ANTITUMOR AGENTSand

MISCELLANEOUS DRUGS

Reilly ThomasClass of 2013

rct2013@uw.edu

Objectives• To have a basic understanding of cancer and its processes

– Types– Causes – What we attempt to do in its treatment

• General Information about the chemotherapeutic agents– Method of Action (MOA)– Route of Administration (ROA)– Side effects (SE)– Indications (ID)– Drug- drug interactions (DDI)– Counseling points for patients (CP)

Cancer is….

• the uncontrolled growth of abnormal cells in the body. Cancerous cells are also called malignant cells.

• There are a number of causes– Chemicals/toxins– Sun exposure– Obesity– Viruses– Genetic factor– Radiation– Some causes are unknown

Overview of Carcinogenesis

• Types of cancer– Leukemia: Cancer of Blood/lymph cells• ALL – Acute lymphoblastic leukemia• AML – Acute myelogenous leukemia• CLL – Chronic lymphocytic leukemia• CML – chronic myelogenous leukemia

Overview Continued

• Types of cancer– Multiple Myeloma – Lymphoma• Hodgkin’s• Non-Hodgkin’s• Burkitt’s

– Specific Tissue Cancers• Carcinoma• sarcoma

Stages of Cancer

• The stages of cancer can be seen below, difficultly in treatment and a decrease in good outcomes increase as the mutated cells grow.

Example

• Melanoma– Asymmetry– Border– Color– Diameter– Elevation/evolution

http://skinipedia.org/skin-diseases/skin-cancer-melanoma-in-children3.html

Goals for Treatment

• #1 – Cure: Complete remission for more than 5 years

• #2 – Disease control: Partial or temporary remission

• #3 – Relieve symptoms: Relieve symptoms of the cancer, and includes pallative care

Classes of Antitumor Agents• Antimetabolites

– Folic acid analogs– Pyrmidine analogs– Purine analogs– Enzymes

• DNA Alkylating agent– Nitrogen mustards– Nitrosoureas– Alkyl sulfonates– Triazene/hydrazines/aromatic

aminotriazene• Metalating Agents

– Platinum Complexes• DNA damaging agents

– Peptide antibiotics• Topoisomerase II inhibitors

– Antracyclines– Epi-Podo Phyllotoxins

• Topoisomerase I inhibitors– Camptothecin

• Antimitotics– Vinca Alkaloid– Taxanes

• Endocrine agents– Adrenocorticosteroids– Antiestrogens– Gonadotropins – Antiandorgens

• Biological Response Modifiers– Glycoprotiens– Recombinant Hematopoietic Growth

Factor– Cytokines

• Chemoprotectants– Thiol donors/thio-phosphonate

• Target agents– Monoconal antibodies (MAB)– MAB’s + radioimmuno conjugate– Tyrosine Kinase inhibitor– Epidermal Growth factor

Classes of Antitumor AgentsOral/Topical dosage forms• Antimetabolites– Folic acid analogs – Pyrimidine analogs– Purine analogs

• DNA Alkylating agent– Nitrogen mustards

Mechanism of antitumor

agents

Antimetabolites: Folic Acid Analogs

Methotrexate• Rheumatrex® and Trexall• MOA: Act by inhibiting

the synthesis of DNA by blocking the synthesis of thymidine

• ROA: injection or tablets

Antimetabolites: Folic Acid Analogs

Methotrexate • SE: Bone marrow depression (BMD), Gastrointestinal (GI)

Ulceration, kidney damage• ID: ALL, Non-Hodkins Lymphoma, head and neck cancers,

breast and lung cancer, there are also non-oncology uses including psoraisis

• DDI:– Ciprofloxacin &Cyclosporine– NSAIDs, penicillin, PPIs, and salicylates

• CP: Take on an empty stomach, avoid in pregnancy (category X), do not take with alcohol or folic acid supplements

Antimetabolites: Pyrmidine Analogs

Fluorouracil (5-FU), Capecitabine

• Carac, Efudex, Fluroplex

• MOA: Inhibits thymidylate synthetase and incorporates into DNA as an abnormal nucleotide

http://www.eu-pharmagate.com/news-dettaglioENG.asp?ID=314&TAB=ultimissime

http://www.medscape.com/viewarticle/588189_2

Antimetabolites: Pyrmidine Analogs

Fluorouracil (5-FU), Capecitabine • ROA: Injection or topical• SE:

