Lisinopril
Pharmacodynamics
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.
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.
Absorption
Approximately 25%, but widely variable between individuals (6 to 60%) in all doses tested (5-80 mg); absorption is unaffected by food
Protein binding
Lisinopril does not appear to be bound to serum proteins other than ACE.
Metabolism
Does not undergo metabolism, excreted unchanged in urine.
Route of elimination
Lisinopril does not undergo metabolism and is excreted unchanged entirely in the urine.
Half life
Effective half life of accumulation following multiple dosing is 12 hours.
Toxicity
Symptoms of overdose include severe hypotension, electrolyte disturbances, and renal failure. LD50= 2000 mg/kg(orally in rat). Most frequent adverse effects include headache, dizziness, cough, fatigue and diarrhea.
Drug drug interaction
spironolactone + lisinopril =may increase the levels of potassium in your blood (hyperkalemia), especially if you are dehydrated or have kidney disease, diabetes, heart failure, or if you are an older adult. Hyperkalemia can cause symptoms such as weaknes
lisinopril +aliskiren = renal complications, hyperkalemia, and hypotension
lisinopril + candesartan = hyperkalemia, hypotension, syncope, and renal dysfunction due to additive or synergistic effects on the renin-angiotensin system.
lisinopril + valsartan = as low blood pressure, kidney function impairment, and a condition called hyperkalemia (high blood potassium). In severe cases, hyperkalemia can lead to kidney failure, muscle paralysis, irregular heart
Food interaction
high levels of potassium in your blood.
Therapeutic uses
Lisinopril is used to treat high blood pressure (hypertension) or congestive heart failure. It is also used to improve survival after a heart attack.
Reference- Tripathi KD "Essential of medical pharmacology" 7th edition, page no- 500, 501,503,558,
Pharmacodynamics
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.
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.
Absorption
Approximately 25%, but widely variable between individuals (6 to 60%) in all doses tested (5-80 mg); absorption is unaffected by food
Protein binding
Lisinopril does not appear to be bound to serum proteins other than ACE.
Metabolism
Does not undergo metabolism, excreted unchanged in urine.
Route of elimination
Lisinopril does not undergo metabolism and is excreted unchanged entirely in the urine.
Half life
Effective half life of accumulation following multiple dosing is 12 hours.
Toxicity
Symptoms of overdose include severe hypotension, electrolyte disturbances, and renal failure. LD50= 2000 mg/kg(orally in rat). Most frequent adverse effects include headache, dizziness, cough, fatigue and diarrhea.
Drug drug interaction
spironolactone + lisinopril =may increase the levels of potassium in your blood (hyperkalemia), especially if you are dehydrated or have kidney disease, diabetes, heart failure, or if you are an older adult. Hyperkalemia can cause symptoms such as weaknes
lisinopril +aliskiren = renal complications, hyperkalemia, and hypotension
lisinopril + candesartan = hyperkalemia, hypotension, syncope, and renal dysfunction due to additive or synergistic effects on the renin-angiotensin system.
lisinopril + valsartan = as low blood pressure, kidney function impairment, and a condition called hyperkalemia (high blood potassium). In severe cases, hyperkalemia can lead to kidney failure, muscle paralysis, irregular heart
Food interaction
high levels of potassium in your blood.
Therapeutic uses
Lisinopril is used to treat high blood pressure (hypertension) or congestive heart failure. It is also used to improve survival after a heart attack.
Reference- Tripathi KD "Essential of medical pharmacology" 7th edition, page no- 500, 501,503,558,
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