Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
91 Cards in this Set
- Front
- Back
|
Natural alkaloid and only natural compound remaining?
|
cocaine
|
|
|
first LA discovered?
|
cocaine
|
|
|
LA acid/base character?
|
weak bases
|
|
|
LA's are prepared as?
|
HCL salts
|
|
|
Also can be Formulated at pH 4.4 – 6.4 if have epinephrine because?
|
epinephrine more stable at acidic pH.
|
|
|
When injected, LA's are converted to more ________ form.
|
non-ionized
|
|
|
amine LA Pka?
|
Pka 7.6 to 9.1 (classic amine pka)
|
|
|
What is the advantage of formulation in bicarbonate solution?
|
more non-ionized
|
|
|
________ pKa's are most ionized?
|
highest
|
|
|
Amides formulated with a _________ which may cause an allergic reaction
|
preservative
|
|
|
________ derivatives used for amide LA preservatives.
|
paraben
|
|
|
If parabens used, cannot use formulation for ____________ because they are neurotoxic.
|
spinal/epidural/IV regional
|
|
|
the amine provides _______ phobic character?
|
hydrophillic
|
|
|
the benzene ring provides _______ phobic character?
|
lipophillic
|
|
|
If inject LA's into area of local infection (these areas are acidotic) then will have ____ absorption/distribution and ______ onset.
|
poor
slower |
|
|
LA lipid solubility effect on potency?
|
increased
|
|
|
the larger number of carbons, the more _________?
|
lipophillic
|
|
|
increased potency with a ______ on the aromatic ring?
|
halide
|
|
|
increased potency with a ______ and ______ on the terminal amine?
|
ester linkage
large alkyl group |
|
|
How does ionization contribute to efficacy?
|
more lipophylic more potent
|
|
|
How does ionization contribute to Absorption?
|
more non-ionized better absorption into tissues
|
|
|
How does ionization contribute to Distribution?
|
more lipophylic/less ionized less distribution away from site
|
|
|
How does ionization contribute to Duration of action?
|
more ionized, less distributed/absorbed)
more lipophylic longer duration (result of less distribution) |
|
|
Lidocaine (Xylocaine)
pKa % non-ionized |
7.9
25 |
|
|
Bupivicaine (Marcaine)
pKa % non-ionized |
8.1
15 |
|
|
Cocaine
pKa % non-ionized |
8.7
5 |
|
|
Procaine
pKa % non-ionized |
8.9
3 |
|
|
Chloroprocaine (Nesacaine)
pKa % non-ionized |
8.7
5 |
|
|
Tetracaine (Pontocaine)
pKa % non-ionized |
8.5
7 |
|
|
Etidocaine (Duranest)
pKa % non-ionized |
7.7 33
|
|
|
Mepivacaine(Carbocaine)
pKa % non-ionized |
7.6
37% |
|
|
Cocaine is the ester of ?
|
benzoic acid
|
|
|
Ester Analogs [4]
|
Cocaine
Procaine Tetracaine Chloroprocaine |
|
|
Amide Analogs [6]
|
Prilocaine
Lidocaine Mepivacaine Bupivicaine Etidocaine Ropivacaine |
|
|
Most Potent (also most toxic) [4]
|
Tetracaine (ester, pKa 8.2)
Etidocaine (amide, pKa 7.7) Bupivicaine (amide, pKa 8.1) Ropivicaine (amide, pKa 8.1 |
|
|
lesser (middle) potency LA's [4]
|
Lidocaine (amide, pKa 7.8)
Mepivacaine (amide, pKa 7.6 Prilocaine (amide, pKa 7.8) Cocaine (ester, pKa 8.7) |
|
|
least potent LA's [2]
|
Chloroprocaine (ester, pKa 9.0)
Procaine (ester, pKa 8.9) |
|
|
LA potency rated by?
|
minimum blocking concentration (Cm) is the lowest concentration that blocks conduction
|
|
|
Potency determined in large part by?
|
lipid solubility (like most compounds)
|
|
|
topical use LA's? [3]
|
tetracaine, lidocaine, cocaine.
