Calcium channel blockers

Question 1

what are ion channels

Answer 1

proteins that form pores in the plasma membrane
these pores allow ions to go through

Question 2

what determines direction of ion flow?

Answer 2

conc gradient
electrical gradient

Question 3

what is membrane potential of K

Answer 3

K is high inside (155 mM) and low outside the cell (4 mM)

Question 4

what is membrane potential of Na

Answer 4

Na is low inside (12 nM) and high outside the cell (145 mM)

Question 5

what is membrane potential of Ca

Answer 5

Ca is very low inside (100 nM) and high outside the cell (1.5 mM)

Question 6

contribution of specific ions to action potentials

Answer 6

Question 7

structure of voltage gated channels

Answer 7

Closed form - helices are crossed, ions can’t get through
open form - inner helices bend away after ion binding happens to open channel

Question 8

Cav1.1 type, location, function

Answer 8

L-type
skeletal muscle
voltage sensor in E/C coupling

Question 9

Cav1.2 type, location, function

Answer 9

L-type
cardiac, smooth muscle
Ca2+ entry triggers contraction

Question 10

Cav1.3 type, location, function

Answer 10

L-type
neurons, endocrine cells
trigger for hormone secretion

Question 11

Cav2.1 type, location, function

Answer 11

P/Q-type
neurons
triggers neurotransmitter release at synapse

Question 12

Cav2.2 type, location, function

Answer 12

N-type
neurons
triggers neurotransmitter release at synapse

Question 13

Cav2.3 type, location, function

Answer 13

R-type
neurons
functions unknown

Question 14

block of channels in VSM effect

Answer 14

vasodilation
decrease in BP
relief of angina pectoris

Question 15

block of channels in cardiac muscle and SA/AV node effect

Answer 15

antiarrhythmic

Question 16

vsm contraction moa

Answer 16

Ca2+ influx via Cav1.2 induces release of Ca from intracellular stores via RYR2 in SR
extracellular Ca is required for contraction of cardiac and smooth muscle

Question 17

Beta adrenergic modulation of Ca2 channels

Answer 17

PKA phosphorylation of Cav1.2 increases Ca2 influx
increases contractility/force of contraction
increases AV nodal action potential conduction rate

Question 18

what is required for contraction of cardiac and vsm but not for skeletal muscle

Answer 18

extracellular ca2

Question 19

how does cardiac muscle contraction occur

Answer 19

Ca2+ ions released from sarcoplasmic reticulum binds to troponin C
Ca2 binding by troponin C causes displacement of tropomysin
displacement of tropomyosin allows myosin to bind actin –> leads to contraction

Question 20

how does skeletal muscle contraction happen

Answer 20

mechanical coupling between Cav1.1 and RYR1

Question 21

what are the clinical applications of CCBs

Answer 21

angina pectoris, arrhythmias, htn

Question 22

what are the 3 distinct chemical classes of CCBs

Answer 22

Dihydropyridines
phenylalkylamines
benzothiazepines

Question 23

Dihydropyridines structure activity

Answer 23

dihydropyridine ring
aryl group
chiral center
ester linked side chains

Question 24

members of the dihydropyridines

Answer 24

Question 25

what is clevidipine (cleviprex)

Answer 25

short acting DHP

Question 26

what is clevidipine (cleviprex) half life

Answer 26

1 min (85-90%) 15 min (10-15%)

Question 27

how is clevidipine given

Answer 27

IV to tx htn when PO admin of drugs not possible/desirable

Question 28

what is clevidipine formulated from

Answer 28

lipids from soy and egg

Question 29

what is the metabolism of clevidipine

Answer 29

cleaved by esterases

Question 30

what does a + enantiomers DHP do

Answer 30

blocks current aka interferes with opening of CBB

Question 31

what does a - enantiomer DHP do

Answer 31

potentiates current aka interferes with closing

Question 32

what tissue is DHP more selective for

Answer 32

more selective and potent in relaxing smooth muscle (esp. coronary artery)

Question 33

what is DHP tissue selectivity result of

Answer 33

aa differences in channel splice variants differences in membrane potential properties

Question 34

what is characteristic of DHP block

Answer 34

voltage dependence binds to closed channels and prevent opening - tonic block no frequency dependence marked tonic block

Question 35

what are clinical considerations for DHPs

Answer 35

vascular selectivity - marked decrease in peripheral resistance, decreased afterload, little effect on HR or force of contraction DHPs reduce heart oxygen demand (efficacy for angina) DHPs (except nifedipine) don't depress cardiac function DHPs may inhibit atherosclerosis

Question 36

which DHPs are vasoselective

Answer 36

nisoldipine, felodipine, nicardipine, isradipine, amlodipine, nifedipine

Question 37

which DHP exhibits selectivity for cerebral arteries

Answer 37

nimodipine - used in sub-arachnoid hemorrhage to prevent neuropathy

Question 38

DHPs pk factors

Answer 38

all dhps are highly bound to serum proteins all dhps undergo extensive first pass metabolism in liver amlodipine has slow onset and long DOA

Question 39

nifedipine risks

Answer 39

increased risk of subsequent MI fast release nifedipine may increase risk of subsequent heart attack

Question 40

verapamil (calan, isoptin) drug class

Answer 40

phenylalkylamine

Question 41

verapamil clinical considerations

Answer 41

causes vasodilation, but less potent than DHPs slows conduction through the SA and AV nodes reflex tachycardia is blunted

Question 42

where does verapamil bind

Answer 42

in the pore and blocks Ca2 influx

Question 43

characteristics of verapamil block

Answer 43

channel has to be open for drug to enter pore - frequency dependent block... ...so marked freqency dependence very little tonic block

Question 44

diltiazem (cardizem) drug class

Answer 44

benzothiazepine

Question 45

diltiazem clinical considerations

Answer 45

causes vasodilation less potent than DHPs slows conduction through SA and AV nodes initial reflex tachycardia

Question 46

diltiazem potency

Answer 46

inhibits heart less than verapamil, but more than DHPs

Question 47

diltiazem block characteristics

Answer 47

some frequency dependent block of Ca2 channels some tonic block

Question 48

summary of cv effects

Answer 48

Question 49

CCBs side effect profile

Answer 49

all classes have 5-10% of ankle edema verapamil has >10% of constipation DHPs have 10-20% of facial flushing DHPs have 5-10% of tachycardia