Module 9 - Antimalarial to Antineoplastic PDF

Module 9 Anti-infectives and Antineoplastic Agents MONECELLE JOY D. PESINABLE, RN Instructor IV. Antimalarial Malaria is a protozoal infection of the genus Plasmodium that produces severe chills, fever and profuse sweating; transmitted by the bite of the infected female Anopheles mosqui...

Module 9 Anti-infectives and Antineoplastic Agents MONECELLE JOY D. PESINABLE, RN Instructor IV. Antimalarial Malaria is a protozoal infection of the genus Plasmodium that produces severe chills, fever and profuse sweating; transmitted by the bite of the infected female Anopheles mosquito* major drugs used to prevent and treat malaria include chloroquine hydrochloride, chloroquine phosphate, and hydroxychloroquine sulfate mefloquine hydrochloride primaquine phosphate pyrimethamine quinidine gluconate and quinine sulfate**  Actions of Antimalarial Drugs* chloroquine** and hydroxychloroquine: disrupt protein synthesis in the parasite and concentrate in the digestive vacuoles of the parasite increasing the pH and interfering with utilization of hemoglobin primaquine: affects the parasite’s mitochondria eventually disrupting cellular metabolism pyrimethamine: selectively inhibits the enzyme dihydrofolate reductase which impedes folic acid reduction and ultimately disrupts parasitic reproduction*** sulfadoxine: competitively inhibits dihydrofilic acid synthesis which is necessary to convert para- aminobenzoic Actions of Antimalarial Drugs quinine: incorporates into the DNA of the parasite rendering it ineffective; may also result from depression of oxygen uptake and carbohydrate metabolism in the parasite* mefloquine: unknown, but thought to be similar to quinine; increases the acidity of plasmodial food vacuoles, causing cell rupture and death** Pharmacokinetics chloroquine: readily absorbed from the GIT, with peak serum levels occurring in 1-6 hrs; concentrated in the liver, spleen, kidney, and brain and is excreted very slowly in the urine, primarily as unchanged drug mefloquine: mixture of molecules that are absorbed, metabolized, and excreted at different rates; terminal half life is 13-24 days; metabolism occurs in the liver; caution should be used in patients with hepatic dysfunction primaquine: readily absorbed and metabolized in the liver; excretion occurs primarily in the urine; safety for use during Pharmacokinetics pyrimethamine: readily absorbed from GIT, with peak levels occurring within 2-6 hrs; metabolized in the liver and has a half life of 4 days; usually maintains suppressive concentrations in the body for about 2 weeks quinine: rapidly absorbed from GIT; peak serum levels occurring in 1-3 hrs; metabolized in the liver with a half-life of 4- 6 hrs and is excreted in the urine Indications of Antimalarial Drugs chloroquine: oral drug of choice to prevent and treat all malaria strains, except chloroquine- resistant or multi- drug resistant strains of P. falciparum hydroxychloroquine: alternative when chloroquine is not available quinine: drug of choice for the treatment of malaria caused by chloroquine-resistant or multi- drug resistant strains of P. falciparum primaquine: drug of choice in combination with chloroquine to treat P. malariae, P. vivax and P. ovale Indications of Antimalarial Drugs mefloquine: used to treat malaria caused by resistant strains of P. falciparum; also administered to prevent malaria infections including chloroquine- resistant strains of P. falciparum quinidine: parenteral drug of choice for the treatment of malaria in patient who cannot tolerate oral therapy* Contraindications and Cautions known allergy to any of these drugs liver disease or alcoholism lactation pregnancy retinal disease or damage psoriasis or porphyria damage to mucous membranes Adverse Effects CNS effects include headache and dizziness Immune reaction effects related to the release of merozoites* include fever, shaking, chills, and malaise nausea, vomiting, dyspepsia, and anorexia** hepatic dysfunction*** dermatological effects include rash, pruritus and loss of hair* visual changes, including possible blindness related to retinal damage from the drug ototoxicity related to nerve damage cinchonism** may occur with high levels of quinine Drug Interactions hydroxychloroquine and quinine increase digoxin and cyclosporine levels mefloquine taken with beta blockers, quinine, quinidine and other drugs that prolong cardiac conduction may produce ECG abnormalities and even cardiac arrest the risk of seizures increases when mefloquine is taken with chloroquine mefloquine reduces valproic acid blood levels, increasing the risk of seizures folic acid reduces the antimicrobial effect of pyrimethamine quinine may increase the effects of neuromuscular blockers leading to Patient Teaching patients traveling to malaria-infested countries should receive prophylactic doses of anti-malarial drugs before leaving, during the visit and upon return take oral antimalarial drugs with food or at mealtime if GI upset occurs patient returning from malaria-infested area should be monitored for malaria symptoms inform patient who takes chloroquine or hydroxychloroquine to report vision changes immediately warn