Science Drug Lisinopril Presentation

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Drug: LISINOPRIL
Drug uses (what it treats & target patient populations)
Lisinopril is a drug in the class dubbed as angiotensin-converting enzyme (ACE)
inhibitors that function by minimizing particular elements that stiffen the blood vessels to
make sure that blood moves effortlessly and that the heart can propel blood further.
Lisinopril is either used as monotherapy or as a combination with other drugs to
treat high blood pressure in children of six years and above as well as in adults. Besides,
the drug is employed with other drugs to treat heart failure. The drug also has another
use of enhancing survival after a heart attack.
The medication is targeted mainly towards people who suffer from hypertension
and heart failure diseases. High blood pressure is a chronic illness, and when left
untreated, it may have serious harm to the heart, brain, kidney, blood vessels and other
body parts. Besides taking the drug, other lifestyle changes such as exercising at least
thirty minutes a day, consuming foods with low salt and fat, avoiding smoking, keeping a
healthy weight, and consuming alcohol in moderation can assist in managing an
individual’s blood pressure.
FDA approval (information on major clinical trials. Any off-label uses? FDA
guidance, or warnings?)
Lisinopril was licensed for medicinal purposes in 1987 in the United States
following its patenting in 1978. It is a drug that is generically available and had about 91
million prescriptions in 2019 and was the third most usually prescribed medicine in 2019
in America. The initial lisinopril oral solution, Qbrelis, became allowed by the FDA in 2016
July. The enzyme which inhibits conversion of angiotensin is applied in hypertension
treatment. Moreover, it is used in minimizing symptoms and signs of death in patients that
are hemodynamically stable.
Weight-based dosage is currently available for kids of six years and above who
had to depend on an adjusted grown-up dose. Qbrelis oral administration can also be of
help to people who have problems swallowing lisinopril tablets. According to the CEO of
Silvergate Pharmaceuticals, Frank Segrave Qbrelis gives the young ones a ready usable
oral solution and the assurance of a drug that is FDA approved. The drug is available via
extensive pharmacies and a reputable mail-order of business. It is cautious about prenatal
toxicity as it operates directly on the renin-angiotensin system that may kill or harm a
growing fetus.
Side effects of Qbrelis include dizziness, cough, and headache in individuals with
high blood pressure; low blood pressure and chest discomfort in those with systolic failure
of the heart; and renal dysfunction and hypotension in persons with acute myocardial
infarction. One should not use the drug if they are pregnant as it may harm the unborn
child, and if they develop pregnancy, they should stop using the drug and see a physician.
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Besides, if one had angioedema, they should not take the medication as well as
within 36 hours prior to or after taking a heart drug comprising sacubitril, for example,
Entresto. Patients who suffer from disabilities or kidney disease should not take Lisinopril
in conjunction with any drug that has aliskiren, for instance, Tekturna, Amturnide, and
Tekamlo. Additionally, one should not use the drug if they are allergic to any other ACE
inhibitor, for example, enalapril, moexipril, fosinopril, Ramipril, benazepril, perindopril,
captopril, trandolapril, and quinapril. Also, the doctor must be aware of the patient’s health
status and know if they recently suffered from liver or kidney disease, are currently on
dialysis, or have had high potassium levels in their blood.
The intake of Lisinopril, however, has some side effects. Some of the most signs
of allergic reactions to Lisinopril include dizziness, cough, and headache in individuals
with high blood pressure, low blood pressure, chest discomfort in those with systolic
failure of the heart and unembellished stomach discomfort, swelling of the face, throat,
swallowing difficulties, tongue, hives, and difficulty breathing. There are also other
significant adverse effects. It can cause hypersensitivities (allergic) reactions such as
swelling of the tongue, face, lips, and throat, woe breathing, and stomach (abdominal)
agony with or deprived of vomiting and seasickness.
Patients may also develop kidney problems, including fatigue, swelling, especially
in the feet, hands, ankles, weight loss, and dumpiness of breath. It can also cause liver
failure, characterized by yellowing the skin and raised liver enzymes, stomach aches,
nausea, and queasiness. Additionally, this medicine has the potential to cause
dangerously high potassium levels. As a result, arrhythmia may develop (heart rate or
rhythm problems) if a patient suffers from kidney disease or takes medications that
escalate potassium rates in the body.
One should not measure their dose with a household spoon if one takes the
solution. They hence should use a special oral syringe for measuring liquid medications.
