Pharmacology I - Local Anesthesia

Front 1

How can you tell if something is a local anesthetic?

Back 1

ends w/ -caine

Front 2

Most local anesthetics are ?

Back 2

Amides

Front 3

Name some local anesthetics that are amides:

Back 3

lidocaine
ropivacaine
mepivacaine
bupivacaine

Hint: Love Riding My Bike

Front 4

FYI:
What is function of alpha-1 glycoprotein?

Back 4

* Carrier of BASIC and neutrally charged lipophilic drug.

* whereas albumin carries ACIDIC drugs (steroids, and protease inhibitors)

Front 5

Name some local anesthetics that are esters:

Back 5

prilocaine, tetracaine, cocaine (used in eye drops)

Front 6

How are local anesthetics classified?


Primary difference?

Back 6

Esters
Amides

* how metabolized, half-life

Front 7

What are some benefits of systemically administered lidocaine?

Back 7

Central analgesic effect
Prokinetic activity in the GI tract
Anti-oxidant and inflammatory modulator activity

FYI: Prokinetic type of drug enhances GI motility

Front 8

How are local anesthetics transported in plasma?

Back 8

Bound to α1 glycoprotein, minimally to albumin

Front 9

What commonly used local anaesthetic agent is anti-arhythmic, rapid onset and short duration of action, addition of epinephrine doubles time for absorption, and tachphylaxis can develop?

Back 9

Lidocaine (recommended dose 4mgkg)

Front 10

Half-life of esters is ______, metabolised by _____?

Back 10

only a few minutes; pseudocholinesterases (PABA) mostly in liver

Hint: Bubba Esta (RIP) had a very short attention span, fake name Ester (pseudocholinesterases)

Front 11

Half life of amides are _____, mainly metabolised by ________

Back 11

a few hours
AMIDES -> long lasting


the liver (95%) with renal (kidney) excretion

Front 12

True or False:
Local anaesthetics never exist as stereo-isomers

Back 12

False: Local anaesthetics DO exist as stereo-isomers

Front 13

What is the mechanism of action of local anaesthetics?

Back 13

Blocking sodium channels in a closed configuration

(Na+ CANNOT depolarize membrane!)
Therefore these are "membrane stabilizing" agents

Front 14

What physicochemical property of local anaesthetics is primarily responsible for anaesthetic POTENCY?

Back 14

Lipid solubility

more lipid soluble it is easier it is for drug to get thr. membrane and into neuron

Front 15

Which local anaesthetic agent has a much longer duration than lidocaine (2-6 hours), 4X more potent that lidocaine, and is much more potentially cardiotoxic?

Why is it more potent?

Back 15

Bupivicaine (pKa 8.1)

-> more lipid soluble

Front 16

In local anaesthetics what is the primary determinant of duration of action?

Back 16

Protein binding

more protein binding, longer going to last

Front 17

What determines the rapidity of ONSET in local anaesthetics?

Back 17

PKa (pH when 50% ionized, 50% not)

Front 18

The closer a drugs PKa is to the physiological pH, then ____?

Back 18

More drug occurs in unionized form and better penetrate membranes

Front 19

The greater the diameter of the nerve, the _________ concentration of LA required to produce blockade.

Back 19

Greater

smaller nerves get blocked first

Front 20

Why is epinephrine only added to Lidocaine and not other drugs?

Back 20

because Lidocaine has intrinsic vasodilative properties

Front 21

Why is epinephrine added to a local anesthetic (Lidocaine) injection?

Back 21

Lidocaine has most vasodilative properties and if you only want to analgesia locally (don't want drug diffusing to other tissues), you need VASOCONSTRICTION

Delays absorption
Prolongs the action
Improves the intensity

Front 22

Should you use epinephrine with local anaesthetics when performing ring blocks?

Should you use epinephrine performing spinal anasthesia?

Back 22

No, because impedes blood supply too much if put all around limb

No, not usually, don't want to impede bloody supply

Front 23

Where is local anaesthetic toxicity most common?

Back 23

In nerve blockades with large vessels, (epidurals)

Front 24

Concentration of local anesthetics in plasma depends on what factors? (name six factors)

Back 24

1. Quantity administered
2. Route of administration
3. Rate of absorption
4. Acid-base status
5. Rate of metabolism
6. Presence of epinephrine

Front 25

What is a toxic dose of lidocaine?

Back 25

10mg/kg

Front 26

What is a toxic dose of bupivacaine?

What dose might you give?

Back 26

4mg/kg (doesn't take much); especially in cats

usually 2 mg/kg

Front 27

If a combination of local anaesthetics is used; then the toxicity of each is _________?

Back 27

Additive

Front 28

Factors contributing to toxicity?

