Cyclophosphamide Action Pathway,Drug Action

Cyclophosphamide is an alkylating agent used in the treatment of certain cancers. Following absorption, cyclophosphamide is converted into 4-hydroxyphosphamide by a variety of cytochrome P450 isozymes in the liver. 4-Hydroxyphosphamide is more soluble than cyclophosphamide and is the primary form of the drug that is transported in blood. 4-Hydroxyphosphamide crosses the plasma membrane of the cancer cell and spontaneuosly forms aldophosphamide. This is a reversible reaction. Aldophosphamide can decompose into acrolein and phosphoramide mustard. Phosphoramide mustard is the active alkylating agent and forms alkyl adducts with DNA through a phosphoramide aziridinium intermediate. Alkylation of DNA causes DNA damage and eventually cell death.


Ifosfamide Action Pathway,Drug Action

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Ifosfamide is an alkylating agent used in the treatment of certain cancers. Following absorption, ifosfamide is converted into 4-hydroxyifosfamide by a variety of cytochrome P450 isozymes in the liver. 4-Hydroxyifosfamide crosses the plasma membrane of the cancer cell and spontaneuosly forms aldoifosfamide. This is a reversible reaction. Aldoifosfamide can decompose into acrolein and ifosforamide mustard. Ifosforamide mustard is the active alkylating agent and forms alkyl adducts with DNA through an ifosforamide aziridinium intermediate. Alkylation of DNA causes DNA damage and ultimately cell death.


Tamoxifen Action Pathway,Drug Action

Tamoxifen is a selective estrogen modulator (SERM) used in the treatment of estrogen-sensitive breast cancer. Tamoxifen itself only has weak anti-estrogen effects and must be converted into more active metabolites to have therapeutic activity. Metabolism takes place in the liver and is carried out primarily by cytochrome P450 enzymes. Tamoxifen is hydroxylated by CYP2D6 and demethylated by CYP3A4 and CYP3A5, producing the active metabolites 4-hydroxytamoxifen and endoxifen. These metabolites inhibit estrogen binding to estrogen receptors in breast cancer cells, which in turn inhibit tumour growth.


Erlotinib Action Pathway,Drug Action

Erlotinib is an anti-EGFR drug used in the treatment of some cancers. EGFR is linked multiple signalling pathways involved in tumour growth and angiogenesis such as the Ras/Raf pathway and the PI3K/Akt pathways. These pathways ultimately lead to the activation of transcription factors such as Jun, Fos, and Myc, as well as cyclin D1, which stimulates cell growth and mitosis. Uncontrolled cell growth and mitosis leads to cancer. Erlotinib acts as an anticancer drug by binding to the intracellular tyrosine kinase domain of the EGFR and blocking its activity. This in turn inhibits downstream signalling and prevents tumour growth.


Gefitinib Action Pathway,Drug Action

Gefitinib is an anti-EGFR drug used in the treatment of some cancers. EGFR is linked multiple signalling pathways involved in tumour growth and angiogenesis such as the Ras/Raf pathway and the PI3K/Akt pathways. These pathways ultimately lead to the activation of transcription factors such as Jun, Fos, and Myc, as well as cyclin D1, which stimulates cell growth and mitosis. Uncontrolled cell growth and mitosis leads to cancer. Gefitinib acts as an anticancer drug by binding to the intracellular tyrosine kinase domain of the EGFR and blocking its activity. This in turn inhibits downstream signalling and prevents tumour growth.


Cetuximab Action Pathway,Drug Action

Cetuximab is an anti-EGFR drug used in the treatment of some cancers. EGFR is linked multiple signalling pathways involved in tumour growth and angiogenesis such as the Ras/Raf pathway and the PI3K/Akt pathways. These pathways ultimately lead to the activation of transcription factors such as Jun, Fos, and Myc, as well as cyclin D1, which stimulates cell growth and mitosis. Uncontrolled cell growth and mitosis leads to cancer. Cetuximab acts as an anticancer drug by binding to the extracellular domain of the EGFR and preventing its activation by epidermal growth factor. This in turn inhibits downstream signalling and prevents tumour growth.


Panitumumab Action Pathway,Drug Action

Panitumumab is an anti-EGFR drug used in the treatment of some cancers. EGFR is linked multiple signalling pathways involved in tumour growth and angiogenesis such as the Ras/Raf pathway and the PI3K/Akt pathways. These pathways ultimately lead to the activation of transcription factors such as Jun, Fos, and Myc, as well as cyclin D1, which stimulates cell growth and mitosis. Uncontrolled cell growth and mitosis leads to cancer. Panitumumab acts as an anticancer drug by binding to the extracellular domain of the EGFR and preventing its activation by epidermal growth factor. This in turn inhibits downstream signalling and prevents tumour growth.


Trastuzumab Action Pathway,Drug Action

Trastuzumab is an anti-EGFR drug used in the treatment of HER2-positive breast cancer. EGFR is linked multiple signalling pathways involved in tumour growth and angiogenesis such as the Ras/Raf pathway and the PI3K/Akt pathways. These pathways ultimately lead to the activation of transcription factors such as Jun, Fos, and Myc, as well as cyclin D1, which stimulates cell growth and mitosis. Uncontrolled cell growth and mitosis leads to cancer. Trastuzumab acts as an anticancer drug by binding to the extracellular domain of the EGFR and preventing its activation by epidermal growth factor. This in turn inhibits downstream signalling and prevents tumour growth.


Capecitabine Action Pathway,Drug Action

Capecitabine is a fluoropyrimidine anticancer drug. After absorption, it is metabolized in the liver to the intermediate 5’-deoxy-5-fluorouridine, which is subsequently converted into 5-fluorouracil (5-FU) by intracellular thymidine phosphorylase. 5-FU exerts cytotoxic effects on the cell by direct incorporation into DNA and RNA as well as by inhibiting thymidylate synthase. Since thymidine phosphorylase is present at 3-10 fold higher concentration in cancer cells compared normal cells, capecitabine’s cytotoxic effect is selective for cancer cells.


Fluorouracil Action Pathway,Drug Action

Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a fluoropyrimidine anticancer drug. By injection into a vein, it is used to treat colon cancer, esophageal cancer, stomach cancer, pancreatic cancer, breast cancer, and cervical cancer. As a cream, it is used for actinic keratosis, basal cell carcinoma, and skin warts. Fluorouracil is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system (Wikipedia). Fluorouracil exerts cytotoxic effects on the cell by direct incorporation into DNA and RNA as well as by inhibiting thymidylate synthase.


Suprofen Action Pathway,Drug Action

Suprofen (also named Profenal and Maldocil) is a nonsteroidal anti-inflammatory drug (NSAID). It can be used to relieve pain (analgesic) and reduce fever (antipyretic). Suprofen is also a type of ophthalmic anti-inflammatory medicines which may be used to help prevent eye constrict for pupil during surgery. Suprofen 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 and inflammation (e.g. in the eyes).


Bromfenac Action Pathway,Drug Action

Bromfenac (also named Prolensa, Bromday or Xibrom) is a nonsteroidal anti-inflammatory drug (NSAID). It can be used to reduce ocular inflammation and pain after cataract surgery. Bromfenac is also a type of ophthalmic anti-inflammatory medicines. Bromfenac 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 in many animal model's cell is caused by presence of bromfenac.


Indomethacin Action Pathway,Drug Action

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.


Mefenamic Acid Action Pathway,Drug Action

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.


Oxaprozin Action Pathway,Drug Action

Oxaprozin (also named Daypro, Dayrun) is a nonsteroidal anti-inflammatory drug (NSAID). It can be used to relieve pain (analgesic) and reduce fever (antipyretic). Oxaprozin is also a type of ophthalmic anti-inflammatory medicines which may be used to help prevent eye constrict for pupil during surgery. Oxaprozin 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 and inflammation.


Nabumetone Action Pathway,Drug Action

Nabumetone (also named Relafen and Relifex) is a nonsteroidal anti-inflammatory drug (NSAID). It can be used to relieve pain (analgesic) and reduce fever (antipyretic). Nabumetone 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.


Naproxen Action Pathway,Drug Action

Naproxen (also named Aleve and Naprosyn) is a nonsteroidal anti-inflammatory drug (NSAID). It can be used to relieve pain (analgesic) and reduce fever (antipyretic). Naproxen is also a type of ophthalmic anti-inflammatory medicines. Naproxen 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 and inflammation.


Diflunisal Action Pathway,Drug Action

Diflunisal (also known as Dolobid) is a prostaglandin G/H synthase inhibitor that can inhibit prostaglandin G/H synthase 1 and 2 which prevent the production of prostaglandin. Therefore, diflunisal can be used for treating prostaglandin-associated pain, fever, swelling, platelet aggregation and inflammation. Diflunisal can also inhibit the relocation of leukocytes to inflammation site and also the production of the aggregating agent of platelets: thromboxane A2.


