RHS Antimycobacterials, Antimalarials, & Chemo Flashcards
Rifampin
Rifamycin. Part of RIPE (first-line anti-Tb drugs). Also part of DR Clof (for Leprosy)
Inhibitor of bacterial RNA polymerase
Resistance: point mutations in rpoB gene (gene for b subunit of RNA pol)
AE: Red body fluids, nephrotoxicity, rashes, hepatotoxicity
CYP inducer, Safe in pregnancy
Rifabutin
Rifamycin. Part of RIPE (first-line anti-Tb drugs).
Inhibitor of bacterial RNA polymerase
Resistance: point mutations in rpoB gene (gene for b subunit of RNA pol)
AE: Red body fluids, nephrotoxicity, rashes, hepatotoxicity
Not a CYP inducer so preferred into Rifampin in HIV patients.
Isoniazid
Part of RIPE (first-line anti-Tb drugs).
Mycolic Acid synthesis inhibitor
Resistance: deletion of Kat G- catalase peroxidase (high resistance), overexpression of inhA and KasA (low resistance)
AE: Neurotoxicity (treatable with vit B6), Lupus-like syndrome, Hemolysis in G6PD, Hepatotoxicity!!
CYP inhibitor. Safe in pregnancy. Metabolized by N-Acetyltransferase so higher dose needed in fast acetylator.
Pyrazinamide
Part of RIPE (first-line anti-Tb drugs).
MOA unclear. Is activated by hydrolysis by mycobacterial pyrazinamidase (pncA).
Resistance: Impaired uptake or mutations in pncA
AE: Non-gouty polyarthalgia, Hyperuricema (not given in gout), Hepatotoxicity, Myalgia, Porphyria, Photosensitivity.
Can be given in pregnancy but has risks.
Ethambutol
Part of RIPE (first-line anti-Tb drugs).
Inhibits arabinosyltransferases (emb) leading to decreased carbohydrate polymerization of bac cell wall.
Resistance: Mutations/Overexpression of emb.
AE: Visual disturbance, colorblindness, retinal damage. Not given in children too young to assess for colorblindness.
Safe in pregnancy.
Streptomycin
Part of SEAL (2nd line anti-Tb drugs)
Aminoglycoside: binds 30s subunit, inhibits bacterial ribosome.
AE: Ototoxicity, Nephrotoxicity, Unsafe in pregnancy.
Ethionamide
Part of SEAL (2nd line anti-Tb drugs)
Isoniazid-like. Inhibits mycolic acid synthesis.
AE: GI upset, neurotoxicity (alleviated by Vit B6)
Amikacin
Part of SEAL (2nd line anti-Tb drugs)
Aminoglycoside: binds 30s subunit, inhibits bacterial ribosome.
AE: Ototoxicity, Nephrotoxicity, Unsafe in pregnancy.
Is still effective in multidrug-resistant strains of TB
Levofloxacin
Part of SEAL (2nd line anti-Tb drugs)
Fluoroquinolone. Inhibits bacterial DNA gyrase
AE: Tendinopathy. Unsafe in pregnancy.
Dapsone
Part of DR Clof- treatment for Leprosy.
Inhibits folate synthesis via dihydropteroate synthetase inhibition.
AE: Hemolysis in G6PD. Methemoglobinema (Fe3 hemoglobin), Erythema nodosum leprosum.
Clofazimine
Part of DR Clof- treatment for Leprosy. Only given in Multi-bacillary leprosy.
Binds bacterial DNA, inhibits replication.
AE: Discoloration of skin and conjunctiva.
Methotrexate
Antimetabolite: Folate Analog
Inhibits dihydrofolate reductase (DHFR), decreasing synthesis of dTMP & purines. Effect potentiated by conversion to polyglutamates (MTX-PG) by folylpolyglutamate synthase (FPGS).
Kills cells in S phase.
Resistance via: Decreased influx, decreased FPGS activity, Altered or amplified DHFR.
AE: Stomatitis, mucositis, BM sup, thrombocytopenia, erythema, rash, alopecia, N/V. Nephrotoxic at high doses. Hepatotoxic. Pneumonitis. Neurotoxic if administered into CSF (spinal).
Leucovorin
Folate Analog
Decreases BM suppressive effect of Methotrexate.
Potentiates 5-FU.
6-Mercaptopurine
Antimetabolite: Purine Analog (Thiol analog of hypoxanthine)
Converted to 6-MPRP/TIMP by HGPRT. TIMP inhibits first step of denovo purine synthesis & blocks formation of AMP & GMP from IMP.
