Pathways

Ardeparin, trade name Normiflo, is low molecular weight heparin with anticoagulant effects used to prevent thrombosis. Ardeparin binds and increases antithrombin III activity and inactivates thrombin, factor Xa and coagulation factors XIIa, XIa, plasmin and kallikrein to prevent clot formation. In addition, heparin cofactor II is bound by ardeparin to inhibit thrombin. Plasma proteins have a smaller affinity for low molecular weight heparins than unfractionated heparin. Low molecular weight heparins also don't undergo the rapid degradation of unfractionated heparins. These properties increase ardeparin's bioavailability and give a more predictable anticoagulant activity.

Arbutamine is a synthetic catecholamine non-selective beta-adrenergic agonist. It is administered a closed-loop, computer-controlled drug-delivery system and is indicated to elicit acute cardiovascular responses, similar to a response by exercise. This is used for diagnosing the presence or absence of coronary artery disease in patients who cannot exercise properly and is used to treat conditions including mild or transient episodes of heart block that doesn't require pacing, extreme cases of heart block and Adams-Stokes attacks (except when caused by ventricular tachycardia or fibrillation), cardiac arrest until electric shock or pacemaker therapy is available, bronchospasm occurring during anesthesia, and as an adjunct to in the treatment of hypovolemic and septic shock, low cardiac output states, congestive heart failure, and cardiogenic shock. The actions of arbutamine are mostly observed in heart muscle, where it binds to beta-1 adrenergic receptors, and smooth muscle (bronchi, blood vessel, GI tract and uterus), where it exerts it’s effects via beta-2 adrenergic receptors. In the heart, arbutamine binds to and activates the beta-1 adrenergic receptor, which is coupled to the G-protein signaling cascade. Activation of the receptor activates the signaling cascade which leads to activated protein kinase. Protein kinase activates calcium channels in the membrane, causing them to open and allow Ca2+ to enter the cell. Due to this effect, there is high concentration of Ca2+ in the cell. Ca2+ activates the ryanodine receptor on the sarcoplasmic reticulum, which transports Ca2+ from the sarcoplasmic reticulum into the cytosol. the high concentration of Ca2+ in the cytosol binds to troponin to cause muscle contraction. The high concentration of Ca2+ means that more Ca2+ binds to troponin, increasing inotropy. In non-cardiac myocytes, an increase in intracellular Ca2+ increases the slop of phase 4 of the action potential. The threshold is reached faster, therefore, the heart rate is increased. In the smooth muscle, Ca2+-calmodulin complex activates myosin-LC kinase which activates myosin-LC. The activated myosin-LC causes contraction. Arbutamine binds to and activates beta-2 adrenergic receptor, activating the G-protein signaling cascade. The G-protein signaling cascade produces cAMP, which inhibits myosin-LC kinase. This prevents the activation of myosin-LC and as a result, decreases smooth muscle contraction. Possible side effects from taking isoprenaline include headache, dizziness, upset stomach, flushing, fatigue, nervousness, angina, hypotension, hypertension, palpitations, ventricular arrhythmia, tachycardia, adams-stokes syndrome, dyspnea, edema, blurred vision, nausea, vomiting, tremor, weakness. Arbutamine is used over isoprenaline because the degree of hypotension that occurs is less with arbutamine because alpha receptor activity is retained.

Arbutamine is a synthetic catecholamine used to initiate a cardiac stress response to mimic exercise to detect coronary artery disease. Arbutamine has nonselective beta and weak alpha-1-adrenergic activity which causes increased chronotropic activity (increase in heart rate) and inotropic activity (increase myocardial contractility). These effects mimic the cardiovascular effects of exercise. For patients with cardiovascular artery disease, arbutamine can induce myocardial ischemia. Arbutamine is delivered via a computer controlled closed-loop system. The infusion of arbutamine is based off the heart rate feedback. The system monitors heart rate and blood pressure throughout infusion with alarms for physiological changes or problems.

Arbekacin, trade name Habekacin, is an aminoglycoside antibiotic derived from dibekacin that inhibits bacterial protein synthesis. Arbekacin is prescribed to patients with sepsis and pneumonia resulting from MRSA. Arbekacin binds the bacterial 50S and 30S ribosomal subunit proteins and prevents the formation of the initiation complex with messenger RNA. More specifically, Arbekacin binds four nucleotides of the 16S rRNA and a single amino acid of protein S12. This interferes with the decoding site in the vicinity of nucleotide 1400 in 16S rRNA of the 30S subunit. This region interacts with the wobble base of the anticodon of tRNA. This causes interference of the initiation complex, misreading of mRNA so that incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides, and the breakup of polysomes into nonfunctional monosomes. Arbekacin is effective at treating Gram-positive bacteria like Staphylococcus aureus and Staphylococcus epidermidis and Gram-negative bacteria such as Pseudomonas aeruginosa.

Arbekacin is a semi-synthetic aminoglycoside that is used to treat multi-resistant bacterial strains such as Staphylococcus aureus which is known to be methicillian-resistant. Its mechanism of action is to bind irreversibly to the bacterial ribosome 30S and 16S subunits which interferes with the decoding site and wobble base pairing of the tRNA. Due to the interference, the mRNA is misread, causing the wrong amino acid to be inserted creating non-functional or even toxic proteins as a result. If too much arbekacin accumulates it can lead to nephrotoxicity or ototoxicity, this is more prone to occur if arbekacin treatment is used for more than 10 days.

