Frequently asked questions (NOT)

1) pKa and pH as applied to local anesthetics

2) The mechansim by which aspirin can induce bronchospasm

• Does not stem from antigen-antibody reaction
• Stems from pharmacologic action of the drug, namely, specific inhibition in the respiratory tract of COX
• The action decreases the synthesis of PGE-2 at the level of the bronchi; this can produce passive bronchoconstriiction
• Furthermore, there may be a shift in the prodcution of leukotrienes, some of which are bronchoconstrictors
• It occurs in 8-20 percent of adult asthmatics

3) Phase I and Phase II blockade mechanism of succinylcholine.

• Phase I
  • Succinylcholine binds to the nicotinic receptor, opens the sodium channels, and causes membrane depolarization, which results in transient fasciculations
  • Flaccid paralysis will follow in a few minutes, because succinylcholine is resistant to acetylcholinesterase and will will cause prolonged depolarization of the end-plate membrane
• Phase II
  • Eventually the membrane will at least partially repolarize.
  • However, the receptor is now desensitized to acetylcholine, thus preventing the formation of further action potentials
  • In other words, succinylcholine is acting in a manner similar to tubocurarine

4) Nalorphine is a mixed agonist/antagonist. What receptors does it work on and what is its activity.

• Used to reverse morphine poisoning in early 1950's (i.e., competitive mu antagonist)
• Higher doses are analgesic in postoperative patients (kappa agonist effect) but the drug is not used clinically as an analgesic because of side effects like anxiety and dysphoria (kappa agonist effects)
• Miixed agonist/antagonist

5) What is specific receptor theory? What is the difference between serum Che and Ache?

• Specific receptor theory explains the mechanism of action of almost all local anesthetics. Local anesthetic agents block nerve conduction by inhibiting the voltage-gated sodium channels of the neuronal membrane. On the other hand, the membrane expansion theory explains the action of benzocaine, a local anesthetic that doesn't have ann amino acid terminus and, therefore, cannot be protonated (i.e., cannot bind electrostatically to the negatively charged group in the sodium channel.
• Acetylcholinesterase (ACHE) is the form of cholinesterase found on pre- and postsynaptic membranes adjacent to synapses. It terminates the action of the neurotransmitter acetylcholne. Sometimes, it is called true cholinesterase. ACHE is also found in other tisues (e.g., red blood cells). Succinylcholine resists degradation by ACHE. Another cholinesterase with a lower specificity for acetylcholine, butyrlcholinesterase (pseudocholinesterase, plasma cholinesterse), is found in blood plasma, liver, glia, and many other tissues. It is this form of cholinesterase that hyrolyzes many drugs including succinylcholine.