patient to avoid consuming large quantities of alcohol V. Antiprotozoal atovaquone: inhibits electron transport causing decreased activity of several enzymes of the mitochondria furazolidone: interferes with bacteria and protozoa’s enzyme systems and by inhibition of monoamine oxidase iodoquinol: acts directly on protozoa in the GIT metronidazole: destroys bacteria, amoebas, and Trichomonas by disrupting DNA and inhibiting nucleic acid synthesis causing cellular death pentamidine: interferes with the organism’s building of DNA, RNA, phospholipids and proteins trimetrexate: inhibits the enzyme V. Antiprotozoals’ Indications used for a wide range of disorders including Pneumocystis carinii infections, amebiasis, giardiasis, trichomoniasis, toxoplasmosis, African trypanosomiasis, and leishmaniasis furazolidone and metronidazole produce a disulfiram-like reaction when taken with alcohol causing flushing, weakness, light- headedness and sweating metronidazole increases the effects of oral anticoagulants trimetrexate plus zidovudine can produce additive toxicity* Pharmacokinetics atovaquone: slowly absorbed and highly protein bound; excreted slowly through the feces; half life of 67 to 76 hrs metronidazole: well absorbed orally, reaching peak levels in 1 to 2 hrs; metabolized in the liver with a half-life of 8 to 15 hrs; excretion occurs primarily through the urine pentamidine: completely absorbed when given intravenously or intramuscularly; readily absorbed through the lungs when given via inhalation; excretion occurs in the urine* Contraindications and Cautions known allergy or hypersensitivity to any of these drugs pregnancy* use with caution when giving to patients with **CNS disease, hepatic disease, candidiasis, and women who are lactating Adverse Effects CNS effects such as headache, dizziness, ataxia, loss of coordination, and peripheral neuropathy* GI effects include nausea, vomiting, diarrhea, unpleasant taste, cramps, and changes in liver function superinfections** VI. Anthelmintics act on metabolic pathways that are present in the invading worm but are absent or significantly different in the human host indicated for the treatment of infections by certain susceptible worms and are very specific in the worms that they affect* include albendazole, ivermectin, mebendazole, praziquantel, and pyrantel** mebendazole is available in the form of a chewable tablet, and a typical 3-day course can be repeated in 3 weeks if needed; very little is absorbed systemically***, metabolized in the body and most are VI. Anthelmintics albendazole is poorly absorbed from the GIT reaching peak plasma levels in 5 hrs; metabolized in the liver and primarily excreted in the urine ivermectin is readily absorbed from the GIT and reaches peak plasma levels in 4 hrs; completely metabolized in the liver with a half life of 16 hrs; excreted thru feces praziquantel is taken in a series of 3 oral doses at 4 to 6-hr intervals; rapidly absorbed from the GIT and reaches peak plasma levels within 1-3 hrs; metabolized in the liver with a half life of 0.8-1.5 hrs; excretion occurs primarily thru the urine VI. Anthelmintics overall contraindications include known allergy to any of these drugs, lactation*, pregnancy** pyrantel has not been established as safe for use in children below 2 years albendazole should be used only after the causative worm has been identified*** use with caution in patients with renal or hepatic disease* and in cases of severe diarrhea and malnourishment** VI. Anthelmintics adverse effects frequently encountered are related to their absorption or direct action in the intestine mebendazole and pyrantel*: abdominal discomfort, diarrhea, or pain those which are systemically absorbed may cause headache and dizziness; fever, shaking, chills and malaise**; rash; pruritus; and loss of hair renal failure and severe bone marrow depression are associated with albendazole*** effects of albendazole may increase if the drug is combined with dexamethasone, praziquantel or cimetidine* Lesson 2 Antineoplastic Agents MONECELLE JOY D. PESINABLE, RN Instructor  I. Alkylating Agents interfere with processes that affect DNA, causing the cell to die cell cycle non-specific* most useful in the treatment of slow- growing cancers** include altretamine, bendamustine, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, cyclophosphamide, dacarbazine, ifosfamide, lomustine, mechlorethamine, melphalan, oxaliplatin, procarbazine, streptozocin, and temozolomide I. Alkylating Agents Actions and Indications Therapeutic produce their cytotoxic effects by reacting chemically with portions of the RNA, DNA, or other cellular proteins, being most potent when they bind with cellular DNA most useful in the treatment of slow-growing cancers such as various lymphomas, leukemias, myelomas; some ovarian, testicular, and breast cancers; and some pancreatic cancers Pharmacokinetics vary in their degree of absorption and little is known about their distribution in the tissues metabolized and sometimes activated in the I. Alkylating Agents Contraindications and Cautions pregnancy and lactation* known allergy to any of them; with bone marrow suppression**; or with suppressed