This pathway describes the production and subsequent metabolism of arachidonic acid, an omega-6 fatty acid. In resting cells arachidonic acid is present in the phospholipids (especially phosphatidylethanolamine and phosphatidylcholine) of membranes of the body’s cells, and is particularly abundant in the brain. Typically a receptor-dependent event, requiring a transducing G protein, initiates phospholipid hydrolysis and releases the fatty acid into the intracellular medium. Three enzymes mediate this deacylation reaction including phospholipase A2 (PLA2), phospholipase C (PLC), and phospholipase D (PLD). Once released, free arachidonate has three possible fates: 1) reincorporation into phospholipids, 2) diffusion outside the cell, and 3) metabolism. Arachidonate metabolism is carried out by three distinct enzyme classes: cyclooxygenases, lipoxygenases, and cytochrome P450’s. Specifically, the enzymes cyclooxygenase and peroxidase lead to the synthesis of prostaglandin H2, which in turn is used to produce the prostaglandins, prostacyclin, and thromboxanes. The enzyme 5-lipoxygenase leads to 5-HPETE, which in turn is used to produce the leukotrienes, hydroxyeicosatetraenoic acids (HETEs) and lipoxins. Some arachidonic acid is converted into midchain HETEs, omega-chain HETEs, dihydroxyeicosatrienoic acids (DHETs), and epoxyeicosatrienoic acids (EETs) by cytochrome P450 epoxygenase hydroxylase activity. Several products of these pathways act within neurons to modulate the activities of ion channels, protein kinases, ion pumps, and neurotransmitter uptake systems, affecting processes such as cellular proliferation, inflammation, and hemostasis. The newly formed eicosanoids may also exit the cell of origin and bind to G-protein-coupled receptors present on nearby neurons or glial cells.

This pathway describes the production and subsequent metabolism of arachidonic acid, an omega-6 fatty acid. In resting cells arachidonic acid is present in the phospholipids (especially phosphatidylethanolamine and phosphatidylcholine) of membranes of the body’s cells, and is particularly abundant in the brain. Typically a receptor-dependent event, requiring a transducing G protein, initiates phospholipid hydrolysis and releases the fatty acid into the intracellular medium. Three enzymes mediate this deacylation reaction including phospholipase A2 (PLA2), phospholipase C (PLC), and phospholipase D (PLD). Once released, free arachidonate has three possible fates: 1) reincorporation into phospholipids, 2) diffusion outside the cell, and 3) metabolism. Arachidonate metabolism is carried out by three distinct enzyme classes: cyclooxygenases, lipoxygenases, and cytochrome P450’s. Specifically, the enzymes cyclooxygenase and peroxidase lead to the synthesis of prostaglandin H2, which in turn is used to produce the prostaglandins, prostacyclin, and thromboxanes. The enzyme 5-lipoxygenase leads to 5-HPETE, which in turn is used to produce the leukotrienes, hydroxyeicosatetraenoic acids (HETEs) and lipoxins. Some arachidonic acid is converted into midchain HETEs, omega-chain HETEs, dihydroxyeicosatrienoic acids (DHETs), and epoxyeicosatrienoic acids (EETs) by cytochrome P450 epoxygenase hydroxylase activity. Several products of these pathways act within neurons to modulate the activities of ion channels, protein kinases, ion pumps, and neurotransmitter uptake systems, affecting processes such as cellular proliferation, inflammation, and hemostasis. The newly formed eicosanoids may also exit the cell of origin and bind to G-protein-coupled receptors present on nearby neurons or glial cells.

This pathway describes the production and subsequent metabolism of arachidonic acid, an omega-6 fatty acid. In resting cells arachidonic acid is present in the phospholipids (especially phosphatidylethanolamine and phosphatidylcholine) of membranes of the body’s cells, and is particularly abundant in the brain. Typically a receptor-dependent event, requiring a transducing G protein, initiates phospholipid hydrolysis and releases the fatty acid into the intracellular medium. Three enzymes mediate this deacylation reaction including phospholipase A2 (PLA2), phospholipase C (PLC), and phospholipase D (PLD). Once released, free arachidonate has three possible fates: 1) reincorporation into phospholipids, 2) diffusion outside the cell, and 3) metabolism. Arachidonate metabolism is carried out by three distinct enzyme classes: cyclooxygenases, lipoxygenases, and cytochrome P450’s. Specifically, the enzymes cyclooxygenase and peroxidase lead to the synthesis of prostaglandin H2, which in turn is used to produce the prostaglandins, prostacyclin, and thromboxanes. The enzyme 5-lipoxygenase leads to 5-HPETE, which in turn is used to produce the leukotrienes, hydroxyeicosatetraenoic acids (HETEs) and lipoxins. Some arachidonic acid is converted into midchain HETEs, omega-chain HETEs, dihydroxyeicosatrienoic acids (DHETs), and epoxyeicosatrienoic acids (EETs) by cytochrome P450 epoxygenase hydroxylase activity. Several products of these pathways act within neurons to modulate the activities of ion channels, protein kinases, ion pumps, and neurotransmitter uptake systems, affecting processes such as cellular proliferation, inflammation, and hemostasis. The newly formed eicosanoids may also exit the cell of origin and bind to G-protein-coupled receptors present on nearby neurons or glial cells.