Drug Structure, and Pharmacology

Therapeutic Effects, Indications, Duration, etc.

Precautions, Adverse effects and Contraindicaitons

Ester Class

Procaine

(Novacaine)

• Hydrolyzes to PABA and diethylamino ethanol (vasodialator)

• previously marketed as 2% solution with .4% propoxycaine.

• No longer available

• Quick onset and short duration

• Safest L.A. due to rapid Hydrolysis

• No topical effect (too weak)

• can be used I.V. for tx of Cardiac Arrhythmias, and seiures of status epilepticus. (also can use procainamide)

• combination with penicillin to form procaine penicillin G

• PABA can interfere with sulfonamide antibiotics (competitively)

Propoxycaine HCL

(Ravocaine)

• A derivative of Procaine

• Has a propoxy group added to the ortho position of aromatic ring. – this increases the hydrophobicity therefore increasing potency

• previously marketed as a .4% solution with 2% procaine

• no longer available

• Propoxy group increases the hydrophobicity leading to an increase in potency, duration, and toxicity

• same diethyamino ethanol vasodialator effect.

Tetracaine HCL

(Pontocaine)

•Hydrolyzes to PABA and diethylamino butanol

•Hydrolyzed by plasma esterases, but more slowly than procaine.

• Slow onset and long duration due to high lipid solubility and serum protein binding.

• Potency and toxicity are at least 10X that of procaine.

• Very effective topically – but has a greater toxic effect when given this way because of rapid absorption.

• As with all PABA derivatives tetracaine can reduce effectiveness of sulfonamide antibacterial drugs

• Too toxic for infiltration or nerve block. Only for topical application as 2% solution with benzocaine

Benzocaine

Only one without an amine group. Making it neutral

• An ester of PABA

• Identical to procaine but without the 3⁰ amine

• not soluble in aq. sol

Amide Class

Lidocaine HCL

(Xylocaine, Octocaine, Alphacaine)

•Amide derivative of Xylidine.

• max blood level occurs at 10min w/out vasoconst., and 60 min with.

• clearance biphasic (t1/2 = 15-20 min for oral tissues. And 90-120 min systemic.

• slow metabolism via P450.

• study catabolic pathway on peach colored handout

• Vasodilation is much less than procaine, so it can be used without vasoconstrictor.

• Rapid Onset, intermediate duration.

• 2-4 X as potent and 2 X as toxic as procaine.

• Some pts experience sedation with lidocaine – probably due to MEGX and MX metabolites. In these pts. CNS excitation stage may be bypassed.

• given I.V. as an antiarrhythmic, to control laryngeal reflexes, and control of status epilepticus ( due to generalized reductionin excitabile tissues)

• effective topically- 2% viscous sol., 3% cream, 5% ointment, 10% spray

• must be very careful with liver damaged pts.

Mepivacaine HCL

(Carbocaine, polocaine, Arestocaine, Isocaine)

•Amide derivative of Xylidine

• Less vasodilation than lido

• 3% w/out vasoconst. Or 2% with vasoconst. (1:20,000 levonordefrin)

• Rate of onset , duration, potency and toxicity Is similar to lidocaine

• Not effective tipically

• used for infiltration ,and block.

• No apparent cross allergenicity with other amide L.A’s or with ester LA.’s

• Does not appear to produce drowsiness like lido

Prilocaine HCL

(Citanest)

• Amide derivative of Toluidine ( xylidine minus a methyl group on aromatic ring)

• Amino terminus is a 2^o amine with a propyl group

• metabolism is does not require de-alkylation, like most because it does not have a 3^o amine

• 4% solution w/ or w/out 1:200,000 epi

• action is similar to lido and mepivacaine, but slightly less potent, and toxic, with a longer duration.

• not for topical use

• indicated for infiltration and block

• can cause cyanosis due to production for methemoglobin.

• do not use in situations where oxygenation is critical ex: pregnancy, genetic methemogl., anemia, COPD, CHF.

• At dental doses. Danger is usually minimal.

• do not combine with other drugs that can cause methemoglobinemia, like acetomenophen, or phenacetin.

Bupiviacaine HCL

(Marcaine, Sensorcaine)

Just pulled from market

• A derivative of Mepivicaine.

