LA Pharmacology Flashcards
What are local anesthetics produced as
2% solutions (20X1.8 = 236mg/carpule)
3% solutions (54mg/carpule)
4% solutions (72mg/carpule)
0.5% solutions (9mg/carpule)
Each carpule = 1.8 ml
What are carpule contents
LA drug
Sodium hydroxide/sodium chloride = buffering agent
Vasoconstrictor (EPI or Levonordefrin)
Vasoconstrictor preservative (sodium bisulfite = increased allergic rxns) - will decrease solution pH = more acidic = delayed onset
What was in LA solutions prior to 1984
Without EPI added METHYLPARABEN as preservative (many allergic rxns, if pt had allergic rxn before 1984 consider allergy to parabens)
What are the 2 groups of LA
Esters and amides
What are the ester local anesthetics?
Increased allergic reactions- 10% (if allergic to one ester probably allergic to all)
- metabolized in BLOOD plasma via pseudocholinesterase
- (small amt metab in liver)
Includes topicals only: benzocaine, tetracaine, procaine
What are the amide local anesthetics
ALL INJECTABLE LA in US are amides, topicals can be amides too
- low cross-hypersensitivity with esters
- metabolized in Liver
Lipocaine, mepivacaine, bupivacaine (metabolized in liver only = increased toxicity in liver disease)
Prilocaine (metabolized by liver+lung, shorter half life from lungs)
Articaine (metabolized by plasma 90% and liver 10%) - shortest half life
What is the chemical structure of LA
Lipophillic Aromatic Ring
-Base = inactive form
-Penetrates membrane (cannot bind receptors unless it picks up H+ ion)
Intermediate Linkage
-Determines if L.A. is ester/amide
Hydrophilic Terminal Amine
-Dissociates becoming tertiary amine → enters nerve → gains H+ ion = ionized = binds to receptor sites = active form
-Must pick up H+ inside the cell. Then becomes ionized again = active and can bind to receptor sites
What is the action of local anesthetics
Cation = active form, binds to receptor but cannot cross membrane
Anion = cannot bind but this is the one that can penetrate membrane
Loses H+ to cross membrane, then picks it up again to bind
What is pharmacodynamics
Physiological effects of drug on body
What are the pharmodynamics of LA
- LA include cations and anions
- All LA are acidic before injection (more cations)
- all LA are vasodialators
- the pKa of LA predicts the proportion of acid:base molecules
What are the cations
Acid - RNH+
Active form of drug that cannot cross membrane but can bind receptor
What are the anions
Base - RN
Lipid soluble form that crosses membrane (inactive, cannot bind membrane, picks back up H+ to bind)
All LA are ______ before injection
Acidic solutions
More cations than anions in cartridge
LA are vaso——?
Vasodialators
Decreased pKa =
Increased anions = increased base (RN molecules) = fast diffusion across membrane = rapid onset
Increased pKa =
Increased cations = decreased base = slow diffusion access membrane = slower onset
What is the effect of infections on LA?
Infected tissues are acidic (pH = 5-6)
LA is acidic, when injected into acidic tissues less molecules can cross the membrane = inadequate anesthesia
RNH+ molecules cannot dissociate H+ ions in acidic tissue = active form cannot enter cell membrane
What is the effect of nerve size on LA
LA must penetrate 8-10mm of myelinated nerve length (3-4 nodes of Ranvier) to block a nerve impulse
Increased volume of LA required for large nerves (like in IAN)
Increased concentration =
Increased diffusion through membrane = RAPID onset
Increased lipid solubility =
Increased potency = decreased dose needed, (enhances diffusion of drug through nerve)
Increased protein binding of molecules =
Increased duration (bind more strongly to receptor, prolonging anesthetic presence at site of action)
Increased vasodilation of LA =
Decreased potency + decreased duration = increased dose needed
(Vasodilation = increase blood flow and increased removal of LA molecules from site)
What is pharmacokinetics and what does it include?
Action of drug within the body
Includes: onset of action, induction, recovery from block, reinvention, duration/potency, distribution, biotransformation/metabolism, excretion, systemic effects
What is onset of action and what is the primary factor
Period from LA deposit to blocked impulse conduction
pKa of LA is primary factor (decrease pKa = rapid onset) - pKa determines amount of ionized molecules in solution
Site is a secondary factor (small diameter nerves = rapid onset)
What is induction of LA and what is the primary factor
Diffusion of molecules across membrane
Initial concentration of LA is primary factor
(Increased conc = increased diffusion = rapid onset)
*anesthetic loses concentration from tissue fluid, capillaries, lymphatics, anatomical barriers (bone)
What is recovery from LA block and what is the primary factor
Reversal of LA action
Degree of binding to receptor site is primary factor (different for each LA = chemical characteristic)
Slower process than induction
The degree of protein binding at the receptor site controls:
Duration of anesthetic action
Speed of nerve recovery from local anesthesia
What happens with reinjection of LA in fully/partially recovered pt?
Partially recovered nerve fibers (pt still numb) = small volume is effective with rapid onset
Fully recovered nerve fibers (no numbness) = tachyphylaxis occurs = tolerance to LA = LA is ineffective
What is duration of LA and what are the 3 factors
duration of LA = potency
- Protein binding of specific LA (stronger = increased duration = increased potency)
- Vascularity of injection site (increased = decreased duration = decreased potency)
- Vasoconstrictor in LA (increased = decreased blood flow = increased duration = increased potency)
What is the distribution of LA and what organs have high concentrations
After absorption —> LA are distributed throughout body
Highly vascular organs have increased concentrations = brain (crosses barrier), heart, lungs, liver, kidneys
What is toxicity directly related to?
Amount of LA accumulated in tissues
Increased absorption =
Increased risk of systemic toxicity
Total dose administered increased =
Increased absorption
(All molecules diffuse out of Na+ channels into bloodstream)
Increased LA concentration =
Increased absorption
What route of administration increased absorption?
Topical
What site of injection increased absorption
Intravascular
Increased vasoconstriction =
Decreased absorption
What are the things that affect absorption of LA
Total dose administered
LA concentration
Route of administration
Vascularity of administration site
Presence of vasoconstrictor
What is the biotransformation of LA
Metabolism of the drug
Measured in half-life (time for 50% to be removed)
Increased half life =
Increased risk for systemic toxicity
What LA has the shortest half life
Articaine
Where are LA excreted
Kidneys - primary excretory organ for all LA
Small amt of ester LA are excreted unchanged in urine, still small but greater percentage of amide LA are excreted unchanged in urine
Increased risk of systemic toxicity in severe renal disease due to build up of drug when not cleared by kidneys
Increased blood levels =
Increased toxicity
What are the systemic effects of LA
Affect CNS and CV system after absorbed into blood (before metabolized)
Toxicity and adverse reactions are directly related to….
1) Nature of specific LA (vasodilation)
2) Concentration of drug
3) Route of administration –>
intravascular = increased absorption
topical = increased absorption
4) Dose administered
5) Rate of injection –> increased rate = increased absorption
6) Vascularity of site
7) Age of patient –> children/elderly = decreased rate of metabolism
8) Weight of patients (decreased dose for decreased weight)
9) Health of patient = decreased metabolism associated with diseases/meds
