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
