Calcium Channel Blockers

Question 1

What is the main determinant of the direction of ion flow through an ion channel?
(Concentration Gradient or Electrical Gradient)

Answer 1

Electrical gradient

Question 2

Which ion is higher INSIDE the cell: K or Na?

Answer 2

K is higher inside the cell

Question 3

Why is it important to keep Ca low inside the cell?

Answer 3

Ca functions in muscle contraction

-So it is important to keep Ca tightly regulated to prevent continuous muscle contraction

Question 4

True or False: Negatively charged ions are able to cross the membrane

Answer 4

FALSE
-negatively charged ions cannot cross the membrane
-basis for potassium and chloride

(potassium and chloride typically balance out charges across the membrane, however, when K moves, Chloride cannot follow and the charge is not balanced)

Question 5

What is the function of sodium channels?

Answer 5

Run opposite potassium channels

-Sodium increase and movement through channels is used to cause depolarization and action potentials

Question 6

What is Kcsa?

Answer 6

A H+ gated K+ channel from bacteria

Question 7

What is MthK?

Answer 7

A calcium gated K channel from bactria

Question 8

What is the function of a voltage sensor in a K channel?

Answer 8

The voltage sensor has positively charged amino acids that allow for responses to voltage changes across the membrane

-The voltage sensor moving pulls the helix away to open the channel

Question 9

Which calcium channel blocker is important for cardiac smooth muscle contraction?

Answer 9

Cav 1.2

Question 10

What calcium channel blocker is important in the skeletal muscle?

Answer 10

Cav 1.1

Question 11

When calcium channel blockers such as Cav 1.1 block channels in the vascular smooth muscle, what does this cause?

Answer 11

Vasodilation

-decrease in blood pressure
-relief of angina pectoris

Question 12

When calcium blockers such as Cav 1.2 block channels in the cardiac muscle, what is the result?

Answer 12

Antiarrhythmic

Question 13

What is the function of the ryanodine receptor 2 (RYR2)?

Answer 13

Membrane depolarization opens calcium channels which allows calcium into the cell where it binds RYR2

-RYR2 opens after binding and functions as a calcium channel which allows calcium to be released out of its intracellular stores in the SR

-The release of calcium from the SR triggers contraction

Question 14

What is the result of PKA phosphorylation of Cav 1.2?

Answer 14

Increases calcium influx

(increasing contraction force and AV node action potential conduction rate)

Question 15

Extracellular Ca is responsible for contraction of what muscle?

Answer 15

Vascular Smooth Muscle

Question 16

What is the mechanism by which calcium released from the SE is able to produce contraction?

Answer 16

Ca bind to troponin C

This causes a displacement of tropomyosin

This allows myosin to bind to actin

Resulting in contraction

Question 17

Is extracellular Ca required for skeletal muscle contraction?

Answer 17

NO

Question 18

What are the indications for calcium channel blockers?

Answer 18

Angina Pectoris

Arrhythmia

Hypertension

Question 19

What are the 3 classes of calcium channel blockers?

Answer 19

Dihydropyridines

Phenylalkylamines

Benzothiazepines

Question 20

Which dihydropyridine blocker does not have a chiral center?

Answer 20

Nifedipine

Question 21

Which calcium diydropyridine has the highest affinity for the calcium channel?

Answer 21

Isradipine

Question 22

Which dihydropyridine has a slow onset of action?

Answer 22

Amlodipine

*is a good thing, blocking channels too quickly can throw off the heart

Question 23

Which calcium dihydropyridine is hydrophobic and used in hemorrhage?

Answer 23

Nimodipine

Question 24

Which calcium dihydropyridine is given IV to treat hypertension when PO drugs cannot be used?

Answer 24

Clevidipine

Question 25

How do the positive and negative enantiomers of dihydropyridines effect gating?

Answer 25

+ enantiomer interferes with gate opening, blocks current - enantiomer interferes with gate closing, potentiates

Question 26

What tissue are dihydropyridines more selective for?

Answer 26

Smooth muscle

Question 27

Due to the selectivity of dihydropyridines, how does this contribute to their effects?

Answer 27

-Do not compromise cardiac function -Not antiarrhythmics

Question 28

At what membrane potential are dihydropyridines more potent?

Answer 28

Positive values

Question 29

Where do dihydropyridines bind on the calcium channel?

Answer 29

On the outside, between helices that are needed for the channel to open *Bind closed channels and prevent opening (tonic block)

Question 30

What are some special considerations with Nimodipine use?

Answer 30

-Selective for cerebral arteries -Used in sub-arachnoid hemorrhage to prevent neuropathy

Question 31

Which dihydropyridine depresses cardiac function?

Answer 31

Nifedipine

Question 32

What are some important pharmacological factors of dihydropyridines?

Answer 32

-Highly bound to serum proteins -Undergo first pass metabolism in the liver

Question 33

What warnings are associated with Nifedipine rapid release?

Answer 33

DO NOT USE -increased risk of myocardial infarction -Rapid BP decrease can cause tachycardia

Question 34

What is the only drug in the phenylalkylamine class?

Answer 34

Verapamil

Question 35

Is Verapamil more or less potent than dihydropyridines?

Answer 35

Less potent

Question 36

What are some important effects of Verapamil?

Answer 36

-Slows conduction through the SA and AV nodes (sometimes good, sometimes bad) Blunts reflex tachycardia Exhibits frequency dependent block

Question 37

Where does verapamil bind on the calcium channel?

Answer 37

In the pore *blocks Ca influx *Channel must be open for drug to bind (frequency dependent block)

Question 38

What drug is the only benzothiazepine?

Answer 38

Diltiazem

Question 39

Is diltiazem more or less potent than dihydropyridines?

Answer 39

Less potent

Question 40

How does diltiazem work?

Answer 40

It directly inhibits the heart (less than verapamil, but more than DHPs)

Question 41

What kind of block does diltiazem use?

Answer 41

Frequency dependent block with some tonic block

Question 42

Where does diltiazem bind on the calcium channel?

Answer 42

Binds on the side but some of it projects into the pore (shows both tonic and frequency dependent block)

Question 43

What are the significant side effects of dihydropyridines?

Answer 43

Ankle edema Facial flushing (vasodilator) Tachycardia

Question 44

What are the significant side effects of diltiazem?

Answer 44

Ankle edema

Question 45

What are the significant side effects of verapamil?

Answer 45

Ankle edema Constipation