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L-ARGININE
Nabin Bist , Pharmacy
Technician
Introduction
 L-Arginine - semi-essential amino acid involved in
numerous areas of human physiology, including
production of nitric oxide (NO) – a key messenger
molecule involved
 vascular regulation
 immune activity
 endocrine function.
Arginine -
 protein production,
 wound healing,
 erectile function, and fertility.
Con ……..
Arginine is not considered essential
“ because humans can synthesize it de novo from
glutamine, glutamate, and proline in adult stage”
But can be considered as semi -essential
( donot sysnthesize in child stage )
 However, dietary intake remains the
primary determinant of plasma arginine
levels, since the rate of arginine
biosynthesis does not compensate for
depletion or inadequate supply.
Con ……..
 Arginine - most abundant nitrogen carrier
in humans, containing four nitrogen atoms
per molecule.
 Arginine is not a major inter-organ
nitrogen shuttle; instead, it plays an
important role in nitrogen metabolism and
ammonia detoxification as an intermediate
in the urea cycle.
Mechanism of Action
 Arginine - biological precursor of nitric oxide
(NO), an endogenous gaseous messenger
molecule involved in a variety of endothelium-
dependent physiological effects in the
cardiovascular system.
 Much of arginineʼs influence on the
cardiovascular system is due to endothelial
NO synthesis, which results in vascular
smooth muscle relaxation and subsequent
vasodilation, as well as inhibition of monocyte
adhesiveness, platelet aggregation, and
smooth muscle proliferation.
Con …………
 A great deal of research has explored the
biological roles and properties of nitric oxide,
which is also of critical importance in
maintenance of
 Normal blood pressure,
 Myocardial function,
 Inflammatory response,
 Apoptosis,
 Protection against oxidative damage
Clinical Indications
 Cardiovascular Conditions
 Hypertension
 Intermittent Claudication
 Preeclampsia
 HIV and AIDS
 Burns and Critical Trauma
 Cancer
 Growth Hormone Secretion and Athletic Performance
 Diabetes and Insulin Resistance Syndrome
Con .
 Gastrointestinal Conditions
 Gastritis and Ulcer
 Gastroesophageal Reflux (GERD) and Sphincter Motility
Disorders
 Genitourinary Conditions
 Erectile Dysfunction (ED)
 Infertility, Female
 Infertility, Male
 Interstitial Cystitis (IC)
 Perioperative Nutrition
 Preterm Labor and Delivery
 Senile Dementia
Preeclampsia
 Preeclampsia Endothelial dysfunction appears to
be involved in the pathogenesis of preeclampsia.
 In an animal model of experimental preeclampsia,
IV administration of arginine (0.16 g/kg body
weight/day) from gestational day 10 until term
reversed hypertension, intrauterine growth
retardation, proteinuria, and renal injury.
 Intravenous infusion of arginine (30 g) in
preeclamptic women has reportedly increased
systemic NO production and reduced blood
pressure
The Use of L-Arginine in the Management of Pre-
Eclampsia and Intrauterine Growth Restriction
 L-arginine is a substrate for nitric oxide
synthesis during pregnancy; preliminary data
suggest that supplemental L-arginine in the
diet may lower the risk of pre-eclampsia
during pregnancy by promoting vasodilatation
through increased production of nitric oxide.
Refrence:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366568
Con ……
 in a study where no effect of L-arginine was
manifest when used in women with pre-
eclampsia beyond 28 weeks of gestation.
Germain et al. disclosed some initial findings
in women at high risk of pre-eclampsia who
received L-arginine from week 10 of
gestation. In a study in 2005 it was seen that
in pre-eclamptic patients prolonged dietary
treatment with low dose of L-arginine
significantly decreased maternal blood
pressure and increased bioavailability of
endothelial nitric oxide
Con ……..
 In the past high doses of intravenous L-
arginine was used to stimulate growth
hormone secretion. However according to
Boger et al. Oral administration of L-
arginine in low doses does not produce
this effect.
The role of L-arginine in the prevention
and treatment of pre-eclampsia: a
systematic review of randomised trials,
 In identified eight randomized trials, seven of which were
included. The methodological quality was fair, with a
combined sample size of 884 women. For women at risk
of pre-eclampsia, L-arginine was associated with a
reduction in pre-eclampsia (RR: 0.34, 95% CI: 0.21–
0.55), when compared with placebo and a reduction in
risk of preterm birth (RR: 0.48 and 95% CI: 0.28 to
0.81). For women with established hypertensive
disease, L-arginine was associated with a reduction in
pre-eclampsia (RR: 0.21; 95% CI: 0.05–0.98). L-arginine
may have a role in the prevention and/or treatment of
pre-eclampsia. Further well-designed and adequately
powered trials are warranted, both in women at risk of
pre-eclampsia and in women with established disease.
Refrence: https://www.nature.com/articles/jhh2013100
Dilated
vessels by
L-arginine
Dosage
 Doses of arginine used in clinical research have
varied considerably, from as little as 500 mg/day
for oligospermia to as much as 30 g/day for
cancer, preeclampsia, and premature uterine
contractions.
 Typical daily doses fall into either the 1-3 g or 7-15
g range, depending on the condition being
treated.
