Chapter 04 - Pharmacology Basics Flashcards
Objective of using LA in dental tx?
Produce anesthesia for a specific area, and sometimes to reduce localized bleeding.
Primary benefit of LA?
Pain sensation suppression without significant CNS depression, allowing most dental tx to be performed under LA without exposing pt to risks of general anesthesia.
Legal & ethical requirements for all health professionals administering LA drugs?
- Sound knowledge of LA drugs & techniques crucial to safe/successful anesthesia
- Understanding of influences of medically compromised function, susceptibility to adverse rxns, awareness of pt’s medications
- Legal & ethical responsibility for these considerations & consequences
Two primary routes of delivery for LA drugs
Topical and submucosal injection
Why is topical more effective on mucosa than on skin?
Because of the ease of penetration through thin mucosal barriers to reach underlying nerves.
Why are injections of LA more effective than topical routes of administration?
Due to the direct placement of drugs in close proximity to nerves
List ideal properties of LA drugs used in dentistry:
- high biocompatibility with no systemic effects
- rapid onset
- no toxicity to tissue (incl. nerve tissue)
- therapeutic duration & potency w/o inducing hypersensitivity or unconciousness
- sterilizeable
- readily biotransformed
- excellent topical effects at low concentrations
List the 5 injectable LA drugs currently available in cartidges
articaine, bupivacaine, lidocaine, mepivacaine, and prilocaine
Name the intermediate chains used to classify injectable anesthetic drugs used in dentistry.
Amides or esters
What is a relatively easy way to distinguish b/w the 2 formulas of intermediate chains in LA drugs?
Amide intermediate chain contains nitrogen.
Ester chain does not.
2 important functions of the amide & ester intermediate chains:
- provide proper spacing b/w the aromatic (lipophilic) end & the secondary or tertiary amine (hydrophilic) end => allows LAD to be effective in the tissues
- provide for major pathways of biotransformation
Define PHARMACODYNAMICS
refers to the actions of a drug on the body
Define PHARMACOKINETICS
refers to the manner in which the body manages the drug, specifically: Absorption, Distribution, Metabolism (biotransformation), elimination
Major difference b/w LADs and the majority of other drugs?
Systemic effects are NOT desired with with local anesthetic drugs
What are the 2 chemical forms of LA molecules in solution?
Neutral base and cation
Explain the effect of LA drugs on nerve membranes based on the SPECIFIC PROTEIN RECPTOR THEORY:
LA molecules bind to structural protein/specific receptor sites = agonist drug effect => impulse propagation is prevented b/c sodium ions cannot pass through channels closed/ blocked by cationic drug molecules (~ 90% of anesth effect)
Explain the effect of LA drugs on nerve membranes based on MEMBRANE EXPANSION THEORY
- modification of the membrane structure in presence of LADs. The diffusion of LA neutral base molecules to the lipophilic regions of the NM => narrowing of the ion channel diameter => limited permeability to Na+ => further blocking the transmission of impulses (~ 10% of anesth. effect)
Which ionic form of a LA molecule diffuses through the nerve membrane?
The neutral base form (RN)
Which ionic form of a LA molecule binds to the receptor sites in the sodium channels of the nerve membrane?
The cation form (RNH+)
Effect of tissue inflammation on LA drugs?
Lowered pH inhibits production of neutral base (RN) molecules => may result in insufficient numbers of RN penetrating the NM => profound anesth. may be difficult to obtain or sustain.
In addition to the increase in hydrogen ions, localized edema & increased circulation can remove drugs from delivery site, further complicating or preventing profound anesthesia
Define pKa
= “dissociation constant”
= equilibrium concentration of cationic (RN+) and neutral base (RN) molecules
* if pKa = pH, then equal distribution of RN+ and RN
What is the clinical application of pKa in LA drugs?
- narow pKa ranges (~ 7.7 to 8.1) are common & include all 5 amide LADs avail for dental
- these values provide clinically useful onsets of LA
- generally, the higher the pKa, the longer the onset
Explain clinical concerns related to the VASOACTIVITY of LA drugs:
- all dental LADs are PERIPHERAL VASODILATORS
- vasodilation = undesirable b/c it limits LAD duration & efficacy while increasing toxicity (rapid systemic uptake -> rapid overdose)
- reason for adding vasoconstrictors
What factors can precipitate toxic OD from LAD?
- excessive dose
- intravascular administration
- rapid delivery
- slower than normal biotransformation or elimination
