SMP0000103
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Cyclothiazide Action Pathway
Cyclothiazide (also known as Anhydron or Acquirel) is an organic compound that used for diuretic. It can inhibit the solute carrier family 12 member 3 (also known as sodium-chloride symporter) in the nephron to prevent water reabsorption. Solute carrier family 12 member 3 is also used for sodium reabsorption that count for 5% of total amount. Solute carrier family 12 member 3 transports chloride and sodium from lumen to epithelial cell, and sodium/potassium ATPases facilitate the export of sodium to basolateral interstitium to provide sodium gradient that will increase the osmolarity in interstitium, which lead to establishment of osmotic gradient for water reabsorption.
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Drug Action
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SMP0000104
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Indomethacin Action Pathway
Indomethacin (also named Amuno or Indocid) is a nonsteroidal anti-inflammatory drug (NSAID). It can be used to treat prostaglandin G/H synthase related fever, swelling, pain and inflammation. Indomethacin can block prostaglandin synthesis by the action of inhibition of prostaglandin G/H synthase 1 and 2. Prostaglandin G/H synthase 1 and 2 catalyze the arachidonic acid to prostaglandin G2, and also catalyze prostaglandin G2 to prostaglandin H2 in the metabolism pathway. Decreased prostaglandin synthesis is caused by presence of indomethacin.
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Drug Action
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- 11,12,15-THETA
- 11,12-DiHETrE
- 11,12-Epoxyeicosatrienoic acid
- 11,14,15-THETA
- 11-Dehydro-thromboxane B2
- 11-Epi-PGF2a
- 11H-14,15-EETA
- 12(R)-HETE
- 12(R)-HPETE
- 12(S)-HETE
- 12(S)-HPETE
- 12-KETE
- 12-Keto-leukotriene B4
- 14,15-DiHETrE
- 14,15-Epoxy-5,8,11-eicosatrien...
- 15(S)-HETE
- 15(S)-HPETE
- 15-Deoxy-d-12,14-PGJ2
- 15H-11,12-EETA
- 16(R)-HETE
- 19(S)-HETE
- 2,3-Dinor-8iso prostaglandin F...
- 2,3-Dinor-8iso prostaglandin F...
- 20-Carboxy-leukotriene B4
- 20-Hydroxy-leukotriene B4
- 20-Hydroxyeicosatetraenoic aci...
- 5,6-DHET
- 5,6-Epoxy-8,11,14-eicosatrieno...
- 5,6-Epoxytetraene
- 5-HETE
- 5-HPETE
- 5-KETE
- 6-Keto-prostaglandin F1a
- 6-Ketoprostaglandin E1
- 8(S)-HPETE
- 8,9-DiHETrE
- 8,9-Epoxyeicosatrienoic acid
- 8-HETE
- 8-Isoprostane
- Arachidonic acid
- Calcium
- Fe3+
- Glutathione
- Heme
- Indomethacin
- L-Glutamic acid
- Leukotriene A4
- Leukotriene B4
- Leukotriene C4
- Leukotriene D4
- LysoPC(14:0/0:0)
- Magnesium
- NADP
- NADPH
- Oxidized glutathione
- Oxygen
- PC(14:0/20:4(5Z,8Z,11Z,14Z))
- Prostaglandin A2
- Prostaglandin B2
- Prostaglandin D2
- Prostaglandin E2
- Prostaglandin F2a
- Prostaglandin G2
- Prostaglandin H2
- Prostaglandin I2
- Prostaglandin J2
- Prostaglandin-c2
- Thromboxane A2
- Thromboxane B2
- Water
- Zinc (II) ion
- δ-12-Prostaglandin J2
- (
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SMP0000105
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Metolazone Action Pathway (old)
Metolazone (also known as Zytanix, Zaroxolyn or Mykrox) is an organic compound that used for diuretic. It can inhibit the solute carrier family 12 member 3 (also known as sodium-chloride symporter) in the nephron to prevent water reabsorption. Solute carrier family 12 member 3 is also used for sodium reabsorption that count for 5% of total amount. Solute carrier family 12 member 3 transports chloride and sodium from lumen to epithelial cell, and sodium/potassium ATPases facilitate the export of sodium to basolateral interstitium to provide sodium gradient that will increase the osmolarity in interstitium, which lead to establishment of osmotic gradient for water reabsorption.