– Injection: BMD, GI-ulceration, N/V/D – Topical: Skin irritation

• ID: actinic keratoses and superficial basal cell carcinoma

• DDI: warfain, cavediolol and phenytion (injection)• CP: Sun sensitivity, wash hands after topical

application, and do not cover with occlusive dressing

Antimetabolites: Purine Analogs

Mercaptopurine (6MP)- Purinethol®

Azathioprine - Azasan®; Imuran®

• MOA: Interferes with steps in the biosynthesis of purine therefore blocking DNA synthesis

• ROA: Tabletshttp://www.medscape.com/viewarticle/499922_3

Antimetabolites: Purine Analogs

Mercaptopurine (6-MP), Azathioprine• SE: BMD, anemia, thrombocytopenia, and

hepatotoxicity• ID: ALL, Crohn’s disease, ulcerative colitis • DDI: Allopurinol and warfarin• CP: May cause fever, bleeding/bruising and

should be taken on an empty stomach and women of child bearing age should take birth control

DNA Alkylating Agents: Nitrogen Mustards

Cyclophosphamide - CytoxanIfosfamide - Ifex• MOA: Crosslinks DNA• ROA: Injection (cyclo only) and tablets

DNA Alkylating Agents: Nitrogen Mustards

cyclophosphamide, ifosfamide• SE:BMD, N/V/D, hemorrhagic cystitis, hair loss • ID: lymphoma, CLL, AML, ALL, etc.• DDI: Vaccines, Succinylcholine, Warfarin• CP: Drink lots of water, take dose early, and

take with food, do not crush or chew

Estrogen Receptor Antagonist

Tamoxifen - Nolvadex®• MOA: Competitively

binds estrogen receptors producing a decrease in DNA synthesis and inhibiting estrogen effect.

• ROA: Tablet

Estrogen Receptor Antagonist

Tamoxifen• SE: Flushing, hypertension, mood changes, skin

changes, pain, hot flashes• ID: Treatment and prevention of breast cancer• DDI: CYP2C9 inducers and inhibitors, 2D6

inhibitors and 3A4 inducers and inhibitors• CP: Avoid grapefruit juice, May need to get bone

density screening, chest pain, difficulty breathing, rash,

Miscellaneous Agents

• 5-Alpha reductase inhibitors (BHP and Alopecia)

• Retinoic Acid derivatives (acne and skin cancers)

• Antigout /Antihyperuricemic agent• Immunosuppressant agents/ Calcineurin

inhibitors

ObjectivesGeneral Information about the miscellaneous

agents– Method of Action (MOA)– Route of Administration (ROA)– Side effects (SE)– Indications (ID) – what is the disease state each

medication treats?– Drug- drug interactions (DDI)– Counseling points for patients (CP)

5-Alpha reductase inhibitors for BPH

Finasteride -Propecia®; Proscar®

• MOA: Competitive inhibitor of 5-alpha reductase which inhibits conversion of testosterone to dihydrotestosterone

• ROA: Tabletshttp://www.mahalo.com/finasteride/

5-Alpha reductase inhibitors for BPH

Finasteride -Propecia®; Proscar®• SE: Rash, swelling reduced libido,

hypersensitivity• ID: BPH (5mg dose), Alopecia (1 mg dose)• DDI: None• CP: Women should not handle, medication

could take months

Retinoic Acid derivatives for Acne

Isotretinoin - Amnesteem®; Claravis™; Sotret®, Accutane®

• MOA: Decrease in sebaceous gland size and secretion, and regulates skin proliferation and differentiation

• ROA: tablets and topical • SE: Pancreatitis, peripheral edema, photosensitivity• ID: Acne and some skin cancers• DDI: Vitamin A derivatives (retinol and Adapalene) and

ethanol

Retinoic Acid derivatives for Acne

Isotretinoin – • CP: – Avoid pregnancy – female patients need to be on 2

effective types of birth control– impaired glucose control – particularly for diabetics– Take with food – decreases N/V, and increase

bioavailability– Limit alcohol- can increase triglyceride levels

• May require liver function

Isotretinoin and iPledge

• This system is used with the intention of preventing pregnancy while patient is taking this medication due to the high incidence of birth defects.

• Doctor, patient, and pharmacist are required to enter information stating they have finished the prerequisites before the prescription can be filled.

Anti-gout

Colchicine - Colcrys®• MOA: Reduces urate crystal deposits in the

joint– Disrupts cytoskeletal functions by inhibiting

tubulin polymerization into microtubules, which inhibits neutrophil migration

• ROA: Tablets

Anti-gout

Colchicines• SE: N/V/D, neuromyopathy, myelosuppression• ID: Gout• DDI: Digoxin, antifungals, macrolides,

diltiazem, grapefruit juice • CP: Low purine diet, and adequate hydration

Anti-gout - Diet• Low-purine foods and

beverages:• Eggs (limit to 3 to 4 per week).• Nuts and peanut butter: limit if

trying to lose weight.• Low-fat and fat-free cheeses and

ice cream.• Pudding.• Milk: (limit to 24 ounces per

day).• Cream-style soups made with

low-fat milk.• Soups made without meat

extract or broth.

