Calcium Channel Blockers

Question 1

Three ways that ion channels are classified

Answer 1

Gating mechanism
Ion Selectivity
Pharmacology

Question 2

Ion channels allow ions to flow…

Answer 2

down their chemical and/or electrical gradient

Question 3

How is membrane potential maintained?

Answer 3

Active transport of Na out and K into the cell

Question 4

Average K inside a cell? outside a cell?

Answer 4

155 mM

4mM

Question 5

Average Na inside a cell? Outside a cell?

Answer 5

12mM

145 mM

Question 6

Average Ca inside a cell? Outside a cell?

Answer 6

100nM

1.5 mM

Question 7

What is Kcsa?

Answer 7

an H+ gated K+ channel from bacteria

Question 8

The MthK Ca gated K channel from bacteria showed that…

Answer 8

The gating processes causes outward bending of iner helices

Question 9

Structure on the inside and outside of the mthK calcium channel?

Answer 9

Outside – Selectivity filter

Inside – Gate

Question 10

In the channel he explained to us (KvAP), what are the roles of S4, S5, S6

Answer 10

S4 is charged, so it moves aroudn in response to potential change in the serum. If negative, it moved inward, pulls S4 down, pushes S5 in, closing the channel. If positiv, S4 goes up, S5 is pulled out, and S6 can now open.

Question 11

The type of Calcium channel we give a shit about?

What is it’s location and function?

Answer 11

The L-type Cav1.2

Cardiac, Smooth muscle/ Ca entry triggers contraction

Question 12

Calcium channels blockers are used to….

Answer 12

Vasodilate
(Decrease BP, relieve angina pectors)
Also, acts as an anti-arrythmetic

Question 13

How does vascular smooth muscle contraction work?

Answer 13

Ca influx via Cav1.2 induces release of Ca in intracellular stores via RYR2. NEEDS extracellular Ca

Question 14

What does released intracellular Ca do in vascular smooth muscle?

Answer 14

Ca –> Calmodulin –> myosin LC kinase –> myosin LC PO4 + Actin = Contraction

Question 15

What happens in cardiac muscle contraction

Answer 15

Ca ions released from SR bind troponin C, displacing tropomyosin, allowing for myosin binding and contraction

Question 16

Skeletal muscle contraction requires what two receptors

Answer 16

Cav1.1, RYR1

These are the two mechanically coupled ones

Question 17

Clinical applications of Calcium Channel Blockers?

Answer 17

Angina Pectoris, Arrythmia, HTN

Question 18

Three chemical classes of Ca Channel Blockers

Answer 18

Dihydropyridines
Phenylalkylamines
Benzothiazepines

Question 19

What did we learn about Dihydropyridines from their enantiomers

Answer 19

The opposite enantiomners have opposite effects on current. This implies that the mechanism involved interference with gating.

Question 20

Which Dihydropyridine enantiomer did what?

Answer 20

+ enantiomer interferes with opening

- enantiomer interferes with closing

Question 21

Seven main classes of Dihydropyridines?

Answer 21

Nifedipine
Isradipine
Felodipine
Amlodipine
Nisoldipine
Nimodipine
Nicardipine

Question 22

Important details for Clevidipine?

Answer 22

Short acting Dihydropyridine. (Half life of about a minute)

Given IV to treat HTN when PO administration isn’t possible

Question 23

Tissue selectivity of Dihydropyridines?

Answer 23

More potent with relaxing smooth muscle, don’t compromise fxn
Not antiarrythmetics

Question 24

Important characteristic of a Dihydropyridine block?

Answer 24

Voltage dependence (the affinity of the drug for the channel is different at different voltages).
NO frequency block, marked TONIC BLOCK

Question 25

What unique about Nimodipine?

Answer 25

Selectivity for cerebral arteries

Used in subarachnoid hemorrhage to prevent neuropathy

Question 26

Which calcium channel blocker avoids reflex tachycardia?

Answer 26

Amlodipine

Question 27

Clinical considerations of using Dihydropyridines?

Answer 27

Reduce Oxygen Demand of the Heart (helps angina)
Don’t depress cardiac fxn (except nifedipine)
May inhibit atherosclerosis

Question 28

Pharmokinetic factors associated with Dihydropyridines?

Answer 28

Highly bound to serum proteins
Extensive first pass metabolism in liver
Amlopidine has slow onset and long duration

Question 29

Classic example of a phenylalkylamine?

Answer 29

Verapamil

Question 30

Clinical considerations of phenylalkylamines?

Answer 30

Vasodilation (but less than DHPs)
Slows nodal conduction, downing HR and contraction)
Blunted Reflex Tachy
FREQUENCY DEPENDENT BLOCK

Question 31

Where does phenylalkylamine bind?

Answer 31

Plug in the drain style

Question 32

Classic example of a benzothiazepine?

Answer 32

Diltiazem

Question 33

benzothiazepine clinical considerations?

Answer 33

Vasodilation, less potent than DHPs
Slows nodal conduction
Initial reflex tachycardia

Question 34

Type of block exhibited by benzothiazepine?

Answer 34

Frequency dependent block
BUT ALSO
Some tonic block

Question 35

Summary. Verapamil, DHPs, Diltiazem.

Compare HR?

Answer 35

Verapamil – Big Drop
DHP – rises a bit (reflex tachy)
Diltiazem – drops a bit (because freq. dep.)

Question 36

Summary. Verapamil, DHPs, Diltiazem.

Compate AV conduction changes.

Answer 36

DHPS don’t mess with it.

Verapamil slows it more than Diltiazem.

Question 37

Summary. Verapamil, DHPs, Diltiazem.

Myocardial contraction.

Answer 37

DHPS don’t mess with it.

Verapamil decreases it more than Diltiazem.

Question 38

Summary. Verapamil, DHPs, Diltiazem.

Arteriol. Vasodil.

Answer 38

DHP – 1st
Verapamil – 2nd
Diltiazem – 3rd

Question 39

Who causes constipation?

Answer 39

Verapamil

Question 40

Who causes facial flushing?

Answer 40

DHPs

Question 41

Who causes tachycardia?

Answer 41

DHPs

Question 42

What kind of nifedipine is contraindicated in MI

Answer 42

Prompt release nifedipine