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Drug Action
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SMP0000106
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Meloxicam Action Pathway
Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) with antipyretic and analgesic properties. Most NSAIDs, such as ibuprofen and naproxen, are non-selective prostaglandin G/H synthase (a.k.a. cyclooxygenase or COX) inhibitors that act on both prostaglandin G/H synthase 1 and 2 (COX-1 and -2). COX catalyzes the conversion of arachidonic acid to prostaglandin G2 (PGG2) and PGG2 to prostaglandin H2 (PGH2). PGH2 is the precursor to a number of prostaglandins (e.g. PGE2) involved in fever, pain, swelling and inflammation. Meloxicam antagonizes COX by binding to the upper portion of the active site, preventing its substrate, arachidonic acid, from entering the active site. Although it was previously thought that meloxicam is a non-selective COX inhibitor, it is now known that it has higher selectivity for COX-2. Selective COX-2 inhibitors are thought to have more potent anti-inflammatory and analgesic properties with decreased adverse gastric effects. The analgesic, antipyretic and anti-inflammatory effects of meloxicam occur as a result of decreased prostaglandin synthesis. The first part of this figure depicts the anti-inflammatory, analgesic and antipyretic pathway of meloxicam.
The latter portion of this figure depicts meloxicam’s potential involvement in platelet aggregation. Prostaglandin synthesis varies across different tissue types. Platelets, anuclear cells derived from fragmentation from megakaryocytes, contain COX-1, but not COX-2. COX-1 activity in platelets is required for thromboxane A2 (TxA2)-mediated platelet aggregation. Platelet activation and coagulation do not normally occur in intact blood vessels. After blood vessel injury, platelets adhere to the subendothelial collagen at the site of injury. Activation of collagen receptors initiates phospholipase C (PLC)-mediated signaling cascades resulting in the release of intracellular calcium from the dense tubula system. The increase in intracellular calcium activates kinases required for morphological change, transition to procoagulant surface, secretion of granular contents, activation of glycoproteins, and the activation of phospholipase A2 (PLA2). Activation of PLA2 results in the liberation of arachidonic acid, a precursor to prostaglandin synthesis, from membrane phospholipids. The accumulation of TxA2, ADP and thrombin mediates further platelet recruitment and signal amplification. TxA2 and ADP stimulate their respective G-protein coupled receptors, thomboxane A2 receptor and P2Y purinoreceptor 12, and inhibit the production of cAMP via adenylate cyclase inhibition. This counteracts the adenylate cyclase stimulatory effects of the platelet aggregation inhibitor, PGI2, produced by neighbouring endothelial cells. Platelet adhesion, cytoskeletal remodeling, granular secretion and signal amplification are independent processes that lead to the activation of the fibrinogen receptor. Fibrinogen receptor activation exposes fibrinogen binding sites and allows platelet cross-linking and aggregation to occur.
Neighbouring endothelial cells found in blood vessels express both COX-1 and COX-2. COX-2 in endothelial cells mediates the synthesis of PGI2, an effective platelet aggregation inhibitor and vasodilator, while COX-1 mediates vasoconstriction and stimulates platelet aggregation. PGI2 produced by endothelial cells encounters platelets in the blood stream and binds to the G-protein coupled prostacyclin receptor. This causes G-protein mediated activation of adenylate cyclase, which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic AMP (cAMP). Four cAMP molecules then bind to the regulatory subunits of the inactive cAMP-dependent protein kinase holoenzyme causing dissociation of the regulatory subunits and leaving two active catalytic subunit monomers. The active subunits of cAMP-dependent protein kinase catalyze the phosphorylation of a number of proteins. Phosphorylation of inositol 1,4,5-trisphosphate receptor type 1 on the endoplasmic reticulum (ER) inhibits the release of calcium from the ER. This in turn inhibits the calcium-dependent events, including PLA2 activation, involved in platelet activation and aggregation. Inhibition of PLA2 decreases intracellular TxA2 and inhibits the platelet aggregation pathway. cAMP-dependent kinase also phosphorylates the actin-associated protein, vasodilator-stimulated phosphoprotein. Phosphorylation inhibits protein activity, which includes cytoskeleton reorganization and platelet activation. Meloxicam preferentially inhibits COX-2 with little activity against COX-1. COX-2 inhibition in endothelial cells decreases the production of PGI2 and the ability of these cells to inhibit platelet aggregation and stimulate vasodilation. These effects are thought to be responsible for the adverse cardiovascular effects observed with other selective COX-2 inhibitors, such as rofecoxib, which has since been withdrawn from the market.
