Calcium Channel Blockers Flashcards
Calcium channels
G-protein gated pores in membranes that regulate entry of calcium ions into cells
Vascular Smooth Muscle (VSM) calcium channels
have G-protein receptors that regulate contraction
Calcium flows into cell and initiates contractile process
Receptors are Alpha-1 adrenergic receptors
CCBs act on peripheral arterioles and arteries and arterioles of heart
- NO significant effect on veins
Heart Calcium Channels
What receptors are they coupled to
regulate myocardium, SA node, and AV node
coupled to Beta1 adrenergic receptors (Gprotein receptors)
- when activated Ca influx ENHANCED
What Ca does at Myocardium, SA and AV node
Myocardium- calcium increases force of contraction
SA and AV node
channels open= node discharge increases
channels closed= node discharge decreases
CCBs 2 Classifications
1) Dihydropyridines
- acts on SYSTEMIC arterioles (alpha 1 receptors)
2) Non dihydropyridines
- acts on arterioles and the heart (Beta 1 receptors
dihydropyridines vs non-dihydropyridines vasodilation and heart fxn
Dihydropyridines
- more effect vasodilation
- less effect heart
Non-dihydropyridines
- less effect vasodilation
- more effect heart fxn
Non Dihydropyridines drug name
Verapamil
What does Non-dihydropyridines do
block calcium channels in blood vessels and heart
indications of non-dihydropyridines
Angina pectoris
Essential Hypertension
Cardiac dysthymias
Directeffects of Non Dihydropyridines
1) blockage in heart arteries/arterioles
= increased coronary perfusion
2) Blockage of SA node
= reduced HR
3) Blockage of AV node
= slows AV nodal conduction
4) Blockage of myocardium
= decreased force of contraction
Indirect Effects of Non Dihydropyridines
Lowering blood pressure
Pharmacokinetics of Non Dihydropyridines
PO- effects in 30 min, peak in 5 hrs
- extensive first-pass metabolism
- 20% reach systemic circulation
IV
Elimination: liver to bile
Therapeutic Use of Non Dihydropyridines
angina pectoris, essential hypertension
cardiac dysrhythmias
-administer via IV - improves atrial flutter/fibrillation
= reduced tachycardia
adverse effects of Non Dihydropyridines
Constipation
- calcium channels blocked in intestinal smooth muscle
cardiac effects
-bradycardia due to blockage of SA node
Dizziness, headache, edema
Non Dihydropyridines drug and food interactions
Digoxin: supresses AV conduction
other Beta-adrenergic blockers
Grapefruit juice: inhibit liver metabolism of drugs
= reaise their level
Toxicity of Non Dihydropyridines
overdose
- severe hypotension and cardiotoxicity (bradycardia, AV block)
Treatment: activated charcoal removes drug from GI tract
Dihydropyridines drug name
Nifedipine
Effects of Dihydropyridines
1) DIRECT - block alpha-1 calcium-chaneels in VSM
= vasodilation = reduced systemic BP
2) INDIRECT- reduce systemic BP
= more flow to heart
= increased HR
NET EFFECT: lowers BP
= increases flow to heart
= INCREASED HR rate and contractile force
Pharmocokinetics of Dihydropyridines
PO
-extensive first pass (50% enters circulation)
Therapeutic uses of Dihydropyridines
Angina pectoris:
prevent reflex tachycardia
Essential Hypertension
Adverse effects of Dihydropyridines
peripheral edema
dizziness
headache
less constipation
TOXICITY = drug loses selectivity
= begins to affect heart
