Calcium Channel Antagonists Flashcards
Response to smooth muscle membrane depolarization
smooth muscle is impermeable to Ca2+ until depolarization occurs. membrane permeability increases due to depolarization because of the voltage gated calcium channels.
movement of calcium
outside to inside, concentration gradient, influx
Where do drugs act on the voltage gated calcium channels- what accessory protein?
alpha subunit, also phosphorylation is a great way to alter the channel
Why are accessory/regulatory proteins different on each channel?
changing tissues will change the voltage gated channel. Each channel is modulated by a different accessory protein.
What is the main role of calcium channel blockers?
decrease permeability to Ca2+ and decreases the contraction to help with pressure
Pathway of calcium channel blockers
calmodulin joins with calcium, this activates the MLCK, causes the MLCK to be phosphorylated, Bridges with actin to cause a contraction
if you decrease the permeability of Ca2+ with a CCB what happens?
blockers decrease contraction which will decrease pressure
VSM membrane voltage
-40 to -30 millivolts
Why is the VSM lower than cardiac and neuronal tissues?
there is always a population of VGCC that is open, results in a basal “tone” of smooth muscle
What does Minoxidil do to the membrane potential
promotes K+ efflux - hyperpolarizes the membrane and stabilizes the membrane potential
What does minoxidil do to the VGCC activity
makes it harder for Ca2+ to open because it is more negative, decreases Ca2+ channel activity
what will happen to the contractile state of VSM in minoxidil
decreases the contractile state and causes relaxation
What are the 2 non-DHP
Verapamil, Diltiazem
What are DHP
Nifedipine
MAP=
CO X TPR and (HR X SV) (TPR)
effect of CCB on SA node and AV node
decreases automaticity, and decreases conduction
effect of CCB on cardiac myocyte
decreases after load (TPR) decreases myocardial O2 demand
effect of CCB on coronary arteries
increase vasodilation, increases myocardial oxygen supply
effect of CCB on peripheral veins
minimal vasodilation
effect of CCB on peripheral arterioles
increases vasodilation, decreases after load, decreases myocardial infarction
what does Ca2+ do to the QRS interval
lengthens the PR interval (conduction of the AV node)
CCB SA node effect
calcium channel blocker decreases the slope and stretches out, tissue still contracts with the same force just at a much slower rate
CCB effect on cardiac myocytes
decreases contraction, less contraction is a negative inotropic agent
CCB effect on coronary arteries
carry oxygenated blood to the heart, increases O2 supply and peripheral arterioles
CCB effect on peripheral veins
none
CCB effect on peripheral arterioles
decrease TPR which decreases resistance which then decreases O2 demand
CCB refractory effect
can’t be affected for a time: resting state stays until stimulus, lots of stimulus- speed through a cycle
where do CCBs require entry from
from the inner side
binding is favored Ca2+
depolarized state
non-DHP active or inactive
bind to the active and inactive - harder for non-DHP to recover less Ca2+ reentry hold on because of the inhibition - use-dependency
VSM and Cardiac VGCC
VSM channels are always open (basal tone)
cardiac channels are always closed
are non-DHP or DHP more selective for cardiac tissues
non-DHP are because in cardiac tissues they are either all open or all closed. non-DHP bind to both and DHP only binds to active.
what type of response do non-DHP cause on the heart what about DHP
negative ionotropic, negative chronotropic, or negative dromotropic (AV nodal conduction response), after load reduction- DHP has no response on the heart except after load reduction
what do DHP and non-DHP have in common
both cause relaxation and dilation of blood vessels, DHP still causes a after load reduction even though it’s not directly working on the heart
why does CCB have more effect on arterioles than it does on veins
arterioles have a higher resting tone (more likely to be able to contract and more pressure)
cardiac effects of CCBs
reduction in SA nodal firing
reduction in AV nodal conduction
reduction in cardiomyocyte contractility
how do CCB change the frank starling curve
only affects FOC (lowers), no affect on preload because preload is a affected by the veins and there is no affect on veins with Ca2+ blockers
verapamil adverse effect
constipation - it decreases the contraction and happens to most of the patient population
general CCB adverse effects
muscle weakness, dry mouth, bradycardia (nodal blocks), hypotension
what two drugs have half lives long enough for once daily administration
amlodipine and felodipine : all others require increased dosing intervals and sustained release preparations
what enzyme involves verapamil and a lesser extent diltiazem
CYP3A4 - any drug that induces or inhibits (I,M)
PGP interactions - what do you not combine?
PGP is used for transport: verapamil, diltiazem, nifedipine, felodipine
do not combine with: digoxin, glucodcorticoids, protease inhibitors, NNRTIs
what agents are approved for angina?
Verapamil (Calan) Amlodipine (Norvasc) Nisoldipine Nifedipine (procardia) Diltiazem (cartia)
what other therapeutic indications are for CCB besides hypertension and angina?
raynauds syndrome
verapamil: arrhythmias, migraines, dosing decreases for headaches so that there is no hypotension if they do not have hypertension
angina and why CCB used
angina is lack of oxygen rich blood delivered to the heart, CCB decreases the lack of oxygen demand so that it can increase the oxygen supply to the heart
heart failure patients and CCB
ejection fraction in patients is really low, CCB = decrease in contractility, decrease in TPR, decrease in heart rate, HF (have a heart time pumping the heart ), only use DHP
pregnant patients and ccb
contraindications- not changing the plasma concentration
patients with hyperkalemia and ccb
no
patients with angioedema
good choice except allergic reaction. try ARB or Ca blocker
