1. Local Anesthesia I Flashcards
(41 cards)
• NSAID > central effects as well
○ Fever lowering (central effect)
• Opioids > peripheral effects
○ ____ (peripheral)
§ Mu receptors in the int tract > dec peristalsis when activated
§ Don’t get ____ to this
□ Will not get tolerant to go into resp dep, nausea/vomiting, to getting high (need more and more); and ability to cause miosis (pinpoint pupils) > may be in withdrawal, the pupils ____ (opposite effect of the drug)
• NSAIDs
○ Aspirin was the first > grouped by itself
§ Properties diff than ibuprofen
○ ____ - number one prescribed in the world (ibuprofen is for US)
○ COX-2 end in coxib
§ Issue w inc incidence of ____ events
□ Block COX2, but COX1 goes wild
○ Primary mechanism: block cyclooxygenase and the synthesis of ____ (inc renal BF and excretion of H2O/Na)
§ Analgesic and anti-inflam, and explains why chronically can cause GI ulcers and bleeds and renal problems
○ Don’t prescribe with ____ problems
• Caine drugs ○ Local anesthetics ○ Cocaine is a local anesthetic that has different properties from the ones we use ○ Block \_\_\_\_ channels - at the peripheral nerve it's good, but too much in body > heart § Used for \_\_\_\_; too much can cause bradycardia Block Na channels in brain > first CNS excitation, but can be followed by \_\_\_\_ depression (inc res depression)
constipation
tolerant
dilate diclofenac cardiovascular prostaglandins kidney
Na
antiarrythmias
CNS
• Centrally-acting analgesics
○ ____ receptors also in the intest tract, and free nerve endings in the periphery
○ Potentially addicting
○ Oral morphine isn’t used > no formulations where it’s combined w ibu/aceto; drugs for pain w/ opioids, pain is mostly ____ > comes from ibu, and most AE comes from opioids
§ Morphine avail in pure form
§ High first pass > dosing is ____
§ Acute post surgical pain > underdosing some people, and some will be overdosed
○ Codeine is found in tyelonal with the number
○ Oxycodone is in percocet
○ Diff bt codeine differences is ____ - oxycodone is the ____, and codeine is the weakest (1:6:12)
○ Propoxyphene is no longer on the market
§ Were in big tables with acetomeniphen
§ Weaker than codeine, but bc DEA schedule ____ drug (hydro is a II - no refills and cannot call it in)
□ Closest chem structure: ____ - opiod agonist (Long-acting) > don’t get an immediate rush and prevents the craving
® Longer acting > not cured > get them clean > slowly wean off the methadone; in 60-70% individuals you cant
○ Fentanyl § Heroin is being laced with it § Chronic pain in \_\_\_\_ ○ Addicting, and work in dorsal horn of spinal cord and medulla by inhibiting release of \_\_\_\_ ○ Activate \_\_\_\_ analgesic pathways ○ Psychological > change perception of pain > they don't \_\_\_\_ anymore (mood altering affects of drugs) § 10% of population has predisposition to get addicted to these drugs
inflammation unpredictable potency strongest IV methadone patches SP and CGRP descending care
• First LA > still availabe in hospitals > cocaine
○ Topically > ophthalmic surgery, and up the nose for nasal surgery
• Only LA that has ____ properties, all the others are vasodilators > why you mix with epinephrine (alpha1 receptors)
• Cocaine is a CNS ____
○ Snort, smoke, or inject it on the streets
○ Coke abusers > get too stimulated > balance it with CNS depressant (dual addiction)
vasoconstrictive
stimulant
NE
End Result: Accumulation of Norepinephrine, Sensitization of receptors,
CNS Stimulation, ____, Tachycardia, Increased ____ Force,
Avoid ____
• Things cocaine does that lidocaine don't do • NE is in vesicles, fuse and spit out > bind alpha and beta receptors ○ Happy chemical ○ \_\_\_\_ and an ADHD drug boosts NE levels in the brain • Some things turn off NE > reuptake, and an enzyme in the cleft/BS (\_\_\_\_) that will degrade NE • Cocaine block the \_\_\_\_ of NE that's released; this itself doesn't make it an addictive drug bc it's the classic mech of antidepressants, but in addition, cocaine can also enhance \_\_\_\_ (amphetamine effect) ○ The combination of the two > more NE in the cleft (in periphery and brain) • Cocaine also sensitizes \_\_\_\_ alpha and beta receptors ands imilar receptors in the brain • Periphery > can speed up the \_\_\_\_, and close BV (stim alpha receptors) > drug-induced \_\_\_\_ ○ Coronary artery vasocon and speeding up the heart • Avoid epi with someone taking cocaine (24-48 hours) ○ Epi will enhance, and some of the way it's turned off > have sensi alpha/beta receptors (larger effect bc of epi), and another way it's cleared some of it is reuptake into symp nerve terminals (it's blocked) ○ Enhanced effect of epi in the brain > NO, doesn't cross the blood brain barrier § All locals do (like cocaine)
