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
List signs & symptoms of CNS overdose toxicity:
- Apprehension, excitement, talkativeness
- Bilateral numbness of tongue
- Disorientation
- Drowsiness (more common with Lidocaine)
- Elevated BP, pulse, breathing
- Headache
- Lightheadedness
- Loss of consciousness
- Muscle twitching/tremors in muscles of face, extremities
- Perioral numbness
- Shivering, chilled feeling of skin
- Slurred speech
- Visual/auditory disturbances
- Warm, flushed feeling of skin
List CVS effects of LA drug overdose
- mild depression of myocardium => decrease of electrical excitability, conduction rate, force of contraction
- peripheral vasodilation (except cocaine)
- relaxation of smooth muscle in vessels => slight or no change in BP, hypotension w/ increasing dose, relaxant action on bronchial smooth muscle
!! during early OD toxicity, HR may increase and hypertension may occur
How does the vascularity of an injection site affect absorption & distribution of LA drugs?
Faster absorption & distribution away from the site of deposition => shortened local action of drugs
What are the 2 MAIN PATHWAYS of BIOTRANSFORMATION of LA drugs.
In the LIVER and in the BLOOD
What is meant by the ELIMINATION HALF-LIFE of a drug?
Rate at which the drug is removed from the systemic circulation by the kidneys.
= the time necessary to metabolize and excrete 50% of a drug
Given the half-life of lidocaine as 1.6 hours, what is the approximate total number of hours to effectively eliminate lidocaine from the body?
Essentially 6 half-lives or more than 9 hours.
- Elimination half-life refers to the time it takes for…
a. a drug to be half-metabolized
b. half of a drug to be out of the system
c. half of a drug to be out of the circulation
d. a drug to be out of half of the circulation
C -Half-life refers to the time it takes for 50% of a drug to be removed from the systemic circulation.
- Ester local anesthetics ae metabolized in which one of the following pathways?
a. In the liver
b. In the blood
c. In the kidneys
d. In the brain
b. Esters are metabolized in the blood via plasma cholinesterase
- CNS toxicity occurs because of:
a. The expected response of neurons int the CNS to the drug dose.
b. Frank neural tissue damage due to the excessive dose
c. Compromised vascular supply in the CNS due to vasoconstrictor doses.
d. None of the above.
A - CNS toxicity is due to conduction blockade of vital functions within the CNS due to the normal function of nerve cells in response to local anesthetic drugs.
- CVS toxicity occurs because of:
a. Compromised vascular supply.
b. Frank tissue damage.
c. Decrease myocardial contractility , vasodilation and hypotension.
d. Decrease myocardial contractility, vasoconstriction, and hypertension.
Check answer - sounds like C is correct
D - decreased myocardial contractility and hypotension due to vasodilation. If they occur, they will further worsen and already developing CNS depression.
! In early overdose, some initial heart rate elevation and hypertension may occur
- Which portion of the anesthetic molecule is responsible for binding to the receptor site inside the nerve membrane, thereby preventing depolarization?
a. Calcium ion
b. Anesthetic free base
c. Anesthetic anion
d. Anesthetic cation
D - only the cation can bind to specific receptor site inside the nerve membrane thereby preventing depolarization
- Which part of a local anesthetic molecule determines the classification of the drug as an ester or amide?
a. Lipophilic portion
b. Hydrophilic portion
c. Intermediate chain
d. Caine linkage
C - LA drugs are classified according to their intermediate chains as esters or amides.
!!! Except for its largely non-hepatic, ester like metabolic pathways and its therefore shorter elimination half-life, articaine cannot be mistaken for an ester.
- Which of the following is not a systemic reaction to an overdose of a local anesthetic agent?
a. CNS stimulation
b. Depression of myocardium
C. Vasodilation of peripheral blood vessels
d. Respiratory arrest
A - An overdose of LA drugs will result in depression of the CNS.
(The initial excitatory phase is actually due to depression of inhibitory actions OF the CNS.)
Ionized salt form (RNH+)
pKa value
pH
solubility
aids in …..
RNH+
- HIGH pKA
- exists in low pH
- is water soluble
- aids in diffusion through tissue
- inflammed tissue = acidic pH, ionized form predominates, cannot penetrate nerve membrane
Free/neutral base form (RN)
pKa value
pH
solubility
aids in …..
- low pKA value
- exists environment w/ neutral or high pH
- lipid soluble
- aids LA in penetrating nerve membrane
- most body tissues have a neutral pH
- Marcaine is the longest acting LA (b/c it has lots of the RN form, i.e. low pKa value)
Why do some LAs “burn”?
LA w/ epinephrine have a low pH, making it “burn” on injection. The also have a slower onset b/c although they diffuse through the tissue well, they can’t penetrate the membrane. Addition of Na-bicarbonate or CO2 to increase pH make injection more comfortable and speeds up onset.
Normal vs Inflamed tissue pH
- 7.4 = Normal tissue pH
- 5-6 = Inflamed tissue pH
- LA without epi pH:
- LA with epi pH:
- 5.5 = LA without epi
- 3.3 = LA with epi
