RESUME FARMAKOLOGI

ANTI CANCER

Nama NIM

Oleh: : Ephysia Ratriningtyas : 115070201131022 K3LN 2011

UNIVERSITAS BRAWIJAYA FAKULTAS KEDOKTERAN JURUSAN KEPERAWATAN 2013

ANTICANCER 1. ANTINEOPLASTIC AGENTS Terdapat 2 agen group utama yaitu: a. CELL CYCLE - NONSPECIFIC (CCNS) ALKYLATING AGENTS Cytotoxix pada fase sel efektif dalam memperlambat pertumbuhan tumor. b. CELL CYCLE - SPECIFIC (CCS) 3 TYPES 1. ANTIMETABOLITES - cytotoxic is S phase 2. MITOTIC INHIBITORS - cytotoxic in M phase 3. CYTOTOXIC ANTIBIOTICS (some are CCNS) Efktif dalam menghambat pertumbuhan tumor yang cepat. Efek samping: Membunuh semua sel yang tumbuh cepat folikel rambut mukosa Saluran pencernaan Penekanan sumsum tulang (BMS) menyebabkan anemia, trombositopenia dan leukopenia Nephro-hepato-cardio-neoro dan ototoxic Ekstravasasi IV dapat menyebabkan kerusakan jaringan memiliki indeks emetik memiliki interaksi yang luas dengan obat lain.

2. ALKYLATING AGENTS (paling sering digunakan) NITROGEN MUSTARDS CNS killing ability mechlorethamine is the prototypical agent USES: Hodgkins disease & lymphomas. leukemias, CANCERS OF lung, breast, ovary, testes, brain, bladder, SELECTED AGENTS: Mechlorethamine (Mustine, Mustargen): diberikan secara IV, dan hanya digunakan pada orang dewasa saja. Cyclophosphamide (Cytoxan, Neosar): diberikan secara IV dan ada yang PO. Dapat diberikan pada usia dewasa dan pediatrik. Carmustine (BiCNU) diberikan secara IV, pada usia dewasa saja. Dapat melewati bloodbrain barrier sehingga digunakan untuk mengobati lesi otak. OTHER AGENTS: Chlorambucil, Streptozotocin

1. 2. 3. 4.

3. ANTIMETABOLITES ACTIONS: Antagonis dari folat. Purin dan pirimidin diperlukan untuk sintesis asam nukleat. Menghentikan replikasi sel. Penggunaan pada: Solid tumors (breast, lung, liver, brain, colon. Stomach, pancreas) Lymphomas, leukemias. Some agents also immunosuppressive, Useful in treating immune-mediated diseases

a. SELECTED AGENTS: 1. FOLIC ACID ANALOG METHOTREXATE (Folex, Rheumatrex, MTx) Folic acid antagonist PO & IM, adult and pediatric use Also used to treat immune-mediated diseases, Used incombination with misoprostol for therapeutic abortion Causes profound anemia (folate depletion) Therefore leucovorin rescue often used to counteract 2. PURINE ANALOG MERCAPTOPURINE (6-MP, Purinethol) - Purine antagonist - PO only, adult and pediatric use 3. PYRIMIDINE ANALOG CYTARABINE (Ara-C, Cytosar-U) - Pyrimidine antagonist - IV and intrathecal (within spinal canal) 4. MITOTIC INHIBITORS ACTIONS: Plant alkaloids (periwinkle, yew tree, mandrake plant, etc.) Bind to and disrupt mitotic spindles USES: - Lymphomas (Hodgkins and non-Hodgkins), - Neuroblastoma - Kaposis sarcoma, - Solid tumors (breast, testicular, etc.) SELECTED AGENTS: ETOPOSIDE (VP-16, VePesid) IV and PO, adult use only

PACLITAZEL (Taxol) IV only, adult use only. drug of choice for ovary and breast ca VINCRISTINE (LCR, VCR,Oncovin) IV only, adult and pediatric use drug of choice for acute leukemia 5. CYTOTOXIC ANTIBIOTICS ACTIONS: Source: Streptomyces mold - work by intercalation (insertion of drug molecule between the 2 DNA strands causing it to (unwind) Kill some bacteria and viruses but are too toxic to use for infections

IV extravasation constant danger ! USES: wide variety of solid tumors, always used in combination with other agents

SELECTED AGENTS: a. DOXORUBICIN (ADR, Rubex, Doxil): diberikan secara IV only, dan hanya boleh diberikan pada usia dewasa. b. BLEOMYCIN (BLM, Blenoxane) :IM, IV, SQ, adult use only Perlu di waspadai karena agen ini sangat toxic. 6. MISCELLANEOUS ANTINEOPLASTICS Various actions: Both CCNS and CCS Used in combinations with other agents SELECTED AGENTS: Cisplatin (Platinol): diberikan secara IV, penggunaan pada adult and pediatric. ALTRETAMINE (Hexalen): diberikan secara PO, hanya diberikan pada orang dewasa. primarily used to treat ovarian cancer ASPARAGINASE (Elspar): diberikan secara IV, adult and pediatric use HYDROXYUREA (Hydrea): diberikan secara IV, adult use only HORMONES AND ANTAGONISTS. 1. Adrenocortical Suppressant: Mitotane, Aminoglutethimide. (Adrenal Cortex) 2. Adrenocortical Steroids. Prednisone. (Lukemias, Lymphomas, Breast) 3. Progestins. Hydroxyprogestrone.(Endometrium, (Breast) Medroprogestrone, Megesterol acetate. 4. Estrogens. DES, Ethinylesterdiol.(Breast, Prostate)

5. 6. 7. 8.

