Chemical: Drug
lisinopril

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.


1. FDA Label for lisinopril

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Angioedema
    • Indications & usage section, Contraindications section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Cough
    • Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Death
    • Contraindications section, Warnings section, Precautions section
    • source: PHONT
  • Diabetes Mellitus, Type 1
    • Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Heart Failure
    • Indications & usage section, Contraindications section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Hypertension
    • Indications & usage section, Contraindications section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Myocardial Infarction
    • Indications & usage section, Contraindications section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Stroke
    • Warnings section, Adverse reactions section
    • source: PHONT

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for lisinopril

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA
rs11122576 NC_000001.10:g.230846679T>C, NC_000001.11:g.230710933T>C, NG_008836.1:g.8658A>G, NM_000029.3:c.-3-80A>G, rs58482950, rs59792559
T > C
SNP
No VIP available CA No Variant Annotations available
rs12143842 NC_000001.10:g.162033890C>T, NC_000001.11:g.162064100C>T, rs59411707
C > T
SNP
No VIP available CA VA
rs1799722 NC_000014.8:g.96671139C>T, NC_000014.9:g.96204802C>T, NM_000623.3:c.-192C>T, XM_005267979.1:c.-197C>T, XM_005267980.1:c.-2965C>T, XM_005267981.1:c.-439C>T, rs60242377
C > T
SNP
rs1799752 NC_000017.10:g.61565890_61565891insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, NC_000017.10:g.61565890_61565891insG, NC_000017.11:g.63488529_63488530insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, NC_000017.11:g.63488529_63488530insG, NG_011648.1:g.16457_16458insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, NG_011648.1:g.16457_16458insG, NM_000789.3:c.2306-119_2306-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, NM_000789.3:c.2306-119_2306-118insG, NM_001178057.1:c.584-119_584-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, NM_001178057.1:c.584-119_584-118insG, NM_152830.2:c.584-119_584-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, NM_152830.2:c.584-119_584-118insG, XM_005257110.1:c.1757-119_1757-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, XM_005257110.1:c.1757-119_1757-118insG, XM_006721737.2:c.644-119_644-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, XM_006721737.2:c.644-119_644-118insG
- > ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC
- > G
indel
No VIP available CA No Variant Annotations available
rs200148 NC_000006.11:g.143345696G>A, NC_000006.12:g.143024559G>A, NR_038987.1:n.595-2606C>T, rs61230468, rs629392
G > A
SNP
No VIP available CA VA
rs3025058 NC_000011.9:g.102715948_102715949insA, NG_012100.1:g.3394_3395insT, NM_002422.4:c.-1672_-1671insT, NW_003871077.1:g.13452_13453insA, rs144886253, rs61423715, rs66847152, rs66847153, rs72520913, rs72562167
- > A
indel
No VIP available CA VA
rs4291 NC_000017.10:g.61554194T>A, NC_000017.11:g.63476833T>A, NG_011648.1:g.4761T>A, NM_000789.3:c.-262T>A, XM_005257110.1:c.-717T>A
T > A
SNP
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
  • lisinopril
Trade Names
  • Acercomp
  • Inhibril
  • Linopril
  • Lisinopril Dihydrate
  • Lisipril
  • Lysinopril
  • Noperten
  • Presiten
  • Prinivil
  • Prinzide
  • Renacor
  • Sinopril
  • Zestoretic
  • Zestril
Brand Mixture Names
  • Prinzide (Hydrochlorothiazide + Lisinopril)
  • Zestoretic Tab 10/12.5mg (Hydrochlorothiazide + Lisinopril)
  • Zestoretic Tab 20/12.5mg (Hydrochlorothiazide + Lisinopril)
  • Zestoretic Tab 20/25mg (Hydrochlorothiazide + Lisinopril)

PharmGKB Accession Id

PA450242

Type(s):

Drug

Description

Lisinopril is a potent, competitive inhibitor of angiotensin-converting enzyme (ACE), the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Lisinopril may be used to treat hypertension and symptomatic congestive heart failure, to improve survival in certain individuals following myocardial infarction, and to prevent progression of renal disease in hypertensive patients with diabetes mellitus and microalbuminuria or overt nephropathy.

Source: Drug Bank

Indication

For the treatment of hypertension and symptomatic congestive heart failure. May be used in conjunction with thrombolytic agents, aspirin and/or beta-blockers to improve survival in hemodynamically stable individuals following myocardial infarction. May be used to slow the progression of renal disease in hypertensive patients with diabetes mellitus and microalbuminuria or overt nephropathy.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Lisinopril, one of the few ACE inhibitors that is not a prodrug, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Lisinopril also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors.