Resistance: HGPRT deficiency, increased metabolism of drug, increased dephosphorylation.
AE: N/V, diarrhea, BM sup, hepatotoxicity.
Special: Used in Acute Lymphatic Leukemia. Dose needs to be reduced in poor TMPT metabolizers. Dose needs to be reduced if given with allopurinol (allopurinol inhibits enzyme that metabolized 6-MP to inactive form).
6-Thioguanine
Antimetabolite: Purine Analog
Converted to TGMP by HGPRT. TGMP inhibits purine ring synthesis & phosphorylation of GMP to GDP.
AE: N/V, diarrhea, BM sup, hepatotoxicity.
Special: Used in Acute non-lymphocytic Leukemia. Dose needs to be reduced in poor TPMT metabolizers. No Allopurinol interactions.
5-Fluorouracil
Antimetabolite: Pyrimidine Analog
Converted to 5-FdUMP which inhibits formation of dTMP from dUMP. Causes thymine-less death. Also converted to 5-FUTP which is incorporated into RNA. Given IV due to GI toxicity.
Resistance: No conversion to 5-FdUMP, altered thimydilate synthase, increased catabolism of 5-FU.
AE: N/V, diarrhea, alopecia, GI ulceration, BM sup, anorexia. Dermatopathy: Hand-Foot syndrome.
Special: Used in colorectal cancer (with Leucovorin)
Cytarabine
Antimetabolite: Pyrimidine Analog
Converted to ara-CTP, incorporated into DNA, inhibits DNA polymerase. Not orally effective.
AE: N/V, diarrhea, Severe BM sup, hepatotoxicity, seizures or AMS.
Special: Used in acute non-lymphocytic leukemia.
Doxorubicin
Antitumor Antibiotic: Anthracycline
Topoisomerase II inhibition, DNA intercalation, iron-dependent generation of free radicals which break DNA strands, altering membrane ion transport & fluidity.
Resistance: P-glycoprotein increased efflux, glutathione peroxidase increase, mutation in topoisomerase 2.
AE: BM suppression, cardiotoxicity (can be alleviated with dexrazoxane).
Daunorubicin
Antitumor Antibiotic: Anthracycline
Topoisomerase II inhibition, DNA intercalation, iron-dependent generation of free radicals which break DNA strands, altering membrane ion transport & fluidity.
Resistance: P-glycoprotein increased efflux, glutathione peroxidase increase, mutation in topoisomerase 2.
AE: BM suppression, cardiotoxicity (can be alleviated with dexrazoxane).
Bleomycin
Antitumor Antibiotic.
Mixture of glycopeptides. Binds to DNA, generates free radicals which cause strand breakage.
Resistance in tissues with Bleomycin hydrolase.
AE: Very mild BM sup. Pulmonary toxicity!
Mechlorethamine
Alkylating Agent: Nitrogen Mustard
Cytotoxic by transfer of alkyl groups to DNA.
AE: N/V, severe BM sup, alopecia.
Special: Unstable & causes blisters (given IV only). Largely replaced by cyclophosphamide & other agents.
Cyclophosphamide
Alkylating Agent: Nitrogen Mustard
Cytotoxic by transfer of alkyl groups to DNA. Prodrug activated by CYP2B. Most widely used.
AE: N/V, BM sup, Hemorrhagic cystitis!!!, Alopecia, Sterility.
Special: Hemorrhagic cystitis caused by Acrolein metabolite. Prevented thru adequate fluid intake + Mesna.
Mesna
Sulfhydryl compound which neutralizes acrolein in the bladder.
Prevents Hemorrhagic Cystitis adverse effect of Cyclophosphamide & Ifosfamide.
Ifosfamide
Alkylating Agent: Nitrogen Mustard
Cytotoxic by transfer of alkyl groups to DNA. Analog of Cyclophosphamide. Prodrug activated by hydroxylation by CYP3A4.
AE: Greater BM sup, Neurotoxicity, Greater urinary tract toxicity. Only given with adequate hydration & mesna.
Melphalan
Alkylating Agent: Nitrogen Mustard
Cytotoxic by transfer of alkyl groups to DNA.
AE: BM sup
Carmustine
Alkylating Agent: Nitrosoureas
Cytotoxic by transfer of alkyl groups to DNA.
Very lipophilic, crosses blood-brain barrier, treats brain tumors.
