DSNM Metabolism Drugs and Rxns Flashcards
Define the function of Azaserine and 6-diazo-oxonorleucine (DON).
These drugs that are structurally similar to glutamine are potent inhibitors of purine nucleotide synthesis. It irreversibly inhibits the enzyme PRPP-amido-transferase.
What is the purpose of Methotrexate and Aminopterin? What are some side effects of their use?
These are inhibitors of mammalian DHF Reductase. These chemotherapeutic drugs inhibit purine and thymidylate synthesis. Side effects include thinning hair, reduced GI lining and immune system defects because also affects rapidly dividing cells.
Trimethoprim is an inhibitor of what enzyme?
Inhibitor of Bacterial Dihydrofolate Reductase than the same enzyme in humans. Making this an effective antibiotic.
What is the purpose of Sulfonamides? What’s their significance?
These drugs are PABA analogues that competitively inhibit synthesis of folic acid in bacteria. They DO NOT block human purine synthesis, also making them effective antibiotics (in addition to trimethoprim)
What 2 drugs is Bactrim composed of? Define the clinical significance.
Bactrim is made of Sulfamethoxazole and Trimethoprim. This mixture selectively inhibits bacterial cells compared to mammalian cells.
This is a famous antiviral used to treat Hepatitis C. It inhibits IMP dehydrogenase, thereby depleting ICF pools of guanine nucleotides.
Ribavarin blocks the replication of RNA viruses such as in Hepatitis C.
What is the function of Mycophenolic Acid?
Blocks T and B cells of nucleotides. Used as an immunosuppresant to prevent graft rejection (esp. for renal transplants).
Define the purpose of Allopurinol and Oxypurinol.
Allopurinol/ Oxypurinol is a Xanthine oxidase inhibitor used for treating gout.
What is Hydroxyurea used for in the clinic?
Hydroxyurea is an inhibitor of ribonucleotide reductase. It is used in cancer treatment since it blocks the cell cycle at G1/S checkpoint.
What does 5-Fluorouracil do?
5-Fluorouracil inhibits thymidylate synthase leading to a “thymineless” cell death. It is an effective cancer treatment and precursor of F-dUMP.
What is Acyclovir? Define the significance of this drug.
Acyclovir is an effective treatment against the viral replication of Herpes Simplex virus (HSV). It looks like a purine but is a “guanosine analogue” that’s missing the 2’ position therefore it cannot be used for synthesis. It is a DNA chain terminator by the viral thymidine kinase (not cellular thymidine kinase).
What is Sovaldi? Define its significance.
Sovaldi is a uridine analog used for treatment of Hepatitis C. It is an obligate chain terminator. It is the miracle cure drug for Hep. C.
Which of the following drugs will have the lowest incidence of causing hypoglycemia in treating a diabetic patient (Sulfonylurea, Metformin, DPP-4 inhibitors, insulin)? What of the highest incidence?
Metformin which functions by inhibiting genes for gluconeogenesis has the lowest hypoglycemic incidence. The highest is from insulin (where an overdose is common).
What reactions are B6 used as a cofactor? Provide an example enzyme.
B6 (pyroxidine phosphate) functions as a cofactor for decarboxylation and transaminase reactions. An example is the enzyme responsible for conversion of NE to Epinephrine.
What types of reactions does Vitamin B7 (biotin) function in? Provide an example enzyme.
B7 functions in carboxylation reactions. This plays a role in the carboxylation activity of PDH complex and ACC for fatty acid synthesis.