renal or hepatic function*** Adverse Effects hematological effects: bone marrow suppression, with leukopenia, thrombocytopenia, anemia and pancytopenia* GI effects: nausea, vomiting, anorexia, diarrhea, and mucous membrane deterioration** hepatic and renal toxicity*** alopecia*; increase in uric acid levels** I. Alkylating Agents Drug Interactions alkylating drugs that are known to cause hepatic or renal toxicity should be used cautiously with any other drugs that have similar effects drugs that are toxic to the liver may adversely affect drugs that are metabolized in the liver or that act in the liver* II. Antimetabolites drugs that have chemical structures similar to those various natural metabolites that are necessary for the growth and division of rapidly growing neoplastic cells and normal cells include capecitabine, cladribine, clofarabine, cytarabine, floxuridine, fludarabine, fluorouracil, gemcitabine, mercaptopurine, methotrexate, pemetrexed, pentostatin, pralatrexate, and thioguanine II. Antimetabolites Therapeutic Actions and Indications inhibit DNA production in cells that depend on certain natural metabolites to produce their DNA* many of these agents inhibit thymidylate synthase, DNA polymerase, or folic acid reductase** most effective in rapidly dividing cells, preventing cell replication, and leading to cell death indicated for the treatment of various leukemias and some GI and basal cell cancers*** II. Antimetabolites Pharmacokinetics methotrexate is absorbed well from the GIT and is excreted unchanged in the urine*; readily crosses the BBB cytarabine, clofarabine, floxuridine, fluorouracil, gemcitabine, pemetrexed, and pralatrexate are not absorbed well from the GIT and need to be administered parenterally; metabolized in the liver and excreted in the urine** mercaptopurine and thioguanine are absorbed slowly from the GIT and are metabolized in the liver and excreted in the urine II. Antimetabolites Contraindications and Cautions pregnancy and lactation* known allergy to any of the drugs bone marrow suppression** renal and hepatic impairment*** known GI ulcerations or ulcerative diseases* Adverse Effects hematological effects: bone marrow suppression, with leukopenia, thrombocytopenia, anemia, and pancytopenia* toxic GI effects: nausea, vomiting, anorexia, diarrhea, and mucous membrane deterioration** CNS effects: headache, drowsiness, aphasia, II. Antimetabolites Adverse Effects (cont) risk of pulmonary toxicity including interstitial pneumonia possible hepatic or renal toxicity* alopecia Drug Interactions antimetabolites that are known to cause hepatic or renal toxicity should be used with care with any other drugs known to have the same effect drugs toxic to the liver may adversely affect drugs that are metabolized in the liver or that act in the liver** III. Antineoplastic Antibiotics selective for bacterial cells, but are also toxic to human cells* include bleomycin, dactinomycin, daunorubicin, doxorubicin, epirubicin, idarubicin, mitomycin, mitoxantrone, and valrubicin Therapeutic Actions and Indications some break up DNA links, and others prevent DNA synthesis are cytotoxic and interfere with cellular DNA synthesis by inserting themselves between base pairs in the DNA chain** main adverse effects are seen in cells that multiply rapidly such as those in the bone III. Antineoplastic Antibiotics Pharmacokinetics not absorbed well from the GIT given IV or injected into specific sites metabolized in the liver and excreted in the urine many have very long half lives* daunorubicin and doxorubicin do not cross BBB but are widely distributed in the body and are taken up by the heart, lungs, kidneys, and spleen** III. Antineoplastic Antibiotics Contraindications and Cautions pregnancy and lactation* known allergy to any of the drugs bone marrow suppression** renal and hepatic impairment*** known GI ulcerations or ulcerative diseases* pulmonary problems with bleomycin or mitomycin, or cardiac problems with idarubicin or mitoxantrone** Adverse Effects hematological effects: bone marrow suppression, with leukopenia, thrombocytopenia, anemia, and pancytopenia* toxic GI effects: nausea, vomiting, anorexia, diarrhea, and mucous III. Antineoplastic Antibiotics Drug Interactions antineoplastic antibiotics that are known to cause hepatic or renal toxicity should be used with care with any other drugs known to have the same effect drugs that result in toxicity to the heart or lungs should be used with caution with any other drugs that produce that particular toxicity IV. Mitotic Inhibitors drugs that kill cells as the process of mitosis begins cell cycle-specific agents that inhibit DNA synthesis main adverse effects occur with cells that multiply rapidly* include cabazitaxel, docetaxel, eribulin, etoposide, ixabepilone, paclitaxel, teniposide, and vinorelbine IV. Mitotic Inhibitors Therapeutic Actions and Indications interfere with the ability of a cell to divide* used for the treatment of a variety of tumors and leukemias Pharmacokinetics generally, they are given intravenously** metabolized in the liver and excreted in the feces*** IV. Mitotic Inhibitors Contraindications and Cautions should not be used during