Exam 5 - Calcium Channel Blockers Hockerman

Question 1

K+ is _____ inside and _____ outside the cell

a. low; high
b. low; low
c. high; low
d. high; high

Answer 1

c. high; low

Question 2

Na+ is _____ inside and _____ outside the cell

a. low; high
b. low; low
c. high; low
d. high; high

Answer 2

a. low; high

Question 3

is calcium low or high INSIDE the cell?

Answer 3

very low (100 nM compared to 1.5 mM outside)

Question 4

is calcium low or high OUTSIDE the cell?

Answer 4

high (1.5 mM compared to 100 nM inside)

Question 5

location of CaV 1.2 receptor (2 locations)

Answer 5

cardiac and smooth muscle

Question 6

function of CaV1.2 receptor

Answer 6

Ca2+ entry triggers contraction

Question 7

membrane potential is set by _____ permeability at rest

a. Ca2+
b. K+
c. Na+

Answer 7

b. K+

Question 8

what structural feature of potassium channels is responsible for the selective and rapid conduction of K+?

Answer 8

selectivity filter

Question 9

blocking of channels in vascular smooth muscle leads to __________

Answer 9

vasodilation

(dec in BP; relief of angina)

Question 10

blocking on channels in cardiac muscle & SA/AV node leads to an __________ effect

Answer 10

antiarrhythmic

Question 11

Ca2+-induced Ca2+ release (CICR):

_____ influx via _____ induces release of _____ from intracellular stores via _____ in the SR

(second and fourth blanks are receptors)

Answer 11

Ca2+
CaV1.2
Ca2+
RYR2 (ryanodine receptor 2)

Question 12

what is required for contraction of cardiac and smooth muscle?

Answer 12

extracellular Ca2+

(not required for skeletal muscle)

Question 13

beta adrenergic modulation of Ca2+ channels: _____ phosphorylation of CaV1.2 inc Ca2+ influx

(the blank is an enzyme)

Answer 13

PKA (protein kinase A)

Question 14

in vascular smooth muscle, what are the two end products that lead to contraction?

Answer 14

myosin LC-PO4 (phosphorylated myosin light chain) + actin

Question 15

cardiac muscle contraction: Ca2+ ions released from the SR binds to _______

Answer 15

troponin C

Question 16

cardiac muscle contraction: Ca2+ binding by troponin C causes displacement of __________

Answer 16

tropomyosin

Question 17

what causes contraction in cardiac muscle contraction?

Answer 17

displacement of tropomyosin allows myosin to bind actin -> contraction

Question 18

skeletal muscle contraction requires mechanical coupling of what two receptors?

Answer 18

CaV1.1 and RYR1

Question 19

what drug is given for subarachnoid hemorrhage (bleeding in space around brain)?

Answer 19

nimodipine

Question 20

3 clinical applications for calcium channel blockers

Answer 20

angina, arrhythmia, HTN

Question 21

which is not one of the 3 distinct chemical classes of calcium channel blockers?

a. dihydropyridines
b. phenylalkylamines
c. organic nitrates
d. benzothiazepines

Answer 21

c. organic nitrates

(these are vasodilators)

Question 22

what do dihydropyridine CCB drugs end in?

Answer 22

“-dipine”

Question 23

what structural element gives nifedipine, amlodipine, isradipine, and other “-dipines” their name?

Answer 23

dihydropyridine ring

Question 24

which drug is a short acting DHP formulated with lipids derived from soy and egg, and is given IV to treat hypertension when PO admin of drugs is not possible/desirable?

a. amlodipine
b. nifedipine
c. nicardipine
d. isradipine
e. clevidipine
f. felodipine

Answer 24

e. clevidipine

Question 25

clevidipine's active form is cleaved by what enzymes?

Answer 25

esterases

Question 26

blockade mechanism of dihydropyridines: the (+) enantiomer of Bay K 8644 __________ current, and interferes with __________ a. blocks; opening b. blocks; closing c. potentiates; opening d. potentiates; closing

Answer 26

a. blocks; opening

Question 27

blockade mechanism of dihydropyridines: the (-) enantiomer of Bay K 8644 __________ current, and interferes with __________ a. blocks; opening b. blocks; closing c. potentiates; opening d. potentiates; closing

Answer 27

d. potentiates; closing

Question 28

dihydropyridines are more potent in relaxing _____ muscle, especially which artery?