Azathioprine Action Pathway,Drug Action

Azathioprine is a purine antimetabolite prodrug that exerts cytotoxic effects via three mechanisms: via incorporation of thiodeoxyguanosine triphosphate into DNA and thioguanosine triphosphate into RNA, inhibition of de novo synthesis of purine nucleotides, and inhibition of Ras-related C3 botulinum toxin substrate 1, which induces apoptosis of activated T cells. Azathioprine is first converted _in vivo_ to mercaptopurine in the liver. Mercaptopurine then travels through the bloodstream and is transported into cells via nucleoside transporters.  Mercaptopurine is converted to thioguanosince diphosphate through a series of metabolic reactions that produces the metabolic intermediates, thioinosine 5’-monophosphate, thioxanthine monophosphate, and thioguanosine monophosphate. Thioguanosine diphosphate is then converted via a thiodeoxyguanosine diphosphate intermediate to thiodeoxyguanosine triphosphate, which is incorporated into DNA. Thioguanosine diphosphate is also converted to thioguanosine triphosphate which is incorporated into RNA. The thioguanosine triphosphate metabolite also inhibits Ras-related C3 botulinum toxin substrate 1, a plasma membrane-associated small GTPase that regulates cellular processes, inducing apoptosis in activated T cells. Finally, de novo synthesis of purine nucleotides is inhibited by the methyl-thioinosine 5’-monophosphate metabolite, which inhibits amidophosphoribosyl-transferase, the enzyme that catalyzes one of the first steps in this pathway.


Mercaptopurine Action Pathway,Drug Action

Mercaptopurine is a purine antimetabolite prodrug that exerts cytotoxic effects via three mechanisms: via incorporation of thiodeoxyguanosine triphosphate into DNA and thioguanosine triphosphate into RNA, inhibition of de novo synthesis of purine nucleotides, and inhibition of Ras-related C3 botulinum toxin substrate 1, which induces apoptosis of activated T cells. Mercaptopurine travels through the bloodstream and is transported into cells via nucleoside transporters.  Mercaptopurine is then converted to thioguanosince diphosphate through a series of metabolic reactions that produces the metabolic intermediates, thioinosine 5’-monophosphate, thioxanthine monophosphate, and thioguanosine monophosphate. Thioguanosine diphosphate is then converted via a thiodeoxyguanosine diphosphate intermediate to thiodeoxyguanosine triphosphate, which is incorporated into DNA. Thioguanosine diphosphate is also converted to thioguanosine triphosphate which is incorporated into RNA. The thioguanosine triphosphate metabolite also inhibits Ras-related C3 botulinum toxin substrate 1, a plasma membrane-associated small GTPase that regulates cellular processes, inducing apoptosis in activated T cells. Finally, de novo synthesis of purine nucleotides is inhibited by the methyl-thioinosine 5’-monophosphate metabolite, which inhibits amidophosphoribosyl-transferase, the enzyme that catalyzes one of the first steps in this pathway.


Methotrexate Action Pathway,Drug Action

Methotrexate is an antifolate antimetabolite used in the treatment of rheumatoid arthritis and cancer. Methotrexate is taken up into the cell by human reduced folate carriers (SLC19A1).  In the cytoplasm, methotrexate is polyglutamated by folylpolyglutamate synthase, which enhances its retention inside the cell. Both methotrexate and methotrexate-polyglutamate inhibit dihydrofolate reductase, an enzyme that catalyzes the conversion of dihydrofolate into tetrahydrofolate, which is the active form of folic acid. Tetrahydrofolate is involved in many single-carbon transfer reactions, including the synthesis of DNA and RNA nucleotides. Inhibition of dihydrofolate reductase causes depletion of intracellular tetrahydrofolate, which has a cytotoxic effect, especially on rapidly dividing cells. Methotrexate-polyglutamate further inhibits de novo purine synthesis and thymidylate synthase, which contribute to methotrexate’s cytotoxic effects.


Lovastatin Action Pathway,Drug Action

Lovastatin (also known as Mevacor or Mevinolin) is a statin drug (hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors) that can be used for lowering cholesterol, treating hypercholesterolemia and preventing myocardial infarction and stroke. Lovastatin is produced by fermentation of Aspergillus terreus. HMG-CoA catalyzes the conversion of HMG-CoA to mevalonic acid, the rate-limiting step of cholesterol biosynthesis. Lovastatin, like simvastin, is a prodrug. These prodrugs are converted to their active form by in vivo hydrolysis of the lactone ring. The hydrolyzed lactone ring resembles the tetrahedral reaction intermediate produced by HMG-CoA reductase and the bicyclic portions of these compounds bind to the coenzyme A site of the enzyme. The active drug concentrates in the liver during first-pass circulation. Cholesterol biosynthesis accounts for approximately 80% of cholesterol in the body; thus, inhibiting this process can significantly lower cholesterol levels.


Zoledronate Action Pathway,Drug Action

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).


Cerivastatin Action Pathway,Drug Action

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.


Risedronate Action Pathway,Drug Action

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).


Pamidronate Action Pathway,Drug Action

Ibandronate (also named ibandronate sodium) is a type of medication that used to treat numbers of bone diseases because of its affinity for hydroxyapatite. Ibandronate 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).


Fluvastatin Action Pathway,Drug Action

Fluvastatin 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. Fluvastatin bears a chemical resemblance to the reduced HMG-CoA reaction intermediate that is formed during catalysis. Fluvastatin was the first synthetically-prepared HMG-CoA reductase inhibitor. Although similar to lovastatin, simvastatin, and pravastatin, it has a shorter half-life, no active metabolites, extensive protein binding, and minimal CSF penetration. Cholesterol biosynthesis accounts for approximately 80% of cholesterol in the body; thus, inhibiting this process can significantly lower cholesterol levels.


Atorvastatin Action Pathway,Drug Action

Atorvastatin 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. Atorvastatin bears a chemical resemblance to the reduced HMG-CoA reaction intermediate that is formed during catalysis. Structure-activity relationship studies have demonstrated that atorvastatin binds to HMG-CoA reductase at the same site as the reduced intermediate and are held in place by similar chemical interactions. Cholesterol biosynthesis accounts for approximately 80% of cholesterol in the body; thus, inhibiting this process can significantly lower cholesterol levels. Atorvastatin has a unique structure, long half-life, and hepatic selectivity, explaining its greater LDL-lowering potency compared to other HMG-CoA reductase inhibitors.


Meloxicam Action Pathway,Drug Action

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.


Valdecoxib Action Pathway,Drug Action

Valdecoxib, a selective prostaglandin G/H synthase 2 (better known as cyclooxygenase-2 or COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Valdecoxib was used for its anti-inflammatory, analgesic, and antipyretic effects in the management of osteoarthritis and for the treatment of dysmenorrhea or acute pain. Unlike celecoxib, valdecoxib lacks a sulfonamide chain and does not require CYP450 enzymes for metabolism. Both COX-1 and COX-2 catalyze the conversion of arachidonic acid to prostaglandin G2 (PGG2) and PGG2 to prostaglandin H2 (PGH2). PGH2 is the precursor of a number of prostaglandins, including prostaglandin E2 (PGE2), prostaglandin I2 (PGI2) and thomboxane A2 (TxA2). Valdecoxib selectively inhibits the cyclooxygenase-2 (COX-2) enzyme, a key enzyme in the production of PGE2. PGE2 is a potent mediator of pain, inflammation and fever. The first part of this figure depicts the anti-inflammatory, analgesic and antipyretic pathway of valdecoxib. The latter portion of this figure depicts valdecoxib’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. Valdexocib 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 rare, but severe, adverse cardiovascular effects observed with rofecoxib, a COX-2 inhibitor which was subsequently been withdrawn from the market. Valdexocib was withdrawn from the Canadian, U.S. and E.U. markets in 2005 due to concerns of possible increased risk of heart attack and stroke.


Candesartan Action Pathway,Drug Action

Candesartan (also named Blopress or Atacand) is an active metabolite of angiotensin II receptor blockers (ARBs) pro drug, candesartan cilexetil. Candesartan cilexetil converts to candesartan rapidly in gastrointestinal tract during absorption. Candesartan competes with angiotensin II to bind type-1 angiotensin II receptor (AT1) in many tissues (e.g. vascular smooth muscle, the adrenal glands, etc.) to prevent increasing sodium, water reabsorption and peripheral resistance (that will lead to increasing blood pressure) via aldosterone secretion that is caused by angiotensin II. Therefore, action of candesartan binding to AT1 will result in decreasing blood pressure. For more information on the effects of aldosterone on electrolyte and water excretion, refer to the description of the \spironolactone\:http://pathman.smpdb.ca/pathways/SMP00134/pathway or \triamterene\:http://pathman.smpdb.ca/pathways/SMP00132/pathway pathway, which describes the mechanism of direct aldosterone antagonists. Candesartan is an effective agent for reducing blood pressure and may be used to treat essential hypertension and heart failure.


