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Anesthesia Pharm Exam 2 > Local Anesthetics > Flashcards

Local Anesthetics Flashcards

1
Q

Review of RMP/Action Potential

A
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2
Q

Local Anesthetics

A

Esters and Amides

  • Impair nerve signal transmission by blocking VGaNa+C anywhere
  • the aromatic ring is lipophilic (hydrophobic)
  • the tertiary amine is hydrophilic (lipophobic)
  • more hydrophobic compounds are more potent and produce longer blockade than less hydrophobic ones

we want MORE hydrophobic/lipophilic… longer lasting!

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3
Q

Esters

A
  • metabolized by P.cholinesterase (except cocaine)
  • one I
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4
Q

Amides

A
  • liver metabolism (therefore hepatic blood flow and function are important!!)
  • Two I’s
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5
Q

Review of Ester/Amide Structures

A
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6
Q

Weak Acid Binding

A

Weak acids bind with positively charged ions like Na+, Mg++, Ca++

  • sodium pentathol is a weak acid
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7
Q

Weak Base Binding

A

Weak bases bind with negatively charged ions like Cl- and SO42-

  • lidocaine hydrochloride and morphine sulfate are weak bases
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8
Q

2 important determinants of LA function:

A

pH and pKa

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9
Q

pKa

A

pKa is pH at which 50% is ionized and 50% is unionized

  • pKa is different for the different LA
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10
Q

pKa Lidocaine example

A
  • pKa Lidocaine is 7.7 - 7.9
  • Standard human pH is 7.35 - 7.45 (7.4)
  • At pH 7.4, lidocaine is more ionized (75% ionized) than at pH 7.7 so less is available to cross membranes
  • base (lidocaine) + acid (human fluids) = ionized LA

generally speaking… lower pKa means more LA in nonionized form and faster onset of block

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11
Q

Most LA are ____ ____ (pKa 7.5 - 9) in solution but salts are ____ _____.

A

Most LA are weak bases (pKa 7.5 - 9) in solution but salts are weak acids.

  • ketamine, opioids, and benzos are weak bases
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12
Q

Weak bases become ____ nonionized as the pH increases.

A

MORE

increased pH = decreased H+ ions = increased nonionized LA = good (but bad w babies and ion trapping)

LA must be in the basic form to be unionized and capable of penetrating the cell membrane to block the Na+ channel

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13
Q

Is LAST worse in basic or acidotic patient?

A

LAST is worse with acidosis because the LA moves into the Na+ channels and gets trapped.

ie: in the heart blocking Na+ channels

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14
Q

How do you increase the ionization of LA?

A

LA premixed w Epi = more acidic (pH 3.5) which increases the ionization of the LA

*has increased duration but also increased onset time. Inversely, you can mix w bicarb to bring pH up and get more in the unionized form to get a faster onset but shorting acting LA.

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15
Q

LA Protein Binding

A

LA have high protein binding (A1AG preferred to Albumin) but more albumin exists in the human body.

  • LA must release from protein to cause Na+ ch block

- protein binding = duration

- high protein binding = long duration of LA

- as pH decreases, % of bound drug decreases

  • protein binding is more important than lipid solubility for duration of aciton
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16
Q

LA protein binding and duration order

A

Bupivacaine

etidocaine

ropivacaine

mepivacaine

lidocaine

procaine

2-chloroprocaine

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17
Q

Acidosis and the LAST patient

A

Do not let a suspected LAST pt become acidotic since the proportion of free LA molecules will increase rapidly!

ie: bupivacaine 95% (5% available for action) protein bound normally decreases to 70% w acidosis (30% available for action!) 6x more blockage

18
Q

Oil:Water Partition Coefficient

A

is equal to lipid solubility = potency

The greater the oil: water PC for an LA, the greater the potency.

19
Q

Blocking the Na+ Channel

A
  • peripheral nerves are mixed (motor/sensory)
  • LA placed near nerve diffuses via concentration gradient from outer sheath to core
  • fibers in outer/proximal/motor are blocked first
20
Q

Steps of Blocking Na+ Channel

A

- unionized LA penetrate cell membrane

  • become ionized
  • bind to Na+ channel
  • prevent opening and Na+ inrush
  • NO action potential!
  • blocking the Na+ ch blocks conduction of nerve impulse to the brain…*

no impulse = no pain

21
Q

Onset of LA Block

A

Closer to the nerve = faster onset!

