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BIOCHEMISTRY
One key, essentially
obvious question still remains, how does ATENOLOL actually
work ? In contrast to the simplicity of the question, the
biochemistry involved with the pharmacology of the drug
involves a diversity of complex interactions with other
chemicals in the body which shall now be explored.
SO HOW DOES IT ACTUALLY
WORK ?
As briefly discussed earlier,
ATENOLOL
is a BETA
BLOCKER, specifically
a beta-1 (ß-1) cardioselective adrenoreceptor
blocking agent. ATENOLOL actively
restricts certain nerve impulses, thereby controlling the
rate and force of contraction, consequently reducing blood
pressure. The impulse hormones inhibited are adrenaline
(left) and noradrenaline (right), as shown below.
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The human body
contains target cells, called receptors which act to receive
chemicals released from glands or nerves. The transmitter
hormone released by the adrenal glands is known as adrenaline
(epinephrine) and for the sympathetic flight or fight
response, the transmitter excreted by the nerves is
called noradrenaline (norepinephrine). The complimentary
receptors for these chemicals are alpha
and beta-adrenergic. Sympathetic activity
is communicated to tissues through involuntary (autonomic)
nerve impulses and through the blood. The acceptor site
and mechanism is demonstrated below, the hormone (adrenaline)
inducing the ATP to cAMP
conversion.
The ß-1
receptors are substantially postsynaptic and are predominately
found in the heart. Their activation causes an increase
in the rate of contraction of the heart and presynaptically
the receptors induces an inflation of noradrenaline production.
ATENOLOL, fundamentally inhibits such mechanisms.
During activation,
whether it be traced to a flight or fight or a
parasympathetic transducer, the body naturally excretes
various hormones to trigger the body into supplying more
oxygen to muscles and cells as a response to the changing
conditions. This inherently means the heart is forced to
work harder in pumping oxygenated blood around the body.
The endocrine system responds to beta-adrenergic receptor
stimulation by increasing blood sugar levels, inducing a
faster heart rate and producing stronger heart contractions
all by means of secreting adrenaline. This fundamentally
results in an increase of blood pressure. This is where
ATENOLOL plays a vital importance. Essentially,
ATENOLOL blocks the receptor targets on
heart muscle cells and prevents epinephrine and norepinephrine
from stimulating the cardiovascular system. These chemicals
typically increase heart rate, strength, and activity leading
to elevated blood pressure. ATENOLOL inhibits
these effects.
The diagram below illustrates
the effect of Beta-blockers, such as ATENOLOL
and the beta blocker Propanolol, which was mentioned earlier.
One key subsequent effect
is the dilation of arteriolar resistance vessels, which
help reduce symptoms of arrhythmias and minimise cardiovascular
stress. This is more widely and specifically known as the
effects of angiotensin-converting enzyme (ACE) Inhibitors,
such the drug, Ramipril ®. In addition to inhibiting
certain hormone receptors, they are also considered vasodilators,
by virtue on their effect of dilating blood vessels which
inherently reduces the effects of hypertension. ATENOLOL
adopts similar properties in the sense that blood is allowed
to flow through a wider area, reducing pressure and minimising
cardiovascular stress. This is vital for conditions such
as Atherosclerosis. Atherosclerosis describes
the narrowing of arteries by virtue of the buildup of plaque
along the inner lumen. The plaques consist fundamentally
from fat and cholesterol deposits but also contain blood
platelets, decomposing muscle cells, and other tissue. The
net effect is the reduction in blood flow through arteries.
As demonstrated above, the beta blockers induce a nitrate
pathway, which give rise to vasodilation. Inherently,
the nitrates are members of a group of drugs known as nitrovasodilators.
The effect of nitrates, includes dilation of stenotic, atherosclerotic
and coronary arteries albeit their biochemical mechanism
is unknown. Nitrogylcerines actively
penetrate the vascular endothelium and are consequently
reduced to nitric oxide (NO), nitrosothiols and s-nitrosocysteine.
Nitric oxide, (NO) is the most vital of these compounds
and it is produced from the amino acid L-arginine.
As mentioned previously, the biomechanics by which nitroglycerine
is denitrogenated to nitric oxide (NO) is uncertain.
One principle idea is that nitric oxide exercises its vascular
effects by activating the enzyme guanylate cyclase, which
converts guanosine triphosphate (GTP) to cyclic guanosine
monophosphate (cGMP). cGMP consequently produces phosphorylation
of protein kinase, which decreases cytosolic calcium and
produces smooth muscle relaxation as illustrated above.