Eprosartan Action Pathway,Drug Action

Eprosartan (also named Teveten) is an antagonist of angiotensin II receptor blockers (ARBs). Eprosartan competes with angiotensin II to bind type-1 angiotensin II receptor (AT1) in many tissues (e.g. vascular smooth muscle, the adrenal glands, etc.) to prevent increasing sodium, water reabsorption and peripheral resistance (that will lead to increasing blood pressure) via aldosterone secretion that is caused by angiotensin II. Therefore, action of eprosartan binding to AT1 will result in decreasing blood pressure. For more information on the effects of aldosterone on electrolyte and water excretion, refer to the description of the \spironolactone\:http://pathman.smpdb.ca/pathways/SMP00134/pathway or \triamterene\:http://pathman.smpdb.ca/pathways/SMP00132/pathway pathway, which describes the mechanism of direct aldosterone antagonists. Eprosartan is an effective agent for reducing blood pressure and may be used to treat essential hypertension and heart failure.


Irbesartan Action Pathway,Drug Action

Irbesartan (also named Avapro) is an antagonist of angiotensin II receptor blockers (ARBs). Irbesartan competes with angiotensin II to bind type-1 angiotensin II receptor (AT1) in many tissues (e.g. vascular smooth muscle, the adrenal glands, etc.) to prevent increasing sodium, water reabsorption and peripheral resistance (that will lead to increasing blood pressure) via aldosterone secretion that is caused by angiotensin II. Therefore, action of irbesartan binding to AT1 will result in decreasing blood pressure. For more information on the effects of aldosterone on electrolyte and water excretion, refer to the description of the \spironolactone\:http://pathman.smpdb.ca/pathways/SMP00134/pathway or \triamterene\:http://pathman.smpdb.ca/pathways/SMP00132/pathway pathway, which describes the mechanism of direct aldosterone antagonists. Irbesartan is an effective agent for reducing blood pressure and may be used to treat essential hypertension and heart failure.


Losartan Action Pathway,Drug Action

Losartan (also named Cozaar) is an active metabolite of angiotensin II receptor blockers (ARBs). Losartan competes with angiotensin II to bind type-1 angiotensin II receptor (AT1) in many tissues (e.g. vascular smooth muscle, the adrenal glands, etc.) to prevent increasing sodium, water reabsorption and peripheral resistance (that will lead to increasing blood pressure) via aldosterone secretion that is caused by angiotensin II. Therefore, action of losartan binding to AT1 will result in decreasing blood pressure. For more information on the effects of aldosterone on electrolyte and water excretion, refer to the description of the \spironolactone\:http://pathman.smpdb.ca/pathways/SMP00134/pathway or \triamterene\:http://pathman.smpdb.ca/pathways/SMP00132/pathway pathway, which describes the mechanism of direct aldosterone antagonists. Losartan is an effective agent for reducing blood pressure and may be used to treat essential hypertension and heart failure.


Olmesartan Action Pathway,Drug Action

Olmesartan (also named Benicar or Olmetec) is an active metabolite of angiotensin II receptor blockers (ARBs) pro drug, olmesartan medoxomil. Olmesartan medoxomi converts to olmesartan rapidly in gastrointestinal tract during absorption. Olmesartan competes with angiotensin II to bind type-1 angiotensin II receptor (AT1) in many tissues (e.g. vascular smooth muscle, the adrenal glands, etc.) to prevent increasing sodium, water reabsorption and peripheral resistance (that will lead to increasing blood pressure) via aldosterone secretion that is caused by angiotensin II. Therefore, action of olmesartan binding to AT1 will result in decreasing blood pressure. For more information on the effects of aldosterone on electrolyte and water excretion, refer to the description of the \spironolactone\:http://pathman.smpdb.ca/pathways/SMP00134/pathway or \triamterene\:http://pathman.smpdb.ca/pathways/SMP00132/pathway pathway, which describes the mechanism of direct aldosterone antagonists. Olmesartan is an effective agent for reducing blood pressure and may be used to treat essential hypertension and heart failure.


Telmisartan Action Pathway,Drug Action

Telmisartan (also named Micardis) is an antagonist of angiotensin II receptor blockers (ARBs). Telmisartan competes with angiotensin II to bind type-1 angiotensin II receptor (AT1) in many tissues (e.g. vascular smooth muscle, the adrenal glands, etc.) to prevent increasing sodium, water reabsorption and peripheral resistance (that will lead to increasing blood pressure) via aldosterone secretion that is caused by angiotensin II. Therefore, action of telmisartan binding to AT1 will result in decreasing blood pressure. For more information on the effects of aldosterone on electrolyte and water excretion, refer to the description of the \spironolactone\:http://pathman.smpdb.ca/pathways/SMP00134/pathway or \triamterene\:http://pathman.smpdb.ca/pathways/SMP00132/pathway pathway, which describes the mechanism of direct aldosterone antagonists. Telmisartan is an effective agent for reducing blood pressure and may be used to treat essential hypertension and heart failure.


Valsartan Action Pathway,Drug Action

Valsartan (also named Diovan) is an antagonist of angiotensin II receptor blockers (ARBs). Valsartan competes with angiotensin II to bind type-1 angiotensin II receptor (AT1) in many tissues (e.g. vascular smooth muscle, the adrenal glands, etc.) to prevent increasing sodium, water reabsorption and peripheral resistance (that will lead to increasing blood pressure) via aldosterone secretion that is caused by angiotensin II. Therefore, action of valsartan binding to AT1 will result in decreasing blood pressure. For more information on the effects of aldosterone on electrolyte and water excretion, refer to the description of the \spironolactone\:http://pathman.smpdb.ca/pathways/SMP00134/pathway or \triamterene\:http://pathman.smpdb.ca/pathways/SMP00132/pathway pathway, which describes the mechanism of direct aldosterone antagonists. Valsartan is an effective agent for reducing blood pressure and may be used to treat essential hypertension and heart failure.


Clopidogrel Action Pathway,Drug Action

Clopidogrel, an antiplatelet agent structurally and pharmacologically similar to ticlopidine, is used to reduce atherosclerotic events such as myocardial infarction, stroke, and vascular death in patients who have had a recent stroke, recent MI, or have established peripheral vascular disease. The active metabolite of clopidogrel prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. It is proposed that the inhibition involves a defect in the mobilization from the storage sites of the platelet granules to the outer membrane. No direct interference occurs with the GPIIb/IIIa receptor. As the glycoprotein GPIIb/IIIa complex is the major receptor for fibrinogen, its impaired activation prevents fibrinogen binding to platelets and inhibits platelet aggregation. By blocking the amplification of platelet activation by released ADP, platelet aggregation induced by agonists other than ADP is also inhibited by the active metabolite of clopidogrel.


Ticlopidine Action Pathway,Drug Action

Ticlopidine, marketed as Ticlid, is an antiplatelet drug that targets the P2Y12 receptor of platelets. Ticlopidine is taken orally and is a prodrug that must be metabolically activated before it can be effective. It first enters the liver and enters the endoplasmic reticulum where it is metabolized to form the active metabolite. First, it is catalyzed by cytochromes P450 2C19, 2B6 and 1A2 into 2-oxoclopidogrel. Secondly, it is processed by cytochromes P450 2B6, 2C9, 2C19, 3A4, 3A5, and serum paraoxonase/arylesterase 1 into the active metabolite of clopidogrel. The active metabolite of clopidogrel then enters the blood stream, where it binds irreversibly to the P2Y purinoreceptor 12 on the surface of platelet cells, preventing ADP from binding to and activating it. Clopidogrel prevents the activation of the Gi protein associated with the P2Y12 receptor from inactivating adenylate cyclase in the platelet, leading to a buildup of cAMP. This cAMP then activates calcium efflux pumps, preventing calcium buildup in the platelet, which would cause activation, and later, aggregation.


Clomocycline Action Pathway,Drug Action

Clomocycline is a tetracycline antibiotic that inhibits bacterial cell growth by inhibiting translation. Clomocycline is lipophilic and easily diffuses across cell membranes or enters cells via porin channels in the bacterial membrane. It binds to the 30S ribosomal subunit and prevents the aminoacyl tRNA from binding to the A site of the ribosome-RNA complex. Clomocycline binding is reversible in nature. Clomocycline may be used to treat acne, gum disease, and other bacterial infections such as chalmydia, brucellosis, bartonellosis and cholera. Clomocycline is also effective against certain strains of malaria and may also be prescribed for the treatment of Lyme disease.


