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Pravastin (use)
Treat high cholesterol and prevent Vascular Disease
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Pravastatin (mechanism)
- HMG-CoA reductase is enzyme that catalyzes the rate limiting step in cholesterol synthesis.
- It is a competitive inhibitor of this enzyme.
- Lowers cholesterol synthesis
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DFP (di-isopropyl flourophosphate) (use)
- Insectide but can be poisonous
- used in neuroscience research
- used in treatment of some glaucomas
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DFP (di-isopropyl flourophosphate) (mechanism)
- Acetylcholinesterase (enzyme the cleaves Acetylcholine at neuronal synapse) is irreversibly inhibited by it by covalent bonding
- potent neurotoxin
- cousin to Sarin nerve gas
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Aspirin (use)
- Treatment of pain
- anti-coagulant
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Aspirin (mechanism)
Irreversible inhibitor of cyclooxygenase 1 and 2 (COX 1 and 2), which is required for blood clotting
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Azidothymidine (AZT) (use)
- Anti-viral nucleoside
- Prolongs life of HIV patients
- Diminishes HIV dementia
- Reduce mother-child transmission by >20%
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Azidothymidine (AZT) (mechanism)
- Analog of nucleoside, deoxythymidine
- Azide group in place of 3'OH group required for nucleic acid polymerization
- Host cell converts drug to AZT-triphosphate via host cell kinase
- Viral reverse transcriptase tries to utilize AZT-triphosphate but the polymerization is interrupted and virus can't procreate
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Didanosine (ddI) (use)
- Anti viral nucleside
- Treatment of HIV
- in combination with other drugs
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Didanosine (ddI) (mechanism)
- Analog of nucleoside, deoxyadenosineMissing 3'OH group
- In host, converts to ddI-triphosphate
- ddI has >100 fold affinity for reverse transcriptase than eukaryotic DNA polymerase
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Acyclovir (use)
- Anti-viral nucleoside
- Used in Herpes simplex and varicella zoster treatment
- High specificity for infected cells
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Acyclovir (mechanism)
- Analog of nucleoside, deoxyguanosine
- missing 3'OH
- Converted to acyclovir-triphosphate via VIRAL kinase (making it have the high specificity for infected cells)
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Tenofovir (use)
- Anti-viral nucleotide
- HIV treatment
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Tenofovir (mechanism)
- Analog of nucleoTIDE, deoxyadenosine monophosphate
- Missing 3'OH
- Convers to tenofovir diphosphate via host kinases
- Competes with deoxyadenosine triphosphate for incorportation into viral DNA strand
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Cytosine Arbinoside (Cytarabine) (use)
- Anti-cancer drug
- Specifically leukemia, esp acute myeloid leukemia and lymphoma
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Cytosine Arbinoside (Cytarabine) (mechanism)
- Cytosine nucleoside analog
- In cells, converts to araC-triphosphate
- Has extra OH at position 2, sterically hindering the next base
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Adenosine Arabinoside (Vidarabine) (use)
- Anti-cancer drug
- Used to treat herpes simplex
- anti-neoplastic agent in Relapsed Childhood Acute Lymphoblastic Leukemia
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Adenosine Arabinoside (Vidarabine) (mechanism)
- Analog of nucleoside, deoxyadenosine
- In host cell, converted to ara-A triphosphate
- It gets incorporated into newly replication strand
- Due to the planar shape of the analog, next base cannot incorporate
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5-Azacytidine and 5-aza-2'-Deoxycytidine (Decitabine) (use)
- DNA Hypomethylation agents
- Used in myelodysplastic syndrome and acute myeloid leukemia
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5-Azacytidine and 5-aza-2'-Deoxycytidine (Decitabine) (mechanism)
- In cancer cells, key cell cycle regulatory genes become methylated. (methylation turns genes OFF)
- Cytidine analogs possesses nitrogen atom in place of 5'Carbon of base where it would normally methylated.
