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BBC Pharm
Ch 14: Inhibitors of DNA Replication
| Term | Definition |
|---|---|
| describe the MOA of anti-folates | inhibit folate synthesis or folate utlization. |
| this drug is used to treat toxoplasmosis. it works to inhibit folate use | pyrimethamine |
| this has the same MOA as pyrimethamine. It is one ofthe drugs of choice for treatment and prophylaxis of pneumocystis, and is part of the prophylactic drug of choice for toxoplasma infection. it is used in combo with sulfa antibiotics, | trimethoprim |
| how do all sulfa antibiotics work? | inhibit folate syntehsis by bacteria (which normally make their own folate). They also cna have similar effects onselect protozoa. sulfa ABX have multiple applications in the prophylaxis and trmt of protozoal infections, S/A toxoplasma, pneumocystitis |
| which calss of durgs is used to treat UTIs in the outpatient population? | sulfa antibiotics. |
| list some of the sulfa antibiotics | sulfadiazine, sulfisoxazole, sulfamethoxazole. |
| this drug has a MOA similar to that of sulfonamides: inhibition of dihydropteroate synthetase, the enzyme that catalyzes manufacture of folates | Dapsone |
| anti folates have ultimately what effect on bacteria? | decrease DNA synthesis. |
| what type of anemia results when human DNA syntheiss is decreased? | macrocytic anemia-RBCs continue to increase in size as DNA is slowly manufactured. specifically, it causes a megaloblastic anemia because the RBC is released before fully reaching maturity. |
| describe how the purine analog 6-MP undergoes conversions to RNA | 6MP (via HGPRT) to thio-IMP to thio-GMP to RNA |
| what does thio-IMP do? | acts to inhibit de novo purine synthesis (and therefore inhibits DNA and RNA production) and the thio-GMP becomes incorporated into the RNA (and DNA) to render it dysfunctional. |
| list the pyrimidine analogs | cytarabine, 5-Fluorouracil |
| how does cytarabine work? | it is phosphorylated to ara-CTP. it acts as a pyrimidine antagonist; its presence inhibits the reduction of CDP to dCDP (therefore, the DNA production ends). by being incorporated into DNA, it serves to terminate DNA chain elongation. |
| what are side effects of Cytarabine? | hepatotoxic, and will cause bone marrow suppression. it can also cause "cytarabine syndrome": fever, malaise, myalgia, bone pain, conjunctivitis, rash, chest pain. |
| describe the MOA of 5-Fluorouracil | inhibits thymidine synthesis |
| what are some uses of 5-fluorouracil | special use in slow growing solid tumors such as breast, colorectal, and gastric tumors. it will cause BMD. |
| these are drugs that were originally determined to have antimicrobial activity, but later discovered to be cytotoxic to human cells, and therefore, useful i the treatment of cancer. | antibiotic cytotoxins |
| actinomycin D is also known as this | dactinomycin |
| what is the MOA of dactinomycin | sits in the small groove of the DNA and interferes with DNA dependent RNA polymerases (interferes with transcrition). Higher doses inhibit DNA synthesis ("replication"), as well. it can cause severe necrosis of tissues if extravasated. |
| dactinomycin cannot be used when/ | during active chickenpox or shingles |
| what is the MOA of doxorubicin and adriamycin | creates ROS that causes DNA breaks, it intercalates between base pairs (slips itself in DNA snugly sitting between nucleotides, interfering with DNA function), binds the plasma membranes to decrease IP3 coupled transport processes. causes BMD |
| what is the MOA of bleomycin | binds to DNA and creates ROS, resulting in DNA breaks. it also has actions similar to those of acitnomycin. it is nephrotoxic, hepatotoxic, toxic to skin, and has ability to cause fibrosis of lung. |
| list some fluoroquinolones | ciproflaxacin, levoflaxacin, moxifloxacin, gemifloxacin. |
| what is the MOA of fluoroquinolones | ciprofloxacin, levofloxacin, mexifloxacin, gemifloxacin. |
| what is the MOA of fluoroquinolones? | work to inhibit bacterial DNA gyrase, a type of topoisomeraseII. they disrupt the process of DNA to be ready by DNA polymeraes. |
| why are quinolones not approved for children less than 16 years of age? | because of joint and cartilage injury. also must be used in caution in those greater than sixty due to increased risk of tendinopathy. |
Created by:
aferdo01
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