What is state dependence

1

• What is state dependence?
• Binding of a drug to a preferred state is
  called state dependence
  
• What state of sodium channels do anesthetics
  prefer?
  
• Open or innactive sodium channels
• Why is that anesthetics prefer rapidily firing
  neurons?
  
• Because in these neurons Na channels open more
  frequently than in slow firing neurons.

2

• Which form of the drug has the greatest affinity
  for the receptor?
  
• The cationic form
• Where are the receptors located?
• Inside the cell, intracellularly
• Which type of drug would be able to bind to the
  receptor without the need of a Na channel?
  
• More lipophilic drugs can access receptors inside
  the cell more easily without the need to use Na
  channels

3

• What are the two categories of local
  anesthetics?
  
• Esters of benzoic acid and amides
• Which type is longer acting?
• Amides
• Why?
• Because esters are metabolized by non-specific
  plasma estereases, which are present everywhere
  in the peripheral circulation, whereas amides are
  metabolized by the livers microsomal enzymes

4

• Why can we say that these two types or
  anesthetics are amphipathic?
  
• Because they have both a hydrophilic and a
  hydrophobic portion in the molecule.
  
• What is the usual hydrophilic portion, and why is
  it important?
  
• It is either a secondary or a tertiary amine.
  These groups are capable to lose a proton to form
  a cation and therefore bind to receptor.
  
• What is the usual hydrophobic region?
• A substituted aromatic ring

5

• Name the ester local anesthetics
• Procaine, chloroprocaine, cocaine, tetracaine and
  proparacaine.
  
• What is procaine used for?
• Infiltration anesthesia in minor surgical and
  dental procedures
  
• Diagnostic nerve blocks by anesthetizing motor
  nerves and increasing muscle relaxation
  
• Diagnostic spinal anesthesia

6

• What two ways are used to control the spread of
  the anesthetic within the subarachnoid space in a
  spinal anesthesia?
  
• Adjusting specific gravity of the solution
• Adjusting the position of the patient.
• What do you call a solution to which 10 glucose
  was added in order to increase its specific
  gravity?
  
• Hyperbaric
• How do you make a solution hypobaric?
• By adding sterile water.

7

• How is chloroprocaine altered from procaine?
• Is a halogenated procaine
• How does halogenation change the drug?
• It decreases the onset time and duration,
  therefore decreases toxicity.
  
• What is chloroprocaine used for?
• Infiltration, peripheral and epidural blocks
• What is the most possible explanation for back
  pain suffered by patients after epidural block?
  
• Tetany due to calcium chelation by preservative
  EDTA

8

• What is the mechanism of action of cocaine?
• It blocks NE and DA uptake
• What type of effect would you expect to see in
  blood vessels?
  
• Vasoconstriction
• Why is vasoconstriction and advantage?
• Decreases bleeding time
• Increases duration of drug (cannot spread
  easily)
  
• Decreases systemic side effects

9

• What disadvantage can you anticipate with the use
  of cocaine?
  
• Vasoconstriction can slow wound healing and cause
  tissue hypoxia and necrosis.
  
• How can you get this vasoconstrictor effect with
  other anesthetics?
  
• By adding epinephrine or phenylephrine (most
  used). Phenylephrine is an alpha 1 agonist and
  vasoconstriction is expected.

10

• What are systemic effects of cocaine?
• Euphoria, tremors and convulsions, respiratory
  depression, tachycardia and vasoconstriction,
  increase in HR and BP, hyperpyrexia.
  
• What is the mechanism associated with euphoria
  produced by cocaine?
  
• Blockage of DA uptake.
• What is the mechanism associated with respiratory
  depression?
  
• Inhibition of sodium channels.

11

• What is the mechanism associated with
  tachycardia?
  
• Block of NE uptake. NE increases
  vasoconstriction (mostly alpha agonist) which
  increases heart rate and blood pressure.
  
• How does vasoconstriction contribute to
  hyperpyrexia?
  
• Heat generated during increased cellular
  metabolism, cannot be dissipated fast enough due
  to vasoconstriction.
  

12

• What is unique about Tetracaine?
• That is causes vasodilation
• What is the major side effect of this drug?
• Cardiac toxicity
• Why?
• Because inhibition of sodium channels slows the
  conduction through AV node and contractility is
  depressed.
  
• Why is vasodilation a concern?
• Because increases systemic absorption and this
  increases systemic side effects
  

13

• What is special about proparacaine?
• It has an ester and an ether link and it does NOT
  exhibit cross-sensitivity to other esters.
  
• What is its most important use?
• Ophthalmic, that is why its trade name is
  ophthaine.
  
• Name the amide local anesthetics
• Bupivacaine, Etidocaine, Levobupivacaine,
  Lidocaine, Prilocaine, Ropivacaine
  
• (bell pri(me)ro)

14

• What is the treatment for methahemoglobinemia
  caused by prilocaine?
  
• Methylene blue
• What are the uses of levobupivacaine?
• Local and regional surgical anesthesia and
  postoperatory pain management
  
• Which drug is approved to use during labor?
• Ropivacaine

15

• True or false. Dubucaine is available in IV,
  oral and cream forms.
  
• Answer False, only available as cream or
  ointment
  
• Which two drugs have 2 ether linkages?
• Dyclonine and pramoxine
• What drug is identical to procaine but without
  the amino group?
  
• Benzocaine.
• What is the advantage of this?
• It is not water soluble without the NH2 group

16

• What is one of the uses of absolute ethanol
  injection?
  
• Trigeminal neuralgia or cancer.