|
|
|
uses for LA's? [6]
|
Surgery
Dentistry Acute Pain Chronic Pain Punctures Endoscopic Procedures |
|
|
Local anesthetics prevent voltage-gated fast sodium channels in nerve axons from _________... Bind to sodium channels inside the neruon when they are in the inactivated state.
|
opening
|
|
|
__________ form crosses the lipid bilayer to enter neuron and the _________ form binds to the gated sodium channel
|
unionized
ionized |
|
|
Sodium channel has three states?
|
closed/open/inactivated
|
|
|
The voltage sensor senses change in _________ due to nerve stimulation
|
voltage
|
|
|
Local anesthetic passes through lipid bi-layer in _________ form and then ionized form (cation) binds within the pore blocking the pore.
|
non-ionized
|
|
|
LA's are more selective for nerves without ________?
|
myelination – but still will get some sensory inhibition (ok and wanted) and some motor inhibiton (maybe don’t necissarily want)
|
|
|
LA's are most specific for what nerve fibers?
|
Most specific for B and C and some alpha delta fibers.
|
|
|
LA's are specific for? [3]
|
Chanel state
channels that are in depolarized (open) state. Axonal Diameter small Degree of myelination Minor Autonomic>sensory>motor |
|
|
Other Receptor InteractionS? [2]
|
NMDA
Calcium and Potassium Channels |
|
|
Other drugs that work at the Sodium Channel?
|
Tricylic Antidepressants
Meperidine Volatile Anesthetics Ketamine Tetrodotoxin |
|
|
factors that affet LA absorption> [7]
|
Delivery Method
Dose Tissue Blood flow Lipid Solubility Protein Binding pH Vasoconstriction |
|
|
tissue blood flow....
we don't want for local use. |
vascularity intravenous>tracheal>intercostal>cadal>paracervical>epidural?brachial plexus>sciatic>subcutaneous
|
|
|
The higher the pH the ____ absorbed .
|
less
mostly an issue for inflammation. Inflammation causes and acidotic state. More drug in ionized form and less absorption. Also can see tachyphylaxis (decreased efficacy of repeated doses) because the acidic formulation makes the area more acidic |
|
|
factors that affet LA Distribution [4]
|
Lipophilicity
Blood Flow intravenous>tracheal>intercostal>cadal>paracervical>epidural>brachial plexus>sciatic>subcutaneous Tissue Perfusion Protein Binding |
|
|
So more lipid soluble, the _____ movement and ____ stays at the site.
|
less
more More lipid soluble will stay in the tissues and not be distributed and this helps contribute to potency. |
|
|
The ________ the metabolism and elimination, the more possibility for toxicity
|
slower
|
|
|
Ester Metabolism?
|
Chloroprocaine>>procaine>tetracaine
|
|
|
Amide Metabolism
|
Prilocaine>lidocaine>mepivicaine>ropivicaine>bupivicaine
Lidocaine specific toxicity Prilocaine specific toxicity Benzocaine specific toxicity |
|
|
PABA metabolite>
|
esters
|
|
|
esters biotransformed by
|
plasma pseudocholinesterase.
|
|
|
Chloro eliminated faster because
|
hydrolysis 3.5 times faster than pro so least toxic
|
|
|
Cocaine metabolization
|
Differently than all other esters because metabolized in the Liver (more unchanged excreted)
|
|
|
PABA allergy?
|
with esters
Cause local edema- urticaria – bronchospasm - anaphylaxis |
|
|
Amides eliminated by?
|
liver metabolism (dealkyl, hydroxylation)
|
|
|
any drug that interferes with liver metabolism will cause _______ toxicity?
|
amide
|
|
|
Decrease in hepatic blood flow with cause ______ toxicity?
causes? |
amide toxicity
(congestive heart failure, vasopressors, H2 receptor blockers, volatile anesthetics, propranolol, cimetidine) |
|
|
Lidocaine is metabolized to?
|
monoethylglycinexylidide which is active and can contribute to toxicity. (elimination does not parallel duration). Lidocaine may be within TI but if metabolite isn’t accounted for, will see toxicity (this can be an issue with repeated dosing)
|
|
|
methhemoglobin issue with?
|
Benzocaine
Prilocaine |
|
|
Prilocaine metabolism?
