Calcium Channel Antagonists

Question 1

Response to smooth muscle membrane depolarization

Answer 1

smooth muscle is impermeable to Ca2+ until depolarization occurs. membrane permeability increases due to depolarization because of the voltage gated calcium channels.

Question 2

movement of calcium

Answer 2

outside to inside, concentration gradient, influx

Question 3

Where do drugs act on the voltage gated calcium channels- what accessory protein?

Answer 3

alpha subunit, also phosphorylation is a great way to alter the channel

Question 4

Why are accessory/regulatory proteins different on each channel?

Answer 4

changing tissues will change the voltage gated channel. Each channel is modulated by a different accessory protein.

Question 5

What is the main role of calcium channel blockers?

Answer 5

decrease permeability to Ca2+ and decreases the contraction to help with pressure

Question 6

Pathway of calcium channel blockers

Answer 6

calmodulin joins with calcium, this activates the MLCK, causes the MLCK to be phosphorylated, Bridges with actin to cause a contraction

Question 7

if you decrease the permeability of Ca2+ with a CCB what happens?

Answer 7

blockers decrease contraction which will decrease pressure

Question 8

VSM membrane voltage

Answer 8

-40 to -30 millivolts

Question 9

Why is the VSM lower than cardiac and neuronal tissues?

Answer 9

there is always a population of VGCC that is open, results in a basal “tone” of smooth muscle

Question 10

What does Minoxidil do to the membrane potential

Answer 10

promotes K+ efflux - hyperpolarizes the membrane and stabilizes the membrane potential

Question 11

What does minoxidil do to the VGCC activity

Answer 11

makes it harder for Ca2+ to open because it is more negative, decreases Ca2+ channel activity

Question 12

what will happen to the contractile state of VSM in minoxidil

Answer 12

decreases the contractile state and causes relaxation

Question 13

What are the 2 non-DHP

Answer 13

Verapamil, Diltiazem

Question 14

What are DHP

Answer 14

Nifedipine

Question 15

MAP=

Answer 15

CO X TPR and (HR X SV) (TPR)

Question 16

effect of CCB on SA node and AV node

Answer 16

decreases automaticity, and decreases conduction

Question 17

effect of CCB on cardiac myocyte

Answer 17

decreases after load (TPR) decreases myocardial O2 demand

Question 18

effect of CCB on coronary arteries

Answer 18

increase vasodilation, increases myocardial oxygen supply

Question 19

effect of CCB on peripheral veins

Answer 19

minimal vasodilation

Question 20

effect of CCB on peripheral arterioles

Answer 20

increases vasodilation, decreases after load, decreases myocardial infarction

Question 21

what does Ca2+ do to the QRS interval

Answer 21

lengthens the PR interval (conduction of the AV node)

Question 22

CCB SA node effect

Answer 22

calcium channel blocker decreases the slope and stretches out, tissue still contracts with the same force just at a much slower rate

Question 23

CCB effect on cardiac myocytes

Answer 23

decreases contraction, less contraction is a negative inotropic agent

Question 24

CCB effect on coronary arteries

Answer 24

carry oxygenated blood to the heart, increases O2 supply and peripheral arterioles

Question 25

CCB effect on peripheral veins

Answer 25

none

Question 26

CCB effect on peripheral arterioles

Answer 26

decrease TPR which decreases resistance which then decreases O2 demand

Question 27

CCB refractory effect

Answer 27

can't be affected for a time: resting state stays until stimulus, lots of stimulus- speed through a cycle

Question 28

where do CCBs require entry from

Answer 28

from the inner side

Question 29

binding is favored Ca2+

Answer 29

depolarized state

Question 30

non-DHP active or inactive

Answer 30

bind to the active and inactive - harder for non-DHP to recover less Ca2+ reentry hold on because of the inhibition - use-dependency

Question 31

VSM and Cardiac VGCC

Answer 31

VSM channels are always open (basal tone) | cardiac channels are always closed

Question 32

are non-DHP or DHP more selective for cardiac tissues

Answer 32

non-DHP are because in cardiac tissues they are either all open or all closed. non-DHP bind to both and DHP only binds to active.

Question 33

what type of response do non-DHP cause on the heart what about DHP

Answer 33

negative ionotropic, negative chronotropic, or negative dromotropic (AV nodal conduction response), after load reduction- DHP has no response on the heart except after load reduction

Question 34

what do DHP and non-DHP have in common

Answer 34

both cause relaxation and dilation of blood vessels, DHP still causes a after load reduction even though it's not directly working on the heart

Question 35

why does CCB have more effect on arterioles than it does on veins

Answer 35

arterioles have a higher resting tone (more likely to be able to contract and more pressure)

Question 36

cardiac effects of CCBs

Answer 36

reduction in SA nodal firing reduction in AV nodal conduction reduction in cardiomyocyte contractility

Question 37

how do CCB change the frank starling curve

Answer 37

only affects FOC (lowers), no affect on preload because preload is a affected by the veins and there is no affect on veins with Ca2+ blockers

Question 38

verapamil adverse effect

Answer 38

constipation - it decreases the contraction and happens to most of the patient population

Question 39

general CCB adverse effects

Answer 39

muscle weakness, dry mouth, bradycardia (nodal blocks), hypotension

Question 40

what two drugs have half lives long enough for once daily administration

Answer 40

amlodipine and felodipine : all others require increased dosing intervals and sustained release preparations

Question 41

what enzyme involves verapamil and a lesser extent diltiazem

Answer 41

CYP3A4 - any drug that induces or inhibits (I,M)

Question 42

PGP interactions - what do you not combine?

Answer 42

PGP is used for transport: verapamil, diltiazem, nifedipine, felodipine do not combine with: digoxin, glucodcorticoids, protease inhibitors, NNRTIs

Question 43

what agents are approved for angina?

Answer 43

``` Verapamil (Calan) Amlodipine (Norvasc) Nisoldipine Nifedipine (procardia) Diltiazem (cartia) ```

Question 44

what other therapeutic indications are for CCB besides hypertension and angina?

Answer 44

raynauds syndrome verapamil: arrhythmias, migraines, dosing decreases for headaches so that there is no hypotension if they do not have hypertension

Question 45

angina and why CCB used

Answer 45

angina is lack of oxygen rich blood delivered to the heart, CCB decreases the lack of oxygen demand so that it can increase the oxygen supply to the heart

Question 46

heart failure patients and CCB

Answer 46

ejection fraction in patients is really low, CCB = decrease in contractility, decrease in TPR, decrease in heart rate, HF (have a heart time pumping the heart ), only use DHP

Question 47

pregnant patients and ccb

Answer 47

contraindications- not changing the plasma concentration

Question 48

patients with hyperkalemia and ccb

Answer 48

no

Question 49

patients with angioedema

Answer 49

good choice except allergic reaction. try ARB or Ca blocker