3010 test 2

Local anesthesia

Prevent the generation and conduction of nerve impulses

Roadblock between source and brain

Neuron types

Sensory (afferent)- carry info toward CNS

Motor (efferent)- carry impulses to muscles

Myelinated vs unmyelinated

Myelinated- fast, wrapped in sheath, jumps node → node

(Myelin= lipid layer formed by Schwann cells)

Unmyelinated - slow, thin or single covering, creeps along membrane

Saltatory conduction

Impulse jumps between nodes of ranvier = faster conduction

This is why we must block 8-10mm of nerve for profound

Fundamentals of impulse transmission

Nerves carry messages as impulses triggered by stimulus usually in form of electrical action potential generated by ionic changes across nerve membrane

Don't loose strength

LA prevents impulse and conduction

Electrophysiology of impulse transmission (membrane excitation steps)

Stimulus excites nerve =

Depolarization (.3msec)- slow depolarization → firing threshold → rapid depolarization → action potential propagation →

Repolarization

In total 1 millisecond

Electrochemistry of nerve conduction

2 important factors influencing electrophysiology

Concentration of electrolytes in axoplasm (inside nerve)

Permeability of nerve membrane to sodium and potassium

Phases of nerve conduction

Resting state → membrane excitation → repolarization → refractory state, return to resting potential

Resting state

-70mv (inside negative)

Mem perm- slight perm to Na+, freely perm to K+ and Cl-

Slow depolarization

Stimulus slightly opens sodium channels → Na+ slowly enters cell

Firing threshold

Slow depolarization → membrane potential shifts from -70 mV → - 55mV

If threshold is reached → action potential occurs opening sodium channels fully

If voltage channel is less than 15mV there will be no creation of action potential

Rapid depolarization

Membrane becomes highly permeable to Na+

Voltage rises to +40mV → impulse propagates along nerve

Repolarization and recovery

Na+ exits to extracellular, K+ returns to intracellular → potential drops back to -70mV

Sodium potassium pump restores ion balance (keep working till @ resting)

Refractory period

Absolute - no new impulse can occur

Relative- stronger than normal stimulus may trigger response

Ensures one way transmission of impulse

Impulse propagation

Impulse crosses gap via neurotransmitters (synapse)

Electrical and chemical signals work together to relay impose to CNS

LA mechanism of action

LA molecules bind to sodium channels blocking Nat influx → prevents depolarization → no impulse transmission

Requires 8-10mm of myelinated nerve coverage to be effective

Local anesthesia definition

Reversible loss of sensation in a limited area by blocking nerve impulses

Only methods that induce transient and completely reversible state of anesthesia in clinical practice

Types of nerve fibers

A fibers, C fibers

Dental pulp contains both w/ a little more C

A fibers

Lightly myelinated, conduct very rapidly (14.8 - 120 m/sec) - responsible for conveying sharp, stabbing pain

C fibers

Unmyelinated, conduct slowly (1.2 m/sec)

Convey dull aching pain

Ideal LA properties

Reversible and non irritating, low toxicity and stable in solution, fast onset W/ appropriate duration, affective whether injected or topical

LA amide

Bio transformed primarily in liver, non allergenic, intermediate chain contains nitrogen atom, injected

LA ester

Hyrolyzed in plasma by pseudocholinesterases, highly allergenic (PABA), intermediate chain doesn't have nitrogen atom, topical only in North America

Exceptions of LA biotransformation

Prilocaone/citanest undergoes some metabolism in lungs

Articaine/septocaine undergoes shared metabolism between liver and blood

Types of LA

Amides- xy/li, art/sept, mep/carb, prilo/cita, marc/bup

Esters- Benz, pro, tetra, coke

All vasodilators except cocaine → ↓ duration and quality, ↑ blood LA

Pharmacodynamics vs pharmacokinetics

Dynamics- actions of a drug on the body

Kinetics- mechanism in which body manages drug (absorption, distribution, metabolism, elimination)

LA mechanism of action

Stops nerve impulses by blocking sodium channels on nerve membrane

(LA has higher binding affinity than sodium, primary effects are during depolarization phase)

Induction time

Within operator control- daw concentration, pH of LA solution and tissue

Outside of control- diffusion constant, anatomic diffusion barriers of the nerve

LA dissociation

Acid salts + sterile water = dissociation into positively charged cations and uncharged/neutral base

RNH+ ←→ RN + H+

2 factors -

-diffusion of drug through nerve sheath: base RN is lipophilic and is the only form of the drug that can pass through mem into intracellular

-binding at the receptor site within the ion channel: hydrophilic cation RNH+, formed once base can enter axoplasm, is responsible for binding to sodium channels and displacing Ca2 and producing blockade

LA dissociation in syringe vs tissue vs nerve cell

In solution- RNH+ → RN + H+ because neutral base is less stable than cation form

In tissue- some cations (RNH+) are converted to RN base which can then diffuse mem into cell

In nerve cell - neutral base combine w/ intracellular H+ to become RNH+ which then binds to Na+ channels to provide conduction blockade

Dissociation availability depends on

pKa (dissociation constant) of specific LA

pH of solution or surrounding tissues

Effect of dissociation constant

pka = measure of affinity of a molecule for H+ ions

When pH=pka exactly 50% exists in cation 50 % base

Lower pka = more rapid onset bc more RN molecules present to pass through

Effects of pH of solution or tissues

↑ H+ (low pH) = more RNH+

↓ H+ (high PH) = more RN + H+

LA w/ lower pH (more acidic) have slower onset bc body has to buffer LA back to physiologic pH