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Drug Action
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- 11,12,15-THETA
- 11,12-DiHETrE
- 11,12-Epoxyeicosatrienoic acid
- 11,14,15-THETA
- 11-Dehydro-thromboxane B2
- 11-Epi-PGF2a
- 11H-14,15-EETA
- 12(R)-HETE
- 12(R)-HPETE
- 12(S)-HETE
- 12(S)-HPETE
- 12-KETE
- 12-Keto-leukotriene B4
- 14,15-DiHETrE
- 14,15-Epoxy-5,8,11-eicosatrien...
- 15(S)-HETE
- 15(S)-HPETE
- 15-Deoxy-d-12,14-PGJ2
- 15H-11,12-EETA
- 16(R)-HETE
- 19(S)-HETE
- 2,3-Dinor-8iso prostaglandin F...
- 2,3-Dinor-8iso prostaglandin F...
- 20-Carboxy-leukotriene B4
- 20-Hydroxy-leukotriene B4
- 20-Hydroxyeicosatetraenoic aci...
- 5,6-DHET
- 5,6-Epoxy-8,11,14-eicosatrieno...
- 5,6-Epoxytetraene
- 5-HETE
- 5-HPETE
- 5-KETE
- 6-Keto-prostaglandin F1a
- 6-Ketoprostaglandin E1
- 8(S)-HPETE
- 8,9-DiHETrE
- 8,9-Epoxyeicosatrienoic acid
- 8-HETE
- 8-Isoprostane
- Arachidonic acid
- Calcium
- Fe3+
- Glutathione
- Heme
- L-Glutamic acid
- Leukotriene A4
- Leukotriene B4
- Leukotriene C4
- Leukotriene D4
- LysoPC(14:0/0:0)
- Magnesium
- Meloxicam
- NADP
- NADPH
- Oxidized glutathione
- Oxygen
- PC(14:0/20:4(5Z,8Z,11Z,14Z))
- Prostaglandin A2
- Prostaglandin B2
- Prostaglandin D2
- Prostaglandin E2
- Prostaglandin F2a
- Prostaglandin G2
- Prostaglandin H2
- Prostaglandin I2
- Prostaglandin J2
- Prostaglandin-c2
- Thromboxane A2
- Thromboxane B2
- Water
- Zinc (II) ion
- δ-12-Prostaglandin J2
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SMP0000107
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Zoledronate Action Pathway
Zoledronate (also named zoledronic acid, Zometa or Reclast) is a type of medication that used to treat numbers of bone diseases because of its affinity for hydroxyapatite. Zoledronate targets farnesyl pyrophosphate (FPP) synthase by inhibiting the function of this enzyme in the mevalonate pathway, which prevent the biosynthesis of Geranyl-PP and farnesyl pyrophosphate. Geranyl-PP and farnesyl pyrophosphate are important for geranylgeranylation and farnesylation of GTPase signalling proteins. Lack of Geranyl-PP and farnesyl pyrophosphate will result in decreased rate of bond resorption and turnover as well as block the osteoclast activity, which lead to an increasing mass gain in bone (i.e. net gain in bone mass).
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Drug Action
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SMP0000108
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Hydroflumethiazide Action Pathway
Hydroflumethiazide (also known as Saluron or Diuredemina) is an organic compound that used for diuretic. It can inhibit the solute carrier family 12 member 3 (also known as sodium-chloride symporter) in the nephron to prevent water reabsorption. Solute carrier family 12 member 3 is also used for sodium reabsorption that count for 5% of total amount. Solute carrier family 12 member 3 transports chloride and sodium from lumen to epithelial cell, and sodium/potassium ATPases facilitate the export of sodium to basolateral interstitium to provide sodium gradient that will increase the osmolarity in interstitium, which lead to establishment of osmotic gradient for water reabsorption.
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Drug Action
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SMP0000109
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Mefenamic Acid Action Pathway
Mefenamic acid (also named Ponstel) is a nonsteroidal anti-inflammatory drug (NSAID). It can be used to relieve pain (analgesic) and reduce fever (antipyretic). Mefenamic acid can block prostaglandin synthesis by the action of inhibition of prostaglandin G/H synthase 1 and 2. Prostaglandin G/H synthase 1 and 2 catalyze the arachidonic acid to prostaglandin G2, and also catalyze prostaglandin G2 to prostaglandin H2 in the metabolism pathway. Since prostaglandin is the messenger molecules in the process of inflammation; hence, inhibition of prostaglandin synthesis can reduce the pain, fever and inflammation.
