local anesthetics

Question 1

esters

Answer 1

chloroprocaine, procaine, tetracaine, cocaine

Question 2

amides

Answer 2

lidocaine, mepivacaine, bupivacaine, prilocaine, ropivacaine

Question 3

LA drugs act by

Answer 3

inhibiting sodium influx through sodium specific ion channels in the neuronal cell membrane.

Question 4

they cross the cell membrane by

Answer 4

corssing in the non ionized lipophillic state

Question 5

the _____________ portion in the cell then binds to the ________ __________

Answer 5

ionized, sodium channel

Question 6

what does Pka correlate with?

Answer 6

onset

Question 7

what does lipid solubility correlate with?

Answer 7

potency

Question 8

what does protein binding correlate with?

Answer 8

duration

Question 9

toxic dose of bupivacaine/ ropivacaine

Answer 9

2. 8 mg/kg (175 max) OR

3. 2 mg/kg (225 max) with EPI

Question 10

toxic dose of lidocaine/ mepivacaine

Answer 10

4.5mg/kg (300 max) or 7 mg/kg (500 max) with EPI

Question 11

absorption of local anesthetics

Answer 11

dose dependent, (high vascular= high absorption)
intercostal> caudal> epidural> brachial plexus> sciatic nerve
vasoconstrictors- especially short, intermediate agents. Not long acting but highly lipophillic. (bupivacaine and etidocaine)
physiochemical/pharm properties- cocaine vasocinstrictor, Bupivacaine has high tissue binding

Question 12

Distribution- amides

Answer 12

wide distribution d/t storage in tissues
Two phases-
rapid: uptake by highly perfused tissues. IE brain, liver, kidney, heart
slower: uptake by moderate perfused tissues. IE muscle and gut

Question 13

distribution of esters

Answer 13

broken down rapidly in plasma

Question 14

metabolism

Answer 14

converted in liver or plasma to water soluble metabolites and excreted

Question 15

metabolism of amides

Answer 15

hydrolyzed by liver enzymes.
rate: prilocaine> etidocaine> lidocaine> mepivacaine> bupivacaine
liver dz, lecresed blood flow increases times for metabolism

Question 16

metabolism of esters

Answer 16

hydrolyzed in plasma rapidly. < 1min procaine, chloroprocaine

Question 17

excretion

Answer 17

unionized not excreted, acidification of urine promotes ionization and renal excretion, renal tubules do not reabsorb chargeed metabolites

Question 18

mechanism of action (9 steps)

Answer 18

1. diffusion of the base form across the nerve sheath and nerve membrane
2. re-equilibration between the base and the cationic forms in the axoplasm
3. Penetration of the cation into and attachment to a receptor site within the sodium channel.
4. blockade of the sodium channel
5. inhibition of sodium conduction
6. decrease in the rate and degree of the depol phase of the action potential.
7. failure to achieve the threshold potential.
8. lack of developement of a propogation action potential
9. blockade of impulse

Question 19

effects on elevated extracellular calcium

Answer 19

partially antagonizes locals anesthetics

Question 20

elevated extracellular potassium

Answer 20

enhances local anesthetics

Question 21

increase in lipophillicity

Answer 21

increase potency

Question 22

increased protein binding

Answer 22

increased duration

Question 23

increased vasodilator activity

Answer 23

decreased potency and decreased duration of action

Question 24

toxicity

Answer 24

most serious reations d/t excessive plasma levels

Question 25

CNS symptoms early to late

Answer 25

circumoral numbness, tongue parasthesia/ metallic taste, tinnitus, blurred vision/dizzy, agitation/ restless, slurred speech/unconciousness, seizures, respiratory arrest/death

Question 26

cardiovascular toxicity

Answer 26

depress: myocardial automaticity, abnormal pacemaker activity, excitability, conduction, contration and cause arteriolar dilations.
benzodizepine lowers resting membrane potential, bupivacaine MOST cardiotoxic, 100ml 10% intralipid may sequester bupivacaine. resuscitate patient

Question 27

respiratory toxicity

Answer 27

lidocaine supresses hypoxic drive, relaxes bronchial smooth muscle. IV lido may block bronchospasm from intubation or reactive airway (1.5mg/kg)

Question 28

immunologic toxicity

Answer 28

true allergic reactions unlikely. Ester derivatives of and metabolized to para-aminobenzoic acid (allergen)
amides may contain methylparaben (smiliar structure to paba)
Treatment: DC drug, 100% O2, eli 0.01-0.5mg IV or IM intubation?, iv fluids 1-2 L, benadryl 25-75mg IV, hydrocortisone 100-200 mg IV

Question 29

hematologic toxicity

Answer 29

prilocaine >10 mg/kg accumulates metabolite o-toludine (oxidizing agent) to convert methemoglobin
methemeglobin 3-5mg/dL causes blood to turn brown and patient to turn blue

Question 30

peripheral neurotoxicity

Answer 30

direct damage to neuronal tissues from high LA

IE cauda equina syndrome 2-5% lidocaine spinal