Calcium channel blockers Flashcards
What is the more determining factor for ion flow? Concentration gradient or Electrical gradient?
Electrical Gradient
Where is K more highly concentrated?
Inside the cell
Where is K more lowly concentrated?
Outside the cell
Where is Na low?
Inside the cell
Where is Na high?
Outside
Ca+ is low where?
Inside the cell
Ca+ is high where?
Outside the cell
Most important Ca voltage gate you need to know for this class?
L-type, Ca 1.2
What triggers contraction of Ca 1.2?
Ca2+ entry
Ca 1.2 is found on what?
Cardiac and smooth muscle
Ca 1.3 is found where?
SA/AV nodes, neurons, and endocrine cells
What is a Ca1.3 a trigger for?
Hormone secretion
Blockage of vascular smooth muscle leads to what?
Vasodilation
Block of channels in cardiac muscle and SA/AV node results in what benefit?
Anti-arrhythmic
What are intracellular stores of Ca2+ called?
RYR@ (ryanodine receptor 2)
What REQUIRES Ca2+?
Cardiac and smooth muscle contraction
What does Ca2+ release from SR bind to?
Troponin C
Ca2+ binding of troponin c leads to what?
Displacement of tropomyosin
Displacement of Tropomyosin causes what?
Allows myosin to bind actin
What coupling allows for skeletal muscle contraction?
Coupling between Ca 1.1 and RYR1
Does skeletal muscle contraction require extracellular Ca2+?
No
Clinical applications for Calcium channel blockers? (3)
Angina Pectoris
Arrhythmia
Hypertension
3 Distinct Chemical Classes of Calcium Channel blockers?
Dihydropyridines
Phenylalkylamines
Benzothiazepines
Main structural feature of Dihydropyridines?
Dihydropyridine ring
+ enantiomer of DHP does what?
Keeps gate closed and blocks current
- enantiomer of DHP does what?
Won’t let gate close and keeps current going
When do you give Clevidipine?
When you want to treat hypertension immediately and oral administration isn’t possible.
What do you have to watch out for when giving clevidipine?
Allergy to soy and egg
Where are DHPs most potent?
Relaxing smooth muscle such as coronary artery
Do DHPs compromise cardiac function?
No
DHPs are dependent on what for their potency?
Voltage of membrane
Binding sites for DHPs, PAAs, and BZPs are what?
Linked, but not identical
Characteristics of DHP block?
No frequency dependence
Marked tonic block
What effects does DHP have on vascular system (3)?
Decrease in peripheral resistance
Decreased after load
Little effect on HR or contraction
Drug listed in packet that has the least vascular specificity?
Nifedipine
Drug used in cases of sub arachnoid hemorrhage to prevent neuropathy?
Nimodipine
Secondary result of DHPs on the heart?
Reflex tachycardia except for amlodipine
How do DHPs reduce angina?
They lower the oxygen demand of the heart
Which DHP does depress cardiac function?
Nifedipine
Why is Amlodipine the most commonly prescribed calcium channel blocker?
It has slow onset and long duration of action
Phenylalkylamine (PAAs) cause what?
Vasodilation, less potent than DHP
Effect of PAA on SA and AV node?
Slows conduction through SA and AV node to reduce heart rate and force of contraction
How severe is the reflex tachycardia from PAA?
Blunted
Characteristics of PAA block?
Marked frequency dependence
Very little tonic block
Benzothiazepine affects the heart how?
Vasodilation, slows conduction, reflex tachycardia, but inhibits less than verapamil but more than DHPs
Characteristics of BZP block?
Some tonic block
Some frequency block
Of the three types of drugs discussed which affects heart rate the most?
Verapamil
Of the three types of drugs discussed which affects AV conductance/Myocardial contraction the most?
Verapamil
Of the three drugs listed which affects arterial vasodilation the most?
DHPs
Most important side effects of calcium channel blockers?
Ankle edema
Constipation
Facial flushing
Tachycardia
Which class of drug causes the most constipation?
Verapamil
Which class of drug causes the most facial flush/
DHPs
Which class of drugs causes the most tachycardia?
DHPs
Danger surrounding prompt release nifedipine?
Increased risk of subsequent heart attack due to reflex sympathetic response tachycardia
