Calcium Blockers Flashcards
what is an ion channel
protein that form pores in plasma membrane
what determines direction of flow?
concentration gradient
electrical gradient
K+, Na+, and Ca2+ conc inside and outside cell
K+ high inside, low outside
Na+ high outside, low inside
Ca2+ high outside, very low inside
what is kcsa channel
H+ gated K+ channel in closed state
what is mthK channel
Ca2+ gated K+ channel in open state, opens when it binds calcium, crystallized in presence of calcium
location and function of L type channel Cav 1.2
cardiac, smooth muscle
Ca entry triggers contraction
block of calcium channels in vascular smooth muscle effect and uses?
vasodilation
used for angina and blood pressure decrease
block of calcium channels in cardiac muscle and SA/AV node uses?
antiarrhythmic
vascular smooth muscle mechanism
calcium induced calcium release
Ca influx via Cav 1.2 releases Ca from intracellular stores via ryanodine (RYR2) in the SR
calcium calmodulin binds myosin LC kinase which becomes myosin LC and gets phosphorylated then acts with actin to contraction
what is required for contraction of cardiac and smooth muscle?
extracellular Ca
how can PKA increase Ca influx
phosphorylation of Cav1.2
increases contractility and av node conduction rate
cardiac muscle contraction mechanism
Ca ions released from SR binds troponin C
displacement of tropomyosin
myosin binds actin and contraction
skeletal muscle contraction? is Ca required?
coupling between Cav1.1 and RYR1
extracellular calcium not required
calcium blockers don’t do much here
what do calcium channel blockers treat?
decrease blood pressure, angina, arrhythmia
three classes of CCbs
dihydropyridines
phenylalkylamines
benzothiazepines
dihydropyridine members
nifedipine
amlodipide
clevidipine
nimodipine
what is clevidipine
short acting DHP
given IV for hypertension when they can’t PO
esterases cleave rapidly
mechanism of DHPs
interferes with gating via enantiomers
+ blocks current
- potentiates current
tissue selectivity of DHPs
vascular smooth muscle, do not compromise cardiac function
are dihydropyridines voltage dependent?
yes
do dihydropyridines bind to open or closed channels?
closed to prevent openeing - tonic block
are dihydropyridines frequency dependent?
no
vascular selectivity of DHPs
arterial dilation
decreased afterload
nimodipine use and selectivity
selective for cerebral arteries
used in sub-arachnoid hemorrhage
which DHP does not have reflex tachycardia secondary to vasodilation
amlodipine
amlodipine onset and duration
slow onset
long duration
nifedipine can cause what
prompt release can cause heart attach, reflex tachycardia serious
phenylalkylamine drug
verapamil
verapamil does what
slows conduction through SA/AV (reduce HR and contraction force)
less potent vasodilation
blunted reflex tachycardia
verapamils inhibitory effect on the heart is due to ____
frequency dependent block
channel has to be ____ for verapamil to enter pore
open (frequency dependent)
does verapamil have tonic block
very little tonic block
benzothiazepine drug
diltiazem
diltiazem inhibits the heart _____ than verapamil
less
does diltiazem have frequency dependent block?
yes
does diltiazem have tonic block
some tonic block
DHPs side effects
ankle edema
flushing
tachycardia
verapamil side effects
ankle edema
constipation
diltiazem side effects
ankle edema