LA and inflammation

When inflammation, lower pH favors production of RNH+ limiting # of base forms to pass

Inflammation causes ↑ circulation → ↑ failure of profound

Epi in LA

LA containing epi are acidified by manufacturer to inhibit oxidation of vasopressor → lowers pH of LA but acidic LA can burn and be slow so buffered solutions ↑ pH

Buffering LA

Neutralizing before can ↓ burn, faster onset, improve effects

LA durations

Short- 20 - 40 min (mep/prilo)

Intermediate- 60-90 (lido/art w

Long- up to 8hrs (bup)

LA distribution after injection

Some solution diffuses toward / into nerve while a significant amount diffuses away

Fasciculi

Near the surface of nerves are mantis bundles (mantle)- exposed to ↑ concentrations, innervate proximal portions of nerve distribution, longest numb

Deeper toward center of nerve use core bundles (core)- exposed to ↓ concentrations, innervate i distal portions of nerve distribution, shortest numb

Tachyphylaxis

The increasing tolerance to a drug that is re-administered repeatedly

Contributors- edema, local hemorrhage, ↓ pH

More weekly to occur it you wait for new restoration before readministration

Metabolites

If allowed to accumulate in blood -

PABA → allergy

Prilo → methoglobinemia

Lido → sedation

Systemic effects and toxicity

CNS- dizzy, anxious, tremor → convulsions → CNS depress

CVS- ↑ HR and BP and strength followed by depression, cardiac arrest, ↑ heart O2 consumption

Respiratory- slow breathing,

Tissue- muscle irritation or necrosis

Prevention of toxicity

Aspirate, slow injection w lowest effective dose, avoid long acting, monitor pt

Max relative dose

Reduce for elderly or med compromised

Why vasoconstrictors in blood

Constrict blood vessels decreasing blood flow to site of admin = slow absorption and creases amount absorbed by nerve

Epinephrine sympathomimetics

Activates alpha and beta receptors

Beta> alpha

Norepinephrine/levonordefrin

Favors alpha receptors thus less effect on the CV and cardiopulmonary systems alpha >beta

Sodium bisulfate

Prevents oxidation/degradation, common allergy

CVS B1 effects

Stimulates B1- ↑ HR, bp, strength

Stimulates B2 - coronary vasodilation, bronchial dilation

Increased dysarrhythmia

Beta stimulation stimulates glycogenolysis (break down of stored sugar) elevating blood sugar levels, inhibits insulin secretion

Alpha and beta vascular effects

Higher dose (initial) = alpha vasoconstriction

Smaller dose (later) = beta2 vasodilation

hemostasis during period of increased dose (due to α stimulation) but as levels fall, β actions predominate (then “β>α”), leading to vasodilation & rebound bleeding

Levonordefrin

Contains sodium bisulfate, available only with 2% mep in 1:20K, direct alpha stimulation w/ some beta (25%)

Less cardiac, CNS and bronchodilation than others w/ epi, can cause hypertension

Signs/symptoms of vasoconstrictor overdose

Generally transient (sec-min)

↑ BP and HR, dysarrhythmia, anxiety, headache, tremor, sweat, pale, weak, respiratory difficulty

Vasoconstrictor compromised pts

Cardiovascular pt, hyperthyroid (poorly controlled), diabetic (poorly controlled), sulfite allergy, certain meds( nonspecific beta blocker, antipsycho, maoi/tca, cocaine/meth, thyroxine)

Vasoconstrictors in cardiovascular patient

No elective tx < 6 month post MI/CVA

Only 1:50K use if angina, arrhythmia

Max recc dose: epi- 40mcg or.04mg, levo- .200mg or 200 mcg

Vasoconstrictors in hyperthyroid pt

↑ risk of arrhythmia, avoid vc in uncontrolled

Vasoconstrictors in diabetic pt

AIC >7 means increased insulin demand and B stimulation inhibits insulin secretion

Use cardiac compromised dosing ( 2 carts 2% lido W 1:100K epi

Vasoconstrictor in sulfite sensitive pts

SMBS- Prevents oxidation of VC

Absolute contraindication, look for reactions to wine, vinegar, dry cheese/fruit/ veg

Asthmatic pts allergy can affect airway of asthmatic

Vasoconstrictor interaction w MAOI

Contraindication, may potentiate VC effects, just keep them in usual dental parameters

Ex. Prenelzine (Nardil), isocarboxazide (marplan), selegiline (eldepryl, zelapar, emsam)

Vasoconstrictor interaction w/ tricyclic antidepressants (TCA)

VC Î risk of BP HR anginal episode, use cardiac dose

Levo is absolutely contraindicated

Ex. Amitriptyline (elavil), nortiptyline (Pamelor, aventyl)

Vasoconstrictor interaction w non specific B blocker

Used to treat cardiovascular problems, but enhances epi response

Limit to cardiac dose

Memory trick for selective vs non selective B blocker

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Some people are way more SELECTIVE with how they spend their spare time. My friend Esme (esmolol) is an ace(prolol) example.  She doesn’t like spending a nebulous (nebivolol) evening.  She loves to dress up like
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Vasoconstrictor interaction wl cocaine/meth

Coke= powerful vasoconstrictor, meth = potent stimulant

Avoid VC if used within 24hrs

Vasoconstrictor interaction ergot preparations

Used to treat migraines, vasoconstrictor

Epi and levo effects are additive to it and can lead to hypertension

VC is absolutely contraindicated