Argesun

Indications

• Urea cycle disorders
• Hyperammonaemia types I and II
• Citrullinaemia
• Arginosuccinic aciduria
• Deficiency of N-acetyl glutamate synthetase
• Acute hyperammonaemia in carbamylphosphate synthetase deficiency
• Acute hyperammonaemia in ornithine transcarbamylase deficiency

Dosage

Children: Neonate: 100–300 mg/kg daily in 3–4 divided doses; Child (body-weight up to 40 kg): 6 mg/kg/hour; Child (body-weight 40 kg and above): 4 mg/kg/hour.

Adults: Refer to BNF for specific dosing based on condition; typically administered as 5–50 mg/kg twice daily, adjusted according to plasma ammonia concentration.

Mechanism of action

Arginine serves as a substrate for the synthesis of nitric oxide (NO), a crucial signaling molecule, and contributes to the urea cycle, facilitating the detoxification of ammonia in the liver.

Pharmacodynamics

As a precursor for nitric oxide, arginine plays a vital role in vasodilation and modulating blood flow. It also aids in protein synthesis and supports metabolic processes in the body.

Pharmacokinetics

Arginine is absorbed from the gastrointestinal tract and is distributed throughout the body. It undergoes hepatic metabolism, primarily via the urea cycle, and its half-life is influenced by renal function.

Pregnancy

Use only if clearly needed; consult specialist.

Breast-feeding

Use with caution; benefits should outweigh risks.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• L-Arginine 500 mg tablets
• L-Arginine 1 gram tablets
• L-Arginine powder for solution
• L-Arginine 500 mg capsules
• L-Arginine 21% concentrate for solution for infusion

Indications

• Severe malaria caused by _Plasmodium falciparum_
• Uncomplicated malaria in combination with other antimalarial agents

Dosage

Adults: For adults, the typical dosing regimen is an initial dose of 2.4 mg/kg intravenously, followed by 1.2 mg/kg at 12 and 24 hours, with subsequent doses depending on clinical response

Mechanism of action

Artesunate is metabolized to dihydroartemisinin (DHA), which reacts with heme, generating free radicals that inhibit protein and nucleic acid synthesis in _Plasmodium_ parasites during all erythrocytic stages. This interaction with free radicals can lead to the alkylation of essential parasitic proteins, disrupting their normal function. Two primary theories explain its action: one suggests that artemisinins are activated by interaction with ferrous iron or reduced heme, producing reactive radicals that alkylate biomolecules; the other posits that the intact artemisinin binds to vital proteins in the parasite, leading to the formation of reactive oxygen species.

Pharmacodynamics

As an artemisinin derivative, artesunate is metabolized to dihydroartemisinin, which generates free radicals that inhibit the function of _Plasmodium_ parasites. It has a short duration of action due to its short half-life, and while it possesses a moderate therapeutic index, patients should be informed about potential post-treatment hemolytic anemia and hypersensitivity reactions.

Pharmacokinetics

Artesunate is rapidly absorbed and converted to DHA, which has a short half-life. The pharmacokinetics of artesunate can be influenced by factors such as the presence of food and other medications. It is primarily metabolized in the liver and excreted in urine, with a rapid onset of action that makes it suitable for emergency treatment of severe malaria.

Adverse effects

• Hypersensitivity reactions
• Hemolytic anemia
• Gastrointestinal disturbances
• Headache
• Dizziness
• Fatigue

Precautions

• Caution in patients with a history of hypersensitivity to artemisinin derivatives
• Monitor for signs of hemolytic anemia
• Use with caution in patients with liver impairment

Pregnancy

Artesunate is classified as category C. The risks versus benefits should be assessed before use in pregnant women.

Breast-feeding

It is not known if artesunate is excreted in human milk. Caution is advised when administering to breastfeeding women.

Storage

Store at room temperature (15-30 degrees Celsius) in a tightly closed container, protected from light and moisture.

