local anesthetics Flashcards
esters
chloroprocaine, procaine, tetracaine, cocaine
amides
lidocaine, mepivacaine, bupivacaine, prilocaine, ropivacaine
LA drugs act by
inhibiting sodium influx through sodium specific ion channels in the neuronal cell membrane.
they cross the cell membrane by
corssing in the non ionized lipophillic state
the _____________ portion in the cell then binds to the ________ __________
ionized, sodium channel
what does Pka correlate with?
onset
what does lipid solubility correlate with?
potency
what does protein binding correlate with?
duration
toxic dose of bupivacaine/ ropivacaine
- 8 mg/kg (175 max) OR
3. 2 mg/kg (225 max) with EPI
toxic dose of lidocaine/ mepivacaine
4.5mg/kg (300 max) or 7 mg/kg (500 max) with EPI
absorption of local anesthetics
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
Distribution- amides
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
distribution of esters
broken down rapidly in plasma
metabolism
converted in liver or plasma to water soluble metabolites and excreted
metabolism of amides
hydrolyzed by liver enzymes.
rate: prilocaine> etidocaine> lidocaine> mepivacaine> bupivacaine
liver dz, lecresed blood flow increases times for metabolism
metabolism of esters
hydrolyzed in plasma rapidly. < 1min procaine, chloroprocaine
excretion
unionized not excreted, acidification of urine promotes ionization and renal excretion, renal tubules do not reabsorb chargeed metabolites
mechanism of action (9 steps)
- diffusion of the base form across the nerve sheath and nerve membrane
- re-equilibration between the base and the cationic forms in the axoplasm
- Penetration of the cation into and attachment to a receptor site within the sodium channel.
- blockade of the sodium channel
- inhibition of sodium conduction
- decrease in the rate and degree of the depol phase of the action potential.
- failure to achieve the threshold potential.
- lack of developement of a propogation action potential
- blockade of impulse
effects on elevated extracellular calcium
partially antagonizes locals anesthetics
elevated extracellular potassium
enhances local anesthetics
increase in lipophillicity
increase potency
increased protein binding
increased duration
increased vasodilator activity
decreased potency and decreased duration of action
toxicity
most serious reations d/t excessive plasma levels
CNS symptoms early to late
circumoral numbness, tongue parasthesia/ metallic taste, tinnitus, blurred vision/dizzy, agitation/ restless, slurred speech/unconciousness, seizures, respiratory arrest/death
cardiovascular toxicity
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
respiratory toxicity
lidocaine supresses hypoxic drive, relaxes bronchial smooth muscle. IV lido may block bronchospasm from intubation or reactive airway (1.5mg/kg)
immunologic toxicity
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
hematologic toxicity
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
peripheral neurotoxicity
direct damage to neuronal tissues from high LA
IE cauda equina syndrome 2-5% lidocaine spinal