- DRUG DEMETHYLATES AND TURNS KEY REGULATORY GENES ON
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Ciprofloxacin (Quinolone) (use)
- DNA gyrase inhibitor
- antibiotic in UTL, prostatis, gastroenteritis, nosocomial infection, STI's
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Ciprofloxacin (Quinolone) (mechanism)
- Prevents re-ligation action of gyrase (only in bacteria) on DNA strand
- Double stranded breaks become permanent
- Cells can either repair the breaks or die (apoptosis)
- Extremely effective at destroying gram- bacteria
- Slightly with gram+
- Kills only aerobic bacteria
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Actinomycin D (use)
- DNA replication inhibitor
- Used in treatment of cancers
- Wilm tumor, rhabdomyosacrcoma, Kapost's Sarcome, gestational trophoblastic tumors, testicular cancers
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Actinomycin D (mechanisms)
- Phenoxazone ring of drug intercalates with adjacent guanine and cytosine residues
- Meanwhile 2 peptide side chains on the drug extend along the minor groove this stabilizing the drug-DNA compound
- Prevents DNA replication
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Campothectin (use)
- Topoisomerase I inhibitor
- Single agent in treatment of cancers including: Ovarian, lung cancers, acutre myelocytic lekemia, and myelodysplastic
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Campothectin (mechanisms)
- Irreversibly binds to and inhibits Topoisomerase I completely, thus inhibits replication
- Isolated from an exotic plant
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Etoposide (use)
- Topoisomerase 2 inhibitor
- ANTI-CANCER DRUG: leukemia, lung, testis and ovary
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Etoposide (mechanism)
- Binds to topoisomerase 2 and stabilizes the cleavage complex
- so topoisomerase 2 cannot proceed with its function
- inhibits replication
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Rifampin (use)
- Prokaryotic transcription inhibitor
- Antibiotic
- Used in gram+ infections and tuberculosis
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Rifampin (mechanisms)
- Bind to prokaryotic polymerase
- Causes conformational change that prevents formation of 1st phosphodieater bond of RNA polymer
- Inhibits transcription
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alpha-Amantin (definition)
- Death cap mushroom poison
- treated by GI decontamination via charcoal, high dose penecillin, liver transplant
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alpha-Amantin (mechanism)
- Forms 1:1 complex with eukaryote RNA polymerase II
- inhibits transcription
- 4 Phases:
- 1. asymptomatic
- 2. gastrointestinal
- 3. apparent recovery
- 4. finally hepatic and renal failure
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Streptomycin (use)
- Antibiotic
- Inhibitor of intiation during translation in prokaryotes
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Streptomycin (mechanism)
- Aminoglycoside structure
- Binds to 30s subunit and prevents assemble of translation machinery
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Tetracycline (use)
- Antibiotic
- Inhibitor of elongation during protein synthesis in prokaryotes
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Tetracycline (mechanism)
- Four ring structure
- Blocks elongation protein synthesis by preventing aminoacyl-tRNA access to the A site
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Erthromycin (use)
- Antibiotic
- Inhibitor of elongation during protein synthesis in prokarytoes
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Erthromycin (mechanism)
- Macrolide structure
- Binds to 50s of the complete ribosomal complex
- Blocks ribosome translocation
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Chloramphenicol (use)
- Antibiotic
- Inhibitor of elongation during protein synthesis in prokaryotes
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Chloramphenicol (mechanism)
- Inhibits peptidyl transferase activity of ribosome
- May inhibit mitochondrial translation as well (so used moreso in third world countries)
- Important for some meningitis treatment
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Cycloheximide (use)
- Research agent
- Inhibitor of elongation during protein synthesis in prokaryotes
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Cycloheximide (mechanism)
- Inhibits peptidyl transferase activity of ribosome
- TOXIC TO EUKARYOTES
- Important experimental tool
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Puromycin (definition)
- Toxin
- Inhibitor of elongation during protein synthesis in ALL organism
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Puromycin (mechanism)
- Prevents elongation by causing premature termination
- Toxic to both prokaryotes and eukaryotes
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Caffeine and Theophylline (definition)
- Stimulants
- Found in many soft drinks and coffee
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Caffeine and Theophylline (mechanism)
- Inhibits phosphodiesterase
- so prolonged signaling by cAMP
- Prolonged stimulatory effects
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Cholera and E.Coli Toxin (definition)
Toxins of Cholera and E. Coli bacteria
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Cholera and E.Coli Toxin (mechanisms)
- Produce their effects by ADP-ribosylating (permanently inactivating), G-stimulatory proteins in cAMP second messenger system.
