Pharmacokinetics Flashcards
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
What organs excrete LA and metabolites
Kidneys
- percentage varies by drug
Between amides and esters, which appears in greater percentage ?
Amides are present in urine as a parent compound in greater percentage than esters (but still small amount)
- esters apear in very small concentrations in urine (almost completely metabolized in plasma)
What disease is a relative contraindication to LA?
Renal disease
Systemic actions of local anesthetics are related to what?
Blood/plasma level
Pharmacological effect of LA
CNS depression.
- Therapeutic doses –> no CNS effects
- Overdose/toxicity –> generalized tonic-clonic convulsions (INHIBIT inhibition = SEIZURE)
LA can also be used to treat what?
Epilepsy
- Some LA have anticonvulsant properties
- Blood level is lower than that which produces seizures
Describe the CVS effects of LA
direct actions on myocardium and peripheral vasculature
- Pharmacological action = myocardial depression
- -> decrease electrical excitability of myocardium
- -> decrease conduction rate (negative chronotropic effect)
- -> decrease force of contraction (negative inotropic effect)
Lidocaine is used how in CVS
As an anti-arrhythmic medication
Describe systemic effects of LA being a vasodilator
- increases blood flow to/away from site of deposition
- increases rate of LA absorption
- Decreases depth and duration of anesthesia
- Increases bleeding
- Increases LA levels in circulation
T or F, LA effect on blood pressure = hypertension
False, hypotension –> they are vasodilators
Describe CVS effects at Non-overdose levels of LA
Slight increase or no change in BP due to increased CO and HR; vasoconstriction of some vascular beds
Describe CVS effects when approaching overdose levels of LA, but still below
Mild hypotension (direct relaxant action on vascular smooth muscle)
Describe CVS effects at overdose levels of LA
PROFOUND HYPOTENSION
- caused by decreased myocardial contractility, decreased CO and decreased peripheral resistance
Describe CVS effects at lethal levels of LA
CARDIOVASCULAR COLLAPSE
- Massive peripheral vasodilation, decreased myocardial contractility and decreased HR (sinus bradycardia)
Bupivacaine may produce what at overdose levels
Fatal ventricular fibrillation
What tissue is more sensitive to irritating properties of LA than other tissues?
Skeletal muscle
Respiratory System effects at non-overdose levels
Direct relaxant action on bronchial smooth muscle
Respiratory system effects at overdose levels
Respiratory arrest due to generalized CNS depression
T or F, Therapeutic dosing produces effects similar to non-overdose levels
False, does not produce any significant effects on respiratory function
Describe how LA can help cause neuromuscular blockage
Additive effects when LA is used with other depolarizing and non-depolarizing muscle relaxants (not typical in a dental patient)
When combined with a certain genetic variant, LA can increase an individual’s susceptibility to this disorder
Malignant hyperthermia
