calcium channel blockers Flashcards

1
Q

what does calcium do

what happens if you block calcium channels

A

the influx of calcium ions through voltage-sensitivity, long lasting (L-type) Ca channels provides the activator calcium required for contraction of cardiac and smooth muscle cells.

Ca influx through L-type Ca channels also contributes to the upstroke of the AP in the SA and AV nodes of the heart.

CCB (calcium channel blockers) reduce cardiac automaticity and Av nodal conduction, cause vasodilation

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2
Q

what are the CCB classes and drugs

A

Phenylalkylamines- Verapamil
Benzothiazipines- Diltiazem
1,4-Dihydropyridines- Nifedipine, Amlodipine

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3
Q

CCB binding sites

A

Each of the different CCB interacts with a specific domain on different spots of the L-type Ca channel

all three classes influences the gating, so only one class is perscribed at a time

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4
Q

factors that account for the preference of CCB for cardiovascular cells

A

the voltage-sensitive L type Ca channels, which is the binding site on a variety of tissues, including neurons, cardiac cells, vascular smooth muscle and sk muscle

But CCBs dont affect all these cells (only cardiac and vascular smooth muscle cells)

CCBs only have a low affinity of the N and P type in the nervous system, CCBs dont do anything from intracellular stores (Sarco-ret)

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5
Q

sk muscle and CCB

A

sk muscle has a large store of Ca but insensitive CCB relatively. the lack of effect of is due to CCBs not messing with intracellular stores of Ca. sk muscle expresses a diifferent isoform compared to cardiac and vascular variants of the channel

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6
Q

neurons and CCs

A

neurons express L-type Ca channels, but Ca influx through N and P type (neuronal, and purkinje) that mediates NT release, so CCBs have little effect on NT release and few CNS SEs

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7
Q

Cardiac cells and CCs

A

all cardiac cells densely express L-type Ca channels
The upstroke of AP in the SA and aV node depends on Ca Channels, required for contraction of atrial and ventricular muscle cells

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8
Q

Vascular smooth muscle cells and CC

A

vascular smooth muscle cells (VSMCs) rely solely on L-type CCs for excitability and contraction. Most VSMCs do not generate action potentials but have a graded membrane potential, as the VSMCs depolarize the CCs open and Ca influx activates the contractile proteins to mediate a graded contraction

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9
Q

selectivity of CCBs for Cardiac versus arterial muscle

A
each of the three classes of CCBs acts preferentially on either Cardiac muscle or vascular smooth muscle. 
The pheylalkylamines (verapamil) and benzothiazepines (diltiazem) act preferentiallu on cardiac cells. whereas the 1,4 dihydropyridines (nifedipine) act preferentially on arterial muscle cells.
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10
Q

use-dependence of CCBs

A

the activity of a CCB in a particular tissue is affected by the location of the binding site on the channel protein and the frequency of the channel opening.

Verapamil and diltazem- located deep in channel, and access is increased when the channel opens with high frequency. so bc cardiac cells are rapidly firing they are more selective than vascular cells

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11
Q

voltage dependence of CCBs

A

dihydropyridines bind to the outside of the CC. They bind to the depolarized state of the channel with extreme high affinity.

resting membrane potential is highly depolarized compared to cardiac, dihydropyridine bind preferentially to smooth muscle to induce vasodilation (specifically arteries not veins)

dihydropyridines significantly reduce cardiac afterload but not preload

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12
Q

angina which ccb do you use

A

diltiazem is used
reduced cardiac workload (decreases SA node firing rate) and reduces cardiac afterload by causing peripheral vasodilation.
diltiazem is a potential dilator of coronary arteries permitting increased blood flow to the myocardium to prevent or reduce ischemia

dihydropyridines are also used as coronary vasodilators, reduce myocardial oxygen demand and in arterial pressure

dark chocolate= good heart health

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13
Q

supraventricular arrythmias

A

atrial flutter/fibrilation, paroxysmal supraventricular tachycardia- diltiazem/verapamil are useful to reduce the firing rate of the SA node and reduce conduction through AV node. Verapamil is helpful in reducing ventricular response rate if the atria is firing too fast

verapamil + diltiazem are indicated for supraventricular tachychardia

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14
Q

hypertension

A

dihydropyridine (potent vasodilator)
reduced blood pressure can trigger reflex tachycardia. This can increase the workload of the heart, nifedipine should dilate the coronary arteries if healthy to partially offset this challenge.
add a beta blocker (propranolol) in conjuction with dihydropyridines to prevent reflex tachycardia. Nifedipine and other dihydropyridine drugs are contraindicated in tachyarrythmias.

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15
Q

pharmacokinetics of CCBs

A

Absorption- well absorbed after oral admin diltiazem, nifedipine, and nicardipine do not undergo lots of 1st pass metabolism, but verapamil and isradipine undergo extensive 1st pass (big difference between IV and oral)

Protein binding- binding % are higher for the dihydropyridines than either diltiazem or verapamil

t.5= 3-6 hours, there are slow release dihydropyridines cause less reflex tachycardia.

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16
Q

Adverse effects and contraindications

A

Vasodilator SE: hypotN, headache, flushing, peripheral edema via dihydropyridines

Constipation: Verapamil (high affinity of L type in GIT)

congestive heart failure worsening- negative inotropic effect of verapamil precipitate CHF symptoms sometimes

AV block: the dampening effect of verapamil on AV node may produce 2nd or 3rd degree heart block

Diltiazem vs Verapamil: diltiazem (similar, less potent CV effects than verapamil and less dramatic peripheral vasodilation than nifedipine) considered best CCB. av block i spossible to a lesser degree than verapamil

Nifedipine worse if short acting, amlodipine are better tolerated