Cilostazol Action Pathway,Drug Action

Cilostazol, also sold as Pletal, is a drug used to prevent platelet aggregation, specifically treating symptoms of intermittent claudication caused by peripheral artery disease as well as preventing strokes.Cilostazol is ingested orally, and it enters the liver, where it is metabolized in the endoplasmic reticulum by cytochrome P450 3A4 into 4-hydroxycilostazol, and by cytochrome P450 2C19 and 3A5 into 4-cis-hydroxycilostazol. Each of these metabolites is further metabolized, 4-hydroxycilostazol into 3,4-dehydrocilostazol and 4-cis-hydroxycilostazol into 4'-trans-hydroxycilostazol respectively. These two metabolites are the active metabolites, and they both act to inhibit the action of cAMP-specific 3',5'-cyclic phosphodiesterase 4D in platelets. With this enzyme inhibited, it is unable to metabolize cAMP into AMP, which leads to a buildup of cAMP in the blood. cAMP in turn is known to prevent aggregation of platelets, by inhibiting their adhesion to collagen, as well as decreasing the amount of calcium within the cytosol, preventing granule release, which then prevents activation of other platelets.


Dipyridamole (Antiplatelet) Action Pathway,Drug Action

Dipyridamole (also known as Persantine) can bind and inhibit cAMP-specific 3',5'-cyclic phosphodiesterase 4D at platelet cell, which prevent the release of arachidonic acid form membrane phospholipids that eventually decreasing thromboxane A2 activity. Dipyridamole can also induce adenylate cyclase activity by releasing prostacyclin, which lead to inhibition of platelet aggregation and increased intraplatelet concentration of cAMP.


Abciximab Action Pathway,Drug Action

Abciximab (also known as c7E3 Fab) is integrin (integrin alpha-IIb and integrin beta-3) receptor antagonist. Binding of abciximab to integrin receptor will block any large molecule to attach on the receptor, which will lead to block any associated signal transduction pathways.


Eptifibatide Action Pathway,Drug Action

Eptifibatide (also named Integrilin) is an anti-coagulant drug that is produced from Sistrurus miliarus barbouri, which can block platelet glycoprotein IIb/IIIa receptor to prevent platelet aggregation. Although, inhibition of platelet aggregation occurs in a dose- and concentration-dependent manner.


Tirofiban Action Pathway,Drug Action

Tirofiban is a reversible antagonist of fibrinogen binding to the GP IIb/IIIa receptor, the major platelet surface receptor involved in platelet aggregation. Platelet aggregation inhibition is reversible following cessation of the infusion of tirofiban.


Enoxaparin Action Pathway,Drug Action

Enoxaparin is a low molecular weight heparin used to reduce cardiovascular events. Enoxaparin's action is antithrombin-dependent. The drug binds to antithrombin III to reduce thrombin inhibition in the plasma. The drug increases the inactivation of coagulation factors IXa, Xa and XIIa. This increases the antithrombin effects. Compared to unfractionated heparin, low molecular weight heparins have lower affinity for plasma proteins and therefore only few are protein bound. They also are not inactivated by platelet factor 4 and does not bind endothelial cells or macrophages thus are not degraded as fast. Therefore, low molecular weight heparins like Enoxaparin are more stable and predictable heparins.


Fondaparinux Action Pathway,Drug Action

Fondaparinux, also known as Arixtra, is an anticoagulant medication. It is part of a class of antithrombotic drugs, the first of this new class. In the blood capillary bed, Fondaparinux sodium activates antithrombin III. Then zooming in even further to the endoplasmic reticulum within the liver, vitamin K1 2,3-epoxide uses vitamin K epoxide reductase complex subunit 1 to become reduced vitamin K (phylloquinone), and then back to vitamin K1 2,3-epoxide continually through vitamin K-dependent gamma-carboxylase. This enzyme also catalyzes precursors of prothrombin and coagulation factors VII, IX and X to prothrombin and coagulation factors VII, IX and X. From there, these precursors and factors leave the liver cell and enter into the blood capillary bed. Once there, prothrombin is catalyzed into the protein complex prothrombinase complex which is made up of coagulation factor Xa/coagulation factor Va (platelet factor 3). These factors are joined by coagulation factor V and prothrombin. Through the two factors coagulation factor Xa and coagulation factor Va, thrombin is produced, which then uses fibrinogen alphabet, and gamma chains to create fibrin (loose). This is then turned into coagulation factor XIIIa, which is activated through coagulation factor XIII A and B chains. From here, fibrin (mesh) is produced which interacts with endothelial cells to cause coagulation. Plasmin is then created from fibrin (mesh), then joined by tissue-type plasminogen activator through plasminogen and creates fibrin degradation products. These are enzymes that stay in your blood after your body has dissolved a blood clot. Coming back to the factors transported from the liver, coagulation factor X is catalyzed into a group of enzymes called the tenase complex: coagulation factor IX and coagulation factor VIIIa (platelet factor 3). This protein complex is also contributed to by coagulation factor VIII, which through prothrombin is catalyzed into coagulation factor VIIIa. From there, this protein complex is catalyzed into prothrombinase complex, the group of proteins mentioned above, contributing to the above process ending in fibrin degradation products. Another enzyme transported from the liver is coagulation factor IX which becomes coagulation factor IXa, part of the tense complex, through coagulation factor XIa. Coagulation factor XIa is produced through coagulation factor XIIa which converts coagulation XI to become coagulation factor XIa. Coagulation factor XIIa is introduced through chain of activation starting in the endothelial cell with collagen alpha-1 (I) chain, which paired with coagulation factor XII activates coagulation factor XIIa. It is also activated through plasma prekallikrein and coagulation factor XIIa which activate plasma kallikrein, which then pairs with coagulation factor XII simultaneously with the previous collagen chain pairing to activate coagulation XIIa. Lastly, the previously transported coagulation factor VII and tissue factor coming from a vascular injury work together to activate tissue factor: coagulation factor VIIa. This enzyme helps coagulation factor X catalyze into coagulation factor Xa, to contribute to the prothrombinase complex and complete the pathway.


Heparin Action Pathway,Drug Action

Heparin (also named unfractionated heparin or Clexane) is an anticoagulant medication. The main mechanism of heparin is acting on increasing the rate of antithrombin-related neutralization of coagulation factors for certain activated type. More specifically, heparin will bind to the antithrombin III (AT) that make antithrombin III changing to its activated form. Activated antithrombin III will inactive prothrombin and factor Xa (also other proteases).


Ardeparin Action Pathway,Drug Action

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.


Argatroban Action Pathway,Drug Action

Argatroban is a synthetic derivate of L-arginine and a direct thrombin inhibitor anticoagulant prescribed to patients with heparin-induced thrombocytopenia. Direct thrombin inhibitors bind plasma and fibrin bound thrombin independently of co-factor antithrombin.The inhibition of thrombin reduces the stability of the clot and promotes clot break down. Argatroban does not effect serine proteases like, trypsin, factor Xa, plasmin, and kallikrein.  Argatroban is advantageous, particularly for renal failure patients, due to its short-half life and hepatic clearance.


Bivalirudin Action Pathway,Drug Action

Bivalirudin, trade name angiomax, is a direct thrombin inhibitor. It is often prescribed to patients who cannot take unfractionated or low molecular weight heparin. Bivalirudin does not need cofactor antithrobin to act. It binds circulating and clot-bound thrombin at the catalytic site and the anion binding exosite. The inhibition of fibrin prevents the cleavage of fibrinogen into fibrin which activates Factor XIII and Factor XIIIa. This destabilizes the thrombus and inhibits the promotion of thrombin production and platelet activation. As a result, bivalirudin prevents or reduces clot formation.


Lepirudin Action Pathway,Drug Action,Lepirudin (also known as Refludan) is an anticoagulant that can be used for inhibiting thrombin (prothrombin) irreversibly. Binding of thrombin can prevent formation of clot as well as thrombus.  Lepirudin can also reduce thrombocytopenia and break up clot.


