pharmacology of LA Flashcards
LA vs most meds in circulatory system
• Most meds Circulatory system >Clinical effect
• Local Anesthesia Circulatory system >will cease to provide desired effect
most LA have what vascular effect, most potent one?
used to tx accidental injection of?
undesireable effect of the vascular change?
– Most local anesthetics have vasodilatation effect
– Procaine: most potent vasodilator
• Treat accidental intra-arterial injection of thiopental, do not remove IV, give procaine to dialate
– Clinical undesirable effect of dialtion
• ↑ rate of absorption into blood =potential systemic overdose
what LA is a constrictor?
inhibits?
Vasoconstrictor
– Cocaine: the only local anesthetic with constrictor effect, ensure pt not on coke/crack if lidocaine is used would exacerbate constriction and stroke could occur
• Inhibition of catecholamine re-uptake
• Oral Route absorbtion
– Poorly absorbed except cocaine
distribution of LA in dif tissues?
where is it highest initally?
what eventually has the most?
Highly perfused organ , initially, have higher blood level of anesthetics
• Skeletal muscle has greatest % of anesthetics
– b/c largest tissue mass in the body
how are drugs eliminated
• Elimination of drug through
– Metabolic pathways
– Excretory pathways
elimination half life
Elimination half-life (t ½)
– Time needed for 50% reduction in blood level
• 1st t ½ 50%
• 2nd t ½ 75%
• 3rd t ½ 87.5%
• 4th t ½ 94 %
All LA cross what barriers?
Cross blood-brain barrier, and placenta
• Ester local anesthesia metabolism
enzyme? Product?
allergic rxn to what?
Atypical pseudocholinesterase? leads to potential for?
– Hydrolyzed in plasma by pseudocholinesterase into paraaminobenzoic acid (PABA)
– Allergic reaction is related to PABA
– Atypical pseudocholinesterase (1/2800 persons)
May lead to potential for toxicity
What is the relationship between cirrhosis patient and metabolism of local anesthetics?
decreased liver function = decreased metabolism of LA amides
How do cirrhosis and/or CHF interfere with the amount of your
local anesthesia injection?
will need to decrease injection amount and MRD in these cases
Amide LA metabolism
primary site of biotransformation?
what can influence this biotransformation?
contraindications?
– Primary biotransformation site is Liver
– Liver function/ hepatic perfusion influence biotransformation
• Cirrhosis / CHF or Hypotension
– Relative contraindication for
• ASA IV to V patient with liver dysfunction, heart failure
– Sedative effect of Lidocaine active metabolite
Does CHF/ chriosis increase the availability of this drug or
decrease the availability. MRD implication?
increased availibilty, less metabolism
factorm into MRD calculations to prevent adverse events
LA excretion
organ?
procaine appears as?
cocaine found here?
amides with parent compounds?
• Kidneys are primary excretory organ
• In urine
– Procaine appears as PABA (90%)
– 10% cocaine found
– Amides with parent compound > esters
Systemic Action of local Anesthesia: Central Nervous System
cross the BBB?
CNS depsressor/stimulant?
initial signs toxicity?
lidocaine has these?
higher toxicity effects?
even higher?
• Local anesthesia readily cross blood-brain barrier
• Pharmacological action is CNS depression
• 1) Initial clinical signs/symptoms of CNS toxicity are Excitatory!!
– Numbness of tongue and circumoral region (symptoms)
– Slurred speech, shivering, A/V disturbances, Disorientation, tremor.. (signs)
– Luckily, lidocaine don’t have these s/s but mild sedation or drowsiness
• 2) Higher level of CNS toxicity >Tonic-clonic convulsion (seizure)
• 3) Further increase
– cessation of seizure activity>respiratory depression >reparatory arrest
Systemic Action of local Anesthesia: Cardiovascular System
directly acts on?
depressor/stimulant?
• Direct action on myocardium
– Produce myocardial depression=Therapeutic advantage
– Management of hyper-excitable myocardium: Premature Ventricular Contraction (PVC)
and Ventricular tachycardia
LA effect on peripheral vasculature
• Direct action on peripheral vasculature
– Cocaine and Ropivacaine are vasoconstrictors
– All other local anesthetics are vasodilators
– Local anesthetics cause hypotension
skeletal mm and LA
Skeletal muscle are more sensitive to local irritant properties, site of highest amount of LA
LA effect on Respiratory system
• Respiratory is generally unaffected unless near overdose
Importance of Vasoconstrictors with LA
perfusion?
absorbtion?
risk of toxicity?
duration of action?
hemorrhage?
↓ Perfusion to site of administration
Slow the absorption of L.A. into Cardiovascular system
Minimize the risk of systemic toxicity
↑Duration of action for L.A.
↓Hemorrhage
types of vasoconstricitors
natural catecholamines
synthetic catecholamines
non-catecholamines
natural catecholamines
epi
NE
dopamine
synthetic catecholamines
isoproterenol
levonordefrin
non-catecholamines
amphetamine, ephedrine, methamphetamine
vasoconstrictors modes of action
direct, indirect, and mixed
how do all catecholamines work on andregenic receptors
direct action
Adrengenic receptors actions
a1,a2, b1, b2
wq
dilution of vasoconstricitors
ratio menaing?
Dilution is commonly referred to as ratio
Example, 1 to 1000 [1:1000]
Concentration of 1:1000 means
1gram (1000mg) of solute (drug) in 1000ml solution
So 1000mg / 1000ml = 1.0mg/ml of solutio
EPi plasma levels with intraoral injections, results of this?
CO/ SV?
bp/HR?
Epinephrine plasma level does increase after “usual” intra oral injection despite of aspiration
Increased in cardiac output and stroke volume
Minimum change in blood pressure and heart rate=This would explain why patient felt palpitation after injection
Intravascular injection of 0.015mg can..
HR?
systolic pressure?
Increase heart rate from 25 bpm to 75 bpm
Systolic blood pressure from 20mmHg to 70mmHg
Norepinephrine, why not used?
Lack significant B2 actions
• Intense vasoconstriction
Almost exclusive alpha action
• Dramatic elevation of blood pressure
9X higher than epinephrine
Levonordefrin, why not used?
Most closely resemble norepinephrine
duration of LA with and without epi
Dependent on the time needed for the procedure
Without epi ~10 mins
With epi ~60 mins
rebound effect with epi
rebound vasodilatory effect
NE tissue necrosis
produces cases of tissue necrosis and slough
Disadvantage outweigh its advantages
Contraindications to Vasoconstrictor
bp levels?
thyroid?
cardio dx?
MI?
cerebrovascular event?
angina?
dysrhythmias?
bypass surgery?
general anesthesia?
B-blocker? MAOi? antidepressants?
1) Blood pressure in excess of 200 mmHg systolic or 115 mmHg
2) Uncontrolled hyperthyroidism
3) Severe cardiovascular disease
a) Less than 6 months after myocardial infarction
b) Less than 6 months after cerebrovascular accident
c) Daily episodes of angina pectoris or unstable angina
d) Cardiac dysrhythmias despite appropriate therapy
e) Postcoronary artery bypass surgery (CABG), less than 6 months
4) Undergoing general anesthesia with halogenated agents
5) Patient receiving nonspecific B-blocker, MAOi, Tricyclic antidepressants
Patients in categories 1 to 3a through 3d are classified as ASA 4 risks and NOT normally considered candidates for elective or emergency dental treatment in the officce
what to do with contraindications of vasoconstrictors
aspirations?
speed of administration?
concentrations?
Multiple aspirations
Slow administration
Minimum concentration of both
• Vasoconstrictor
• Local anesthetic
