two Discussion Responses
REPLY1:
Some people have a genetic predisposition to high blood cholesterol, which may
necessitate medication to reduce the levels. Low-density lipoprotein (LDL) cholesterol is
crucial as high levels can increase individuals’ risk for stroke and heart disease. For this
reason, several drugs have been instituted that may be prescribed to decrease LDL.
Among these therapies, statin and nicotinic acid (niacin) are notable examples. Here,
these two drugs have distinct mechanisms of action, side effects, and efficacies.
Statins are a widely prescribed class of drug for lowering LDL cholesterol. According
to Ward et al. (2019), the medication’s mechanism of action entails blocking
hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase’ active site. Inhibiting this
enzyme’s active site blocks its conversion to mevalonic acid (Ward et al., 2019). The
blockage decreases the liver’s hepatic cholesterol synthesis, which results in higher
production of microsomal HMG-CoA and higher LDL receptor expression. These
increases allow increased clearance of LDL cholesterol from the bloodstream, resulting
in reduced LDL cholesterol levels (Ward et al., 2019). Therefore, statins work by blocking
HMG-CoA reductase, which the liver uses to make cholesterol.
Several side effects and efficacy issues emerge from the use of Statins. Regarding
the side effects, muscle pain and liver damage are common. Ward et al. (2019) highlight
that muscle problems are the most prevalent, with up to 72% of statin side effects being
muscle-related. The problems can present as myopathy, myalgia, and, in rare cases,
rhabdomyolysis (life-threatening muscle damage) (Newman et al., 2019). Occasionally,
statins increase the level of enzymes that cause liver inflammation and whose
prolonged production can result in tissue damage. Blood sugar levels may also increase
with statin use, leading to the development of type 2 diabetes. The last notable side
effect is an increased risk of hemorrhagic stroke (Ward et al., 2019; Newman et al.,
2019). Regarding efficacy, statins have been noted to be largely effective in reducing
LDL levels and associated conditions. In fact, Newman et al. (2019) note that these
drugs lower LDL cholesterol levels by 55-60% at the maximal doses. Likewise, these
drugs have been found effective in reducing the incidence of cardiovascular diseases.
Niacin (nicotinic acid) is another common class of drugs employed in blood LDL
reduction. In contrast to statins, niacin’s working mechanism involves inhibiting adipose
tissue lipolysis by activating the hydroxycarboxylic acid 2 receptor (GPR 109A) (Romani
et al., 2019)). This inhibition reduces triglycerides’ breakdown to free fatty acids and
their subsequent transport to the liver, which decreases hepatic triglyceride synthesis.
Once triglyceride synthesis is reduced, very low lipoprotein (VLDL) secretion is inhibited
from hepatocytes, which eventually decreases LDL cholesterol production (Romani et
al., 2019). Thus, niacin’s primary mechanism of action involves inhibiting adipose tissue
lipolysis by activating the GPR 109A receptor.
Like statin, niacin also presents several side effects. One significant effect is skin
flushing, which is characterized by warmth and redness due to the vasodilation of blood
vessels (Feingold, 2021). This symptom is common in the neck and head region. The
other significant side effect is liver toxicity. Here, high niacin serum levels can
overwhelm nicotinic acid receptors, which can cause a form of hepatotoxicity in the liver
(Feingold, 2021). Other notable effects include abdominal discomfort, coughing,
nausea, and increased blood sugars. Regarding the efficacy, niacin has been shown
through several meta-analyses to reduce LDL cholesterol by up to 14% (Feingold, 2021).
Such effectiveness is significant given niacin’s manageable side effects.
Statin and niacin are among the most common LDL cholesterol-reducing drugs.
Concerning their mechanisms of action, statin blocks HMG-CoA reductase, while niacin
activates the GPR 109A receptor to inhibit adipose tissue lipolysis. Statin side effects
include muscle problems, liver damage, and increased risk for hemorrhagic stroke and
type 2 diabetes, while niacin’s encompass skin flushing, nausea, liver toxicity, abdominal
discomfort, and increased blood sugars. Concerning the efficacies, statin reduces LDL
cholesterol by 55-60%, while niacin manages a 14% maximum reduction. Regardless of
the outcomes or effects, both drugs have distinct benefits as LDL cholesterol-lowering
therapies.