  • within the sheath is good, but not on the actual nerve
  • intraneural and sub-epineural = faster onset dur to proximity of LA to nerve
  • small block faster than large
  • myelineated block easier than un
  • NO DIFFERENCE in motor vs. sensory
22
Q

Factors determining rate of diffusion across nerve sheath:

A
  • concentration of LA (higher concentration diffuses faster)
  • degree of ionization (UNionized faster)
  • hydrophobicity
  • physical characteristics of tissue around nerve (ie: more vascular taken up faster and not get to nerve)
23
Q

Increased lipid solubility… (4 things)

A
  • increases potency
  • increases duration
  • increases toxicity
  • decreases therapeutic index
24
Q

What 3 factors determine ability of LA to stay near the nerve? (and therefore duration)

A

1) lipid solubility
2) vascularity of tissue
3) presence of vasoconstrictors (which prevent vascular uptake of LA molecules)

25
Q

Order of Loss of Nerve Sensations

A
  1. Autonomics
  2. Pain
  3. Cold
  4. Warmth
  5. Touch
  6. Pressure
  7. Vibration
  8. Proprioception
  9. Motor function
26
Q

Desireable Properties of LA

A
  1. reversible conduction block
  2. compatible w vasoconstrictors
  3. rapid onset
  4. non-irritating
  5. low potential for LAST
  6. long duration w short recovery
  7. effective in different delivery modalities
27
Q

Cocaine

A
  • ester
  • blocks nerve impulses
  • local vasoconstriction d/t inhibition of local NE reuptake
  • euphoria d/t blockade of dopamine reuptake in CNS
  • good for LA in nasal passages (because it is a LA that also vasoconstricts)
28
Q

procaine

A

ester

  • 1st synthetic LA (synthetics get rid of the SE we don’t want)
  • low potency, slow onset, short duration
29
Q

2-chloroprocaine

A

ester

  • chlorinated procaine, most rapidly metabolized by Pcholinesterase
30
Q

tetracaine

A

longest duration ester!

  • more potent, slowly metabolized
  • too toxic for peripheral blocks but OK for long acting spinals
  • sometimes mixed w lidocaine for peripherals
31
Q

lidocaine

A

amide

  • rapid absorption paernteral, GI, and resp
  • intermediate duration
  • 1.5-2% for most regional blocks
  • more dilute concentrations for pain mgmt
32
Q

mepivacaine

A

amide

  • intermediate duration
  • pharm similar to lido
  • similar onset w slightly longer duration (3-6 hr)
  • toxic to neonates - NOT used in OB!
33
Q

prilocaine

A

amide

  • intermediate duration w pharm like lido
  • lacks vasodilation, increased Vd (limits CNS toxicity)
  • causes methmeglobinemia at 8 mg/kg (tx w methylene blue 1-2mg/kg)
  • uncommon in peripheral nerve blocks
34
Q

etidocaine

A

amide

  • longer duration
  • onset like lido, duration like bup
  • alkyl sub on aliphatic group between hydrophilic amine and amide increases lipid solubility
  • increased lipid solubility = increased potency = increased duration
  • downlide is motor block that outlasts sensory!
  • not useful for peripheral nerve blocks
35
Q

bupivacaine

A

amide

  • long duration (longer w EPI)
  • slower onset w variable duration (2-3 hours spinal, 12-24 for peripheral)
  • cardiotoxic (direct inj into medulla = v-arrhythmias, difficult to dissociate from Na+ ch)
  • widely used for peripheral blocks in dilute concentrations of <0.5%
  • careful use in OB epidurals (<0.25%)
36
Q

ropivacaine

A

amide

  • S-enantionmer of bup = lower toxicity, less potent at <0.5%
  • slower uptake thus lower blood levels
  • extensive hepatic metabolism
  • >0.5% dense block w shorter duration than Bup
  • at 0.75%, onset is fast, CNS and cardiotoxicity are reduced, and motor block is less than Bup
  • popular for peripheral nerve blocks
37
Q

levobupivacaine

A
  • another single enantiomer of bup
  • less toxic than Bup but works in similar fashion w similar duration
38
Q

LA Percentages

A
  1. 25% = 2.5 mg/mL
  2. 5% = 5 mg/mL

1% = 10 mg/mL

2% = 20 mg/mL

39
Q

Plasma concentration of LA is determined by what 4 things? (LAST)

A
  1. DOSE of drug
  2. RATE OF ABSORPTION
  3. SITE of injection
  4. biotransformation and ELIMINATION from circulation
    * same dose injected in different locations in diff patients = diff peak plasma levels!*
40
Q

Blood flow and LA absorption (I think I can push each bolus Sslowly for safety)

A

From shortest to fastest:

  1. IV
  2. Tracheal
  3. Intercostal
  4. Caudal
  5. Paracervical
  6. Epidural
  7. Brachial Plexus
  8. Subarachnoic, sciatic, femoral
  9. SubQ
41
Q

LAST

A

Anesthesia Pharm Exam 2 (5 decks)

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