Formulations

• Injectable solution
• Oral tablets

Indications

• Metabolic acidosis
• Acid-base imbalance
• Urinary alkalinization
• Treatment of certain poisonings
• Cardiac arrest in the context of metabolic acidosis

Dosage

Children: Refer to the BNF for Children for specific pediatric dosages, as they depend on the clinical condition

Adults: Refer to local guidelines and BNF for specific dosing recommendations as they may vary based on clinical condition and severity. General adult dosing for bicarbonate may range from 1 to 2 mEq/kg IV initially, followed by maintenance doses as needed.

Mechanism of action

Bicarbonate acts as a buffer that neutralizes excess acids in the body. It dissociates in solution to produce bicarbonate ions (HCO3-) which can react with hydrogen ions (H+) to form carbonic acid (H2CO3), subsequently leading to the production of carbon dioxide (CO2) and water (H2O). This process helps to raise the pH of the blood and other fluids, counteracting acidosis. Bicarbonate is involved in several metabolic pathways, including the urea cycle and various biosynthetic pathways.

Pharmacodynamics

Bicarbonate's primary pharmacodynamic effect is its ability to buffer hydrogen ions, thus increasing blood pH. This is essential in conditions such as metabolic acidosis, where the body accumulates excess acid. By raising blood pH, bicarbonate can help alleviate symptoms associated with acidemia, such as fatigue, confusion, and shortness of breath. Its effects can also influence the renal and respiratory systems to regulate acid-base homeostasis.

Pharmacokinetics

Bicarbonate is rapidly absorbed from the gastrointestinal tract. It is distributed throughout the body fluids, and its effects can be seen within minutes of administration. The kidneys play a significant role in bicarbonate homeostasis by reabsorbing bicarbonate from urine and excreting hydrogen ions. The elimination half-life can vary, depending on the patient's metabolic state and renal function.

Pregnancy

Use with caution. Consult with a healthcare provider before use.

Breast-feeding

Use with caution. Consult with a healthcare provider before use.

Storage

Store in a cool, dry place away from light.

Mechanism of action

Many of supplemental L-arginine's activities, including its possible anti-atherogenic actions, may be accounted for by its role as the precursor to nitric oxide or NO. NO is produced by all tissues of the body and plays very important roles in the cardiovascular system, immune system and nervous system. NO is formed from L-arginine via the enzyme nitric oxide synthase or synthetase (NOS), and the effects of NO are mainly mediated by 3,'5' -cyclic guanylate or cyclic GMP. NO activates the enzyme guanylate cyclase, which catalyzes the synthesis of cyclic GMP from guanosine triphosphate or GTP. Cyclic GMP is converted to guanylic acid via the enzyme cyclic GMP phosphodiesterase. NOS is a heme-containing enzyme with some sequences similar to cytochrome P-450 reductase. Several isoforms of NOS exist, two of which are constitutive and one of which is inducible by immunological stimuli. The constitutive NOS found in the vascular endothelium is designated eNOS and that present in the brain, spinal cord and peripheral nervous system is designated nNOS. The form of NOS induced by immunological or inflammatory stimuli is known as iNOS. iNOS may be expressed constitutively in select tissues such as lung epithelium. All the nitric oxide synthases use NADPH (reduced nicotinamide adenine dinucleotide phosphate) and oxygen (O2) as cosubstrates, as well as the cofactors FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), tetrahydrobiopterin and heme. Interestingly, ascorbic acid appears to enhance NOS activity by increasing intracellular tetrahydrobiopterin. eNOS and nNOS synthesize NO in response to an increased concentration of calcium ions or in some cases in response to calcium-independent stimuli, such as shear stress. In vitro studies of NOS indicate that the Km of the enzyme for L-arginine is in the micromolar range. The concentration of L-arginine in endothelial cells, as well as in other cells, and in plasma is in the millimolar range. What this means is that, under physiological conditions, NOS is saturated with its L-arginine substrate. In other words, L-arginine would not be expected to be rate-limiting for the enzyme, and it would not appear that supraphysiological levels of L-arginine which could occur with oral supplementation of the amino acid^would make any difference with regard to NO production. The reaction would appear to have reached its maximum level. However, in vivo studies have demonstrated that, under certain conditions, e.g. hypercholesterolemia, supplemental L-arginine could enhance endothelial-dependent vasodilation and NO production.

