Term
| What is the name of the enzyme that makes Dihydropteroic acid from Pteridine and PABA? Is this pathway common to humans and bacteria or is it only present in bacteria? |
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Definition
| Dihydropteroate Synthase. This pathway is only found in bacteria. |
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Term
| What three molecules make up Folic Acid? |
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Definition
| Pteridine, PABA, and Glutamate |
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Term
| Which antibiotics inhibit the formation of Dihydropteroic Acid? Describe the mechanism. |
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Definition
| Sulfonamides inhibit the formation of Dihydropteroic acid by inhibiting the utilization of p-aminobenzoic acid (PABA). Sulfonamides compete with PABA to bind Dihydropteroate Synthase. |
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Term
| Are sulfonamides bactericidal or bacteriostatic? Are they active against Gram-postitive or Gram-negative bacteria? |
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Definition
| Sulfonamides are bacteriostatic, and active against both Gram-positive and Gram-negative bacteria. |
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Term
| Name 4 mechanisms of Sulfonamide resistance. And specify which is most clinically releavant |
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Definition
- Over production of PABA (most clinically relevant)
- Inhibit binding of Sulfonamide by mutation in Dihydropteroate Synthase
- Import Folate from environment
- Break down Sulfonamide
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Term
| What is the primary method of administration of sulfonamides? What is their tissue distribution? How are they metabolized? |
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Definition
| Sulfonamides are normally given orally (oral bioavailability is 70-100%). They are distributed to all tissues, including CSF. They are metabolized by acetylation in liver (genetically determined). |
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Term
| How are sulfonamides excreted? What is the clinical relevance? |
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Definition
| Sulfonamides are excreted by glomerular filtration. They achieve high concentrations in urine and are therefore good for treating UTI. |
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Term
| Name the two main oral sulfonamides, and specify their half-life. Which is better absorbed? |
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Definition
- Sulfisoxazole has a 6hr half-life.
- Sulfamethoxazole has an 11hr half-life.
- Sulfisoxazole is better absorbed
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Term
| Why do patients need to be well hydrated when taking Sulfonamides? |
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Definition
| Sulfonamides can cause the formation of crystalline aggregates in the urinary tract. This occurs primarily with older forms of the drug. Newer forms like Sulfisoxazole and Sulfamethoxazole have higher urine solubility. |
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Term
| Name two hematopoetic disorders that can be caused by Sulfonamides. |
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Definition
- acute hemolytic anemia
- bone marrow toxicity (agranulocytosis)
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Term
| Why might a patient with a genetic deficiency of glucose-6-phosphate dehydrogenase (G6PD) be wary of taking Sulfonamides? |
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Definition
| Because they may get acute hemolytic anemia. Patients with G6PD cannot recycle glutathione, an important antioxidant, therefore they are more susceptible to oxidative damage. Sulfonamides put extra oxidative stress on red blood cells. |
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Term
| True or false: Sulfonamides can cause GI irritation. |
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Definition
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Term
| Name 3 hypersensitivity reactions caused by Sulfonamides. |
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Definition
- Skin Rash
- Fever
- Stevens-Johnson syndrome
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Term
| What is Stevens-Johnson Syndrome? |
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Definition
| Stevens-Johnson Syndrome is a severe skin problem that presents with many red skin lesions (petichiae). The condition is an immune mediated hypersensitivity, and patients can die as a result |
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Term
| Name three drugs/kinds of drugs that Sulfonamides can potentiate. |
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Definition
- Oral anticoagulants (warfarin)
- Sulfonylurea hypoglycemic drugs (tolbutamide)
- Hydantoin anticonvulsants (phenytoin)
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Term
| How do Sulfonamides potentiate warfarin, and what serious side effect does this cause? |
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Definition
| Sulfonamides interfere with the P450 metabolisom of anticoagulants like warfarin. Warfarin has a very narrow therapeutic index, therefore even small drug concentration changes can be problematic. The increased concentration resulting from Sulfonamides is associated with upper GI bleeding |
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Term
| How does Trimethoprim inhibit Folic Acid Synthesis? Does it act on a part of the pathway that is specific to bacteria, or common to both humans and bacteria? |
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Definition
- Trimethoprim inhibits the reduction of dihydrofolate by the enzyme dihydrofolate reductase through competitive inhibition.
- This pathway is common to both bacteria and humans, however the IC50 for human cells is ~50,000 times higher than that for bacteria.
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Term
| Is Trimethoprim Bactericidal or Bacteriostatic? |
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Definition
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Term
| Name the 2 major forms of resistance to Trimethoprim. |
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Definition
- Mutation in dihydrofolate reductase enzyme preventing binding of trimethoprim
- Overproduction of dihydrofolate reductase so that trimethoprim will not be able to bind all enzyme
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Term
| How is Trimethoprim administered, and how is it distributed throughout the body? |
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Definition
| It is administered orally; its oral bioavailability is >60%. It is distributed to most tissues and body fluids. It penetrates CSF. |
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Term
| What is Trimethoprim's half-life and how is it excreted? |
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Definition
| 11hr half life. It is excreted renally |
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Term
| How would you describe the effectiveness of antibiotic activity when Sulfonamides like Sulfamethoxazole are administered together with Trimethoprim? |
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Definition
| They act synergistically. For UTIs they are as least as good if not better than Amoxicillin, and has less adverse effects and recurrence. |
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Term
| Name 4 adverse affects of Trimethoprim-Sulfamethoxazole. |
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Definition
- Higher incidence of dermatologic reactions with combination
- Folate-deficient patients may develop hematologic toxicities
- Patients with AIDS have a higher incidence of adverse reactions
- GI disturbances
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Term
| Name 3 clinical uses of Trimethoprim-Sulfamethoxazole. |
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Definition
- UTIs
- Respiratory tract infections (Pneumocystitis Jiroveci)
- Other infections (Shigella)
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Term
| What kinds of bacteria is it active against (Gram-pos/neg, aerobic/anaerobic)? |
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Definition
| Chloramphenicol is active against against a wide range of bugs: both Gram-positive and negative, aerobes and anaerobes, and intracellular bacteria like mycoplasma. |
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Term
| How does Chloramphenicol work? Is it bactericidal or bacteriostatic? |
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Definition
| Chloramphenicol inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit (similar to macrolides). It is bacteriostatic. |
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Term
| How is chloramphenicol metabolized and excreted? |
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Definition
| It is glucuronidated in the liver. (Probably goes out with the poo :P) |
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Term
| Name 2 kinds of Chloramphenicol Bone Marrow Toxicities. |
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Definition
- Temporary Bone marrow depression (reversible, goes away when drug treatment stops)
- Aplastic Anemia: creates an absence of WBCs, patients are at risk of developing leukemia later in life.
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Term
| What is "Grey Baby Syndrome" and how is it caused? |
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Definition
Grey Baby Syndrome is characterized by severe GI and respiratory disturbances, and babies actually look ashen. 40% of neonates with grey baby syndrome will die.
It is caused by chloramphenicol - the drug shuts down mitochondria in baby. |
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Term
| When is Chloramphenicol used clinically? |
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Definition
| Because of severe toxicities, choramphenicol is rarely used. It is never used as a first line of defense. It is often prescribed only as an alternative treatment for difficult infections. |
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