SUBMITTED BY:

FAIZA LIAQAT ~ L1F20PHMD0002

SUBMITTED TO:

Mam Maria

ASSIGNMENT

Calcium Channel
Blockers
Calcium Channel Blockers
Calcium channel blockers work to decrease the amount of calcium that enters cardiac and
smooth muscle cells. This is done by blocking voltage-gated calcium channels which results in
dilation of blood vessels hence improving oxygen supply to the cardiac tissue

Calcium channel blockers (CCBs) are used in the management of hypertension, angina pectoris,
supraventricular arrhythmias, subarachnoid hemorrhage, pulmonary hypertension, and for the
prevention of migraine

They work by preventing calcium from entering the cells of the heart and arteries. Calcium
causes the heart and arteries to contract more strongly. By blocking calcium, calcium channel
blockers allow blood vessels to relax and open.. Some calcium channel blockers can also slow
the heart rate, which can further lower blood pressure.

Mechanism Of Action
Calcium is an electrolyte, which means it has a positive charge when it’s dissolved in water.
Your body uses ions (atoms with an electrical charge) in electrolytes to transport things into and
out of your cells. Your body is always working to balance things out. That means when calcium
ions enter a cell, sodium ions leave, and vice versa.

Those ions enter and exit your cells using channels, which act just like doorways to the inside of
your cells. Those channels also have a type of security feature, which only allows ions that have
the right type of charge (either positive or negative) and the right size to enter and exit.

Calcium channel blockers take advantage of the fact that certain types of calcium channels tend
to exist only in certain parts of the body. This allows targeting of medications depending on
which channels they affect.

There are many calcium channels on each of the cells in question. At the right dosage, calcium
channel blockers (sometimes calcium channel antagonists) only block some — but not all — of
them. That slows down those cells’ use of calcium because there are fewer ways to bring it
inside.
Calcium-channel blockers target L-type calcium channels and binds to them. These L-type
calcium channels are located on the smooth muscle of vessels, cardiac myocytes, and nodal
tissues in heart. These channels regulate the entry of calcium into muscle cells, which stimulates
smooth muscle and cardiac myocyte to contract.Vasodilation occurs when calcium entry is
blocked this way into cells. Hence there will be decrease in myocardial force generation
(negative inotropy), decrease in heart rate (negative chronotropic), and decrease in conduction
velocity within the heart (negative dromotropic)

Categories
CCBs are often classify into two major categories, either non-dihydropyridines or
dihydropyridines, based on their primary physiologic effects.

 Dihydropyridine
Dihydropyridine (DHP) calcium channel blockers are derived from the
molecule dihydropyridine and often used to reduce systemic vascular resistance and arterial
pressure. Sometimes when they are used to treat angina, the vasodilation and hypotension can
lead to reflex tachycardia, which can be detrimental for patients with ischemic symptoms
because of the resulting increase in myocardial oxygen demand. Dihydropyridine calcium
channel blockers can worsen proteinuria in patients with nephropathy

General chemical structure of dihydropyridine calcium channel blockers (dipines)

 Non-dihydropyridine
 Phenylalkylamine

Skeletal formula of verapamil

Phenylalkylamine calcium channel blockers are relatively selective for myocardium, reduce
myocardial oxygen demand and reverse coronary vasospasm, and are often used to treat angina.
They have minimal vasodilatory effects compared with dihydropyridines and therefore cause less
reflex tachycardia, making it appealing for treatment of angina, where tachycardia can be the
most significant contributor to the heart's need for oxygen. Therefore, as vasodilation is minimal
with the phenylalkylamines, the major mechanism of action is causing negative inotropy.
Phenylalkylamines are thought to access calcium channels from the intracellular side, although
the evidence is somewhat mixed.
 Benzothiazepine
 Structural formula of diltiazem
Benzothiazepine calcium channel blockers belong to the benzothiazepine class of compounds
and are an intermediate class between phenylalkylamine and dihydropyridines in their selectivity
for vascular calcium channels. By having both cardiac depressant and vasodilator actions,
benzothiazepines are able to reduce arterial pressure without producing the same degree of reflex
cardiac stimulation caused by dihydropyridines.
Diltiazem (Cardizem) (also used experimentally to prevent migraine)[citation needed]
Nonselective[edit]
While most of the agents listed above are relatively selective, there are additional agents that are
considered nonselective. These
include mibefradil, bepridil, flunarizine (BBB crossing), fluspirilene (BBB crossing), and fendiline