Lisinopril will most likely be started at a low dose and gradually increased by a doctor. It
may last two to four weeks before one reaches therapeutic effect of this medicine for the
management of hypertension. Besides, it may last weeks or months for this medicine to
assist them in treating heart failure thoroughly. If their illness does not improve or worsen,
one should contact a physician (for example, if their blood pressure readings remain high
or increase).
It is unknown if this medicine goes into breast milk in breastfeeding mothers. If it
occurs, it could have negative consequences for a breastfed infant. If someone plans to
nurse their child, it is essential to consult a doctor. One may have to choose between
stopping nursing and stop taking this medication. Drugs may be processed more slowly
by seniors. The levels of this medicine in your body may be higher than usual if you take
a standard adult dose. Hence one may require a lesser dose or a different schedule if a
senior. This medicine has not been researched in children under the age of six, and it
should not be used in children under the age of six.
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This medicine may not function as effectively for white patients compared with
black patients in lowering blood pressure. Lisinopril may be used with another medication
prescribed by the doctor, and therefore it’s important to consult a doctor if you an
individual has any concerns.
Physical properties of the drug and how it’s typically formulated and marketed
Lisinopril with the scientific formula C21H31N3O5 and a molecular weight of
405.488 g/mol forms white to off-white crystals. The medication is soluble in methanol to
14 mg/ml and water to around 97 mg/ml. However, it is insoluble in fewer than 0.1 mg/ml
in chloroform, ethanol, acetone, methylene chloride, and dimethylformamide. The drug
lisinopril half-life is 12.6hr and elimination rate is 46.7hr.
Besides the vital component, Lisinopril, every tablet entails sedentary constituents
such as starch, calcium phosphate, magnesium stearate, and mannitola. Also, the 10 mg
and 20 mg doses do have iron oxide. Lisinopril is available as a tablet and a liquid solution
to be taken by mouth. It’s typically just taken once each day. A patient should take
Lisinopril at the same time every day to help you remember to take it. It is essential to trail
the instructions on their drug label prudently. If there is anything they do not comprehend,
they should enquire from a pharmacist or a medic to elucidate it. Lisinopril should be
administered exactly as prescribed. Please, one ought not to take more or less of it or
take it more frequently than the doctor has suggested.
Although higher doses may be required in some patients to get symptomatic relief,
the associated increases have been determined to surpass hazards such as undesirable
side effects and renal damage. Enalapril and captopril are often administered nowadays,
though not as much as Lisinopril. With the exception of Lisinopril, they are primarily used
to treat hypertension and heart failure; nonetheless, they are rarely given for heart attack
recovery. Individual responses to ACE inhibitors have also been researched extensively,
with findings suggesting that particular groups may not benefit in the same way. To
determine the right prescription for you, your doctor will look at your medical history, family
history, and other biological or health behaviors, just like they would with any other drug.
If the doctor or health care provider prescribes Lisinopril for a medical issue, one
can get it with a prescription from any pharmacy. Lisinopril has become much more
affordable for individuals with many of these insurance plans over the years. However,
because Lisinopril is frequently recommended as a long-term medication, people typically
seek to save money on it. Prescription medicine coupons, such as lisinopril coupons, are
available through USA Rx and can help you save money on expensive or routinely
acquired prescriptions for chronic diseases such as hypertension or heart disease. A free
general pharmacy card is also available to help one save money on all FDA-approved
pharmaceuticals and medications.
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Background on the drug, including aspects of its discovery and optimization
Angiotensin-converting enzyme blocker lisinopril is commonly used to treat high
blood pressure, cardiac arrest, and ischemic stroke. Patients are often given 10-80mg
once daily, it has a significant therapeutic index and a lengthy sustained release.
The discovery of ACE inhibitors in the 1960s led to the development of Lisinopril.
ACE inhibitors have their origins in snake venom. A compound recovered from the venom
of the Brazilian snake, Bothrops jararca, was identified to suppress the activity of ACE in
the 1960s. This chemical could connect to ACE in the same way it does spontaneously,
culminating in lowering blood pressure. A quest commenced for synthetic substances
equivalent to the ACE inhibitory substance found in snake venom that might produce
significant symptoms and consequences for blood pressure.
Scientists from the Bristol Meyers Squibb pharmaceutical company sifted through
thousands of components before identifying a synthetic ACE inhibitor that could prevent
additional vessels from contracting. Captopril, the first ACE inhibitor medicine from which
Lisinopril is derived today, was developed from this molecule. Captopril’s potential to
lower blood pressure was established in clinical trials, but the drug’s use eventually led
to a slew of side effects. Captopril required high doses, which resulted in undesired side
effects such as a persistent rash and a loss of taste in people who took it.
