Chart For Final - Laic Shizzle

Page 1 of 3 Types of Insulin Rapid Acting Analogues Short-Acting Intermediate-Acting Long-Acting Extended long-Acting Analogue

Lispro Aspart Regular (Humulin) Lente (Humulin-L) NPH (Humulin-N) Unltalente (Humulin-U) Glargine Detemir

Oral Hypoglycemic Agents

Drug

Sulfonylureas - First Generation

Tolbutamide Chloropropamide

MOA

Drug Information Shortest duration of action, safe in renal failure, poorly tolerated Longest acting sulfonylurea. Avoid in renal failure, Stimulates release of insulin from pancreatic beta poorly tolerated cell and enhance beta cell sensitivity to glucose.

Adverse Effects

Drug interactions

GI symptoms, dermatological reactions, hypoglycemia, disulfirim reaction, weight gain.

Direct interaction: Sulfonamides, chloramphenicol, clofibrate. Meds that increas blood sugar: corticosteroids, estrogen, phenytoin. Meds that decrease blood sugar: salicylates, propranolol. Alcohol - may increase risk of lactic acidosis. Cimetidine (H2 antagonist) may inc metformin by 60%. May interfere with absorption of B12.

Sulfonylureas - Second Generation 1000x more potent than 1st generation

Glyburide Glicazide Glimerperide

Biguanide

Metformin

No effect on pancreatic cells; facilitates insulin's action of peripheral receptor sites

Dec HgA1C by 1.5-2%. Does not cause hypoglycemia. Beneficial effects on lipid profile and modest weight loss. Taken with meals.

Risk of lactic acidosis. CI in renal failure bc of lactic acid. Abdominal discomfort, metallic taste, nausea, anorexia.

Alpha-glucosidase inhibitor

Acarbose

Delay the absorption of glucose in the intestinal system, resulting in lower postprandial blood glucose level.

Must be taken with 1st bite of meal. Can be use alone or in combo.

Abdominal cramps, Diarrhea, flatulence (77%!), increase of liver enzymes

Thiazolidinediones (TZD)

Rosiglitazone

Enhance insulin action at the PPAR-y receptor side without increasing insulin secretion from the beta cells of the pancreas

May be taken irrespective of meals. Does not cause Weight gain, effects on cholesterol (inc HDL, inc TG), fluid hypoglycemic events. Safe in renal failure. Can be retention. Watch for hepatotoxi city. alone or in combo

Pioglitazone Troglitazone Meglitinides

Repaglinide

Fast onset, short half life. Taken before each meal. Stimulates the release of insulin from the beta cells Can cause hypoglycemia. Alone or in combo with of the pancreas metformin. Dec HgA1C by 0.6-1%.

Headache, hypoglycemia, weight gain

CYP substrate, Inducers: rifampin, carbamazepine, can decrease hypoglycemic effects. Inhibitors: ketoconazole, micoconazole can inc hypoglycemic effects

Page 2 of 3 Cancer

Drug

Antimetabolites

MOA

Drug Information

Methotrexate (immunosuppressant)

DNA synthesis inhibitors: Purine antagonist Mercaptopurine

DNA synthesis inhibitors: Pyrimidine Cytarabine antagonist (5-Fluorouracil)

(analogue of hypoxanthine and guanine base). Must be activated by enzyme HGPRTase (inhibits several steps in biosynthesis of purine base and their salvage) C: kills cells in S phase by inhibiting DNA polymerase causing chain termination F: must 1st be converted to active nucleotide metabolite by tumor cell enzymes; has 2 active metabolites Damage or disrupt DNA, interfere with topoisomerase activity or alter RNA strucutre

Alkylating agents, intercalators, antibiotics

Mechlorethamine Nitrogen Mustards Cyclophosphamide

Nitrosurea Drugs Carmustine

Platinum Compounds Cisplatin

Bleomycin

Intercalating Drugs

Inhibits dihydrofolate reductase, DHFR, (so dietary folate does not get activated and decreased purines and thymidines available)

Dactinomycin

Doxorubicin / Daunorubicin

Drug interactions

Most common toxicity to this group: Dermatological (SKIN RASHES) GIT (STOMATITIS and DIARRHEA) Hematopoietic (NEUTROPENIA and THROMBOCYTOPENIA)

Inhibit DNA synthesis

DNA synthesis inhibitors: Folate antagonist

Adverse Effects

Most widely used antimetabolite in CA tx. Also used as immunosuppressive drug in RA and LUPUS tx. Oral and parentral routes. Only low doses completely absorbed. May crystallize in urine thus important to stay hydrated and alkalinize the urine.