vasoconstriction contraction epinephrine antidepressants COMT reuptake release peripheral heart heart attack
DA
End Result: Dopamine Accumulation, Receptor sensitization, ____, Physical and Psychological Dependence, ____ Stimulation
• Does same thing to the precursor of NE ○ \_\_\_\_ can go to epi ○ The \_\_\_\_ only have machinery to go to NE ○ \_\_\_\_ in the brain can only go to DA • Cocaine can block reuptake, enhance release of DA > accumulation in the periphery ○ Also stims \_\_\_\_ receptors (DA) ○ Also opens up renal vasculature (DA) • Most drugs of abuse have some enhancing effect on DA system (block reuptake, accel release) • Cocaine sensitizes receptors in the brain • \_\_\_\_ - more durg to get same effect • \_\_\_\_ - stop taking drug you go into withdrawal (opposite effect of drug) ○ \_\_\_\_: croggy, can't get out of bed • \_\_\_\_ > you're an addict ○ Going to stupid things to get the drug
euphoria
cardiac
adrenal medulla nerve terminals basal ganglia B1 tolerance physical dependence withdrawal psychological dependence
Cocaine + Vasoconstrictors =
• Taking cocaine into a dental office > HTN > \_\_\_\_ (epi) > death
cardiac arrythmia
Esters - \_\_\_\_ - procaine - \_\_\_\_ Other ester: \_\_\_\_ PABA
• Cocaine is a member of the ester class of LA • All have ○ \_\_\_\_ - gives lipid solubility ○ \_\_\_\_ terminus - water soluble > need it so its soluble in carpule (H2O); also want it so it doesn't precipitate into interstitial fluid ○ Intermediate chain > separates into esters and amides § Esters have \_\_\_\_ group in it • Benzocaine has no \_\_\_\_ terminus > poor water solubility; can be dssolved into \_\_\_\_ (can cause nerve damage) > only used topically (oragel) ○ PG has resemblence to antifreeze • Procaine used to go under novacaine > coke analog ○ Issue: has a significant anesthetic \_\_\_\_ > takes a long time to get someone number § Has a short duration of \_\_\_\_ (30 mins w epi) Bc it's an ester, when processed > give off paraaminobenzoic acid > can act as a \_\_\_\_ > binds tissue proteins and see mild allergic rxn (tissue sloughing, rash) > RARE
benzocaine
tetracaine
cocaine
aromatic amino C=O amino polyethylene glycol lag action hapten
Benzocaine Background
• OTC since 1926 for temporary relief of toothache
• Category I status for temporary relief of ____
– Apthous ulcers
– ____ irritation
– Orthodontic appliances
– ____
• ____ status for temporary relief of toothache
• First studies were toothache studies • Category I ○ Drugs OTC are given I-III categories; you don't want to be a \_\_\_\_ (don't work or you're toxic > pulling off the market) ○ FDA warnings don't use on teething infants (overdoses) ○ Toxicity is \_\_\_\_ • Category III is relatively safe, but show us that it works ○ Not \_\_\_\_ patients
oral mucosal pain
denture
teething
category III
II
methemoglobenemia
dental impaction
Esters
• Procaine > form tetracaine ○ Found in intranasal stuff > trade name Covanase ○ Took procaine and added \_\_\_\_ > when add carbons to most drugs > more \_\_\_\_ soluble and more \_\_\_\_ > you need less ○ Procaine when available in injections > injected at 2-4% ○ Tetracaine (used for epidurals during birth) > injected at 0.2% • Inc lipid solubility > more vigorously and more tightly bind the nerve membrane > longer duration of \_\_\_\_ ○ Tetracaine is not only found intranasally, also found in cetocaine spray > newly formulated cetocaine ○ Used by dentists > as long as you push down the nozzle keeps coming out > newly formulated > 90% of their market
carbons
lipid
potent
action
Clinical Presentation of Toothache Patient
Definitive therapy is ____ or extraction and NOT ANALGESICS!!!
• Show up in ER clinic on M or F > F bc they don't want to suffer all weekend, or M bc they suffered all weekend • 2-3 hour window > worked up > don't get the extraction/initiation of RC until 1-2pm ○ Quick study ○ Comparing benzocaine 20% (oragel) to placebo (the vehicle) § The vehicle is polyethylene glycol > alcohol like drug > dealing w a placebo that has some \_\_\_\_
RCT
activity
• Bought OTC and self-medicating
• Temporary bridge for definitive ____
○ Don’t want it working for 10 hours
• Place a tiny amount on the gums and hole of the tooth
dental care
• Want to see how many people were putting in excess?
