocks (risk of TNS)
Which amide has the highest rate of clearance?
Prilocaine
What are contraindications of Prilocaine?
Cardiac or respiratory disease
What is the use of Prilocaine?
Limited use in denistry
What is the use of Bupivacaine? (4)
Preferred epidural during labor
Post-operative pain control
Spinal anesthesia
Infiltration blocks
What is the S-enantiomer of Bupivacaine?
Ropivacaine
What is the difference between Bupivacaine and Ropivacaine?
Ropivacaine is less lipid soluble and cleared more rapidly than Bupivacaine (less cardio toxic)
What are the uses of Ropivacaine?
Peripheral and epidural blocks (Bupivacaine is preferred b/c of its differential block)
What amide has intermediate duration of action and is preferred for peripheral nerve blocks?
Mepivacaine
Which AMIDE has an additional ester group which subjects it to metabolism by plasma esterases?
Articaine
What is the use of Articaine?
Dental medicine (large therapeutic window and low potential for systemic toxicity)
What is a SE of Articaine?
Persistent paraesthasias
What is the use of Dibucaine?
Topical (in the US)
Dibucaine number test (measure butyrylcholinesterase activity)
What are the centrally acting muscle relaxants (spasmolytics)?
“Brilliant Cops Detained Trump”
- Baclofen
- Cyclobenzaprine
- Diazepam
- Tizanidine
What are the direct acting muscle relaxants (spasmolytics)? -work at NMJ
Dantrolene
Botulinum Toxin
What is the MOA of Diazepam?
Acts on the GABA receptor to facilitate GABA-mediated presynaptic inhibition in the spinal cord
What are the uses of Diazepam? (4)
Alcohol/BZ withdrawal
Status Epilepticus
Local muscle trauma
Adjunct for chronic spasticity
What is the MOA of Baclofen?
Agonist at GABA receptors
- Stimulation opens K+ channels –> hyperpolarizes
- Presynaptic inhibition of Ca2+ influx –> decreases transmitter release
What is the MOA of Tizanidine?
Alpha2 receptor agonist (pre and post synaptic inhibition)
What are the uses of Tizanidine?
Chronic and acute muscle spasms
What is the MOA of Dantrolene?
Inhibits Ca2+ release from the SR by blocking the ryanodine receptor 1 (RyT1) channel
(Interferes with excitation-contraction coupling of actin/myosin in SKELETAL muscle)
What are the uses of Danrolene? (2)
Neuroleptic malignant syndrome
Malignant hyperthermia
What is the MOA of Botulinum Toxin?
Inhibits ACh release from nerve at the NMJ
What are the uses of Botulinum Toxin?
Injected locally to control muscle spasm following stroke
What 2 drugs can be used for acute local muscle spasms?
Cyclobenzaprine
Carisoprodol
