Local anesthetics and spasmolytics Flashcards
define local anesthetic
any agent that can reversibly block electrical activity of excitable tissues
- decreases neuronal conduction
- blocks impulse conduction in heart
For what are painkillers used?
temporary analgesia without the loss of consciousness
Provide a brief commentary on the pertinent historical facts regarding local analgesics
cocaine - 1884 - used as local anesthetic in eye
1905 - procaine aka novocaine (antiquated)
1943 - lidocaine aka xylocaine
comment on the effect of structure on function of the local anesthetics
all have an aromatic (lipophilic) end and an amino (hydrophilic) end
- the aromatic end gets the molecule into the neuronal membrane
- the amino end becomes ionized inside the membrane
Describe the mechanism of action of local anesthetics. What effects does the mechanism have?
the non-ionized from get through the membrane. inside, the hydrophilic side is ionized and binds to a specific site on Na+ channels of excitable membranes. This blocks the Na+ channel.
As a result, you have:
- decreased neuronal induction
- decreased repolarization rate
- increased refractory period
Ultimately, effect is greater when Na+ channels are open. Neurons that fire more rapidly can be affected more often.
In regard to local anesthetics, which nerves are affected?
Smaller neurons (pain) are generally more susceptible than larger neurons (motor)
myelinated neurons are more susceptible
the faster the firing rate, the more susceptible is the neuron.
Rank susceptibility to local anesthetics. Neurons that translate:
- warmth
- touch / pressure
- pain
- motor
- cold
pain > cold > warm > touch / pressure > motor
What is the major distinction between local anesthetics
duration of action. all act by same mech.
Does the ester linkage have a long or short duration of action?
Short. Ester is metabolized in plasma. Half-life is a matter of minutes. Cholinesterase exerts its effects here.
Does the amide linkage have a long or short duration of action?
The amide linkage has a longer duration of action in comparison to the ester linkage. It is metabolized in the liver by CYT P450. Half-life is hours long.
Are local anesthetics weak acids or bases?
In what environment are they ionized?
Weak bases
- more acidic environment
- In infected tissue (more acidic) molecules don’t readily enter the cell = local anesthetic activity is decreased.
what are the routes of administration of local anesthetics?
topical - skin, mucosa, eye
injection - infiltration, direct nerve block, spinal (subarachnoid space), epidural ( just outside dura mater… child birth)
Can local anesthetics be systemically absorbed?
Yes, regardless of administration
Which specific local anethetics are more likely to cause allergic reactions?
The esters
Name and describe the ester local anesthetics discussed in class.
cocaine - opthalmic, nasal surgery, inhibits NE reuptake in CNS
benzocaine - low solubility, absorbed slowly, long duration of action, used topically
procaine - short half-life, not used topically, doesn’t readily pass mucous membranes
Whats the trick to realize when a drug is an amino amide?
it has two letter i’s
what doeth procainamide?
used IV for cardiac arrhythmia
-causes lupus-like syndrome in slow acetylators (same as the antihypertensive, hydralazine)
what does lidocaine do?
causes CNS side effects, tremors, slurred speech, drowsiness, used IV for arrhythmias
What are the CNS and cardiovascular side effects caused by the esters?
CNS: disorientation, dorwsiness, slurred speech, tinnitus, blurred vision
Cardio: alter heart rhythm, tachycardia, arrhythmia
What is special about cocaine?
CNS effects. strong vasoconstrictor.
What are unique about Tetrodotoxin and saxitoxin?
both are very potent toxins.
TTX: irreversible Na+ channel blocker - Pufferfishes
Saxitoxin: “red tide” aka shell fish causes muscle weakness, resp. paralysis and deaf (as in dead)
spasmolytic agents have something known as spasticity. what is spasticity?
muscle hypertonia, excessive contraction of skeletal muscle
-can result from neuronal damage: injury, stroke, MS, ALS, cerebral palsy
How does one treat spasticity?
either alter the innervating neurons or act directly on muscle
name the 4 neuronal class drugs used to treat spasticity
- baclofen
- botulinum toxin
- diazepam
- tizanidine
how does baclofen work?
GABA agonist - increase activity of inhibitory neurons
how do diazepam and other benzodiazepines work?
increase GABA - minor tranqs and muscle relaxers
how does tizanidine work?
alpha 2 agonist - inhibit motor neurons
clonidine and alpha-methyl DOPA also function this way
How does botulinum toxin work?
inhibits Ach release
what antispastic drug acts directly on the muscle? and how?
dantrolene - acts directly on muscle cells - inhibits stimulus induced release of Ca2+ = decreased availability of Ca2+ for muscle
SE: muscle weakness, hepatitis
