CCB Flashcards
Ion Channels
proteins that form ___ in the plasma membrane
categorized by:
- ___ opening and closing mechanism
- ion ___
- pharmacology
___ - allow ions to flow down their electrochemical gradient
pores
- gate
- selectivity
passive
Ion Channels and the Electrochemical Gradient
- ions can flow in ___ directions through most ion channels
- ___ and ___ gradients determine direction of flow
both
- concentration, electrical
Membrane Potential
excitable cells have a ___ inward potential across the membrane due to the selective permeability of the resting membrane to ___
negative, K+
Membrane Potential
- ___ is high inside (155 mM) and low outside the cells (4 mM)
- ___ is low inside (12 mM) and high outside the cell (145 mM)
- ___ is very low inside (100 nM) and high outside the cell (1.5 mM)
- Nernst Equation: ?
K+
Na+
Ca2+
Membrane Potential
membrane potential is set by ___ permeability at rest
- note that ___ charged ions do not cross the membrane
K
- negatively
CCB
block channels in vascular smooth muscle: ___
- decrease in ___
- relief of ___
block of channels in cardiac muscle and SA/AV node: ___
vasodilation
- BP
- angina
antiarrhythmic
voltage gated Ca2+ channel family
cardiac, smooth muscle, Ca2+ entry triggers contraction
L-type
Cav 1.2
vascular smooth muscle contraction
Ca2+ influx via Cav 1.2 induces release of Ca2+ from ___ stores via ___ receptor in the SR
___ Ca2+ is required for contraction of cardiac and smooth muscle
- intracellular, ryanodine 2 (RYR2)
- extracellular
B-adrenergic modulation Ca2+ channels
PKA phosphorylation of Cav1.2 increases Ca2+ ___
- increases contractility/force of contraction
- increases AV nodal action potential conduction rate
influx
T or F: extracellular Ca2+ is required for contraction of cardiac and vascular smooth muscle (not skeletal)
True
Cardiac Muscle Contraction
1) the Ca2+ ions released from the SR binds to ___
2) Ca2+ binding by ___ causes displacement of ___
3) displacement of ___ allows for ___ to bind actin
= CONTRACTION
- troponin C
- troponin C, tropomyosin
- tropomyosin, myosin
Skeletal Muscle Contraction
Mechanical coupling between ___ and ___
- extracellular Ca is not required; therefore ___ do not interfere with coupling
- Cav1.1, RYR1
- CCB
CCBs
clincal applications: angina pectoris, arrhythmia, HTN
Three distinct chemical classes
1) dihydropyridines
2) phenylalkylamines
3) benzothiazepines
CCBs Dihydropyridines
dihydropyridine ring
aryl group
chiral center
ester linked side chains
CCBs Dihydropyridines
- nifedipine (Procardia)
- isradipin (DynaCirc)
- felodipine (Plendil)
- amlodipine (Norvasc)
- nisoldipine (Sular)
- nimodipine (Nimotop)
- nicardipine (Cardene)
- clevidine (Cleviprex)
CCBs Dihydropyridines - Clevidipine (Cleviprex)
- ___ acting
- given ___ when PO is not desirable
- formulated with lipids derived from ___ and ___
- short
- IV
- soy, egg
very rapid
CCBs Dihydropyridines
MOA: (+) enantiomer ___ current , (-) enatiomer ___ current
- mechanism involves interference with ___
- (+) enantiomer interferes with ___
- (-) enantiomer interferes with ___
- blocks, potentiates
- gating
- opening
- closing
CCBs Dihydropyridines
tissue selectivity - more potent in relaxing smooth muscle, esp. ___
- do not compromise cardiac function
- not ___
- selectivity result of amino acid differences in channel splice variants, differences in membrane potential properties
coronary artery
antiarrhythmics
CCBs Dihydropyridines
characteristics of dihydropyridine block
- ___ dependence
- the ___ of drug for the channel is different at different voltages
voltage
affinity
CCBs Dihydropyridines
binding site is allosteric ( ___ of the pore_
- DHP drugs bind to closed channels and prevent opening - ___ block
- outside
- tonic
CCBs Dihydropyridines
- no ___ dependence
- marked tonic block
frequency
CCBs Dihydropyridines - Clinical Considerations
- marked decrease in peripheral resisitance (dilation of ___ ; little affect on ___ )
- decreased ___
- little effect on HR or force of contraction
- ___ exhibits selectivity for cerebral arteries - is used in sub-arachnoid hemorrhage to prevent neuropathy
- reflex tachycardia secondary to vasodilation (except ___ )
- arterioles, venules
- afterload
- nimodipine
- amlodipine
CCBs Dihydropyridines - Clinical Considerations
- reduce oxygen demand in heart - efficacy in ___
- do not depress cardiac function, except ___
- may inhibit ___
- all DHPs are highly bound to ___ ___ and undergo extensive first pass metabolism
- ___ has slow onset and long duration of action
angina
nifedipine
atherosclerosis
serum proteins
amlodipine
T or F: prompt release nifedipine formulations may increase risk of subsequent heart attack
True
- rapid decrease in BP may lead to reflex sypathetic response tachycardia
CCB - Phenylalkylamine
Verapamil
Clinical considerations
- causes ___ but less potent than ___
- slows conduction through ___ and ___ nodes (reducing HR and force of contraction)
- reflex tachycardia is ___
- inhibitory effect on heart is due to ___ dependent block
- binds in pore and blocks ___ influx; channel has to ___ for drug to enter the pore = ___ dependent block
- vasodilation, DHPs
- SA, AV
- blunted
- Ca2+, open, frequency
CCB - Phenylalkylamine
characteristics of block
- marked ___ dependence
- very little ___ block
- frequency
- tonic
CCB - benzothiazepine
diltiazem (Cadizem)
Clinical consideration
- less potent vasodilation than ___
- slows conduction through ___ and ___ nodes
- initial reflex ___
- diltiazem directly inhibits the heart less than ___ but more than ___
- exhibits ___ dependent block of Ca2+ channels
- DHP
- SA, AV
- tachycardia
- verapamil, DHPs
- frequency
CCB - benzothiazepine
characteristics of block
- ___ tonic block
- ___ frequency dependence
some
some