pregnancy or lactation* use caution when giving these drugs to anyone with a known allergy to the drug or related drugs** care is necessary for patients with following conditions***: bone marrow suppression, renal or hepatic dysfunction, and known GI ulcerations or ulcerative diseases prolonged QT interval when using eribulin* IV. Mitotic Inhibitors Adverse Effects frequently encountered include bone marrow suppression, with leukopenia, thrombocytopenia, anemia and pancytopenia* GI effects include nausea, vomiting, anorexia, diarrhea, and mucous membrane deterioration eribulin is associated with prolonged QT interval hepatic or renal toxicity** alopecia necrosis and cellulitis if extravasation occurs*** Drug Interactions V. Hormones and Hormone Modulators* used to block or interfere with receptor sites to prevent growth of the cancer and in some situations to cause cell death some hormones are used to block the release of gonadotropic hormones in breast and prostate cancer if the tumors are responsive to gonadotropic hormones others may block androgen receptor sites directly and are useful in the treatment of advanced prostate cancers include abiraterone, anastrazole, bicalutamide, degarelix, enzalutamide, estramustine, exemestane, flutamide, fulvestrant, goserelin, histrelin, letrozole, leuprolide, megestrol, mitotane, nilutamide, tamoxifen, toremifene, and triptorelin V. Hormones and Hormone Modulators* Therapeutic Actions and Indications the hormones and hormone modulators used as antineoplastics are receptor site specific or hormone specific that block the stimulation of growing cancer cells that are sensitive to the presence of that hormone indicated for the treatment of breast cancer in postmenopausal women or in other women without ovarian function some are indicated for the treatment of prostatic cancers that are sensitive to hormone manipulation Pharmacokinetics readily absorbed from the GIT, metabolized in the liver, and excreted in the urine V. Hormones and Hormone Modulators* Contraindications and Cautions contraindicated in pregnancy and lactation* hypercalcemia is contraindicated to the use of torimefene** use caution when giving to anyone with a known allergy to any of these drugs care is necessary in patients with bone marrow suppression*, and in those with renal or hepatic dysfunction** V. Hormones and Hormone Modulators* Adverse Effects* menopause-associated effects include hot flashes, vaginal spotting, vaginal dryness, moodiness, and depression others include bone marrow suppression, GI toxicity including hepatic dysfunction hypercalcemia** increase the risk of cardiovascular disease*** abiraterone can increase the risk of adrenocortical insufficiency Drug Interactions increased risk of bleeding if taken with oral anticoagulants VI. Cancer Cell-Specific Agents* would not have devastating effects on healthy cells in the body and would be more effective against particular cancer cells include protein tyrosine kinase inhibitors, an epidermal growth factor inhibitor, and a proteasome inhibitor VI. Cancer Cell-Specific Agents Protein Tyrosine Kinase Inhibitors act on specific enzymes that are needed for protein binding by specific tumor cells* inhibits a very specific protein kinase and acts on very specific tumors do not affect healthy human cells** imitanib – the first drug approved in this class*** others include afatinib, axitinib, bosutinib, cabozantinib, ceretinib, crizotinib, dabrafenib, everolimus, ibrutinib, idelalisib, imatinib, lapatinib, nilotinib, palbociclib, pazopanib, ponatinib, regorafenib, ruxolitinib, sorafenib, sunitinib, temsirolimus, trametinib, VI. Cancer Cell-Specific Agents Epidermal Growth Factor erlotinib: inhibits cell epidermal growth factor receptors growth factor is found on normal and cancerous cells but is more abundant on rapidly growing cells Proteasome Inhibitor bortezomib: approved by FDA for the treatment of multiple myeloma in patients whose disease had progressed after two other standard therapies inhibits proteasome in human cells* delay growth in selected tumors  VI. Cancer Cell-Specific Agents Actions and Indications Therapeutic imatinib: given orally; selectively inhibits Bcr-Abl tyrosine kinase created by Philadelphia chromosome abnormality in CML*; also inhibits a specific receptor site in GI stromal tumor patients** all of the other kinase inhibitors work by inhibiting various kinases in specific cancer cells Pharmacokinetics imatinib: slowly absorbed from the GIT, reaching peak levels in 2-4 hours; extensively metabolized in the liver*** erlotinib: well absorbed orally from the GIT, reaching peak levels in 4 hours; metabolized VI. Cancer Cell-Specific Agents Contraindications and Cautions all of drugs are pregnancy category D* can enter the breastmilk** several of the drugs are contraindicated with patients who have or at risk for prolonged QT intervals*** should not be given to anyone who has a history of hypersensitivity to any component of the drug being given Adverse Effects imatinib: GI upset, muscle cramps, heart failure, fluid retention, and skin rash several of the drugs prolong QT interval and need to be used with caution in patients with cardiac problems