- Producing profuse diarrhea
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Pertussis Toxin (definition)
- Toxin of pertussis bacteria.
- Caused Whooping cough
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Pertussis Toxin (mechanism)
- Toxin ADP-ribosylates the G-inhibitory proteins of the cAMP second messenger system.
- Produces drying mucus membranes of respiratory tractand a dry whooping cough persisting over weeks
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Nitroglycerin and Nitroprusside (use)
Vasodilators used in treatment of high blood pressure
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Nitroglycerin and Nitroprusside (mechanism)
- Metabolizes to Nitric Oxide in cells
- NO activates cGMP that causes relaxation in smooth muscle by decreasing phosphorylation of myosin chains
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Arsenate (definition)
Deadly toxin
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Arsenate (mechanism)
- Bypasses Glyceraldehyde 3 phosphate dehydrogenase step in glycolysis,
- thus decreasing amount of energy produced per glucose
- bings to lipoic acid and inhibits pyruvate dehydrogenase
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Fluoride (use)
Used in blood glucose test to inhibit glycolysis to the accurate glucose levels are obtained
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Fluoride (mechanism)
Inhibits enolase (step 9) in glycolysis, prevents formation of second ATP and pyruvate
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Malonate (definition)
Toxin produced by some plant and bacteria
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Malonate (mechanism)
- Inhibits Succinate Dehydrogenase of TCA
- Can deadly
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Rotenone (use)
- Commonly used insectide
- Linked to development of parkinsons disease
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Rotenone (mechanism)
Inhibits NADH Dehydrogenase (Complex 1) of ETC
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Piericidin A (use)
Bacterial Antibiotic
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Piericidin A (mechanism)
Inhibits NADH Dehydrogenase (Complex 1) of ETC
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Amystal (definition)
- Barbituate
- Psychoactive sedative hypnotic
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Amystal (mechanism)
Inhibits NADH Dehydrogenase (Complex 1) of ETC
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Antimycin A (use)
Bacterial Antibiotic
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Antimycin A (mechanism)
Inhibits Cytochrome b of cytochrome reductase complex (complex 3) of ETC
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CO, Azide, Hydrogen Sulfide, and Cyanide (definition)
- Toxins
- Cyanide is highly acutely toxic
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CO, Azide, Hydrogen Sulfide, and Cyanide (mechanism)
Inhibit Cytochrome Oxidase (Complex 4) of ETC
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Oligomycin (definition)
Streptomyces toxin
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Oligomycin (mechanism)
- Toxin produced by streptomyces bacteria
- Inhibits F0 subunit of ATP synthase
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Atractyloside (definition)
Toxin produced by thistle plant
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Atractyloside (mechanism)
- Binds outward facing side of ADP/ATP transporter
- Effects similiar to Oligomycin
- so it inhibits the transporter
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Bongkrekic Acid (definition)
Respiratory toxin produced in coconuts infected with Burkholderia toxin
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Bongkrekic Acid (mechanism)
- Binds inward facing side of ADP/ATP transporter
- Effects similiar to Oligomycin
- so inhibits the transporter
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Dinitrophenol (DNP) (use)
Research agent
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Dinitrophenol (DNP) (mechanism)
- Electron transport chain uncoupler
- Destroy proton gradient across inner mitochondrial membrane by allowing H+ to leak through without generating ATP
- Energy is lost through generation of heat
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Gramicidin (use)
Antibiotic produced by Bacillus brevis
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Gramicidin (mechanism)
- Channel forming ionophore
- Non specific ion gradient destruction
- disrupts ETC
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Valinomycin (use)
Antibiotic produced by streptomyces
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Valinomycin (mechanism)
- Carrier Ionphore
- Disrupts ion gradient across inner mitochondrial membrane by carrying K+ into matrix
- Disrupts ETC
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