Antiestrogens. Tamoxifen .(Breast) Androgens. Testosterone (Breast) Antiandrogens. Flutamide (Prostate). Gonadotropin Releasing Hormone Analog. Leuprolide. (Prostate)

Manajemen Keperawatan Sebelum program kemoterapi perlu dilakukan penilaian status fisik dan data dasar serta memantau berbagai hasil uji laboratorium. Beberapa tes diperlukan tergantung dengan obat-obatannya ((bone marrow suppression, cardiotxic, nephrotoxic, neurotoxic, ototoxic, hepatotoxic) PLANNING Decrease anxiety, understand of the chemotherapy program, adaptation to changes in body appereance and function, absence of the variety of injury, absence of diarrhea/ constipation, maintanance of oral mucous membrane integrity, maintanance of optimal nutritional status, maintanance of fluid and electrolyte balance, achievement of maximal physical mobility, peformance of self care activities within physical limitations.

INTERVENTIONS Body image disturbance (alopecia High risk for infection ~ bone marrow supp. High risk for nephrotoxicity Altered oral mucous membrane Altered nutrition High risk for drug extravasation (tissue damage,loss of function, infection, necrosis) Antidotum:10% sodium thiosulfate ~ mechloretamine, pyridoxine~ mitomycin, hyaluronidase and warming ~ vinca alcaloids, dimethyl sulfoxide ~ daunorubicin/doxorubicin)

Local Reactions from Chemotherapy Administration Extravasation: kebocoran atau infiltrasi agen kemoterapi yg menyebabkan bengkak ke dalam jaringan lokal Vesicant: agen yang memiliki potensi untuk menyebabkan blistering atau jaringan nekrosis Irritant: agen yang menyebabkan reaksi inflamasi lokal tetapi tidak menyebabkan nekrosis jaringan Flare reaction: vena respon inflamasi dengan pelepasan histamin berikutnya yang dapat mengakibatkan reaksi suar, kejadian biasanya sekitar 3% dan durasi biasanya kurang dari 45 menit

Ekstravasasi treatment AT FIRST SIGN, stop chemo Attempt to aspirate residual drug Remove IV Notify physician Administer antidote (if ordered) Heat/Cold as appropriate Elevate extremity Document extravasation and management

1. Neutropenia Decreased number of granulocytes Granulocytes - one of the white blood cells Absolute neutrophil count (ANC) = number of granulocytes in the blood. Measures the first line of defense against infection ANC = total WBC x (% polys + % bands) [example: 5000 x ( 40% + 10%) = 2,500]

Resiko infeksi pada neutropenia ANC of > 1000 = No risk of infection ANC 500 to 1000 = Mild to moderate risk ANC < 500 = Severe risk of infection Semakin lama neutropenia yang parah berlangsung, semakin besar risiko infeksi yang mengancam jiwa Pemeriksaan Demam adalah monitor utama dalam infeksi Monitor ANC Perhatikan timbulnya rasa sakit, kemerahan di lokasi luka, daerah terbuka, sering buang air kecil, perubahan status mentalPemeriksaan head to toe Teach patient to observe for signs of infection Lakukan pemeriksaan temperatur secara berkala selama 24jam

Manajemen Neutropenia Temperatures q 4 hours around the clock Limit Tylenol; can mask fever Cultures done with first fever (before abx) Antibiotik pertama diberikan sebagai STAT dosis ( ~ 1 jam) Memantau tanda-tanda vital- sepsis kills rapidly Jika demam berlanjut perlu mengubah antibiotik menambahkan agen anti-jamur Temp harus turun 1 derajat dalam 24 jam dan hilang setelah 48 jam jika abx bekerja

Pencegahan Neutropenic NOT reverse isolation Controversial whether infection risk is lowered Private room No fresh fruits or vegetables to eat No live plants/flowers/standing water No sick visitors or caregivers No small children (very controversial) No caregivers taking care of other infected pts Pt wears mask when out of room

2. Trombositopenia Decreased number of platelets Risk of bleeding increases below 50,000 Risk of bleeding substantial under 20,000 Transfusions may not be done until 10-15,000 (risk of auto-immunizing patient) Manajemen: Assess head to toe for bleeding/petechiae

Monitor platelet count Teach patient to report signs of bleeding or increased petechiae Transfuse as ordered (pre-medicate usually)