Lomustine
Alkylating Agent: Nitrosoureas
Cytotoxic by transfer of alkyl groups to DNA.
Very lipophilic, crosses blood-brain barrier, treats brain tumors.
Busulfan
Alkylating Agent
Cytotoxic by transfer of alkyl groups to DNA.
AE: BM sup!, Pulmonary fibrosis!
Dacarbazine
Alkylating Agent
Cytotoxic by transfer of alkyl groups to DNA. Prodrug activated in the liver.
AE: N/V, BM sup.
Procarbazine
Alkylating Agent
Cytotoxic by transfer of alkyl groups to DNA. Prodrug activated in the liver.
AE: N/V, BM sup, MAO inhibitor- hypertensive reactions with tyramine foods or sympathetic agents, disulfuram-like reactions, teratogen.
Cisplatin
Platinum Coordination Complex
Cytotoxic by covalently bonding to DNA & cross-linking.
AE: N/V, Ototoxic, Peripheral Neuropathy, Nephrotoxic, BM sup.
Special: Treatment of Testicular & Ovarian cancer. Treatment of cancers of head, neck, bladder, esophagus, lung & colon. Amifostine can reduce nephrotoxicity.
Carboplatin
Platinum Coordination Complex
Cytotoxic by covalently bonding to DNA & cross-linking.
AE: Dose-limiting myelosuppression. Also N/V, neurotoxic, ototoxic, nephrotoxic- but these are less than in Cisplatin.
Special: Treatment of Testicular & Ovarian cancer. Treatment of cancers of head, neck, bladder, esophagus, lung & colon.
Amifostine
Reduces Nephrotoxicity of Cisplatin.
Vincristine
Microtubule Inhibitors: Vinca Alkaloid
Destabilizing agents, arresting cells in metaphase.
AE: Severe Peripheral Neuropathy, mild BM sup, Alopecia
Vinblastine
Microtubule Inhibitors: Vinca Alkaloid
Destabilizing agents, arresting cells in metaphase.
AE: Peripheral Neuropathy, severe BM sup, Alopecia
Paclitaxel
Microtubule Inhibitors: Taxane
Stabilizing agent, arrests cells in mitosis.
AE: Hypersensitivity, BM sup, peripheral neuropathy, alopecia.
Special: Hypersensitivity reduced by premedicating with dexamethasone, diphenhydramine & H2 blocker.
Etoposide
Epipodophyllotoxin.
Topoisomerase 2 inhibitor. Arrests cells in late S, G2 phase.
AE: N/V, alopecia, BM sup.
Topotecan
Camptothecin
Topoisomerase 1 inhibitor.
AE: BM sup, diarrhea.
Irinotecan
Camptothecin
Topoisomerase 1 inhibitor.
AE: BM sup, diarrhea.
Prednisone
Glucocorticoid
Steroid action suppresses lymphocytes
Used in acute leukemia & malignant lymphomas.
Tamoxifen
Estrogen Inhibitor: Selective Estrogen-Receptor Modulator (SERM)
Estrogen antagonist in breast tissue. Estrogen agonist elsewhere. Activated by CYP2D6.
AE: Hot flashes, N/V, fluid retention, vaginal bleeding, venous thromboembolism, increased risk of endometrial cancer.
Use: Metastatic breast cancer. Preventative agent in women at risk for breast cancer. Avoid using with CYP2D6 inhibitors- Bupropion, Fluoxetine, Paroxetine.
Raloxifene
Estrogen Inhibitor: Selective Estrogen-Receptor Modulator (SERM)
Estrogen antagonist in breast and uterus. Estrogen agonist in bone.
AE: Hot flashes, leg cramps, venous thromboembolism.
Use: Treatment & prevention of osteoporosis in postmenopausal women. Prophylaxis of breast cancer in postmenopausal women.
Fulvestrant
Estrogen Inhibitor: Pure Estrogen Antagonist
Use: Treatment of metastatic breast cancer in post-menopausal woman when initial therapy fails.
Anastrozole
Estrogen Inhibitor: Aromatase Inhibitor
Non-steroidal, reversible competitive inhibitor.
Use: Standard adjuvant treatment for breast cancer in postmenopausal women.
Letrozole
Estrogen Inhibitor: Aromatase Inhibitor
Non-steroidal, reversible competitive inhibitor.
Use: Standard adjuvant treatment for breast cancer in postmenopausal women.
Exemestane
Estrogen Inhibitor: Aromatase Inhibitor
Steroidal, irreversible inhibitor.