Ximelagatran Action Pathway,Drug Action

Ximelagatran is an anticoagulant drug used to prevent and treat blood clots, and was the first drug in the anticoagulant drug class to be able to be ingested orally. It was discontinued from distribution by its parent company AstraZeneca in 2006 as it was found to raise liver enzyme levels in patients and cause liver damage as a result. Ximelagatran inhibits prothrombin. Then zooming in even further to the endoplasmic reticulum within the liver, vitamin K1 2,3-epoxide uses vitamin K epoxide reductase complex subunit 1 to become reduced vitamin K (phylloquinone), and then back to vitamin K1 2,3-epoxide continually through vitamin K-dependent gamma-carboxylase. This enzyme also catalyzes precursors of prothrombin and coagulation factors VII, IX and X to prothrombin, and coagulation factors VII, IX and X. From there, these precursors and factors leave the liver cell and enter into the blood capillary bed. Once there, prothrombin is inhibited by ximelagatran, and is catalyzed into the protein complex prothrombinase complex which is made up of coagulation factor Xa/coagulation factor Va (platelet factor 3). These factors are joined by coagulation factor V and ximelagatran inhibits prothrombin. Through the two factors coagulation factor Xa and coagulation factor Va, thrombin is produced and inhibited by ximelagatran, which then uses fibrinogen alphabet, and gamma chains to create fibrin (loose). This is then turned into coagulation factor XIIIa, which is activated through coagulation factor XIII A and B chains. From here, fibrin (mesh) is produced which interacts with endothelial cells to cause coagulation. Plasmin is then created from fibrin (mesh), then joined by tissue-type plasminogen activator through plasminogen and creates fibrin degradation products. These are enzymes that stay in your blood after your body has dissolved a blood clot. Coming back to the factors transported from the liver, coagulation factor X is catalyzed into a group of enzymes called the tenase complex: coagulation factor IX and coagulation factor VIIIa (platelet factor 3). This protein complex is also contributed to by coagulation factor VIII, which through prothrombin is catalyzed into coagulation factor VIIIa. Prothrombin is inhibited by ximelagatran here as well. From there, this protein complex is catalyzed into prothrombinase complex, the group of                                                                                proteins mentioned above, contributing to the above process ending in fibrin degradation products. Another enzyme transported from the liver is coagulation factor IX which becomes coagulation factor IXa, part of the tense complex, through coagulation factor XIa. Coagulation factor XIa is produced through coagulation factor XIIa which converts coagulation XI to become coagulation factor XIa. Coagulation factor XIIa is introduced through chain of activation starting in the endothelial cell with collagen alpha-1 (I) chain, which paired with coagulation factor XII activates coagulation factor XIIa. It is also activated through plasma prekallikrein and coagulation factor XIIa which activate plasma kallikrein, which then pairs with coagulation factor XII simultaneously with the previous collagen chain pairing to activate coagulation XIIa. Lastly, the previously transported coagulation factor VII and tissue factor coming from a vascular injury work together to activate tissue factor: coagulation factor VIIa. This enzyme helps coagulation factor X catalyze into coagulation factor Xa, to contribute to the prothrombinase complex and complete the pathway.


Alteplase Action Pathway,Drug Action

Alteplase is the generic version of the drugs Activase and Actilyse. It is a thrombolytic drug prescribed to treat acute myocardial infarctions and other blood clotting conditions. Alteplase if often used to treat ischaemic stroke within hours of onset. The drug acts by breaking up blood clots. Alteplase binds fibrin in the blood clot to converts plasminogen to plasmin. Plasmin is a proteolytic enzyme that causing the degradation of fibrin. A side effect of the drug is bleeding, angioedema, allergic reactions and fever.


Anistreplase Action Pathway,Drug Action

Anistreplase, trade name Eminase, is a thrombolytic drug prescribed to treat acute myocardial infarction. The drug is an acylated streptokinase-plasminogen complex. The acylation of the drug renders it temporarily inactive, protecting it from plasmin inhibitors. Anistreplase is deacylated following injection, activating the drug to increase thrombolysis by increasing plasminogen's conversion to plasmin. Plasmin breaks down the fibrin of the thrombus to break up the clot and release arterial blockages. Anistreplase has been shown to be very effective when administered shortly after onset of chest pain. Compared to other thrombolytic drugs, Anistreplase has a longer plasma half-life. It also advantageous as it can be given as a single bolus intravenous injection.


Streptokinase Action Pathway,Drug Action

Streptokinase, or SK, is an enzyme and also a thrombolytic medication. We are focusing on the medication in this pathway, which is used to dissolve clots in patients experiencing heart attacks, or arterial/pulmonary embolisms. Streptokinase works through enabling cleavage of the Arg/Val bond in plasminogen, so that plasmin is formed which breaks down fibrin matrix in the thrombus which in turn creates thrombolytic action. Streptokinase activates plasminogen. Then zooming in even further to the endoplasmic reticulum within the liver, vitamin K1 2,3-epoxide uses vitamin K epoxide reductase complex subunit 1 to become reduced vitamin K (phylloquinone), and then back to vitamin K1 2,3-epoxide continually through vitamin K-dependent gamma-carboxylase. This enzyme also catalyzes precursors of prothrombin and coagulation factors VII, IX and X to prothrombin, and coagulation factors VII, IX and X. From there, these precursors and factors leave the liver cell and enter into the blood capillary bed. Once there, prothrombin is catalyzed into the protein complex prothrombinase complex which is made up of coagulation factor Xa/coagulation factor Va (platelet factor 3). These factors are joined by coagulation factor V. Through the two factors coagulation factor Xa and coagulation factor Va, thrombin is produced, which then uses fibrinogen alpha, beta, and gamma chains to create fibrin (loose). This is then turned into coagulation factor XIIIa, which is activated through coagulation factor XIII A and B chains. From here, fibrin (mesh) is produced which interacts with endothelial cells to cause coagulation. Plasmin is then created from fibrin (mesh), then joined by tissue-type plasminogen activator through plasminogen, which is activated by streptokinase and creates fibrin degradation products. These are enzymes that stay in your blood after your body has dissolved a blood clot. Coming back to the factors transported from the liver, coagulation factor X is catalyzed into a group of enzymes called the tenase complex: coagulation factor IX and coagulation factor VIIIa (platelet factor 3). This protein complex is also contributed to by coagulation factor VIII, which through prothrombin is catalyzed into coagulation factor VIIIa.  From there, this protein complex is catalyzed into prothrombinase complex, the group of proteins mentioned above, contributing to the above process ending in fibrin degradation products. Another enzyme transported from the liver is coagulation factor IX which becomes coagulation factor IXa, part of the tense complex, through coagulation factor XIa. Coagulation factor XIa is produced through coagulation factor XIIa which converts coagulation XI to become coagulation factor XIa. Coagulation factor XIIa is introduced through chain of activation starting in the endothelial cell with collagen alpha-1 (I) chain, which paired with coagulation factor XII activates coagulation factor XIIa. It is also activated through plasma prekallikrein and coagulation factor XIIa which activate plasma kallikrein, which then pairs with coagulation factor XII simultaneously with the previous collagen chain pairing to activate coagulation XIIa. Lastly, the previously transported coagulation factor VII and tissue factor coming from a vascular injury work together to activate tissue factor: coagulation factor VIIa. This enzyme helps coagulation factor X catalyze into coagulation factor Xa, to contribute to the prothrombinase complex and complete the pathway.


Tenecteplase Action Pathway,Drug Action

Tenecteplase is an enzyme that is part of the thrombolytics drug class, used to dissolve or break down blood clots. Tenecteplase activates plasminogen. Then zooming in even further to the endoplasmic reticulum within the liver, vitamin K1 2,3-epoxide uses vitamin K epoxide reductase complex subunit 1 to become reduced vitamin K (phylloquinone), and then back to vitamin K1 2,3-epoxide continually through vitamin K-dependent gamma-carboxylase. This enzyme also catalyzes precursors of prothrombin and coagulation factors VII, IX and X to prothrombin, and coagulation factors VII, IX and X. From there, these precursors and factors leave the liver cell and enter into the blood capillary bed. Once there, prothrombin is catalyzed into the protein complex prothrombinase complex which is made up of coagulation factor Xa/coagulation factor Va (platelet factor 3). These factors are joined by coagulation factor V. Through the two factors coagulation factor Xa and coagulation factor Va, thrombin is produced, which then uses fibrinogen alpha, beta, and gamma chains to create fibrin (loose). This is then turned into coagulation factor XIIIa, which is activated through coagulation factor XIII A and B chains. From here, fibrin (mesh) is produced which interacts with endothelial cells to cause coagulation. Plasmin is then created from fibrin (mesh), then joined by tissue-type plasminogen activator (tenecteplase) through plasminogen,  and creates fibrin degradation products. These are enzymes that stay in your blood after your body has dissolved a blood clot. Coming back to the factors transported from the liver, coagulation factor X is catalyzed into a group of enzymes called the tenase complex: coagulation factor IX and coagulation factor VIIIa (platelet factor 3). This protein complex is also contributed to by coagulation factor VIII, which through prothrombin is catalyzed into coagulation factor VIIIa.  From there, this protein complex is catalyzed into prothrombinase complex, the group of proteins mentioned above, contributing to the above process ending in fibrin degradation products. Another enzyme transported from the liver is coagulation factor IX which becomes coagulation factor IXa, part of the tense complex, through coagulation factor XIa. Coagulation factor XIa is produced through coagulation factor XIIa which converts coagulation XI to become coagulation factor XIa. Coagulation factor XIIa is introduced through chain of activation starting in the endothelial cell with collagen alpha-1 (I) chain, which paired with coagulation factor XII activates coagulation factor XIIa. It is also activated through plasma prekallikrein and coagulation factor XIIa which activate plasma kallikrein, which then pairs with coagulation factor XII simultaneously with the previous collagen chain pairing to activate coagulation XIIa. Lastly, the previously transported coagulation factor VII and tissue factor coming from a vascular injury work together to activate tissue factor: coagulation factor VIIa. This enzyme helps coagulation factor X catalyze into coagulation factor Xa, to contribute to the prothrombinase complex and complete the pathway.