Source: Drug Bank

Pharmacology

Lisinopril is an orally active ACE inhibitor that antagonizes the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may further sustain the effects of lisinopril by causing increased vasodilation and decreased blood pressure.

Source: Drug Bank

Food Interaction

Lisinopril decreases the excretion of potassium. Salt substitutes containing potassium increase the risk of hyperkalemia.|High salt intake may attenuate the antihypertensive effect of lisinopril.|Herbs that may attenuate the antihypertensive effect of lisinopril include: bayberry, blue cohash, cayenne, ephedra, ginger, ginseng (American), kola and licorice.|Take without regard to meals.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Does not undergo metabolism, excreted unchanged in urine.

Source: Drug Bank

Protein Binding

Lisinopril does not appear to be bound to serum proteins other than ACE.

Source: Drug Bank

Absorption

Approximately 25%, but widely variable between individuals (6 to 60%) in all doses tested (5-80 mg); absorption is unaffected by food

Source: Drug Bank

Half-Life

Effective half life of accumulation following multiple dosing is 12 hours.

Source: Drug Bank

Toxicity

Symptoms of overdose include severe hypotension, electrolyte disturbances, and renal failure. LD 50= 2000 mg/kg(orally in rat). Most frequent adverse effects include headache, dizziness, cough, fatigue and diarrhea.

Source: Drug Bank

Route of Elimination

Lisinopril does not undergo metabolism and is excreted unchanged entirely in the urine.

Source: Drug Bank

Chemical Properties

Chemical Formula

C21H31N3O5

Source: Drug Bank

Isomeric SMILES

c1ccc(cc1)CC[C@@H](C(=O)O)N[C@@H](CCCCN)C(=O)N2CCC[C@H]2C(=O)O

Source: OpenEye

Canonical SMILES

NCCCC[C@H](N[C@@H]

Source: Drug Bank

Average Molecular Weight

405.4879

Source: Drug Bank

Monoisotopic Molecular Weight

405.226371117

Source: Drug Bank

SMILES

NCCCC[C@H](N[C@@H](CCC1=CC=CC=C1)C(O)=O)C(=O)N1CCC[C@H]1C(O)=O

Source: Drug Bank

InChI String

InChI=1S/C21H31N3O5/c22-13-5-4-9-16(19(25)24-14-6-10-18(24)21(28)29)23-17(20(26)27)12-11-15-7-2-1-3-8-15/h1-3,7-8,16-18,23H,4-6,9-14,22H2,(H,26,27)(H,28,29)/t16-,17-,18-/m0/s1

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
ACE (source: Drug Bank )
ACE2 (source: Drug Bank )
AGT (source: Drug Bank )

Drug Interactions

Interaction Description
amiloride - lisinopril Increased risk of hyperkaliemia (source: Drug Bank )
amiloride - lisinopril Increased risk of hyperkaliemia (source: Drug Bank )
clozapine - lisinopril Lisinopril increases the effect and toxicity of clozapine (source: Drug Bank )
clozapine - lisinopril Lisinopril increases the effect and toxicity of clozapine (source: Drug Bank )
lisinopril - amiloride Increased risk of hyperkaliemia (source: Drug Bank )
lisinopril - amiloride Increased risk of hyperkaliemia (source: Drug Bank )
lisinopril - clozapine Increases the effect and toxicity of clozapine (source: Drug Bank )
lisinopril - clozapine Increases the effect and toxicity of clozapine (source: Drug Bank )
lisinopril - drospirenone Increased risk of hyperkaliemia (source: Drug Bank )
lisinopril - lithium The ACE inhibitor increases serum levels of lithium (source: Drug Bank )
lisinopril - lithium The ACE inhibitor increases serum levels of lithium (source: Drug Bank )
lisinopril - potassium Increased risk of hyperkaliemia (source: Drug Bank )
lisinopril - potassium Increased risk of hyperkaliemia (source: Drug Bank )
lisinopril - spironolactone Increased risk of hyperkaliemia (source: Drug Bank )
lisinopril - spironolactone Increased risk of hyperkaliemia (source: Drug Bank )
lisinopril - tizanidine Tizanidine increases the risk of hypotension with the ACE inhibitor (source: Drug Bank )
lisinopril - tizanidine Tizanidine increases the risk of hypotension with the ACE inhibitor (source: Drug Bank )
lisinopril - triamterene Increased risk of hyperkaliemia (source: Drug Bank )
lisinopril - triamterene Increased risk of hyperkaliemia (source: Drug Bank )
lithium - lisinopril The ACE inhibitor increases serum levels of lithium (source: Drug Bank )
lithium - lisinopril The ACE inhibitor increases serum levels of lithium (source: Drug Bank )
tizanidine - lisinopril Tizanidine increases the risk of hypotension with the ACE inhibitor (source: Drug Bank )
tizanidine - lisinopril Tizanidine increases the risk of hypotension with the ACE inhibitor (source: Drug Bank )
treprostinil - lisinopril Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use. (source: Drug Bank )
triamterene - lisinopril Increased risk of hyperkaliemia (source: Drug Bank )
triamterene - lisinopril Increased risk of hyperkaliemia (source: Drug Bank )