Use: Standard adjuvant treatment for breast cancer in postmenopausal women.
Goserelin
Androgen Inhibitor: GNRH Agonist
Cause GNRH receptor desensitization, lowering FSH, LH and Androgen levels.
Use: Advanced prostate cancer, advanced breast cancer in premenopausal women, management of endometriosis.
Special: Flare phenomenon initially due to normal effects of GNRH receptor activation, countered by flutamide.
Leuprolide
Androgen Inhibitor: GNRH Agonist
Cause GNRH receptor desensitization, lowering FSH, LH and Androgen levels.
Use: Advanced prostate cancer, advanced breast cancer in premenopausal women, management of endometriosis.
Special: Flare phenomenon initially due to normal effects of GNRH receptor activation, countered by flutamide.
Flutamide
Androgen Inhibitor: Androgen Receptor Blocker
Prodrug. Blocks flare phenomenon of GNRH agonist.
Gefitinib
EGFR Tyrosine Kinase Inhibitor
Use: Nonsmall cell lung cancer
Erlotinib
EGFR Tyrosine Kinase Inhibitor
Use: Nonsmall cell lung cancer. Pancreatic cancer.
Lapatinib
EGFR and Her2 tyrosine kinase inhibitor
Use: Breast Cancer with Her2 overexpression
Imatinib
Bcr-Abl tyrosine kinase inhibitor
Use: CML, ALL, Myelodysplastic/Myeloproliferative diseases
Trastuzumab
Monoclonal antibody against Her2 Tyrosine Kinase
Use: DOC for breast cancer with Her2 overexpression
Bevacizumab
Monoclonal Antibody against VEGF
Use: Metastatic Colorectal cancer, non-small cell lung cancer, glioblastoma, renal cell carcinoma.
Asparaginase
Hydrolyzes serum asparagine, depriving tumors of asparagine.
AE: Hypersensitivity, hepatotoxicity, decrease in clotting factors, pancreatitis, ammonia toxicity.
Hydroxyurea
Ribonucleotide reductase inhibitor
Depletes DNA nucleotides, kills cells in S phase.
INF-a
Use: Hairy Cell Leukemia, CML, malignant melanoma, Kaposi sarcoma.
Chloroquine
DOC for non-falciparum and uncomplicated falciparum malaria.
Preferred chemoprophylactic agent in areas without resistant malaria.
AE: Hemolysis in G6PD. Can’t be given IV. Visual problems.
Special: Safe in pregnancy.
Hydroxychloroquine
Alternative for chloroquine in chemoprophylaxis and treatment of uncomplicated malaria.
AE: Hemolysis in G6PD, visual problems, pruritus.
Special: Safe in pregnancy & children
Quinine/Quinidine
First-line treatment for severe falciparum malaria. Treatment of CR uncomplicated falciparum & other species.
AE: Blackwater fever, uterine contractions, cinchonism, cardiotoxicity, hypersensitivity, hypoglycemia, cytopenia, hemolysis.
Sulfadoxine + Pyrimethamine
No longer recommended because of resistance.
Folate synthesis inhibitors.
Atovaquone + Proguanil (Malarone)
Treatment & prophylaxis of CR falciparum.
AE: Avoid in pregnancy, unknown safety.
Disrupts mitochondrial electron transport.
Doxycycline
Treatment & prophylaxis of uncomplicated CR falciparum & other species. Treatment of severe falciparum.
AE: Photosensitivity, teeth discoloration, growth stunting, avoided in pregnancy and kids under 8.
Binds 30s ribosome.
Clindamycin
Alternative to doxycycline in treatment of severe falciparum & uncomplicated malaria in pregnancy.
AE: Pseudomembranous colitis.
Safe in pregnancy & children.
Mefloquine
Last resort treatment of severe falciparum. Only chemoprophylaxis for CR strains in pregnancy. Treatment of uncomplicated CR falciparum & other species.
AE: Neuropsychiatric, don’t administer with quinidine.
Safe in pregnancy & children.
Artemisinin
Treatment of uncomplicated CR falciparum & other species. Treatment of severe falciparum (IV). Not used as prophylaxis.
Safe in pregnancy, more safety evidence in 2nd and 3rd trimesters.
Primaquine
DOC for eradication of Vivax & Ovale hypnozoites. Only gametocidal agent. Prophylaxis of CRstrains.
AE: Hemolysis, Methemoglobinemia.