Urokinase Action Pathway,Drug Action,Urokinase acts on the endogenous fibrinolytic system. It cleaves the Arg-Val bond in plasminogen to produce active plasmin. Plasmin degrades fibrin clots as well as fibrinogen and other plasma proteins.

Urokinase is an enzyme that is part of the thrombolytics drug class, used to dissolve or break down blood clots. Urokinase activates plasminogen. Then zooming in even further to the endoplasmic reticulum within the liver, vitamin K1 2,3-epoxide uses vitamin K epoxide reductase complex subunit 1 to become reduced vitamin K (phylloquinone), and then back to vitamin K1 2,3-epoxide continually through vitamin K-dependent gamma-carboxylase. This enzyme also catalyzes precursors of prothrombin and coagulation factors VII, IX and X to prothrombin, and coagulation factors VII, IX and X. From there, these precursors and factors leave the liver cell and enter into the blood capillary bed. Once there, prothrombin is catalyzed into the protein complex prothrombinase complex which is made up of coagulation factor Xa/coagulation factor Va (platelet factor 3). These factors are joined by coagulation factor V. Through the two factors coagulation factor Xa and coagulation factor Va, thrombin is produced, which then uses fibrinogen alpha, beta, and gamma chains to create fibrin (loose). This is then turned into coagulation factor XIIIa, which is activated through coagulation factor XIII A and B chains. From here, fibrin (mesh) is produced which interacts with endothelial cells to cause coagulation. Plasmin is then created from fibrin (mesh), then joined by tissue-type plasminogen activator (urokinase) through plasminogen,  and creates fibrin degradation products. These are enzymes that stay in your blood after your body has dissolved a blood clot. Coming back to the factors transported from the liver, coagulation factor X is catalyzed into a group of enzymes called the tenase complex: coagulation factor IX and coagulation factor VIIIa (platelet factor 3). This protein complex is also contributed to by coagulation factor VIII, which through prothrombin is catalyzed into coagulation factor VIIIa.  From there, this protein complex is catalyzed into prothrombinase complex, the group of proteins mentioned above, contributing to the above process ending in fibrin degradation products. Another enzyme transported from the liver is coagulation factor IX which becomes coagulation factor IXa, part of the tense complex, through coagulation factor XIa. Coagulation factor XIa is produced through coagulation factor XIIa which converts coagulation XI to become coagulation factor XIa. Coagulation factor XIIa is introduced through chain of activation starting in the endothelial cell with collagen alpha-1 (I) chain, which paired with coagulation factor XII activates coagulation factor XIIa. It is also activated through plasma prekallikrein and coagulation factor XIIa which activate plasma kallikrein, which then pairs with coagulation factor XII simultaneously with the previous collagen chain pairing to activate coagulation XIIa. Lastly, the previously transported coagulation factor VII and tissue factor coming from a vascular injury work together to activate tissue factor: coagulation factor VIIa. This enzyme helps coagulation factor X catalyze into coagulation factor Xa, to contribute to the prothrombinase complex and complete the pathway.


Reteplase Action Pathway,Drug Action

Reteplase is an enzyme that is part of the thrombolytics drug class, used to dissolve or break down blood clots. Reteplase activates plasminogen. Then zooming in even further to the endoplasmic reticulum within the liver, vitamin K1 2,3-epoxide uses vitamin K epoxide reductase complex subunit 1 to become reduced vitamin K (phylloquinone), and then back to vitamin K1 2,3-epoxide continually through vitamin K-dependent gamma-carboxylase. This enzyme also catalyzes precursors of prothrombin and coagulation factors VII, IX and X to prothrombin, and coagulation factors VII, IX and X. From there, these precursors and factors leave the liver cell and enter into the blood capillary bed. Once there, prothrombin is catalyzed into the protein complex prothrombinase complex which is made up of coagulation factor Xa/coagulation factor Va (platelet factor 3). These factors are joined by coagulation factor V. Through the two factors coagulation factor Xa and coagulation factor Va, thrombin is produced, which then uses fibrinogen alpha, beta, and gamma chains to create fibrin (loose). This is then turned into coagulation factor XIIIa, which is activated through coagulation factor XIII A and B chains. From here, fibrin (mesh) is produced which interacts with endothelial cells to cause coagulation. Plasmin is then created from fibrin (mesh), then joined by tissue-type plasminogen activator (reteplase) through plasminogen,  and creates fibrin degradation products. These are enzymes that stay in your blood after your body has dissolved a blood clot. Coming back to the factors transported from the liver, coagulation factor X is catalyzed into a group of enzymes called the tenase complex: coagulation factor IX and coagulation factor VIIIa (platelet factor 3). This protein complex is also contributed to by coagulation factor VIII, which through prothrombin is catalyzed into coagulation factor VIIIa.  From there, this protein complex is catalyzed into prothrombinase complex, the group of proteins mentioned above, contributing to the above process ending in fibrin degradation products. Another enzyme transported from the liver is coagulation factor IX which becomes coagulation factor IXa, part of the tense complex, through coagulation factor XIa. Coagulation factor XIa is produced through coagulation factor XIIa which converts coagulation XI to become coagulation factor XIa. Coagulation factor XIIa is introduced through chain of activation starting in the endothelial cell with collagen alpha-1 (I) chain, which paired with coagulation factor XII activates coagulation factor XIIa. It is also activated through plasma prekallikrein and coagulation factor XIIa which activate plasma kallikrein, which then pairs with coagulation factor XII simultaneously with the previous collagen chain pairing to activate coagulation XIIa. Lastly, the previously transported coagulation factor VII and tissue factor coming from a vascular injury work together to activate tissue factor: coagulation factor VIIa. This enzyme helps coagulation factor X catalyze into coagulation factor Xa, to contribute to the prothrombinase complex and complete the pathway.


Aminocaproic Acid Action Pathway,Drug Action

Aminocaproic acid, brand name Amicar, is a derivate of lysine and is an antifibrinolytic drug. Antifibrinolytics drugs are commonly used during major surgery to prevent significant blood loss. These drugs reversibly blocks the binding sites on plasminogen. This blockade inhibits plasminogen binding to fibrin and the conversion of plasminogen to plasmin. These prevents fibrin degradation and maintains the stability of fibrin clots.


Tranexamic Acid Action Pathway,Drug Action

Tranexamic acid is a synthetic version of an amino acid found in the body called lysine that plays a role in antifibrinolytic processes. It is used to stop bleeding and hemorrhaging in patients. Tranexamic acid works by inhibiting the activation of plasminogen, which reduces the amount of plasmin that can be produced, thereby slowing the amount of clot degradation that can occur. Tranexamic acid inhibits plasminogen. Then zooming in even further to the endoplasmic reticulum within the liver, vitamin K1 2,3-epoxide uses vitamin K epoxide reductase complex subunit 1 to become reduced vitamin K (phylloquinone), and then back to vitamin K1 2,3-epoxide continually through vitamin K-dependent gamma-carboxylase. This enzyme also catalyzes precursors of prothrombin and coagulation factors VII, IX and X to prothrombin, and coagulation factors VII, IX and X. From there, these precursors and factors leave the liver cell and enter into the blood capillary bed. Once there, prothrombin is catalyzed into the protein complex prothrombinase complex which is made up of coagulation factor Xa/coagulation factor Va (platelet factor 3). These factors are joined by coagulation factor V. Through the two factors coagulation factor Xa and coagulation factor Va, thrombin is produced, which then uses fibrinogen alpha, beta, and gamma chains to create fibrin (loose). This is then turned into coagulation factor XIIIa, which is activated through coagulation factor XIII A and B chains. From here, fibrin (mesh) is produced which interacts with endothelial cells to cause coagulation. Plasmin is then created from fibrin (mesh), then joined by tissue-type plasminogen activator through plasminogen, at which point tranexamic acid inhibits plasminogen which does not allow fibrin degradation products to be created as a result. These are enzymes that stay in your blood after your body has dissolved a blood clot. Coming back to the factors transported from the liver, coagulation factor X is catalyzed into a group of enzymes called the tenase complex: coagulation factor IX and coagulation factor VIIIa (platelet factor 3). This protein complex is also contributed to by coagulation factor VIII, which through prothrombin is catalyzed into coagulation factor VIIIa.  From there, this protein complex is catalyzed into prothrombinase complex, the group of proteins mentioned above, contributing to the above process ending in fibrin degradation products. Another enzyme transported from the liver is coagulation factor IX which becomes coagulation factor IXa, part of the tense complex, through coagulation factor XIa. Coagulation factor XIa is produced through coagulation factor XIIa which converts coagulation XI to become coagulation factor XIa. Coagulation factor XIIa is introduced through chain of activation starting in the endothelial cell with collagen alpha-1 (I) chain, which paired with coagulation factor XII activates coagulation factor XIIa. It is also activated through plasma prekallikrein and coagulation factor XIIa which activate plasma kallikrein, which then pairs with coagulation factor XII simultaneously with the previous collagen chain pairing to activate coagulation XIIa. Lastly, the previously transported coagulation factor VII and tissue factor coming from a vascular injury work together to activate tissue factor: coagulation factor VIIa. This enzyme helps coagulation factor X catalyze into coagulation factor Xa, to contribute to the prothrombinase complex and complete the pathway.


