Test 2: lecture 19 voltage gates ion channel drugs

Question 1

positive in causes

Answer 1

depolarization
excitatory

Question 2

positive out of cell causes

Answer 2

hyperpolarization
inhibitory

K out or Cl in

Question 3

N-type voltage dependent Ca channels are found where?

Answer 3

on neurons

important for release of neurotransmitters

Question 4

L-type voltage dependent Ca channels are found where?

Answer 4

on cardiac cells

important for action potential in cardiac cells

Question 5

ion current is dependent on what two things

Answer 5

amount of channels open

electrochemical potential (what is the difference between the inside and outside of cell of a certain ion)

Question 6

volatge gated ion channels close —

Answer 6

spontaneously - becomes inactivated

will stay closed until next repolarization

ion current is transient

Question 7

what is modulated receptor hypothesis of voltage gated ion channels

Answer 7

channel can be in one of three states depending on membrane potential

Question 8

how does voltage gated ion channel change form inactivated to closed state

Answer 8

cell must go through repolarization

Question 9

what is use dependence of VGIC

Answer 9

effect of drug depends on the channel’s activity or state

drug works better if channels are open and drug can get into cell and bind to intracellular bind site

Question 10

what is state dependence of drugs for VGIC

Answer 10

certain drugs have affinity for ion channels in different states (open, resting, inactive)

Question 11

what does this show

Answer 11

use and state dependence of a drug, that the more the channels opens the more drug gets inside and causes a block/decrease of the sodium current

Question 12

how can a drug change the gating behavior

Answer 12

can make it easier or harder for impulse to cause channel to open

Question 13

how do local anesthetics work

Answer 13

block voltage gated Na channels on the nocicpetors- specialized neurons that respond to pain stimuli

blocks pain stimuli signal

Question 14

— are specialized neurons that respond to pain stimuli

Answer 14

nociceptors

you can block pain impulse by blocking the VG Na channels with local anesthetics

Question 15

local anesthetics block initiation and propagation of AP by blocking —

Answer 15

VG Na channels

attach on inside of channel pore → needs to get into cell to work

Question 16

local anesthetics bind to what state of VG Na channels?

Answer 16

will bind to all three states but prefers intacte state

results in very slow change from inactive to closed during repolarization= prologoned refractory period

Question 17

how does pH effect how lidocaine gets into cell

Answer 17

high pH/ basic extracellular will make ↑ unprotonated lidiocaine, which can penetrate membrane and get into cell

the inside of the cell is more acidic
low pH/acidic= ↑ protonated lidocaine which will bind to channel

extracellular pH is more acidic in tissues under infection- this will decrease permability of lidocaine

Question 18

infection will do what to pH of an area?
how will this effect lidocaine?

Answer 18

infection causes more acidic environment

this leads to more protonated lidocaine in the extracellular space, protonated lidocaine can NOT get into cell to work

infection will slow/stop permeability, will need to use more drug to be effective

Question 19

local anesthetics (lidocaine) binds to what state of VG Na channels on nociceptors

Answer 19

all three but binds more strongly to inactive and/or open then closed state

Question 20

class I antiarrhthmic drugs block what channels

Answer 20

voltage gated Na channels

Question 21

many antiarrhythmic drugs will show a use dependence for —state of VG NA channels

Answer 21

open and/or inactive

will block high frequency excitation= tachycardiac or premature beats

also blocks depolarized/injured tissue preferentially, these channels are in the inactive state

Question 22

Class I antiarrhythmic drugs are classified by how quickly they — the sodium channel

Answer 22

dissociate/unbind

if drug unbinds quickly: have stronger activity during high rates of depolarization (tachycardia)

if drug unbinds slowly: there is an accumulation of block

Question 23

lidocaine will unbind — from the VG Na channels in the heart

Answer 23

quickly- will have stronger activity during high rates of depolarization (tachycardias)

Question 24

quinidine will undind — flow VG Na channels in the heart

Answer 24

slowly leads to accumulation of block

Question 25

some anticonvulsants such as — work as Na channel blockers. Block is strongest when nerves fire at high frequency (during convulsions/seizures)

Answer 25

dilantin (phenytoin)

Question 26

how does grayanotoxins work

Answer 26

will stabilize open conformation of VG Na channels

too much Na into cell

can be found in rhododendrons and azaleas, can be in unpasteurized honey of bees that feed off these plants

Question 27

indirect method of opening VG Ca channels

Answer 27

will act on β adrenergic receptors(G protein receptor) in cardiac muscle and cause down stream activation that leads to increase in cAMP kinase, ⍺ subunit will also bind to calcium channel

this will increase the probability of Ca channel opening at any given volatage

inotopic β-adrenergic effect

Question 28

nifedipine(dihydropyridine) binds to the — state of the VG Ca channel

Answer 28

resting

Question 29

verapamil ( phenylalkylamine) binds to the — state of the VG Ca channel

Answer 29

open

Question 30

diltiazem(benzothiazepine) binds to the — state of the VG Ca channel

Answer 30

inactivated

Question 31

antagonist VG Ca channel drugs such as diltiazem will do what ?

Answer 31

will lower the amount of calcium into a cell

Cardiovascular implications
* Decreased sinoatrial (SA) node pacemaker rate
* Decreased atrioventricular (AV) node conduction velocity
* Reduced cardiac muscle contractility
* Vascular smooth muscle relaxation

Nifedipine: binds to the RESTING state
Verapamil: binds to the OPEN state
Diltiazem: binds to the INACTIVATED state

Question 32

Nifedipine, Verapamil, Diltiazem act as — on — channel drugs

Answer 32

antagonists
L-type Ca channels in the heart

Calcium channel blocker drugs: will cause decrease of Ca into a cell, which leads to slower NR, reduced cardiac output/contraction, will cause relaxation/dilation of vascular smooth muscle

used to stop supraventricular tachycardias

Question 33

Calcium channel blockers will do what to blood pressure

Answer 33

will cause arteriole dilation → decrease in BP

Nifedipine is a more potent vasodilator, has stronger affinity for Ca channels on smooth muscle then L type Ca channel on the heart like verapamil and diltiazem

Question 34

unwanted side effects of Ca channel blockers

Answer 34

other type of smooth muscle can relax
headaches and flushing
constipation
AV block and negative inotropic effects

Question 35

what does cantharidin do?

Answer 35

toxin in blister beetles

will cause Calcium channels to open leading to increased contractions/activation of cells

horses very susceptible- can die within 24-74 hrs