|
o-toluidine analogs can accumulate and convert hemoglobin to methemoglobin (oxidation-reduction reaction-of iron) so interfere with oxygen transport (can be issue in baby after epidural use during labor)
|
|
|
Methhemoglobin treated with
|
methylene blue to reduced iron III to iron II.(reduction) OIL-RIG we are going from 3+ to 2+
|
|
|
the toxicant are _______?
|
The toxants are oxidants, they take fe2+ to fe3+
|
|
|
LA with longest t1/2?
|
Bupivicaine (one of the most potent) has longest halftime for elimination
|
|
|
Elimination of LA'S?
|
Protein Binding
Mostly Urinary elimination |
|
|
LA S/A's?
|
Excitatory
Dermal Blanching, edema, etc. Neurological Cardiovascular Blockade of sodium channels Inhibit autonomic nervous system Neurological Respiratory Immulogical Musculoskeletal Hematological |
|
|
first S/A's seen?
|
Neurological
See this first They can be nuerotoxic Cirumoral numbness, tongue paresthesia, diziness, restlessness, aginitation complaints of tinnitus blurred vision Muscle twitching shows headed into tonic-clonic seizures -Etido can cause at lower serum concentrations than the others can reduces CBF and hyperventilate can mediate (benzodiazepines, thipental 1-2 mg/kg quickly terminates seizure) Lidocaine – decreases CBF which attenuates ICP that sometimes see with intubation |
|
|
most cardiotoxic?
|
Bupivicaine is most cardiotoxic because It is highly lipid soluble and only slowly dissociates from sodium channels so more blockade. This exaggerates the depressive effects and is also persistent
|
|
|
Cardiovascular S/A's?
|
depress myocardial automaticity (phase 4 depolarization) and reduce duration of refractory period. Depress contractility and conduction velocity at higher concentrations. Relax smooth muscle so vasodilatation except cocaine which is a vasoconstrictor.
Bradychardia/heart block/vasodilatation can lead to cardiac arrest. But usually this is at levels higher than used and would actually see seizures first. Signs of toxicity may be CNS excitement (tachycardia and hypertension) Bupivicaine>Etidocaine> Ropivicainepi (ropi also less motor blockade good for obstetric patients) |
|
|
resp S/A's?
|
Lidocaine depresses hypoxic drive (apnea), can cause bronchospasm is used in spray, may be effective in blocking the bronchoconstriction after intubation
Relax bronchial smooth muscle |
|
|
immunological s/a's
|
Allergies from PABA from ester hydrolysis and allergies from methylparaben sometimes used to formulate amides
|
|
|
musculoskeletal s/a's
|
Myotoxic if injected into muscle (bupi>lido>pro)
|
|
|
hemotalogical s/a's
|
Lidocaine can decrease coagulation and enhances fibrinolysis
Etido and bupi lowest max dose Subcu etido is _ as toxic as subcu bupi |
|
|
contraindications? [4]
|
Atypical Plasma pseudocholinesterase
Allergies Cardiac Drugs Drug-drug interactions |
|
|
what LA can you give to a patient with atypical/depressed plasma cholinesterase?
|
cocaine (liver metab)
|
|
|
Avoid drugs to minimize cardiac toxicity
|
Beta-adrenergic blockers (labetalol, propranol)
Digitalis Calcium channel blockers (verapamil) These drugs inhibit impulse propagation and may decrease the threshold for cardiac toxicity especially if the cardiotoxin bupivicaine is used. |
|
|
Drug-drug interactions competing for pseudocholinesterases ?
|
(succinylcholine)
|
|
|
Opioids and alpha-adrenergic agonists_______ the pain relief of local anesthetics
|
enhance
|
|
|
Epidural chloroprocaine may _________ with intraspinal morphine analgesia (less anlagesia)
|
interfere
|
|
|
Anticholinesterases [4]
|
Echothiophate (irreversible)
Neostigmine (reversible) Pyridostigmine (reversible) Edrophonium (reversible) Inhibit the acetylcholinesterases prolonging activity (with esthers) |
|
|
irreversible Anticholinesterase?
|
Echothiophate
|
|
|
epi effect on LA's
|
less (slower) distribution
|