• Vegetables not on the lists above• Fruits and juices.• Breads and cereals: low fiber,

white flour, or refined grain types.

• Pasta and macaroni.• Rice.• Soda, Coffee and tea.• Gelatin.• Cake and cookies in small

amounts.• Fats and oils in small amounts.• Sugar, syrup, and other sweets in

small amounts.

Anti-gout - Diet• Medium-purine foods:• Fish and shellfish not on

the high purine list above.• Poultry foods not on the

high purine list above.• Beef, lamb, pork, and

other red meats not on the high purine list above.

• Dried beans, peas, lentils.• Asparagus.

• Mushrooms.• Spinach.• Cauliflower.• Green peas.• Oats and oatmeal.• Wheat germ and bran.• Whole grain breads and

cereals.

Anti-gout - Diet

• High-purine foods:• Anchovies.• Roe (fish eggs).• Fish such as herring and

mackerel.• Sardines.• Scallops and mussels.• Game meats, like goose,

duck, and partridge.

• Organ meats: brains, heart, kidney, liver, and sweetbreads.

• Meat extracts.• Mincemeat.• Broth, bouillon, and

consomme.• Gravy.• Yeast (baker's and

brewer's) taken in the form of a supplement.

Anti-gout

Allopurinol• MOA: Blocks uric acid

production by inhibiting xanthine oxidase

• ROA: Tablets and injection

http://www.thekanjifoundrypress.com/a.html

Anti-gout

Allopurinol• SE: Rash and puritis, thrombocytopenia,

hepatitis and renal failure• ID: Gout• DDI: ACE inhibitors, thiazide diuretics,

antacids, and amoxicillin• CP: Report any rash, fever or painful urination,

take with food to minimize GI side effects

Immunosuppressant agents/ Calcineurin inhibitorsfor Transplant rejection prevention

Cyclosporine - Gengraf®, Neoral®, Restasis®, Sandimmune®

• MOA: Inhibit interleukin-2 production which leads to inhibition of T-cell differentiation

• ROA: Tablet, oral solution, and injection

Immunosuppressant agents/ Calcineurin inhibitorsfor Transplant rejection prevention

Cyclosporine - SE: Hypertension, headache, tremor

• ID: Transplant rejection, Rheumatoid arthritis and psoriasis

• DDI: phenytoin, phenobarbital, azole antifungals, allopurinol, vancomycin, Statins, digoxin

• CP: Take dose at same time everyday, mix in glass container, do not take with grapefruit juice

Immunosuppressant agents/ Calcineurin inhibitorsfor Transplant rejection prevention

Tacrolimus - Prograf®; Protopic®• MOA: same as cyclosporine• ROA: Tablets, topical, and injection• SE: N/V/D, anemia, rash, headache, insomnia• ID: Prevention of organ transplant rejection• DDI: CYP 3A4 inducers and inhibitors• CP: Take dose at same time everyday, do not

take with grapefruit juice

Oh you wantz to Sleep?

We don’t thinkz so.

sources

• http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002267

• http://en.wikipedia.org/wiki/Leukemia• http://en.wikipedia.org/wiki/Multiple_myeloma• http://en.wikipedia.org/wiki/Lymphoma• http://www.cancer.org/Treatment/Treatmentsan

dSideEffects/TreatmentTypes/Chemotherapy/ChemotherapyPrinciplesAnIn-depthDiscussionoftheTechniquesanditsRoleinTreatment/chemotherapy-principles-goals-of-chemo

• http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001028

• http://www.uptodate.com.offcampus.lib.washington.edu/contents/colchicine-drug-information?source=search_result&selectedTitle=1~131

• http://www.uptodate.com.offcampus.lib.washington.edu/contents/all-trans-retinoic-acid-tretinoin-drug-information?source=search_result&selectedTitle=1~70

• http://www.uptodate.com.offcampus.lib.washington.edu/contents/topical-tretinoin-topical-all-trans-retinoic-acid-drug-information?source=search_result&selectedTitle=4~70

Need to know!

• What is cancer?• What are the goals of treatment?• What are the classes of drugs we went over? – What drugs are in these classes and what are their

MOAs?– Side effects, Drug-drug interactions, and patient

counseling points

Questions