Pharmacodynamics

Studies have shown that is has improved immune responses to bacteria, viruses and tumor cells; promotes wound healing and regeneration of the liver; causes the release of growth hormones; considered crucial for optimal muscle growth and tissue repair.

Mechanism of action

Artesunate is metabolized to the active DHA. the endoperoxide bridge of DHA reacts with heme, generating free radicals which inhibit protein and nucleic acid synthesis of the _Plasmodium_ parasites during all erythrocytic stages. Reactions with these free radicals can also lead to alkylation of parasitic proteins such as a calcium adenosine triphosphatase and EXP1, a glutathione S-transferase. Two theories have been put forward for the mode of antimalarial action of the artemisinin antimalarials, in accodance with the known properties of peroxides with medicinal activity. The first assumes that the artemisinins must be activated by contact with either reduced haem (ferrous haem, Fe(ll)PPIX) or non-haem ferrous iron (exogenous iron), causing cleavage of the peroxide to generate oxygen-centered radicals (alkoxy radicals') which are the presumed to be converted into carbon-centered radicals by transfer of proximate hydrogen atoms from the periphery of the peroxide molecule. These carbon-centered radicals are then thought to alkylate sensitive, yet unspecified, biomolecules in the parasite. A second theory argues for a process in which the intact artemisinin binds to a site within a vital protein in the parasite. The act of binding causes the peroxide to be converted to hydroperoxide or similar open peroxide, which in accordance with known properties of such compounds, generates one or more active chemical entities, either oxidizing agents or oxygen transfer agents per se, or oxygen-centered free radicals. This would be associated with the binding process. In such a way, the artemisinins might act as (irreversibile) inhibitors. Iron may, or may not, be associated with the activation process. No specific biological target in the parasite has yet been identified in support of this theory, but it may be membrane-bound proteins. Artesunate is a water soluble derivative of artemisinin, an antimalarial compound isolated from the Chinese herb Qinghao (Artemisia annua). Artesunate is rapidly metabolized to dihydroartemisinin (DHA) in the body. Chemically, artesunate, and its active metabolite, DHA, are sesquiterpene lactones with a trioxane ring containing a peroxide bridge. The peroxide bridge appears to be essential for the antimalarial activity of artesunate. Structure-activity relationship studies show that the deoxy derivative of DHA (that lack the peroxide bridge) was 277-fold less active than DHA. The activity of deoxyartesunate was not measured. Deoxy derivatives of other artemisinin analogs were 10- to 1000-fold less active compared to the parent compounds. Artesunate increases superoxide anion production and lipid peroxidation in falciparum-infected erythrocytes in vitro. However, artesunate does not suppress the activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase) in infected or uninfected erythrocytes. Erythrocytes infected with the ring or trophozoite forms in vitro accumulate 100- and 180- fold higher concentrations of DHA (12 nM ie, 3.40 ng/mL), respectively, compared to uninfected erythrocytes. These experiments were performed in a medium containing 10% human serum. The relevance of these findings to the uptake in vivo is unclear. The precise mechanism by which artesunate exhibits antiplasmodial activity is not understood. A 2025 systematic review notes Artesunate's pharmacological activities (antimalarial, antiparasite,antitumor, antivirus, antiinflammation, and antibacterial),and that it is a highly effective antimalarial agent with the potential to induce organ toxicity under certain conditions. The authors note that mechanisms of Artesunate-induced toxicity include oxidative stress, inflammation, and apoptotic signaling patthhways.They also note that Artesunate ameliorates MASH (Metabolic Dysfunction-Associated Steatohepatitis) by reducing inflammation and lipid accumulation by regulating NLRP3 inflammasome and reducing lipid accumulation (SREBP-1c, FAS).

Pharmacodynamics

Artesunate is an artemisinin derivative that is metabolized to DHA, which generates free radicals to inhibit normal function of _Plasmodium_ parasites. It has a short duration of action due to its short half life, and a moderate therapeutic index. Patients should be counselled regarding the risk of post treatment hemolytic anemia and hypersenstivity.