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
May Prevent
Contraindicated With

Publications related to lisinopril: 17

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
A new adverse drug reaction - Schamberg's disease caused by amlodipine administration - a case report. British journal of clinical pharmacology. 2015. Schetz Daria, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Pharmacogenetic effects of 'candidate gene complexes' on stroke in the GenHAT study. Pharmacogenetics and genomics. 2014. Sørensen Izel F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Adoption of a clinical pharmacogenomics implementation program during outpatient care-initial results of the University of Chicago "1,200 Patients Project". American journal of medical genetics. Part C, Seminars in medical genetics. 2014. O'Donnell Peter H, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
The effects of angiotensinogen gene polymorphisms on cardiovascular disease outcomes during antihypertensive treatment in the GenHAT study. Frontiers in pharmacology. 2014. Do Anh N, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacogenetic effect of the stromelysin (MMP3) polymorphism on stroke risk in relation to antihypertensive treatment: the genetics of hypertension associated treatment study. Stroke; a journal of cerebral circulation. 2011. Sherva Richard, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacogenetic association of hypertension candidate genes with fasting glucose in the GenHAT Study. Journal of hypertension. 2010. Irvin Marguerite R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB summary: very important pharmacogene information for angiotensin-converting enzyme. Pharmacogenetics and genomics. 2010. Thorn Caroline F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Interaction between polymorphisms in the renin-angiotensin-system and angiotensin-converting enzyme inhibitor or beta-blocker use and the risk of myocardial infarction and stroke. The pharmacogenomics journal. 2008. Schelleman H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetic association of the NPPA T2238C genetic variant with cardiovascular disease outcomes in patients with hypertension. JAMA : the journal of the American Medical Association. 2008. Lynch Amy I, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Antihypertensive therapy, the alpha-adducin polymorphism, and cardiovascular disease in high-risk hypertensive persons: the Genetics of Hypertension-Associated Treatment Study. The pharmacogenomics journal. 2007. Davis B R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetic association of the angiotensin-converting enzyme insertion/deletion polymorphism on blood pressure and cardiovascular risk in relation to antihypertensive treatment: the Genetics of Hypertension-Associated Treatment (GenHAT) study. Circulation. 2005. Arnett Donna K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Crystal structure of the human angiotensin-converting enzyme-lisinopril complex. Nature. 2003. Natesh Ramanathan, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Association of polymorphisms of the renin-angiotensin system and bradykinin B2 receptor with ACE-inhibitor-related cough. Journal of human hypertension. 2002. Mukae S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Regression of left ventricular hypertrophy by lisinopril after renal transplantation: role of ACE gene polymorphism. Kidney international. 2000. Hernández D, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Effect of angiotensin-converting enzyme (ACE) gene polymorphism on progression of renal disease and the influence of ACE inhibition in IDDM patients: findings from the EUCLID Randomized Controlled Trial. EURODIAB Controlled Trial of Lisinopril in IDDM. Diabetes. 1998. Penno G, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Effect of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene on response to angiotensin-converting enzyme inhibitors in patients with heart failure. Journal of cardiovascular pharmacology. 1998. O'Toole L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Prediction of patient responses to antihypertensive drugs using genetic polymorphisms: investigation of renin-angiotensin system genes. Journal of hypertension. 1996. Dudley C, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0006-0019-54
DrugBank:
DB00722
PDB:
LPR
ChEBI:
43755
KEGG Drug:
D00362
PubChem Compound:
5362119
PubChem Substance:
205105
46504893
Drugs Product Database (DPD):
2217538
ChemSpider:
4514933
HET:
LPR
Therapeutic Targets Database:
DAP000587
FDA Drug Label at DailyMed:
f6f3c339-2c9d-4d07-14a1-6d6c7daf26c6

Clinical Trials

These are trials that mention lisinopril and are related to either pharmacogenetics or pharmacogenomics.

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Sources for PharmGKB drug information: DrugBank, PubChem.