Merck scientists created enalapril, a second-generation ACE inhibitor, many years
later in the early 1980s. This medicine has various advantages over captopril, including
a slightly lower dosage requirement and the elimination of captopril’s undesired side
effects. The Co-operative North Scandinavian Enalapril Survival Study found that patients
with heart failure who administered enalapril had a 31 percent lower mortality rate than
those who did not. This groundbreaking study ushered in the use of ACE inhibitors.
However, because these were fast-acting medications, some issues were still with
these early ACE inhibitors. This indicates that the drug is swiftly digested in the body, and
the effects are just temporary. The more frequent dosing can result in additional side
effects and become a financial burden for patients who take the prescription regularly for
chronic disease. This prompted researchers to look for an ACE inhibitor that didn’t require
high doses and lasted longer in the body to treat high blood pressure. Lisinopril was the
name of the new medicine.
Merck later teamed with AstraZeneca to offer Lisinopril under the brand name
Zestril. Lisinopril was approved by the FDA for the treatment of heart failure a few years
later. The generic variant of Lisinopril was introduced to the market in 2002. The generic
medication lisinopril is marketed under the brand names Zestril and Prinivil. Lisinopril is
now also available as lisinopril hydrochlorothiazide, which is a combination of lisinopril
and the diuretic medication hydrochlorothiazide.
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Lisinopril is sourced from enalapril and captopril, but it has been architecturally
changed to be a long-acting, low-side-effect medication. Merck scientists developed
Lisinopril by changing the building elements of the dynamic version of enalapril one by
one. They discovered that adding the amino acid lysine to one end of the medication gave
it the long-acting influence they were after. Lisinopril was named after the amino acid
lysine. Lisinopril became accessible on the market as an FDA-approved medicine,
branded Prinivil, to treat hypertension in 1987, following fruitful clinical trials to evaluate
the effects of the novel treatment.
Ultimately, the invention of Lisinopril has accomplished the goal for which it was
created. It varies from first-generation ACE inhibitors primarily in that it is longer acting
and has improved ‘oral availability,’ which means that more of the drug reaches the
circulation than captopril or enalapril. Lisinopril, unlike enalapril, is not processed by the
liver. Instead, it is dependent on uremic toxins or kidney catabolism. Patients receiving
Lisinopril are regularly checked for normal renal function as a result of this. Patients with
cardiomyopathy are administered Lisinopril with other medicines such as diuretics.
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References
Agarwal, R., Sinha, A. D., Pappas, M. K., Abraham, T. N., & Tegegne, G. G. (2014).
Hypertension in hemodialysis patients treated with atenolol or lisinopril: a
randomized controlled trial. Nephrology Dialysis Transplantation, 29(3), 672-681.
Eveson, D. J., Robinson, T. G., & Potter, J. F. (2007). Lisinopril for the treatment of
hypertension within the first 24 hours of acute ischemic stroke and followup. American journal of hypertension, 20(3), 270-277.
Cappuccio, F. P., Markandu, N. D., Singer, D. R., & MacGregor, G. A. (1993). Amlodipine
and lisinopril in combination for the treatment of essential hypertension: efficacy
and predictors of response. Journal of hypertension, 11, 839-839.
Chrysant, S. G. (1994). Antihypertensive effectiveness of low-dose lisinoprilhydrochlorothiazide combination: a large multicenter study. Archives of internal
medicine, 154(7), 737-743.
Gomez, H. J., Cirillo, V. J., & Moncloa, F. (1987). The clinical pharmacology of
lisinopril. Journal of Cardiovascular Pharmacology, 9, S27-34.
Hertzman, M., Adler, L. W., Arling, B., & Kern, M. (2005). Lisinopril may augment
antidepressant response. Journal of clinical psychopharmacology, 25(6), 618-620.
Naidu, M. U. R., Usha, P. R., Rao, T. R. K., & Shobha, J. C. (2000). Evaluation of
amlodipine, lisinopril, and a combination in the treatment of essential
hypertension. Postgraduate Medical Journal, 76(896), 350-353.
Reisin, E., Weir, M. R., Falkner, B., Hutchinson, H. G., Anzalone, D. A., & Hypertension,
M. L. T. F. T. T. I. O. P. W. (1997). Lisinopril versus hydrochlorothiazide in obese
hypertensive patients: a multicenter placebo-controlled trial. Hypertension, 30(1),
140-145.
Simpson, K., & Jarvis, B. (2000). Lisinopril. Drugs, 59(5), 1149-1167.