Back 28

* route of administration
* rate of absorption from injection site
* acid-base status: acidosis incr. risk of toxicity (rare)
* rate of metabolism of specific drug
* addition of epinephrine

Front 29

Which routes of admin. are most conducive to toxic (systemic) reaction?

Back 29

route of administration: interpleural > intercostals > epidural > infiltration

Front 30

In local anaesthetic overdose what do we see signs of first, CNS or CVS?

Some symptoms?

Back 30

CNS signs first

Initial state of excitement possible due to blockade of inhibitory centers in cortex
Followed by CNS depression, respiratory arrest and CVS depression

Front 31

What are some signs of local anaesthetic overdose?

Back 31

CNS depression
Twitching and convulsions

Front 32

What are some cardiovascular effects of local anaesthetic toxicity?

Which drug is more likely to cause toxicity?

Back 32

Myocardial depression
Hypotension
Arrhythmia

->Bupivacaine toxicity more likely, because of high binding affinity for cardiac myocetes/muscle cell, also long acting

Front 33

How do you treat local anaesthetic overdose?

Back 33

IV diazepam for seizures
Fluids, oxygen, antimuscarinics for CVS

Front 34

Affect of epinephrine on local anesthetic

Back 34

not sure yet

Front 35

Lidocaine pump spray in cats has been associated with what?

Back 35

Laryngeal edema

FYI: this lidoc. spray is used stops spasm of laryngeal folds to facilitate intubation

Front 36

What local anaesthetic agent is slightly less irritant than lidocaine and is used in horse nerve blocks?

Back 36

Mepivicaine (recommended dose 4mg/kg)

Front 37

What local anaesthetic agent is similar to lidocaine except slightly less irritant and is used in horse nerve blocks?

Back 37

Mepivicaine (pKa 7.7 slightly lower than Lidocaine)

Front 38

What is a less neurotoxic and cardiotoxic isomer of bupivicaine?

Back 38

L-bupivicaine

Front 39

Which local anaesthetic agent is closely related to bupivacaine, but significantly less cardiotoxic than bupivicaine, acts on sensory fibers, and recommended safe dose of 2 mg/kg?

Back 39

Ropivicaine, significantly less cardiotoxic than bupivicaine

Front 40

What is commonly used to treat local anaesthetic toxicity?

Back 40

Intralipid

Front 41

Which isomer less toxic?

Back 41

S/L isomer (not R/D)

Front 42

Which longer acting Bupivicaine or Lidocaine? Why?

Back 42

Bupivicaine (6-8 hours)

b/c Bupivicaine is 96% protein bound while Lidocaine is only 64% protein bound (2 hours)

Front 43

What is appropriate ratio of lidocaine to epinephrine?

What happens if use more than this?

Back 43

1:200,000 epinephrine

could impair blood supply to brain

Front 44

Give example of how altering pH of drug solution could change onset?

Back 44

Add Sodium bicarbonate, this will produce more unionized drug, to increase onset of action

Front 45

Repeated of injection of lidocaine has what effect on efficacy of action?

Back 45

Reduces (onset, duration), body stops reacting to it

Front 46

How does site of injection affect of drug effect on efficacy of action?

Back 46

if inject in a site with high blood supply get faster uptake, and reduced duration of action

Front 47

In general, which nerve fibers require more local anesthesia to be administered?

autonomic preganglionic fibers
motor (skeletal) fiber
Motor (proprioception)
sensory fibers

Back 47

motor (skeletal) fiber > sensory fibers > Motor (proprioception) > autonomic preganglionic fibers least b/c smallest fibers
(unmyelinated fiber would be about same)

Front 48

anticdote for overdose?

Back 48

Not much can do aside from waiting; can try treating symptomatically with diazepam (Why would this help?)

Front 49

Would you use local anesthesia in joint if operating on it?

Back 49

Yes, except new evidence that Bupivicaine damage arterial cartilage

Front 50

Can you give lidocaine as intravenous infusion?

Back 50

Yes, to treat systemically, but not so much in cat

Front 51

What route of admin. might use for thoracic surgery in high risk patient?

Back 51

epidural (not sure why)

Front 52

MLK cocktail?

Back 52

morphine, lidocaine, ketamine for multimodal anesthesia in dogs/horses

(not so much in cats for obvious reasons)

Front 53

Do lidocaine patches work in animals?

Back 53

No, not good absorption, only for treating people

Front 54

True or False:
Methemoglobinemia (reduced form of Hb) common side effect of treatment with local anasthetics?

Back 54

False

Front 55

Which is more lipid soluble lipid soluble: Ropivacaine or bupivacaine?

Back 55

Bupivacaine is 10X more lipid soluble than Ropivacaine

* also more cardiotoxic