Aprotinin Action Pathway,Drug Action

Aprotinin, trade name Trasylol is a bovine serine protease inhibitor of trypsin, chymotrypsin, kallikrein and plasmin. Aprotinin is administered prophylactically to patients undergoing surgery with a high risk of bleeding to block fibrinolysis and prevent the breakdown of blood clots. The inhibition of kallikrein inhibits factor XIIa production to reduce fibrinolysis and coagulation. Inhibition of plasmin slows down fibrinolysis. Hypersensitivity reactions may occur after repeat exposure to Aprotinin.


Warfarin Action Pathway,Drug Action

Warfarin is a drug part of the anticoagulant drug class, used to dissolve or break down blood clots. Warfarin inhibits vitamin K epoxide reductase complex subunit 1. In the endoplasmic reticulum within the liver, vitamin K1 2,3-epoxide would regularly use vitamin K epoxide reductase complex subunit 1 to become reduced vitamin K (phylloquinone), and then back to vitamin K1 2,3-epoxide continually through vitamin K-dependent gamma-carboxylase, but as warfarin inhibits vitamin K epoxide reductase complex subunit 1, this causes a decreased amount of the reduced form of vitamin K, which in turn causes a decreased coagulability of the blood. The enzyme vitamin K-dependent gamma carboxylase catalyzes precursors of prothrombin and coagulation factors VII, IX and X to prothrombin, and coagulation factors VII, IX and X. From there, these precursors and factors leave the liver cell and enter into the blood capillary bed. Once there, prothrombin is catalyzed into the protein complex prothrombinase complex which is made up of coagulation factor Xa/coagulation factor Va (platelet factor 3). These factors are joined by coagulation factor V. Through the two factors coagulation factor Xa and coagulation factor Va, thrombin is produced, which then uses fibrinogen alpha, beta, and gamma chains to create fibrin (loose). This is then turned into coagulation factor XIIIa, which is activated through coagulation factor XIII A and B chains. From here, fibrin (mesh) is produced which interacts with endothelial cells to cause coagulation. Plasmin is then created from fibrin (mesh), then joined by tissue-type plasminogen activator (reteplase) through plasminogen,  and creates fibrin degradation products. These are enzymes that stay in your blood after your body has dissolved a blood clot. Coming back to the factors transported from the liver, coagulation factor X is catalyzed into a group of enzymes called the tenase complex: coagulation factor IX and coagulation factor VIIIa (platelet factor 3). This protein complex is also contributed to by coagulation factor VIII, which through prothrombin is catalyzed into coagulation factor VIIIa.  From there, this protein complex is catalyzed into prothrombinase complex, the group of proteins mentioned above, contributing to the above process ending in fibrin degradation products. Another enzyme transported from the liver is coagulation factor IX which becomes coagulation factor IXa, part of the tense complex, through coagulation factor XIa. Coagulation factor XIa is produced through coagulation factor XIIa which converts coagulation XI to become coagulation factor XIa. Coagulation factor XIIa is introduced through chain of activation starting in the endothelial cell with collagen alpha-1 (I) chain, which paired with coagulation factor XII activates coagulation factor XIIa. It is also activated through plasma prekallikrein and coagulation factor XIIa which activate plasma kallikrein, which then pairs with coagulation factor XII simultaneously with the previous collagen chain pairing to activate coagulation XIIa. Lastly, the previously transported coagulation factor VII and tissue factor coming from a vascular injury work together to activate tissue factor: coagulation factor VIIa. This enzyme helps coagulation factor X catalyze into coagulation factor Xa, to contribute to the prothrombinase complex and complete the pathway.


Acenocoumarol Action Pathway,Drug Action

Acenocoumarol (also known as Nitrowarfarin or Sinthrome) is an anticoagulant that inhibit the liver enzyme vitamin K reductase, which cause Vitamin K1 2,3-epoxide could not be catalyzed by vitamin K reductase to form vitamin KH2, the reduced form of vitamin K. Vitamin K-dependent coagulation factors (II, VII, IX, and X) requires its cofactor, vitamin K to facilitate the activation and gamma-carboxylation. Inhibition of vitamin K reductase results in reduced concentration of vitamin KH2, which will ultimately lead to decreased coagulability of the blood and reduced cleavage of fibrinogen into fibrin.


Dicumarol Action Pathway,Drug Action

Dicumarol (also known as bishydroxycoumarin) is an anticoagulant that inhibit the liver enzyme vitamin K reductase, which cause Vitamin K1 2,3-epoxide could not be catalyzed by vitamin K reductase to form vitamin KH2, the reduced form of vitamin K. Vitamin K-dependent coagulation factors (II, VII, IX, and X) requires its cofactor, vitamin K to facilitate the activation and gamma-carboxylation. Inhibition of vitamin K reductase results in reduced concentration of vitamin KH2, which will ultimately lead to decreased coagulability of the blood and reduced cleavage of fibrinogen into fibrin.


Phenprocoumon Action Pathway,Drug Action

Phenprocoumon is an anticoagulant that inhibits the liver enzyme vitamin K reductase. This leads to the depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulation factors (II, VII, IX, and X), this ultimately results in reduced cleavage of fibrinogen into fibrin and decreased coagulability of the blood.


Esomeprazole Action Pathway,Drug Action

Esomeprazole is a compound that inhibits gastric acid secretion and is indicated in the treatment of gastroesophageal reflux disease (GERD), the healing of erosive esophagitis, and H. pylori eradication to reduce the risk of duodenal ulcer recurrence. Esomeprazole belongs to a new class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or H2 histamine antagonistic properties, but that suppress gastric acid secretion by specific inhibition of the H+/K+ ATPase enzyme system at the secretory surface of the gastric parietal cell. Because this enzyme system is regarded as the acid (proton) pump within the gastric mucosa, Esomeprazole has been characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid production. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.


Omeprazole Action Pathway,Drug Action

Omeprazole is a compound that inhibits gastric acid secretion and is indicated in the treatment of gastroesophageal reflux disease (GERD), the healing of erosive esophagitis, and H. pylori eradication to reduce the risk of duodenal ulcer recurrence. Omeprazole belongs to a new class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or H2 histamine antagonistic properties, but that suppress gastric acid secretion by specific inhibition of the H+/K+ ATPase enzyme system at the secretory surface of the gastric parietal cell. Because this enzyme system is regarded as the acid (proton) pump within the gastric mucosa, omeprazole has been characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid production. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.


Lansoprazole Action Pathway,Drug Action

Lansoprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or histamine H2-receptor antagonist properties, but rather suppress gastric acid secretion by specific inhibition of the (H+,K+)-ATPase enzyme system at the secretory surface of the gastric parietal cell. Because this enzyme system is regarded as the acid (proton) pump within the parietal cell, Lansoprazole has been characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid production. This effect is dose-related and leads to inhibition of both basal and stimulated gastric acid secretion irrespective of the stimulus.


Pantoprazole Action Pathway,Drug Action

Pantoprazole is a proton pump inhibitor (PPI) that suppresses the final step in gastric acid production by forming a covalent bond to two sites of the (H+,K+ )- ATPase enzyme system at the secretory surface of the gastric parietal cell. This effect is dose-related and leads to inhibition of both basal and stimulated gastric acid secretion irrespective of the stimulus.