Tindakan pencegahan pendarahan NO ASA or NSAIDS Tidak memasukan sesuatu kedalam rectum atau vagina Tidak ada penggunaan kateter Foley jika mungkin Tidak ada suntikan IM Meminimalkan tindakan venipunctures dan prosedur invasif Penggunakan sikat gigi yang lembut-no flossing - electric razor No vigorous exercise Hindari mengejan

3. Anemia Decreased number of red blood cells Transfusions given when Hgb < 8, Hct < 24 or patient is symptomatic Elderly patients or those with history of cardiac problems may not tolerate anemia Epogen (Procrit) given to stimulate RBC production Helps combat fatigue

4. Fatigue Multiple causes Most common side effect from chemo Not relieved by sleep Prevention of anemia can reduce incidence Short periods of mild exercise can reduce severity Teach energy conservation and appropriate rest periods - Need for caregiver assistance 5. Mual dan Muntah Stimulation of vomiting center (brain) by chemo-receptor trigger zone (CTZ), vagal stimulation, seratonin, etc. Most distressing side effect of chemo Acute, delayed, anticipatory

Not all chemo drugs have same emetic potential

Manajemen Mual dan Muntah Very sensitive to smells (may be abnormal) TAKE antiemetics as ordered Room temperature or cold foods smell less Frozen juice or popsicles are soothing Avoid fatty, greasy, spicy, sweet foods Eat small meals Avoid favorite foods at this time 6. Anorexia Taste changes last ~ 1 week Smells become acute; lasts 1-3 weeks Mild exercise or wine may stimulate appetite Avoid too much liquid near mealtime Eat high calorie, nutritious foods Avoid junk food Use supplements as needed Megace can stimulate appetite (> 350 mg/day) 7. Diare Increase in liquidity and frequency of stool (> 3 stools above usual amount) Destruction of epithelium of GI tract Related to medication, dose and frequency Worse with RT to abdomen/gut area Drugs: Camptosar, Methotrexate, 5-FU May be dose-limiting toxicity of drug May be concommitant infection (C. diff) Manajemen Diare Camptosar: treat early diarrhea with Atropine and late diarrhea with Immodium-prophylactically BRAT diet -- low residue diet -- clear liquids Avoid milk products Scrupulous peri care; keep area dry Use moisture barrier cream (Desitin) Use anti-diarrheals: Lomotil, Immodium, Kaopectate, Pepto-bismol, Sandostatin (last resort)

8. Konstipasi

Infrequent hard, dry, bowel movements that may cause pain or bleeding Vinca Alkaloids - Vincristine worst Other reasons: dehydration, no activity, opioid use, low residue diet May cause bloating, pain, N&V, obstruction or ileus, rectal bleeding, hemorrhoids, tears.

Manajemen Konstipasi Treat prophylactically - Adequate fluid intake - Increased fiber intake - Increased activity - Stool softeners taken routinely (Senekot) Laxative or Cathartic if no BM in 3 days Try to avoid enemas

9. Stomatiti/ mucotitis Inflammation or ulceration of mouth which can progress to entire GI tract Destruction of fast-growing epithelial cells Drugs: 5-FU, Methotrexate, Xeloda, Bleomycin, HD chemo Radiation fields that include mouth or throat Alcohol, tobacco use Poor oral hygiene, dental caries Causes pain, infection, dehydration, weight loss Manajemen Mucositis Daily/Bid oral assessment Frequent (q 2 hr) mouth care o NS rinse (avoid alcohol-containing mouthwash) o Brush with soft toothbrush--also brush tongue o Keep lips and mouth moist Soft diet with high caloric bland foods Topical anesthetic agents Treat infections quickly PREVENTION is best 10. Alopecia Temporary - begins in 2 to 3 weeks Hair regrows 4 to 6 weeks after chemo - Texture and color may be different in new hair Degree of alopecia related to drug, dose, schedule, and amount of hair patient had prior to chemo MOST distressing symptom - May be equally distressing for men and women

Manajemen Alopecia PATIENT TEACHING is very important May lose hair on entire body (taxanes, high dose chemo or total body radiation) Cut hair short to reduce irritation from shedding Wig or headcovering resources available-may be insurance benefit--can get script for wig Wear headcovering to reduce temperature loss Protect scalp from sun (may be photosensitive) 11. Photosensitif Increased skin sensitivity to UV exposure Drugs causing: 5-FU, Methotrexate, Taxol, Adriamycin, Vincristine Sunburn with blisters and erythema; hyperpigmentation Avoid tanning booths, sunbathing even on cloudy days Wear sunscreen (> 15 spf) or protective clothing 12. Pengaruh terhadap seksual Related to drug, dose, length of treatment, age and sex of patient Men: impotence, decreased libido, hot flashes, decreased sperm count, gynecomastia, body image changes Women: irregular or no menses, vaginal dryness, decreased ova production, painful intercourse, decreased libido, hot flashes, body image changes Manajemen Patient education Discuss concerns frankly Sperm banking Birth control Lubrications Position changes Counseling (time of high stress)