References
● Feingold, K. R. (2021). Triglyceride lowering drugs. Endotext [Internet].
https://www.ncbi.nlm.nih.gov/books/NBK425699/
● Newman, C. B., Preiss, D., Tobert, J. A., Jacobson, T. A., Page, R. L., Goldstein,
L. B., Chin, C., Tannock, L. R., Miller, M., Raghuveer, G., Duell, B., Brinton, E. A.,
Pollak, A., Braun, L. T., & Welty, F. K. (2019). Statin safety and associated
adverse events: A scientific statement from the American Heart Association.
Arteriosclerosis, Thrombosis, and Vascular Biology, 39(2), 38-81.
https://doi.org/10.1161/ATV.0000000000000073
● Romani, M., Hofer, D. C., Katsyuba, E., & Auwerx, J. (2019). Niacin: An old lipid
drug in a new NAD+ dress. Journal of Lipid Research, 60(4), 741-746.
https://doi.org/10.1194/jlr.S092007
● Ward, N. C., Watts, G. F., & Eckel, R. H. (2019). Statin toxicity: Mechanistic
insights and clinical implications. Circulation Research, 124(2), 328-350.
https://doi.org/10.1161/CIRCRESAHA.118.312782
REPLY2:
According to Mandeville et. all (2019), bile acid sequestrants are a medication that can be used
alone or in tandem with statins and often alongside exercise in order to treat high cholesterol. Bile
acid sequestrants are one of the generally accepted alternatives to the use of statins. They are both
used to lower the levels of LDL cholesterol and both slightly raise the levels of HDL. Some possible
side effects of statins are constipation, elevated levels of blood sugar, cramps, nausea, diarrhea,
higher levels of enzymes in the liver, stomach pain, muscle pain, etc. According to Ezad et. all (2018),
in some, but very rare, serious cases of affliction due to statins, some individuals have developed
rhabdomyolysis. Some possible side effects of bile acid sequestrants are heartburn nausea, gas,
bloating, and constipation. The side effects of bile acid sequestrants are generally lesser than that of
the standard statins. The reason for this is simple: they are not absorbed in the gastrointestinal tract.
The side effects of bile acid sequestrants are also more evident in cases where large doses are
taken or the individual is older. The mechanism of bile acid sequestrants works since it is insoluble
by nature, so it passes straight through our digestive tracts. Doing so directly causes a decline of bile
acids to virtually zero within the enterohepatic circulation. Due to its indigestible nature, the chemical
nature of the complex that was formed from the drug remains unchanged. When the bile acid levels
continue to decline within the body, hepatic cholesterol begins to be converted into bile acids since
there is no longer an inhibition from cholesterol 7-alpha hydroxylase. Since cholesterol 7-alpha
hydroxylase is the rate-limiting step in bile acid production, there begins a reduction in the overall
hepatic cholesterol as well as the upregulation of hepatic LDL receptors. One is also able to witness
a direct decline in the levels of LDL-C concentrations within the blood, and consequently there is a
decrease in LDL blood concentrations. Next, statins specifically and selectively inhibit
hydroxymethylglutaryl-CoA reductase. Hydroxymethylglutaryl-CoA reductase is an enzyme that is
directly responsible for the conversion of HMG-CoA to mevalonate within the cholesterol synthesis
pathway. Since cholesterol synthesis becomes stunted, both LDL receptors and uptake of LDL itself
from within the circulation begins to occur. The method of administration for the two are mostly the
same as they both come and are taken in pill form. With that being said, bile acid sequestrants are
also offered via oral suspension generally in the form of powder in a packet. It is standard with these
medications just as many others to be recommended to take them around the time of a meal. The
possible issues with administration have not been fully investigated yet. For example, there is no
evidence or data to conclude about the safety of taking bile acid sequestrants for pregnant mothers,
individuals with hepatic impairment, as well as several other specific cases. According to
Lent-Schochet et. all (2022), there exist quite specific contraindications such as the involvement of
Cholestyramine in the medication. Some individuals that have biliary obstruction where bile is not
secreted into the intestine will exhibit further issues due to the medication. Within the formula for the
drug is also phenylalanine, so individuals who are afflicted with phenylketonuria (inherent inability to
metabolize phenylalanine) should avoid use of the drug.
References:
Mandeville, W. H., & Arbeeny, C. (2019). Bile acid sequestrants: their use in combination with other
lipid-lowering agents. IDrugs : the investigational drugs journal, 2(3), 237–242.
Ezad, S., Cheema, H., & Collins, N. (2018). Statin-induced rhabdomyolysis: a complication of a
commonly overlooked drug interaction. Oxford medical case reports, 2018(3), omx104.
https://doi.org/10.1093/omcr/omx
Order an Essay Now & Get These Features For Free:
Turnitin Report
Formatting
Title Page
Citation
Outline
