10/19 Flashcards

1
Q

ion channels definition

A

proteins that form pores in the plasma membrane

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2
Q

ion channels categorized by

A

gating (opening and closing) mechanism
ion selectivity
pharmacology

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3
Q

passive

A

allow ions to flow down their electrochemical gradient

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4
Q

ion flow is determined by

A

concentration gradient and electrical gradient

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5
Q

membrane potential overviw

A

excitable cells have a negative inward potential across the membrane due to the selective permeability of the resting membrane K+

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6
Q

K+ is high ___ and low ___

A

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

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7
Q

Na+ is high ___ and low ___

A

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

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8
Q

Ca is very low ___ and high ___

A

Ca is very low inside (100 nM) and high outside the cell (1.5 mM)
calcium can start to activate many pathways

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9
Q

need a ___ resting membrane potential

A

negative inward resting

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10
Q

type of channel expressed in cardiac smooth muscle

A

L-type, Cav1.2

this is the channel we want to block

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11
Q

CCBs block of channels in vascular smooth muscle:

A

vasodilation
-decrease BP
-relief of angina pectoris
block of channels in cardiac muscle and SA/AV node: antiarrhythmic

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12
Q

vascular smooth muscle contraction

A

Ca moves through (L type) channels, inc Ca conc., myosin LC kinase -> myosin LC -> phosphorylation + actin –> contraction

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13
Q

CCBs mechanism

A

if CCs are blocked, Ca can’t enter cell, Ca can’t be released from the SR, muscle can’t contract

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14
Q

CICR

A
  • calcium influx (Cav1.2) induces release of Ca from intracellular stores vie RYR2 in the SR
  • extracellular Ca is required for contraction of cardiac and smooth muscle (not skeletal)
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15
Q

cardiac smooth muscle contraction

A

Ca ions released from SR bind to troponin C, causes displacement of tropomyosin, allows myosin to bind actin -> CONTRACTION

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16
Q

skeletal muscle contraction

A

mechanical coupling between Cav1.1 RYR1, extracellular Ca is not required -> CCBs do not interfere with coupling

17
Q

CCB clinical applications

A

HTN, angina pectoris, arrythmia

18
Q

3 classes of CCBs

A

dihydropyridines, phenylalkylmines, benzothiapines

19
Q

dihydropyridine members

A

nifedipine (Procardia), isradipine
amlodipine (Norvasc)
clevidipine = short acting, efficacy ends when drug is not being infused

20
Q

dihydropyridines blockade mechanism

A

(+) enantiomer blocks current, intereferes w opening

(-) enantiomer potentiates current, interferes w closing

21
Q

tissue selectivity of DHPs

A

more potent in relaxing smooth muscle
do not compromise cardiac function
not antiarrythmics

22
Q

characteristics of DHP block

A

voltage-dependent
affinity depends of voltage
NOT frequency dependent
tonic block - closed channel block

23
Q

clinical considerations from DHPs

A

vascular selectivity (decreases hearts work), reflex tachycardia secondary to vasodilation (except amlodipine), reduce oxygen demand of the heart (efficacy in angina), don’t depress cardiac function

24
Q

phenylalkylamine

A

verapamil

25
Q

verapamil clinical considerations

A

vas][odilator (less potent than DHPs), slows conduction through the SA/AV nodes (reduced HR and force of contraction), blunts reflex tachycardia

26
Q

verapamil charactersitics of block

A

frequency dependent

very little tonic block (blocks open channels)

27
Q

benxothiazepine

A

diltiazem

28
Q

diltiazem clinical considerations

A

causes vasodilation (less potent than DHPs), slows conduction through SA/AV nodes, initial reflex tachycardia, exhibits frequency dependent block of Ca channels

29
Q

CCB CV effect summary

A

verapamil: 2x dec HR, 2x dec AV cond, 2x dec myocard contract, 2x inc arteriol vasodil
DHPs: inc HR, 4x inc arteriol vasodil
Diltiazem: dec HR, dec AV cond, dec myocard contract, inc arteriol vasodil

30
Q

CCBs SE profile

A

ankle edema present in all
DHPs: facial flushing and tachycardia
verapamil: constipation (>20%)