I like to research drugs that my doctor prescribes me. In this case lisinopril. From wikipedia we can learn a lot about this prescription pharmaceutical drug. I take 20mg twice daily! I like that its a water soluble lysine analog of a poisonous venom extract from the Brazilian Pit Viper snake :) This an example where nature gives a good bioactive template for molecular drug design, onto which good organic biochemistry can be applied to improve the efficacy & reduce toxic side effects!
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 Chemical structure of lisinopril | |
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| Pronunciation | /laɪˈsɪnəprɪl/, ly-SIN-ə-pril |
| Trade names | Prinivil,[1] Zestril,[2] Qbrelis,[3]Dapril,[4] others[5] |
| Other names | (2S)-1-[(2S)-6-amino-2-{[(1S)-1-carboxy-3-phenylpropyl]amino}hexanoyl]pyrrolidine-2-carboxylic acid |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a692051 |
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| Pregnancy category | |
| Routes of administration | By mouth |
| ATC code | |
| Legal status | |
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| Pharmacokinetic data | |
| Bioavailability | approx. 25%, but wide range between individuals (6 to 60%) |
| Protein binding | 0 |
| Metabolism | None |
| Elimination half-life | 12 hours |
| Excretion | Eliminated unchanged in urine |
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| DrugBank | |
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| KEGG | |
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| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.071.332 |
| Chemical and physical data | |
| Formula | C21H31N3O5 |
| Molar mass | 405.495 g·mol−1 |
| 3D model (JSmol) | |
  (what is this?) (verify) | |
Lisinopril is a medication of the angiotensin-converting enzyme (ACE) inhibitor and is used to treat high blood pressure, heart failure, and after heart attacks.[7] For high blood pressure it is usually a first-line treatment. It is also used to prevent kidney problems in people with diabetes mellitus.[7] Lisinopril is taken by mouth.[7] Full effect may take up to four weeks to occur.
Lisinopril was patented in 1978 and approved for medical use in the United States in 1987.[7][9] It is available as a generic medication.[7] In 2019, it was the third most commonly prescribed medication in the United States, with more than 91 million prescriptions.
Lisinopril has a proline group that is responsible for the availability of the drug in oral formulation. The carboxylate group interacts with zinc ions to inhibit the ACE enzyme found in the kidneys and lungs. Lisinopril has a longer duration of action of 24–36 hours.
Lisinopril is an ACE inhibitor, meaning it blocks the actions of angiotensin-converting enzyme (ACE) in the renin–angiotensin–aldosterone system (RAAS), preventing angiotensin I from being converted to angiotensin II. Angiotensin II is a potent direct vasoconstrictor and a stimulator of aldosterone release. Reduction in the amount of angiotensin II results in relaxation of the arterioles. Reduction in the amount of angiotensin II also reduces the release of aldosterone from the adrenal cortex, which allows the kidney to excrete sodium along with water into the urine, and increases retention of potassium ions.[20] Specifically, this process occurs in the peritubular capillaries of the kidneys in response to a change in Starling forces.[21] The inhibition of the RAAS system causes an overall decrease in blood pressure.
Lisinopril has a bioavailability of ~25% (reduced to 16% in people with New York Heart Association Functional Classification (NYHA) Class II–IV heart failure).[1][20] Its time to peak concentration is 7 hours.[1][20] The peak effect of lisinopril is about 4 to 8 hours after administration.[22] Food does not affect its absorption.
Lisinopril does not bind to proteins in the blood.
Lisinopril is the only water-soluble member of the ACE inhibitor class, with no metabolism by the liver.
Lisinopril leaves the body completely unchanged in the urine.[1][20] The half-life of lisinopril is 12 hours, and is increased in people with kidney problems.[1][20] While the plasma half-life of lisinopril has been estimated between 12 and 13 hours, the elimination half-life is much longer, at around 30 hours.[22] The full duration of action is between 24 and 30 hours.
Captopril, the first ACE inhibitor, is a functional and structural analog of a peptide derived from the venom of the jararaca, a Brazilian pit viper (Bothrops jararaca).[24]Enalapril is a derivative, designed by scientists at Merck to overcome the rash and bad taste caused by captopril.[25][26]: 12–13 Enalapril is actually a prodrug; the active metabolite is enalaprilat.[27]
Lisinopril is a synthetic peptide derivative of captopril.[23] Scientists at Merck created lisinopril by systematically altering each structural unit of enalaprilat, substituting various amino acids. Adding lysine at one end of the drug turned out to have strong activity and had adequate bioavailability when given orally; analogs of that compound resulted in lisinopril, which takes its name from the discovery with lysine. Merck conducted clinical trials, and the drug was approved for hypertension in 1987 and congestive heart failure in 1993.[27]
The discovery posed a problem, since sales of enalapril were strong for Merck, and the company did not want to diminish those sales. Merck ended up entering into an agreement with Zeneca under which Zeneca received the right to co-market lisinopril, and Merck received the exclusive rights to an earlier stage aldose reductase inhibitor drug candidate, a potential treatment for diabetes. Zeneca's marketing and brand name, "Zestril", turned out to be stronger than Merck's effort.[28] The drug became a blockbuster for AstraZeneca (formed in 1998), with annual sales in 1999 of $1.2B.[29]
The US patents expired in 2002.[29] Since then, lisinopril has been available under many brand names worldwide; some formulations include the diuretichydrochlorothiazide.[5]
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