Dihydropyridines Non- Diyhydropyridines

Amlodipine Diltiazem (benzothiazepine)

Felodipine Verapamil (phenylalkamine)

Nicardipine

Nifedipine
 Nimodipine

Nisoldipine

Isradipine

Side effects
Side effects of these drugs may include but are not limited to:
o Constipation
o Peripheral edema, which can occur in as much as 70% of people receiving calcium
channel blocker, is caused by calcium channel blockers' preferential arteriolar or
precapillary dilation without commensurate dilation in the venous or postcapillary
circulationSince lymphatic drainage relies on contraction of the smooth muscle inside the
lymphatic vessel supported by voltage-gated calcium channels, inhibition of voltage-
gated calcium channel poses a threat towards lymphatic removal of interstitial fluid
essential for normal lymphatic system functioning
o Gingival overgrowth

Contraindications
Non-dihydropyridines are contraindicated in those with heart failure with reduced ejection
fraction, second or third-degree AV blockade, and sick sinus syndrome because of the possibility
of causing bradycardia and worsening cardiac output.

Calcium channel antagonists are also contraindicated in patients with known hypersensitivity to
the drug or its components. Other contraindications include sick sinus syndrome (except in
patients with an artificial pacemaker), severe hypotension, acute myocardial infarction, and
pulmonary congestion. Calcium channel antagonists may cause AV blockade or sinus
bradycardia, especially if taken with agents known to slow cardiac conduction. There are reports
of dermatologic reactions and hypotension with or without syncope with calcium channel
antagonist use. Peripheral edema may occur within 2 to 3 weeks of initiating calcium channel
blocker therapy.

Toxicity
Hypotension and bradycardia are the primary features seen in calcium channel antagonist
poisoning. These findings are due to peripheral vasodilatation and reduced cardiac contractility.

Hypotension may be profound and life-threatening; it results from peripheral vasodilation,

bradycardia, and decreased ionotropy. Cardiac conduction may also suffer impairment with AV
conduction abnormalities, complete heart block, and idioventricular rhythms.

Patients may present asymptomatic initially and progress rapidly to severe hypoperfusion and
cardiovascular collapse. Symptoms may include lightheadedness, fatigue, change in mentation,
syncope, coma, and sudden death. Non-cardiac symptoms may include nausea and vomiting,
metabolic acidosis secondary to hypoperfusion, and hyperglycemia from the blockade of insulin
release in the pancreas. The insulin blockade also impairs the uptake of glucose by myocardial
cells, which further contributes to the reduction of cardiac contractility and worsens hypotension.
Severe poisoning can lead to pulmonary edema, presumably as a result of precapillary
vasodilation and increased transcapillary pressure.

References
 https://www.physio-pedia.com/Calcium_Channel_Blockers
 https://www.ncbi.nlm.nih.gov/books/NBK482473/
 https://my.clevelandclinic.org/health/treatments/22316-
calcium-channel-blockers
 https://www.mayoclinic.org/diseases-conditions/high-blood-
pressure/in-depth/calcium-channel-blockers/art-
20047605#:~:text=Calcium%20channel%20blockers%20are
%20medicines,vessels%20to%20relax%20and%20open.
 https://www.osmosis.org/learn/Calcium-
channel_blockers:_Nursing_Pharmacology