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ASSIGNMENT-8: Drug: Lisinopril
Lisinopril is a medication used to treat high blood pressure. Lowering blood
pressure can reduce the risk of stroke, heart attack, or kidney disease. It is also used to
treat heart failure and increase the likelihood of surviving a heart attack.
ADME properties of the drug
Formulations & routes of administration
When novel drug delivery systems are combined with pharmacological parameters
inherent in the route of administration, it is possible to manipulate the pharmacokinetic
and pharmacodynamic parameters of pharmaceutically active moieties (Trachtman et al.,
2015) Lisinopril should be taken once a day by mouth with a glass of water. Every day,
at the same time, Lisinopril, like other once-daily medications, should be taken to maintain
consistency. We don’t have to be concerned about whether or not the foods we eat will
affect how well lisinopril tablets are absorbed. The medication lisinopril, either alone or in
combination with other antihypertensive medications, can be used to treat high blood
pressure. Patients with high blood pressure are usually prescribed a starting dose of ten
milligrams (mg). Patients with a highly active renin-angiotensin-aldosterone system (such
as those suffering from renovascular hypertension, salt and volume depletion, cardiac
decompensation, or severe hypertension) may experience an excessive drop in blood
pressure following the first dose of this medication. If you have this condition, you should
start with a daily dosage of 2.5 to 5 milligrams to see if it helps.
Distribution patterns in the body
Because of lower lisinopril clearance, the reduced absorption of Lisinopril
(approximately 30% as determined by urinary recovery) in cirrhotic patients with impaired
liver function is more significant (about 50%) than in healthy subjects. However, when a
patient has renal impairment, the amount of Lisinopril excreted by the kidneys is reduced;
however, this reduction is only clinically significant when the patient’s GFR falls below
30ml/min. When comparing patients with mild to moderate renal impairment (creatinine
clearance 30-80 mL/min) to patients with severe renal impairment (creatinine clearance
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5-30 mL/min), there was a 13 per cent increase in the mean AUC. Dialysis can be used
to remove Lisinopril from your system if it is no longer needed. During four hours of
hemodialysis, lisinopril plasma concentrations were reduced by 60 per cent on average,
with a dialysis clearance ranging between 40 and 55 millilitres per minute. The AUC of
Lisinopril in heart failure patients is 125 per cent higher than in healthy individuals.
Lisinopril is excreted in the urine by patients with heart failure, whereas it is passed by
healthy subjects by 16 per cent less. When comparing elderly patients to younger ones,
there is a 60% increase in the area under the plasma concentration-time curve for the
elderly. The drug lisinopril was found to reach steady-state plasma concentrations in six
hours and to have a urinary recovery rate of 28 per cent when administered at doses
ranging from 0.1 to 0.2 mg/kg. It’s reassuring to see values in children that are so similar
to those found in their elders.
Metabolism
&
excretion
of
drugs,
including
key
interactions
with
CYPs/transporters/etc
Following oral lisinopril administration, patients with acute myocardial infarction
(AMI) may experience a slight delay in reaching peak serum concentrations. This delay,
however, usually resolves within 7 hours. According to urinary recovery data, Lisinopril
has a mean absorption rate of approximately 25%, with inter-patient variability ranging
from 6 per cent to 60% over the study dose range. (5-80mg). Patients suffering from heart
failure have a 16 per cent reduction in absolute bioavailability. Food has no effect on
Lisinopril absorption, which means it can be taken with food. Lisinopril does not appear
to be bound to serum proteins except in the presence of a circulating angiotensinconverting enzyme (ACE). According to the researchers, the preliminary findings suggest
that Lisinopril has a limited ability to cross the blood-brain barrier in rats. Because it does
not undergo oxidation or metabolization within the body, a pure form of Lisinopril is
excreted in the urine as a metabolite. Once the half-life of accumulation of Lisinopril has
been reached after multiple doses have been taken, it takes 12.6 hours. In healthy
individuals, Lisinopril is excreted in the urine at a rate of 50 mL per minute, and it is
eliminated through the kidneys. There is a prolonged terminal phase during which serum
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concentrations decrease, but this does not contribute to drug accumulation and is not
harmful to the patient’s health. If the ACE binding has reached its maximum saturation
point, this final phase is most likely the result of that saturation point.
