biochem exam 1

Rifampicin

Treats tuberculosis

Inhibits BACTERIAL RNA polymerase, binds to the beta subunit of bacteria, RNA polymerase

Actinomycin D (dactomycin)

Binds to dsDNA and prevents transcription

Treats rhabdomyosarcoma and Wilma tumor in children

Nalidixic acid

Quinolone

quinolones

Inhibit DNA replication

Type II topoisomerases

Levofloxacin

GI gram negative bacteria, pseudomonas aeruginosa, streptococci

UTIs

GI/abdominal infections

Pneumonia

Bone and joint infections

Levofloxacin

GI gram negative bacteria, pseudomonas aeruginosa, streptococci

UTIs

GI/abdominal infections

Pneumonia

Bone and joint infections

Tetracycline (doxycycline, minocycline)

Bacterial ribosome A site on the 30s subunit

Macrolides (erythromycin, clarithromycin, azithromycin)

Bacterial 50s ribosome subunit

Lincosamides (clindamycin)

Bacterial 23s on the 50s subunit

Aminoglycosides (gentamicin, tobramycin)

Bacterial 30s subunit

Oxazolidinones (linezolid)

bacterial 50s subunit

Rifamycins (rifampin, rifapentine, rifaximin)

Bacterial RNA polymerase

remdesivir (Covid) and molnupiravir

Inhibits RNA dependent RNA polymerase for a broad range of viruses

R - mild to moderate, on supp oxygen, serve Covid, on invasive ventilation (don’t use)

M - mild to moderate , progression of severe disease possible

Paxlovid (COVID)

Nirmatrelvir: peptidomimetic inhibitor of Mpro, the SARS-CoV-2 main

protease

Ritonavir: HIV protease inhibitor used as a pharmacokinetic booster

Mild to moderate patients, at high risk for progression of disease, drug to drug interactions

Tenofovir (HIV)

Nucleotide reverse transcription inhibitors (NRTIs) (viral RNA reverse transcription)

Efavirenz (HIV)

Non nucceloside reverse transcription inhibitors (viral RNA reverse transcription)

Bictegravir ( HIV)

Integrate inhibitors (DNA integration)

Possible combinations for HIV treatment

1. Bictegravir/emtricitabine/tenofovir AF (Biktarvy)

3. Dolutegravir (Tivicay) + emtricitabine/tenofovir AF (Descovy)

4. Dolutegravir/lamivudine (Dovato)

Beta lactams

Penicillins, cephalosporin, monobacta,, and carbapenems

Alkylating agents

Messes up replication fork - leads to cell death but can also lead to mutations

5-FU (antimetabolites)

Suicide, disrupts rRNA and tRNA maturation

• Target: Thymidylate synthase

• What it does: Blocks thymidylate synthase, preventing the cell from making thymidine, a building block needed for DNA.

• Result: Cancer cells cannot make DNA properly, so they cannot grow and divide normally.

Methotrexate dihydrofolate reductase (antimetabolites)

• Target: Dihydrofolate reductase (DHFR)

• What it does: Blocks DHFR, preventing the conversion of dihydrofolate into tetrahydrofolate (THF).

• Result: Decreases the folate needed to make DNA building blocks, so cancer cells cannot make DNA and divide normally.

Gemcitabine (antimetabolites)

inhibits ribonucleotide reductase and gets incorporated into DNA, which stops DNA replication.

6-MP (antimetabolites)

6-MP blocks purines — fewer purine building blocks means less DNA and RNA can be made.

Hydroxyurea (antimetabolites)

Hydroxyurea inhibits ribonucleotide reductase, reducing the building blocks needed for DNA synthesis and preventing cells from replicating their DNA.

Irinotecan, topotecan (camptothecins)

Target topoisomerase I (single strand cuts) - releases strain ahead of replication fork and RNA polymerase

Etoposide, anthracyclines

Topoisomerase II (double strand cuts) - untangling sister chromotids, removal of knots, essential for chromosome segregation

Doxorubicin

Doxorubicin is an anthracycline chemotherapy drug that intercalates into DNA, inhibits topoisomerase II, and generates free radicals, leading to DNA damage and cancer cell death

Taxol (paclitaxel)

Stabilizes (freezes) microtubles (prevent mitosis)

Vincristine, vinblastine (vinca alkaloids)

Destabilizing microtubes and inhibit polymerization (prevent mitosis)

Bortezomib and carfilzomib (proteasome inhibitors)

• Normal proteasome: Gets rid of unwanted proteins.

• Proteasome inhibitor: Blocks the garbage disposal.

• Result: Waste proteins build up, the cell becomes stressed, and the cancer cell may die.

Vorinostat and romidepsin

HDAC inhibitors, HDAC enzymes remove acetyl groups, helping close the book.

• HDAC inhibitors block HDAC enzymes, helping open the book.

• This allows certain genes to become active, which can help stop cancer cells from growing or cause them to die.

Imatinib

Chronic myeloid leukemia, chromosomal translocation (blocks ATP from binding to the BCR-ABL kinase so it can’t work

Fluorouracil (FOLFOX)

Antimetabolite, S phase specific

Oxaliplatin (FOLFOX)

Alkylating agent, cell cycle independent

Leucovorin (FOLFOX)

Reduced folate, biochemical modulator