Calcium Channel Blockers Flashcards
(50 cards)
What determines the direction of flow for ions?
concentration gradient and electrical gradient
What kind of potential do excitable cells have?
negative inward potential across the membrane due to the selective permeability of the resting membrane to K+
Describe the concentration gradient of K+ across an excitable cell membrane
K+ is high inside (155 mM) and low outside the cell (4 mM)
Describe the concentration gradient of Na+ across an excitable cell membrane
Na+ is low inside (12 mM) and high outside the cell (145 mM)
The membrane potential gradient across a cell membrane is maintained by what?
maintained by active transport of Na+ out of the cell and K+ into the cells, and by channels that selectively permit K+ to run out of the cell at voltages near the resting membrane potential
Nerst Equation
Emem = (RT/F) ln ([K+out]/[K+in])
at 37 degrees C, Emem = -98 mV
Calcium distribution across the cell membrane
Ca2+ is very low inside (100 nM) and high outside the cell (1.5 mM)
Location/Function of L-type Cav1.2 voltage gated channel
cardiac, smooth muscle / Ca2+ entry triggers contraction
Location/Function of L-type Cav1.3 voltage gated calcium channels
neurons, endocrine cells / trigger for hormone secretion
What is the result of blocking calcium channels in vascular smooth muscle?
Vasodilation, decrease in blood pressure, and relief of angina pectoris
What is the result of blocking calcium channels in cardiac muscle and SA/AV node?
antiarrhythmic
Describe Ca2+-inducedd Ca2+ release (CICR)
Ca2+ influx via Cav1.2 induces release of Ca2+ from intracellular stores via RYR2 (ryanodine receptor 2) in the SR
What is required for the contraction of cardiac and smooth muscle?
Extracellular Ca2+
Describe cardiac muscle contraction
Ca2+ ions released from the SR binds to troponin C; Ca2+ binding by troponin C causes displacement of tropomyosin; displacement of tropomyosin allows myosin to bind actin; contraction
In skeletal muscle contraction, mechanical couple occurs between what?
mechanical coupling between Cav1.1 and RYR1
Clinical applications of calcium channel blockers
angina pectoris, arrhythmia, and hypertension
Three distinct classes of calcium channel blockers
Dihydropyridines, Phenylalkylamines, and Benzothiazepines
Structure activity of dihydropyridines
dihydropyridine ring, aryl group, chiral center, ester linked side chains
What does the (+) enantiomer of dihydropyridines do?
blocks current; interferes with opening
What does the (-) enantiomer of dihydropyridines do?
potentiates current; interferes with gate closing
Mechanism of Dihydropyrdines involves
involves interference with gating
Members of the dihydropyridine class
Nifedipine (Procardia)
Isradipine (DynaCirc)
Felodipine (Plendil)
Amlodipine (Norvasc)
Nisoldipine (Sular)
Nimodipine (Nimotop)
Nicardipine (Cardene)
Clevidipine
What is Clevidipine metabolized by?
esterases
What is significant about Amlodipine (Norvasc)
slow-onset of action; less likely to produce reflex tachycardia