General PK parameters
Participants in the study who received high doses of the medication were
compared to those who received low doses (2.5mg or 5mg once daily). According to a
survey of 364 patients with a median follow-up period of 46 months, patients taking high
doses of Lisinopril were 12 per cent less likely to die from any cause and 8 per cent less
likely to be admitted to the hospital than those taking low doses of the drug, according to
the findings. It was discovered that there was an 8 per cent reduction in all-cause mortality
risk and a 10 per cent reduction in cardiovascular mortality risk. When comparing patients
receiving high doses of Lisinopril to those receiving low doses, it was found that the
number of heart failure hospitalizations was reduced by 24 per cent.
Important drug-drug PK interactions
Angiotensin-converting enzyme inhibitors, such as Lisinopril, are not affected by
our foods. The oral bioavailability of this medication is 25 per cent +/- 4 per cent, and it
does not affect the oral bioavailability of other medicines. A 40-hour terminal serum halflife is required to account for the average accumulation half-life of 12.6 hours, but more
evidence is needed to support this estimate. A steady state is reached after two daily
doses of the drug are administered to healthy volunteers for an extended period (every
24 hours). This medication is excreted by the kidneys rather than being metabolized, as
is the case with most drugs. The kidneys filter, secrete, and then reabsorb Lisinopril back
into the tubules in most cases.
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Likely & confirmed biological targets of the medication and the mechanism(s) of
action
Efficacy? Potency? Selectivity?
According to the findings, patients at high risk (those aged 70 and older) and females
were found to benefit from combined mortality and cardiac function endpoint. Lisinopril or
Lisinopril combined with glyceryl trinitrate for six weeks was significantly beneficial in all
patients and high-risk subgroups, suggesting that Lisinopril has a preventive effect after
six months. As would be expected for a vasodilator drug, hypotension and renal
dysfunction were more common than expected. Still, the increased risk of death was not
proportional to these side effects as would be expected.
When taken once daily for 12 months, Lisinopril reduced blood pressure by
13/10mmHg and urinary albumin excretion by 40% in patients with Type 2 diabetes who
were also hypertensive and had incipient nephropathy, according to a three-centre study.
Participants taking Lisinopril had significantly lower urinary albumin excretion rates than
those taking a calcium channel blocker, suggesting that the drug’s ACE inhibitory action
reduces microalbuminuria through a mechanism unrelated to its blood-pressure-lowering
effects. By their HbA1c levels, patients taking Lisinopril had no statistically significant
impact on their glycemic control (HbA1c) levels.
Important drug-drug PD interactions
It is believed that Lisinopril’s primary mechanism of action is suppression of the
renin-angiotensin-aldosterone system; however, it has antihypertensive effects even in
patients with low renin hypertension (low renin hypertension) (renin-deficient
hypertension). In terms of structure, Kininase II, an enzyme that degrades the
neurotransmitter bradykinin, is very similar to the enzyme ACE. Although it has not been
thoroughly investigated, increased levels of the vasodilatory peptide bradykinin may be
responsible for the heart-healthy effects of Lisinopril.
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References
Hachad, H., Ragueneau-Majlessi, I., & Levy, R. H. (2010). A valuable tool for drug
interaction evaluation: the University of Washington Metabolism and Transport
Drug Interaction Database. Human genomics, 5(1), 1-12.
Leary, A. C., Dowling, M., Wilson, A., McKenna, B., & Rothwell, J. (2006). A single-dose,
randomized, crossover study to compare the rate and extent of absorption of
lisinopril solution versus tablets in healthy volunteers. Paediatric and Perinatal
Drug Therapy, 7(4), 178.
Benet, L. Z., Cummins, C. L., & Wu, C. Y. (2003). Transporter-enzyme interactions:
implications for predicting drug-drug interactions from in vitro data. Current drug
metabolism, 4(5), 393-398.
Li, E. C., Heran, B. S., & Wright, J. M. (2014). Angiotensin-converting enzyme (ACE)
inhibitors versus angiotensin receptor blockers for primary hypertension. Cochrane
Database of Systematic Reviews, (8).
Ogawa, R., Stachnik, J. M., & Echizen, H. (2014). Clinical pharmacokinetics of drugs in
patients with heart failure: an update (part 2, drugs administered orally). Clinical
pharmacokinetics, 53(12), 1083-1114.
Trachtman, H., Frymoyer, A., Lewandowski, A., Greenbaum, L. A., Feig, D. I., Gipson, D.
S., … & Best Pharmaceuticals for Children Act–Pediatric Trials Network
Administrative Core Committee. (2015). Pharmacokinetics, pharmacodynamics,
and safety of Lisinopril in pediatric kidney transplant patients: implications for
starting dose selection (2012). Clinical Pharmacology & Therapeutics, 98(1), 2533.