• Identical to mepicavaine except the methyl group on the amino terminus is replaced by a butyl chain.

V Much more lipid soluble. • .5% solution with 1:200,000 epi.

• 4X as potent and toxic as mepivacaine ( due to lipophylicity)

• Slower onset than mepivacaine, but with longer duration for block.

• Excellent long acting postoperative anesthesia

•Not used topically

• The only long acting L.A. currently available for use in dentistry,

Etidocaine HCL

(Duranest)

• A derivative of Lidocaine. Identical except and ethyl group is attached to the intermediate carbon and one amino terminal ethyl group is replaced with a propyl group.

• extremely lipophylic

• 1.5% solution with 1:200,000 epi

• Less potent and less toxic than Bupivacaine

• Clinically similar to Bupivacaine. Long duration but shorter post-op analgesia than bupivacaine.

• Not used topically

Articaine

(Septocain)

• Thiophene ring structure, instead of benzene

• Has both an ester bond and an amide bond- the amide bond is the critical functional subgroup while the rapid cleavage of the ester bond is responsible for deactivation.

• 4% solution

• Peak plasma conc. Is in 15 min, with clearance t^1/2 being 20 min

• Intermediate duration

• Similar potency and todxicity to lidocaine despite theoretical superiority ( due to solubility and deactivation)

• Faster onset due to High lipic solubility( similar to prilocaine – also a 4% sol.)

• some dentist claim fast and profound anesth. Permiting decreased dose

• No- Lidocaine cross-reaction

• Sulfite sensitivity due to thiophene group – reported parasthesia fo the lip and tongue perhaps due to greater poteny than lido and higher concentration. This means inject less than half the amount you would give for lido

H-1 receptor agonists

1)Diphenhydramine

(Benadryl)

2) Promethazine

3)Pyrimaline

Block Na⁺ similar to other local anesthetics

• May be useful if pt cant tolerate esters or amides.

Topical Anesthetics

Lido and Tetracaine

• The only anesthetics used locally in dentistry

• selected based n ability to penetrate oral mucosa

• concentration is much greater- up to 20%

• No vasoconstrictor

• Absorption is rapid and I.V Level doses can be obtained

• Potential toxicitiy is much greater than injectable anesthetics.

• Locals produce a greater number of toxic rxns htan other forms of administration.

Cocaine HCl

• Alkaloid ester of Benzoid acid

• Excreted unchanged in the urine

• Only L.A. to cause vasoconstriction (intense)

• Not used in dentistry

Benzocaine HCl

• An ester of Paba

• Has a slower absorption from the mucosa

Dyclonine HCl

(DyClone)

discontinued

• A Keytone

• Long lasting

• Low toxicity

Vasoconstrictors

Remember to study the contraindication to vasoconstrictor use from handout

• Low toxicity as long as not injected in to blood stream

• Pts at cardiac risk get no more than 40 micrograms (two cartridges)

• Cardiac stimulation increase the spread to CNS leading to increased toxicity - as much as 2 times

Epinepherine

• Alpha _1, Beta _1,2 agonist

•effect on different receptor depends on the concentration.

•described as being above or below alpha threshold because below a certain conc. There is no effect on alpha₁ receptors, and therefore no vasoconst. Above threshold Alpha₁ masks the relatively weak Beta₂ Vasodilation effect .

• local doses at injection site are at conc. Above the apha threshold while the more diffuse concentrations systemically are below.

• Low dose levels do not effect the Mean B.P. – systolic Pressure increases due to Beta₁ induced greater contractility, while peripheral Beta₂ induced Vasodilation causes decreased diastolic pressure.—they balance out.

• At higher doses Beta₁ effect can lead to cardiac irritability and increased risk of arrhythmias and fibrillation

Phenylepherine

• A pure Alpha agonist

• Not typically used due to side effects

• Gives too much vasoconstriction leading to necrosis

• also causes peripheral vasocontriciton leading to increased B.P. and a reflex bradycardia. (HTN + Bradycardia = Bad

Norepinephrine

• Similar to Epi, but the Beta₂ effect is minimal

Levonordephrine

• Similar to Epi but it has a greater Beta₂ effect

• 1/5^th as potent so the dose is 5 times as high as epi