The primary dose-limiting toxicity is BMS with STOMATITIS also necessitating dose changes. Greatest danger of high dose tx is RENAL toxicity. Other serious side effects include: PNEUMONITIS and LV TOXICITY.

One of the 1st tx for Acute Lymphocytic Leukemia. LV toxicity occurs in 1/3rd and manifests as Metabolic inactivation by xanthine oxidase. Toxicity is CHOLESTATIC JAUNDICE. Includes: BMS, N+V, LV dose dependent. Toxicity.

cytarabine crosses BBB and reaches 50% of plasma concentration - tx for brain cancer

Cerebral damage. BMS, n+v, stomatitis. At high dosages causes organ damage (heart, liver)

Largest class of CA drugs. The degree of DNA alkylation correlates strongly with cytotoxicity (nonphase specific)

In long term : sterility, increased risk of acute non-lymphocytic leukemia

MOST USED anticancer drugs. Very UNSTABLE, dosed IV. Mechlorethamine is used to tx Hodgkin’s First is converted to Active metabolite (P450). Kills dz (MOPP cocktail). proliferating cells in S and G1 phase, blocking the G2 phase resulting in cell death. Attaches to guanine base (G) preventing DNA replication and Cyclophasphamide has pronounced effect on transcription. This group is non-phase specific. lymphocytes and used as IS (immune system) suppressant

BMS N+V Extravasations Latent viral infections (Herpes Zoster) Leukemia development BMS N+V Diarrhea Immunosuppresion Hemorrhagic cystitis

Need to be activated. Results in DNA cross-linking. Lipophilic, therefore into CSF (30%). Has limited use: Delayed and prolonged BMS (severe Alkylates resting cells but cytotoxicity is only brain tumors, melanoma, multiple myeloma, cumulative depressive effect on BM). Thrombocytopenia > expressed on cell division (non-dividing cells can malignant glioma leukopenia. At high doses affects PULMONARY TISSUE escape if DNA repair occurs) KI Toxicity Broad range of anti-tumor activity (especially (hypomagnesia + hypocalemia) Causes intra-strand cross-linking at guanine solid tumors: TESTICULAR / OVARIAN). Given as Ototoxicity (tinnitus and hearing loss) molecules, therefore denatures DNA. Not phase- slow IV. Water soluble therefore not cross BBB. N+V (tx with Ondansetron) specific High protein bound. Prolonged t1/2 detectable in Mild BMS fluids and tissue up to 4 months later) Peripheral neuropathy Pulmonary fibrosis (10%) , fatal in 1% Causes scissions of DNA (degrades Isolated from streptomyces verticillus. Group of Hyperpyrexia preformed DNA causing fragmentation to metal-chelating glycopeptide antibiotics. Localized in Hypertrophic skin and increase pigmented hands chain and release of free bases). Cells accumulate epithelial organs (SKIN, Alopecia in the G2 phase. Chelated ferrous Fe and oxidizes LU, peritoneum, lymph). Indications: Testicular Anaphylaxis it to produce hydroxyl radicals tumors. Squamous cell CA and lymphomas. Little / NO BMS Dose limiting toxicity is BMS First antibiotic to find therapeutic application N+V Initially it interferes with RNA polymerase. At high in tumor chemo tx. Concentrates in the liver Excreted Diarrhea doses interferes with DNA synthesis by preventing in the bile. Indications: Wilm’s tumor Stomatitis transcription of RNA Choriocarcinoma (soft tissue sarcomas) Alopecia Sensitization to radiation Cardiotoxicity (Irreversible , dose dependent) : dysrrhythmia , HT failure Intercalation of DNA. Altered transport across Severe ALOPECIA Given IV. Does not penetrate CSF. Excretion via membrane. Generates lipid peroxidation. Only S BMS Liver and bile. phase cells affected. Stomatitis GI disturbance Makes URINE RED

Use of Leucovorin (Folinic acid) as ‘rescue process’ controversial.