Answer 28

smooth; coronary artery (DHPs do not compromise cardiac function)

Question 29

tissue selectivity of CCBs are the result of what 2 things?

Answer 29

-amino acid differences in channel splice variants -differences in memb potential properties

Question 30

vascular selectivity of DHPs is observed in _____ assays but not _____ assays a. functional; binding b. binding; functional

Answer 30

a. functional; binding (Idk what this means though)

Question 31

what does voltage-dependence block mean?

Answer 31

affinity of drug for the channel is diff at diff voltages

Question 32

what is it called when DHP drugs bind to closed channels (at allosteric site) and prevent opening?

Answer 32

tonic block

Question 33

clinical considerations for DHPs: reflex tachycardia secondary to vasodilation occurs in all drugs except _________

Answer 33

amlodipine (due to slow onset of action)

Question 34

why is nimodipine used for subarachnoid hemorrhage?

Answer 34

it's selective for cerebral arteries (it can relax arteries in brain that have been contracted due to a brain bleed)

Question 35

clinical considerations for DHPs: DHPs reduce oxygen demand in heart, may inhibit atherosclerosis, and all (except ________) do not depress cardiac function

Answer 35

nifedipine

Question 36

true or false: all DHPs are not highly bound to serum proteins and undergo extensive first pass metabolism in liver

Answer 36

false (they are all highly bound)

Question 37

amlodipine has _____ onset and _____ duration of action

Answer 37

slow; long

Question 38

rapid release __________ may inc risk of subsequent heart attack due to tachycardia a. amlodipine b. nifedipine c. clevidipine d. nisoldipine

Answer 38

b. nifedipine

Question 39

only drug in phenylalkylamine CCB class

Answer 39

verapamil

Question 40

verapamil inhibitory effect on heart is due to what type of block?

Answer 40

frequency dependent block

Question 41

which is the most potent for vasodilation, DHPs, verapamil, or diltiazem?

Answer 41

DHPs

Question 42

verapamil and diltiazem _____ conduction through the SA and AV nodes, reducing heart rate and force of contraction

Answer 42

slows

Question 43

why is reflex tachycardia blunted for verapamil?

Answer 43

bc it is also inhibiting channels in the heart

Question 44

where does verapamil bind in calcium channels? a. allosteric site b. pore

Answer 44

b. pore (blocks Ca2+ influx through pore)

Question 45

true or false: verapamil has marked tonic block and very little freq dependent block

Answer 45

false (marked freq dependece, very little tonic block)

Question 46

what is the only drug in benzothiazepine class (that we talked about)?

Answer 46

diltiazem

Question 47

diltiazem directly inhibits the heart _____ than verapamil, but _____ than DHPs a. less; more b. more; less

Answer 47

a. less; more

Question 48

characteristics of benzothiazepine (diltiazem) block: is it tonic, frequncy dependent, or both?

Answer 48

both (some tonic block, some freq dependence)

Question 49

most common side effect of DHPs (slide 39)

Answer 49

flushing (they are good vasodilators)

Question 50

which is considered a clinically significant side effect of all 3 drugs: diltiazem, DHPs, and verapamil? a. constipation b. ankle edema c. rash d. facial flushing e. dizziness

Answer 50

b. ankle edema

Question 51

what are the 3 clinically significant side effects of DHPs? a. ankle edema b. constipation c. dizziness d. facial flushing e. headaches f. ischemia g. rash h. tachycardia

Answer 51

a, d, h

Question 52

what are the two clinically significant side effects of verapamil? a. ankle edema b. constipation c. dizziness d. facial flushing e. headaches f. ischemia g. rash h. tachycardia

Answer 52

a. ankle edema b. constipation

Question 53

diltiazem's clinically significant side effect (1)

Answer 53

ankle edema

Question 54

potential for drugs selective for CaV1.3: treatment of ______ ______ (studies with _____) (Last blank is a drug)

Answer 54

drug addiction; isradipine

Question 55

potential for drugs selective for CaV2.1: treatment of ______ ______ ______, some types of ______

Answer 55

familial hemiplegic migraine; ataxia

Question 56

potential for drugs selective for CaV2.2: treatment of refractory chronic pain due to what toxin? What drug can treat this?

Answer 56

Conus magus; omega-Conotoxin MVIIA (Ziconotide, Prialt)