Ahmad Alsawaie ‫بسم هللا الرحمن الرحيم‬ Medicine and surgery (MD)-

Genetics

Lecture 1

 Hydroxyurea is a Drug inhibit this Enzyme → decrease Deoxyribonucleotides for DNA Synthesis
→no cell division → treatment of cancer

Lecture 2

 Endogenous Purine → Produced and degraded mostly in the liver

 Treatment of Gout
 Anti-inflammatory drugs to relieve inflammation and pain such as Colchicine, Prednisone
and Indomethacine (have no effect on uric acid levels).
 Allopurinol (suicide “Irreversible” Inhibitor) which is Hypoxanthine analog that inhibit
Xanthine Oxidase So the End product of Purine catabolism will be Hypoxanthine and
Xanthine which are more water soluble and do Not form crystals
 Uricosuric agents, such as probenecid or sulfinpyrazone increase renal excretion of uric acid
 Treatment of ADA deficiency
 Isolate the patient from the environment by incubator “Bubble boy”
 Enzyme replacement therapy
 Bone marrow transplantation, here we need appropriate donor

Lecture 3

 Group of antibiotics sulfonamides (Sulfa-Drugs / Para-amino benzoic acid analogs “PABA

analogs”) such as Sulfamethoxazole inhibit the synthesis of folic acid in bacteria → No A, G and T
→ No division → bacterial Death
 Methotrexate is a folate analog Irreversibly inhibit Dihydrofolate Reductase “the enzyme that
generate the active form of folic acid”
 So methotrexate prevent formation of THF → prevent synthesis of A, G, and T→ No DNA
synthesis and Cell division → anticancerous “chemotherapeutic” agent “
 alopecia, immunosuppression, vomiting, diarrhea are side effects of chemotherapeutic
agents”
 Antibiotic called Trimethoprim is also a folate analog but with high selectivity for bacterial
Dihydrofolate reductase prevent → formation of THF in bacteria → prevent synthesis of A, G,
and T→ No DNA synthesis and Cell division → Bacterial Death
 Trimethoprim is usually combined with sulfamethoxazole for treatment of UTIs “Urinary Tract
Infections”
 Treatment of Orotic Aciduria: UMP
 A Drug called Leflunomide inhibit this step (step 4 in pyrimidine de novo synthesis) → no
pyrimidine nucleotides→ affect T-lymphocytes → work as immunosuppressant for treatment of
Rheumatoid arthritis
 5-Flourouracil is a Thymine Analoge Irreversibly inhibit Thymidylate Synthase → No dTMP
synthesis → No DNA synthesis → No Cell division → treat cancer
 Mycophenolic Acid is a drug Reversible inhibitor of IMP dehydrogenase, this will deprive cells
from Guanine nucleotide for DNA and RNA synthesis, affect B and T- Cells and used as
immunosuppressant to prevent graft rejection

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