Cross reaction with allopurinol (CI)

Page 3 of 3 Plant Alkaloids

Distrupt mitosis Paclitaxel (Taxane Mitotic inhibitor family)

Mitotic inhibitor - Vinka alkaloids Vincristine/ Vinblastine

Topoisomerase Inhibitor Etoposide

“freezes” microtubules in polymerized state

Binds to tubuline and inhibits polymerisation of microtublules. This disrupts spindle apparatus causing termination of assembly of cytoskeletal protein, preventing segregation. Thus prevents spindle formation in mitosing cells and causes arrest at, metaphase. Cycle and phase specific

Blocks cells in late S-G1 phase.

Hormones

Estrogen antagonist Tamoxifen

Non-phase specific. Non-productive binding to estrogen receptor causing depletion of estrogen receptors available to bind estrogen. Inhibits receptors growth promoting effects. Cardioprotective effects (prevents LDL oxidation)

Aromatase Inhibitor Arimidex

Aromatase inhibitor (decreasing circulating estradiol).

Androgen Antagonist Flutamide

Synthetic Estrogen Diethylstillbestrol

Gonadotropin releasing hormone Leuprolide Asparaginase Growth Factors

Originates from plant alkaloid of Yew tree (Taxus brevifolia). Given IV. LV metabolized, KI excreted. Indication: Metastatic ovarian CA after failure of first time drug. Metastatic BrCA

Dose-limiting BMS (esp NEUTROPENIA) Alopecia Neurotoxicity (cumulative)

Hyperuricemia, Gout Phlebitis / cellulitis N+V, diarrhea Alopecia From periwinkle plant (Vinca rosea). Peripheral neuropathy (Vincristine) - dose limiting neurotoxicity (only one!) BMS (Vinblastine). No BMS supression with Vincristine and Bleomycin. Plant alkaloid (Mandrake root), semi-synthetic. Highly BMS (dose-limiting) protein bound. Not enter BBB. Excreted via KI. Alopecia Indication: Oat cell CA of LU. Refractory testicular N+V CA. Anaphylactic reaction NO BMS HOT FLASHES Vaginal bleeding Oral. LV metabolized. bile excreted. Indications: Vaginal discharge Estrogen dependent BrCA. Endometrial CA Skin rash N+V Increases pain of bone metastasis New class of BrCA drugs. Shown better than Tamoxifen in 5yr study to prevent re-occurance. Bone fractures. Joint pain. Found to be more effective than tamoxifen in CI: pre-menopausal women / nonhormone sensitive OLDER pts. May ward off 70-80% of tumors tumors common in menopause.

Treatment of Prostate CA: Prostate tissue is STIMULATED by androgens and SUPPRESSED by estrogen. Therefore tx with ANDROGEN ANTAGONIST (i.e. Flutamide), that block testosterone stimulation of prostate CA cells Prostate CA also tx with SYNTHETIC ESTROGEN (i.e diethylstilbestrol) which directly suppresses prostatic proliferation. Other option is GONADOTROPIN-RELEASING HORMONE (i.e. Leuprolide) which inhibits FSH and LH release, decreasing androgen synthesis. Destroy essential AA needed for translation Act through signal transduction pathways Adverse Reaction NO BMS GIT toxicity - N&V, mucositis Hair follicles

NO BMS

Drug Bleomycin, hormones, L-asparaginase, vincristine Doxorubicin, Daunorubicin, Vincristine, Cyclophsophamide, Methotrexate

Radiation Recall Reactions (dermatitis / Doxorubicin, Daunorubicin esophagitis flare ups in previously irradiated areas) Hepatic Toxicity Urinary Tract Toxicity Acute Hemorrhagic Cystitis Cardiac toxicity Pulmonary Toxicity Lung Injury Hypersensitivity pneumonitis/ allergic interstitial pneumonia Neurological toxicity Peripheral neuropathy ANS tocxicity (constipation, ortho hypotension) Reproductive function toxicity Teratogenic risk Carcinogenic properties

Methotrexate Cisplatin Cyclophosphamide Doxorubicin Bleomycin (lethal in 1%) Carmustine Methotrexate Vincristine Cisplatin Vinblastin Alkylating agents Methotrexate Alkylating agents

In comparison to Tamoxifen: 10% extra CA-free life 20% longer time b/f reoccurrence of dz 14% less spread of metastasis 40% decreased risk of occurrence in opposite breast