 Because of the pharmacokinetics of L-arginine,
use of a sustained-release preparation may be
preferable, in order to keep blood levels more
constant over time.
L-Arginine

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L-Arginine

  • 1. L-ARGININE Nabin Bist , Pharmacy Technician
  • 2. Introduction  L-Arginine - semi-essential amino acid involved in numerous areas of human physiology, including production of nitric oxide (NO) – a key messenger molecule involved  vascular regulation  immune activity  endocrine function. Arginine -  protein production,  wound healing,  erectile function, and fertility.
  • 3. Con …….. Arginine is not considered essential “ because humans can synthesize it de novo from glutamine, glutamate, and proline in adult stage” But can be considered as semi -essential ( donot sysnthesize in child stage )  However, dietary intake remains the primary determinant of plasma arginine levels, since the rate of arginine biosynthesis does not compensate for depletion or inadequate supply.
  • 4. Con ……..  Arginine - most abundant nitrogen carrier in humans, containing four nitrogen atoms per molecule.  Arginine is not a major inter-organ nitrogen shuttle; instead, it plays an important role in nitrogen metabolism and ammonia detoxification as an intermediate in the urea cycle.
  • 5. Mechanism of Action  Arginine - biological precursor of nitric oxide (NO), an endogenous gaseous messenger molecule involved in a variety of endothelium- dependent physiological effects in the cardiovascular system.  Much of arginineʼs influence on the cardiovascular system is due to endothelial NO synthesis, which results in vascular smooth muscle relaxation and subsequent vasodilation, as well as inhibition of monocyte adhesiveness, platelet aggregation, and smooth muscle proliferation.
  • 6. Con …………  A great deal of research has explored the biological roles and properties of nitric oxide, which is also of critical importance in maintenance of  Normal blood pressure,  Myocardial function,  Inflammatory response,  Apoptosis,  Protection against oxidative damage
  • 7. Clinical Indications  Cardiovascular Conditions  Hypertension  Intermittent Claudication  Preeclampsia  HIV and AIDS  Burns and Critical Trauma  Cancer  Growth Hormone Secretion and Athletic Performance  Diabetes and Insulin Resistance Syndrome
  • 8. Con .  Gastrointestinal Conditions  Gastritis and Ulcer  Gastroesophageal Reflux (GERD) and Sphincter Motility Disorders  Genitourinary Conditions  Erectile Dysfunction (ED)  Infertility, Female  Infertility, Male  Interstitial Cystitis (IC)  Perioperative Nutrition  Preterm Labor and Delivery  Senile Dementia
  • 9. Preeclampsia  Preeclampsia Endothelial dysfunction appears to be involved in the pathogenesis of preeclampsia.  In an animal model of experimental preeclampsia, IV administration of arginine (0.16 g/kg body weight/day) from gestational day 10 until term reversed hypertension, intrauterine growth retardation, proteinuria, and renal injury.  Intravenous infusion of arginine (30 g) in preeclamptic women has reportedly increased systemic NO production and reduced blood pressure
  • 10. The Use of L-Arginine in the Management of Pre- Eclampsia and Intrauterine Growth Restriction  L-arginine is a substrate for nitric oxide synthesis during pregnancy; preliminary data suggest that supplemental L-arginine in the diet may lower the risk of pre-eclampsia during pregnancy by promoting vasodilatation through increased production of nitric oxide. Refrence: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366568
  • 11. Con ……  in a study where no effect of L-arginine was manifest when used in women with pre- eclampsia beyond 28 weeks of gestation. Germain et al. disclosed some initial findings in women at high risk of pre-eclampsia who received L-arginine from week 10 of gestation. In a study in 2005 it was seen that in pre-eclamptic patients prolonged dietary treatment with low dose of L-arginine significantly decreased maternal blood pressure and increased bioavailability of endothelial nitric oxide
  • 12. Con ……..  In the past high doses of intravenous L- arginine was used to stimulate growth hormone secretion. However according to Boger et al. Oral administration of L- arginine in low doses does not produce this effect.
  • 13. The role of L-arginine in the prevention and treatment of pre-eclampsia: a systematic review of randomised trials,  In identified eight randomized trials, seven of which were included. The methodological quality was fair, with a combined sample size of 884 women. For women at risk of pre-eclampsia, L-arginine was associated with a reduction in pre-eclampsia (RR: 0.34, 95% CI: 0.21– 0.55), when compared with placebo and a reduction in risk of preterm birth (RR: 0.48 and 95% CI: 0.28 to 0.81). For women with established hypertensive disease, L-arginine was associated with a reduction in pre-eclampsia (RR: 0.21; 95% CI: 0.05–0.98). L-arginine may have a role in the prevention and/or treatment of pre-eclampsia. Further well-designed and adequately powered trials are warranted, both in women at risk of pre-eclampsia and in women with established disease. Refrence: https://www.nature.com/articles/jhh2013100
  • 14.
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  • 18. Dosage  Doses of arginine used in clinical research have varied considerably, from as little as 500 mg/day for oligospermia to as much as 30 g/day for cancer, preeclampsia, and premature uterine contractions.  Typical daily doses fall into either the 1-3 g or 7-15 g range, depending on the condition being treated.  Because of the pharmacokinetics of L-arginine, use of a sustained-release preparation may be preferable, in order to keep blood levels more constant over time.