Pharmacokinetics Flashcards
(45 cards)
What makes LA different from other drugs used in medicine and dentistry?
Local anesthetics stop providing clinical effects once they enter the circulation
- We don’t want to inject dental LA into the bloodstream
What is the termination of action of LA?
Redistribution from nerve to CVS
What does it mean to have LA in circulation?
Drug can exert effects on other cells in the body
- Detrimental effects
LA injected into soft tissues = What?
Local effect on blood vessels in area
- VASODILATORY effect
Which is the most potent vasodilator?
Procaine (ester)
Which is the only local anesthetic that produces vasoconstriction?
Cocaine
How does cocaine work?
Prohibits uptake of catecholamines (especially norepinephrine) into tissue binding sites
- Prolonged, intense vasoconstriction
What is the significance of the vasodilatory effect of LA?
Increases rate of absorption into the blood
- Decreases duration and quality of pain control
- -> Anesthetic gets carried away from site of administration
- Increases blood concentration of anesthetic and potential for overdose (toxicity)
Routes of administration for LA
Oral route = poorly absorbed from GI tract (except for cocaine)
Topical route = different rates of absorption on mucous membranes
Parenteral route = injection
–> in dentistry: subcutaneous injection
How is LA distributed?
Once in bloodstream, LA distributed throughout the body to all tissues
- Highly perfused organs obtain higher blood levels of LA
- Skeletal muscle contains greatest percentage of LA (largest mass of tissue in body) even though not as highly perfused.
T or F, LA readily crosses blood-brain barrier but not placenta
False, both
blood level of the LA is determined by what:
- Rate of absorption into CVS
- Rate of distribution from vascular compartment to the tissues
- Healthier people can redistribute the drug more quickly, leading to lower blood levels
- Elimination of drug through metabolic or excretory pathways
LA follows what elimination kinetics?
First order kinetics
- drug is removed in 4 to 5 half-lives
T or F, Metabolism of esters and amides occur in a similar manner
False, they differ
Describe the biotransformation of esters
Hydrolyzed in the blood by plasma cholinesterase
- also called cholinesterase and pseudocholinesterase
What is the metabolic byproduct of esters being hydrolyzed by cholinesterase?
PABA - paraminobenzoic acid
- This triggers allergy
- Excreted in urine
What is Atypical Pseudocholinesterase?
Inherited disorder
- Unable to hydrolyze ester local anesthetics and related drugs
- Prolongation of higher LA blood levels = risk for toxicity
- **Relative contraindication to use of ester local anesthetics
Describe the biotransformation of amides
Metabolized in liver
-
Describe the role of liver function in biotransformation of amides
Liver function and hepatic perfusion influence rate of biotransformation
- Liver disease
- Lower than usual hepatic blood flow (hypotension, congestive heart failure)
- ->both lead to slower rates of biotransformation, increased anesthetic blood levels = risk for toxicity
Name the contraindications for both amides and esters
Amides = significant liver dysfunction or heart failure Esters = Atypical pseudocholinesterase
T or F, rates of biotransformation of amides are relatively similar
True
- lidocaine, mepivacaine, artisane, and bupivacaine
Where does prilocaine undergo metabolism
Primary metabolism in liver, with some also in lung
What is the primary metabolite in prilocaine
Orthotoluidine = primary metabolite
- induces the formation of methemoglobin
- leads to methemoglobinemia
What are the metabolites in Lidocaine?
monoethylglycinexylidide
glycine xylidide
–> may be responsible for producing sedation