Rabeprazole Action Pathway,Drug Action

Rabeprazole is a drug that belongs to the anti secretory drug class. It is used as an anti-ulcer medication, and helps relieve gastric acid reflux, gastric irritation and gastric pain. It inhibits the proton pump action of ATPase, which blocks the final step of gastric acid secretion. The pathway begins in the parietal cell in the stomach, where rabeprazole and a hydrogen ion use the active metabolite in rabeprazole —rabeprazole thioether — to inhibit potassium-transporting ATPase at the secretory surface of the gastric parietal cell. Now in the gastric endothelial cell, these secretory surfaces are inhibited by rabeprazole and by G-Protein signalling cascade through somatostatin receptor type 4, which is activated by somatostatin. At the same time, potassium-transporting ATPase is activated by the G-protein signalling cascade, through histamine H2 receptor, gastrin/cholecystokinin type B receptor, and muscarinic acetylcholine receptor M3 which are activated by histamine, gastrin and acetylcholine, respectively. The potassium transporting ATPase also converts water and ATP to a phosphate molecule and ADP. Alongside the transporters, potassium is brought into the cell. Carbonic anhydrase 1 uses water and carbon dioxide to create hydrogen carbonate and a hydrogen ion, which are both transported out of the endothelial cell, into the gastric lumen. A chloride ion is transported into the gastric endothelial cell through a chloride anion exchanger and is transported out of the cell through a chloride intracellular channel protein 2, back into the gastric lumen.


Ranitidine Action Pathway,Drug Action

Ranitidine is an anti-ulcer agent, that works through antagonizing the histamine H2 receptor. It is used to reduce abdominal pain, heartburn, acid indigestion and acid reflux. The pathway begins in the stomach, where ranitidine inhibits the histamine H2 receptor on the surface of the parietal cell. Now in the gastric endothelial cell, potassium-transporting ATPase units are inhibited by G-Protein signalling cascade through somatostatin receptor type 4, which is activated by somatostatin. At the same time, potassium-transporting ATPase is activated by the G-protein signalling cascade, through histamine H2 receptor which is inhibited by ranitidine, gastrin/cholecystokinin type B receptor, and muscarinic acetylcholine receptor M3 which are activated by histamine, gastrin and acetylcholine, respectively. The potassium transporting ATPase also converts water and ATP to a phosphate molecule and ADP. Alongside the transporters, potassium is brought into the cell. Carbonic anhydrase 1 uses water and carbon dioxide to create hydrogen carbonate and a hydrogen ion, which are both transported out of the endothelial cell, into the gastric lumen. A chloride ion is transported into the gastric endothelial cell through a chloride anion exchanger and is transported out of the cell through a chloride intracellular channel protein 2, back into the gastric lumen.


Famotidine Action Pathway,Drug Action

Famotidine (also known as Pepcid) can bind and inhibit histamine H2 receptor on parietal cell's basolateral membrane. Binding of famotidine can effectively inhibit the histamine effects, which lead to reduced nocturnal gastric acid and basal secretion; it can also decrease gastric volume, gastric acid and acidity.


Cimetidine Action Pathway,Drug Action

Cimetidine binds to histamine H2-receptors located on the basolateral membrane of the gastric parietal cell, blocking histamine effects. This competitive inhibition results in reduced gastric acid secretion and a reduction in gastric volume and acidity.


Nizatidine Action Pathway,Drug Action

Nizatidine (also known as Axid or Acinon) is a histamine H2 receptor antagonist, that can bind to histamine H2 receptor on gastric basolateral membrane, which can reduce the gastric acid response. Blocking of histamine binding to histamine H2 receptor can reduce the secretion of nocturnal and basal gastric acid.


Pirenzepine Action Pathway,Drug Action

Pirenzepine (also known as Gastrozepin) is a selective antagonist (antimuscarinic) that will inhibit the muscarinic acetylcholine receptor M3 inside the stomach. Binding of pirenzepine on the receptor will decrease the level of exertion of gastric acid secretion, and also it can reduce muscle spasms. Therefore, pirenzipine can be used for treating peptic ulcers, prevent motion sickness, vomiting and nausea.


Chlorothiazide Action Pathway,Drug Action

Chlorothiazide (also known as Diuril) 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.


Polythiazide Action Pathway,Drug Action

Polythiazide (also known as Renese or Drenusil) 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.


Methyclothiazide Action Pathway,Drug Action

Methyclothiazide (also known as Enduron or Methyclothiazid) 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.


Bumetanide Action Pathway,Drug Action

Bumetanide, trade name Bumex, is a loop diuretic that increases urine production by inhibiting the reabsorption of water in the nephron. In the thick ascending limb of the loop of Henle, the sodium-potassium-chloride cotransporter (NKCC2) is competitively inhibited at the chloride binding site blocking sodium transport from the lumen to the interstitium. This results in the lumen becoming hypertonic and a decreased osmotic gradient thereby reducing the water reabsorption. In the nephron, the think ascending limb reabsorbs 25% of sodium and is a good target for diuretics.


Bendroflumethiazide Action Pathway,Drug Action

Bendroflumethiazide (also known as  bendrofluazide (BAN) or Aprinox) 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.


Quinethazone Action Pathway,Drug Action

Quinethazone, also known under the brand-name Hydromox, is a pharmacologically-active small molecule that belongs to a class of drugs called thiazides. Thiazides and thiazide-like drugs are diuretics commonly employed to control hypertension. The short term mechanism of action is relatively well-understood: thiazides inhibit sodium-chloride co-transport into the renal distal convoluted tubule of the nephron and therefore increase fluid loss which decreases extracellular fluid (ECF), plasma volume, and ultimately blood pressure. In the case of quinethazone, it inhibits the sodium-chloride symporter, solute carrier family 12 member 3. Thiazides also inhibit sodium ion transport. However, the long-term mechanism of action isn’t as well-characterized and it is thought that other processes beyond regulating plasma and ECF volumes are involved as these two volumes return to baseline within 4-6 weeks of first use of thiazides.


Ethacrynic Acid Action Pathway,Drug Action

Etacrynic acid (also known as ethacrynic acid and Edecrin) is a loop diuretic that can inhibit water reabsorption by binding and inhibiting solute carrier family 12 member 1 (also known as sodium-potassium-chloride cotransporter) in the loop of Henle. Binding of the transporter can prevent import of sodium from lumen from loop of Henle to basolateral interstitium, which lead to more hypertonic environment in lumen than interstitium, and result in prevention of water reabsorption due to diminished osmotic gradient in nephron.


Hydrochlorothiazide Action Pathway,Drug Action

Hydroflumethiazide (also known as Esidrix or Oretic) 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.


Cyclothiazide Action Pathway,Drug Action

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.


Metolazone Action Pathway,Drug Action

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.


Hydroflumethiazide Action Pathway,Drug Action

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.


Indapamide Action Pathway,Drug Action

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.


Furosemide Action Pathway,Drug Action

Furosemide (also named Lasix) is a medication that can be used for high blood pressure and fluid build-up which caused by heart failure, liver scarring, or kidney disease. Furosemide can bind and inhibit sodium-potassium-chloride cotransporter (NKCC2/SLC22A1) to prevent the water reabsorption in nephron. Inhibition of sodium-potassium-chloride cotransporter can prevent transportation of sodium from lumen to basolateral interstitium, which lead to more hypertonic in lumen and less hypertonic in basolateral interstitium that will allow water reabsorption through nephron.


Torsemide Action Pathway,Drug Action

Torsemide, also known as torasemide is a pharmacologically-active small molecule that belongs to the drug class of loop diuretics. It is commonly used to manage hypertension and  edema in cases of congestive heart failure as it acts as a diuretic by blocking sodium transporters NKCC2 on the thick ascending limb of the Loop of Henle in the renal tissues. Specifically it acts on solute carrier family 12 member 1. This prevents the reuptake of sodium into the Loop of Henle which consequentially reduces the uptake of water and serves to both increase water loss and reduce blood pressure. Torsemide appears to reduce blood pressure beyond its action in reducing salt uptake in the Loop of Henle; it also seems to be involved in reducing vasoconstriction by blocking the action of angiotensin II.


Trichlormethiazide Action Pathway,Drug Action

Trichlormethiazide is a pharmacologically-active small molecule that belongs to a class of drugs called thiazides. Thiazides and thiazide-like drugs are diuretics commonly employed to control hypertension. Trichloromethiazide acts by inhibiting chloride and potentially sodium reabsorption in the ascending loop of Henle, specifically at solute carrier family 12 member 3. This action results in increased fluid loss which ultimately reduces blood volume and pressure. Trichlormethiazide also acts to inhibit sodium uptake and increase potassium excretion which also serves to increase fluid loss. The long-term antihypertensive effects of thiazides and thiazide-like drugs such as trichlormethiazide are not well-characterized but may involve its action on carbonic anhydrases.


Chlorthalidone Action Pathway,Drug Action

Chlorthalidone (also known as chlorthalidone or phthalamudine) 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.