• Underpowered study > but the benzo was separating from placebo
○ Too few patients
• Several time points > asterisk > stat significant > 95% sure the difference is real
○ Hybrid measure in red of intensity and pain relief > ____
• Surprised that any breakout w an underpowered study > placebo not like lactose
○ Ran to FDA > but they want more safety data
○ Want to know about extra strength over regular strength
PRID
- Responder rate
- People in first 20 mins > had two timepoints where pain intensity went down one unit (moderate to slight pain)
- High placebo response > 47% > ____
- 87% response rate in the benzocaine group
polyethylene glycol
• 100 of them to be 12-17 y/o > so they can get it
○ They’re in school, and they don’t want to spend extra time here
• When finished: went to endo or OS
• ____ response > much higher > 70%
• 81% response and 87% response rate
○ Same response rate as the little study
placebo
• All stat significant into 35 mins
• 20% ES was better than ____
• 10% only showed efficacy compared to placebo at 5 and 10 mins
○ Timepoint where 20% was better than 10%
• Don’t advertise for this study: everyone would say they have toothache pain
vehicle
Global efficacy evaluation
• At the end of the study > overall rating of the drug > poor to excellent ○ Both separated from \_\_\_\_ ○ 80% rated as good/vg/excellent for alleviating acute pulpitis ○ Where only 60% in the vehicle • Global/overall evaluation of study drug
placebo
• Did people follow instructions on the label > didn’t tell how to self apply
• Need ab a ____mg on benzo in an adult to cause significant methemoglobenmia
• 400mg of product > hoping that it was a cutoff > not worried about anything
○ It’s not 400 of benzo > 10-20% gel > ____ mg benzocaine (way below the threshold); in a 10% solution it’s only 40 mg
• Most people (>500) they were at 400 or less
○ ____ was very good
• Some overachievers > 600-800 > 20% is only 160 mg of benzocaine
• One guy went over 1000 mg of product
○ Didn’t breka the “code” bc he didn’t have AE
○ He got over ____ mg of benzocaine > still didn’t get it
1000
80
compliance
200
Methemoglobinemia
Fe++ (____) > Fe+++ (____ or meth)
Threshold dose for benzocaine = 15 mg/kg 150 pound adult = ____ mg benzocaine
15 pound teething infant = ____ mg benzocaine
Vast majority of published cases (>95%) associated with ____, fiberoptic intubations, bronchoscopies and transesophageal echocardiography.
Antidote = ____
reduced oxidized 1000 100 endoscopy intravenous methylene blue
Methemoglobemia
• Benzo is a strong \_\_\_\_ (so it nitroglyc) > convert iron to Fe3+ > now oxidized ○ Oxidized Hb > doesn't pick up \_\_\_\_, or when picks up it doesn't let \_\_\_\_ ○ People become \_\_\_\_ and have trouble breathing ○ What MetHb level do you need > § Sample of blood \_\_\_\_% would be in the MetHb state naturally; 99% is in the reduced Hb state • OD of benzo issues > hasn't been of toothache ○ Mainly: \_\_\_\_ infants (bc it's weight based) ○ Also in hospitals > \_\_\_\_, endoscopies (look for ulcers) • Antidote: methylene blue ○ \_\_\_\_ agent ○ Given IV ○ Sends the chemical rxn in the other direction ○ Also found in histology labs > \_\_\_\_ § Cells take up meth blue > they're dead
oxidizing agent O2 go cyanotic 0.5-1.5 teething intubations reducing H&E
Other drugs associated with Methemoglobenmia
• Not just benzocaine ○ \_\_\_\_ (cipro) § Strong oxidizing drug (not w mechanism of action) ○ \_\_\_\_ ○ \_\_\_\_ (injectable) § Metabolite > otuledene > strong oxidizing agent • MetHb warning > wants on all locals ○ Two biggies: \_\_\_\_ and \_\_\_\_ • \_\_\_\_ ○ GERD and drug-induced vomitting ○ Too much > strong oxidizing drug • Doesn't matter what type of \_\_\_\_ the drug is!
antibiotics
nitrates
prilocaine
benzo
prilocaine
reglan
class
____ to gray skin, mucous membranes, nail beds
____ blood
Difficulty ____
• Blood looks brown > all in the MetHb state
blue
chocolate brown
breathing
• Newly formulated cetocaine studies > CTY5339
○ 14% benzo + 2% tetra
• Each depression is ab .2ml
• Maximum recommended dose > MetHb levels don’t ____ > use correctly > no issue
• OD them > big issue
• ____ alone > the levels didn’t move
• One patient goes up to ____% (not real danger) > but getting to a level where they’re turning blue > cut the study off
move
benzo
5
• Frying the gingiva
○ Ramp the temp up from 35 to 50.6C
• ____ alone incs heat pain threshold
○ Most people w/o drug on board > hit the mouse at 42C
• ____ > sig further inc heat pain threshold over benzo alone
• Two component product was better than the one component product
benzo
tetra+benzo
• Why does benzo work in toothache?
○ If pulp is staring in the face > anesthetizing the pulp
• Apply to gingiva > gets in the tongue > ____ numbness > conversions of primary afferent nerve fibers > when hits CNS > patient may perceive as ____; or the ____ effect (distracts them from the pain)
○ Doesn’t actually have an ACTUAL effect
soft tissue
pain relief
counter irritation