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Drug Action
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- 11,12,15-THETA
- 11,12-DiHETrE
- 11,12-Epoxyeicosatrienoic acid
- 11,14,15-THETA
- 11-Dehydro-thromboxane B2
- 11-Epi-PGF2a
- 11H-14,15-EETA
- 12(R)-HETE
- 12(R)-HPETE
- 12(S)-HETE
- 12(S)-HPETE
- 12-KETE
- 12-Keto-leukotriene B4
- 14,15-DiHETrE
- 14,15-Epoxy-5,8,11-eicosatrien...
- 15(S)-HETE
- 15(S)-HPETE
- 15-Deoxy-d-12,14-PGJ2
- 15H-11,12-EETA
- 16(R)-HETE
- 19(S)-HETE
- 2,3-Dinor-8iso prostaglandin F...
- 2,3-Dinor-8iso prostaglandin F...
- 20-Carboxy-leukotriene B4
- 20-Hydroxy-leukotriene B4
- 20-Hydroxyeicosatetraenoic aci...
- 5,6-DHET
- 5,6-Epoxy-8,11,14-eicosatrieno...
- 5,6-Epoxytetraene
- 5-HETE
- 5-HPETE
- 5-KETE
- 6-Keto-prostaglandin F1a
- 6-Ketoprostaglandin E1
- 8(S)-HPETE
- 8,9-DiHETrE
- 8,9-Epoxyeicosatrienoic acid
- 8-HETE
- 8-Isoprostane
- Arachidonic acid
- Calcium
- Fe3+
- Glutathione
- Heme
- L-Glutamic acid
- Leukotriene A4
- Leukotriene B4
- Leukotriene C4
- Leukotriene D4
- LysoPC(14:0/0:0)
- Magnesium
- Mefenamic acid
- NADP
- NADPH
- Oxidized glutathione
- Oxygen
- PC(14:0/20:4(5Z,8Z,11Z,14Z))
- Prostaglandin A2
- Prostaglandin B2
- Prostaglandin D2
- Prostaglandin E2
- Prostaglandin F2a
- Prostaglandin G2
- Prostaglandin H2
- Prostaglandin I2
- Prostaglandin J2
- Prostaglandin-c2
- Thromboxane A2
- Thromboxane B2
- Water
- Zinc (II) ion
- δ-12-Prostaglandin J2
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SMP0000110
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Indapamide Action Pathway
Indapamide (also named as Noranat or Veroxil) is a thiazide-like diuretic drug that can be used to treat hypertension and decompensated heart failure. Indapamide can inhibit sodium-chloride symporter in distal convoluted tubule to prevent sodium reabsorption (5% of total sodium reabsorption), so that the osmotic gradient is decreased which lead to reduced water reabsorption or totally inhibition of water reabsorption in nephron. Sodium-chloride symporter (also known as solute carrier family 12 member 3) can translocate chloride and sodium from lumen to epithelial cell. Sodium-potassium ATPase can export sodium from cell to basolateral interstitium, which lead to increased osmolarity in interstitum for later water reabsorption.
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Drug Action
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SMP0000111
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Cerivastatin Action Pathway
Cerivastatin inhibits cholesterol synthesis via the mevalonate pathway by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase is the enzyme responsible for the conversion of HMG-CoA to mevalonic acid, the rate-limiting step of cholesterol synthesis by this pathway. Cerivastatin bears a chemical resemblance to the reduced HMG-CoA reaction intermediate that is formed during catalysis. Cerivastatin, like fluvastatin, atorvastatin and rosuvastatin, is one of the synthetically derived statins. Cholesterol biosynthesis accounts for approximately 80% of cholesterol in the body; thus, inhibiting this process can significantly lower cholesterol levels.
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Drug Action
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SMP0000112
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Risedronate Action Pathway
Risedronate (also named Actonel, Atelvia or Benet.) is a type of medication that used to treat numbers of bone diseases because of its affinity for hydroxyapatite. Risedronate targets farnesyl pyrophosphate (FPP) synthase by inhibiting the function of this enzyme in the mevalonate pathway, which prevent the biosynthesis of Geranyl-PP and farnesyl pyrophosphate. Geranyl-PP and farnesyl pyrophosphate are important for geranylgeranylation and farnesylation of GTPase signalling proteins. Lack of Geranyl-PP and farnesyl pyrophosphate will result in decreased rate of bond resorption and turnover as well as block the osteoclast activity, which lead to an increasing mass gain in bone (i.e. net gain in bone mass).
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Drug Action
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