Nervous System Pharm Flashcards
1
Q
Ionic Permeability of Nerve Cells
A
- Nerve cell membrane = lipid bilayer so impermeable to ions
- Overcome by ion channels (ion selective pores in membrane)
- More Na++ / Cl- outside cell and more K+ in cell
- Maintained via Na/K pump - 3 Na+ out and 2 K+ in using ATP hydrolysis
- Also ion channels that are open at rest are mainly permeable to K+ (passive diffusion)
2
Q
Action Potential (3 steps)
A
- 1- Depolarization: Excitatory input to dendrites —> voltage-gated Na+ channels open (rapid kinetics)
- Moving toward Na+ equilibrium potential
- 2- Repolarization: soon after, slower voltage-gated K+ channels open and Na+ channels become inactive and close
- Moving toward K+ equilibrium potential
- 3- After Hyperpolarization: undershoot below resting membrane potential b/c K+ channels still open
3
Q
How is resting membrane potential maintained?
A
- Passive diffusion of ions through channels down conc gradient - eventually opposed by electrostatic force as charge builds up
- Equilibrium Potential = voltage when net flow of ion is 0 b/c passive diffusion countered by electrostatic force
- Resting Membrane Potential = weighted combo of all ions in cell
- Mainly based on the open K+ channels at rest (passive diffusion)
4
Q
Refractory Period
A
- Na+ channels spont deactivate when membrane is cont depolarized (by loop in intracellular domain that plugs the channel)
- Na+ channels take tome to recover from inactivation SO…period of time when membrane is not able to generate another AP
- Limits frequency at which APs can be generated AND prevents APs from bouncing back at nerve terminal
5
Q
Multiple Sclerosis
A
- Demyelinating disease
- Can effect motor, somatosensation, vision, speech, etc
- Might be autoimmune? NO cure but given immune suppressants
6
Q
EEG and EMG
A
- even though individual APs are always the same magnitude, you can measure the summation/ensemble of APs to diagnose pathology
- EEG - meas electrodes in head (seizures)
- EMG - meas how many muscle fibers are firing simultaneously via electrode in muscle
- Normal - consistent magnitude
- Abnormal- waxing/waning
7
Q
How do action potentials propagate?
A
- Action potential opens more Na+ channels as it moves down axon
- B/c myelin inc resistance (inc length constant) and dec capacitance (dec time constant- faster)
- Node of Ranvier have local pockets of more Na+ channels to maintain AP
- “Saltatory conduction”
8
Q
Different Local Anesthetic Structures
A
- Aniline or benzoic acid linked to tertiary amine via ester or amide bond
- Esters hydrolyzed in plasma by esterase so short-lived
- Procaine - ester linkage (less stable and shorter action) Novocaine®- Amide bond more stable and longer lasting
- Lidocaine Xylocaine®
- Amide bond more stable and longer lasting
9
Q
Impact of pH on local anesthetics
A
- Dec pH (more acidic environment) —> less conc of neutral form/more protonated form—> less effective LA
- How is pH lowered?
- Constricted infection
- If use acidic vehicle to deliver LA to low perfused area like spinal cord
10
Q
General Mechanism of Local Anesthetics
A
Na Channel Gating
- Stabilize inactive form of ion channels…inability to produce action potential
- DO NOT BLOCK CHANNEL ITSELF
- Bind to the wall of the channel pore —> conformational change
11
Q
Use-dependent v use-independent action
A
- The charged form gives use-dependent inhibition while the neutral form gives use-independent inhibition b/c must get INTO cell to work/bind
- Use-dependent = the more channels are open; the more effective the drug inhibition is because must enter via channel to bind
- Use-independent= channel does not have to be open b/c drug goes through membrane (permeable) to bind
12
Q
Proximal v Distal Nerve Block
A
- Drug permeates nerve from outside so affects mantle first
- Proximal -early block
- Distal - delayed- block
13
Q
Passive Propagation
A
- If smaller diameter the diffusion of Na+ cannot span the width of the bolus of drug; if larger diameter the Na+ can diffuse and bridge the gap of the bolus
- Dep on space constant - This Na+ diffusion to create downstream AP is “passive propagation”
14
Q
Differential Blockade
A
- specificity of blockage depends on which axons are blocked first
- Small diameter, shorter length (2-3 nodes) and mantle (periphery) blocked before core
- Order: Pain, cold, warmth, touch, deep pressure, motor
15
Q
Side Effects of Local Anesthetics
A
- Safety- if end up in bloodstream they will have effects all over body b/c Na+ channels all over body
- Numb tongue, light-headed, visual/auditory disturbances, muscular twitching, unconscious —> seizures (no GABA inhibition)—> coma —> resp arrest —> CVS depression
