Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
68 Cards in this Set
- Front
- Back
|
UTIs may be classified according to their location:
|
• Infections in the upper urinary tract (kidney) include acute pyelonephritis (inflammation of the kidney and its pelvis) and acute bacterial prostatitis (inflammation of the prostate)
• Infections in the lower urinary tract (bladder and urethra) include acute cystitis (inflammation of the urinary bladder) and acute urethral syndrome (inflammation of the urethra) |
|
|
Complicated UTIs:
|
Complicated UTIs occur in both males and females and are associated with a predisposing factor such as kidney stones, prostatic hypertrophy, or an indwelling catheter (e.g. physical obstructions).
|
|
|
Uncomplicated UTIs:
|
Uncomplicated UTIs occur primarily in women of child-bearing age and are not associated with a predisposing factor.
|
|
|
The most frequently utilized treatment for oral therapy of UTIs is __________
|
Trimethoprim-sulfamethoxazole is the most frequently utilized treatment for oral therapy of UTIs.
|
|
|
Nitrofurantoin: Therapeutic uses
|
Nitrofurantoin [Furadantin], a broad-spectrum antimicrobial drug.
o The agent is bacteriostatic at low concentrations and bactericidal at high concentrations. Therapeutic drug levels are achieved only in urine, hence the drug is useful only against infections of the urinary tract. o Nitrofurantoin injures bacteria by causing damage to DNA. However, in order to damage DNA, the drug must first be converted to a reactive form. Nitrofurantoin is selectively toxic to bacteria because, unlike mammalian cells, bacteria possess relatively high levels of the enzyme that activates the drug. o Nitrofurantoin is indicated for acute infections of the lower urinary tract and for prophylaxis of recurrent lower UTI. |
|
|
Nitrofurantoin: Adverse effects
|
o Adverse effects to nitrofurantoin include GI effects (anorexia, nausea, vomiting, diarrhea), pulmonary reactions (acute pulmonary reactions are hypersensitivity reactions, while subacute reactions occur during prolonged treatment), hematologic effects (agranulocytosis, leucopenia, thrombocytopenia, and anemia), and peripheral neuropathy (damage to motor and sensory neurons)
|
|
|
Methenamine: Therapeutic uses
|
Methenamine [Mandelamine] is able to decompose (under acidic conditions = pH less than 5.5) into ammonia and formaldehyde. The formaldehyde denatures bacterial proteins, causing cell death.
o Urine pH is generally low enough for methenamine to decompose, while systemic pH is too high for the drug to cause toxicity o Methenamine is used for chronic lower UTIs, but is not recommended for acute infection |
|
|
Methenamine: Adverse effects
|
o Methenamine is safe and well tolerated. Chronic high dose therapy can cause bladder irritation, manifested by proteinuria and hematuria. Since decomposition of methenamine generates ammonia, the drug is contraindicated in patients with liver dysfunction or renal impairment (crystalluria)
|
|
|
Nalidixic acid: Therapeutic uses
|
Nalidixic acid [NegGram] inhibits replication of bacterial DNA, thereby causing DNA degradation and cell death. The precise target of nalidixic acid is DNA gyrase.
o Nalidixic acid is approved only for UTIs. The drug has been used to control acute infection and to prevent recurrent UTI, but for both applicantions other drugs are preferred. |
|
|
Nalidixic acid: Adverse effects
|
o Nalidixic acid may cause multiple adverse effects but the incidence of severe reactions is low. The most common effects are GI disturbances, visual disturbances, rash, photosensitivity reactions, and convulsions.
|
|
|
Cinoxacin
|
Cinoxacin [Cinobac] is a close chemical relative of nalidixic acid
|
|
|
Treatment for tuberculosis can be divided into two phases:
|
1) Induction phase, during which the goal is to eliminate actively dividing extracellular tubercle bacilli, and thereby render the sputum noninfectious
2) Continuation phase, during which the goal is to eliminate intracellular “persisters” |
|
|
Therapy for drug-sensitive TB:
|
If the infecting organism is not resistant to isoniazid or rifampin, treatment can be relatively simple. The induction phase, which lasts two months, consists of daily therapy with four drugs: isoniazid, rifampin, pyrazinamide, and ethambutol (IRPE). The continuation phase, which lasts four months, consists of daily or biweekly therapy with just isoniazid and rifampin (IR)
|
|
|
Therapy for multidrug-resistant TB:
|
Multidrug resistance is defined as having resistance to at least isoniazid and rifampin. Treatment requires at least three drugs to which the organism is sensitive, and should continue for 1 to 2 years after sputum conversion. Initial therapy may consist of 5-7 drugs, including isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin, kanamycin, and ciprofloxacin.
|
|
|
The preferred treatment of latent TB is ______
|
Isoniazid
|
|
|
Short-course therapy of latent TB consists of:
|
For short-course therapy of TB, four months of daily rifampin is an alternative.
|
|
|
Isoniazid: Applications
|
Isoniazid (INH) [Laniazid] is the primary agent for treatment and prophylaxis of tuberculosis. Isoniazid is indicated for treating active tuberculosis (isoniazid alone) and latent tuberculosis (in combination with other drugs).
It is bactericidal to dividing mycobacteria, but bacteriostatic to resting organisms. It is thought that the drug suppresses bacterial growth by inhibiting synthesis of mycolic acid, a component of the mycobacterial cell wall. |
|
|
Isoniazid: Resistance
|
Acquired resistance to isoniazid results from spontaneous mutations (not from transfer of R factors) and also results in cross resistance to ethionamide.
|
|
|
Isoniazid: Adverse effects
|
The principle adverse effect to isoniazid is dose-related peripheral neuropathy, resulting from a isoniazid-induced deficiency in pyridoxine (vitamin B6). Other adverse effects include hepatotoxicity, CNS effects (optic neuritis, dizziness, and ataxia), and anemia
|
|
|
Rifampin: Applications
|
Rifampin [Rifadin] is broad spectrum antibiotic that inhibits bacterial DNA-dependant RNA polymerase and consequently, protein synthesis. It is bactericidal.
Rifampin is one of our most effective anti-tuberculosis drugs. It is also an important agent for treating leprosy and infections with Haemophilus influenzae or Legionella spp. |
|
|
Rifampin: Adverse effects
|
The most common adverse effect of rifampin is hepatotoxicity, manifested by hepatitis and jaundice. Rifampin also frequently imparts a discoloration of body fluids: a red-orange color of urine, sweat, saliva, and tears may occur, but is generally harmless.
|
|
|
Rifampin: Drug interactions
|
Because rifampin induces cytochrome P450 enzymes, it can hasten the metabolism of many drugs. This is particularly of concern with oral contraceptives, warfarin, and certain drugs for HIV infection (protease inhibitors). Isoniazid, rifampin, and pyrazinamide are all hepatotoxic, and when they are used in combination, the risk of liver injury is greater than when they are used alone.
|
|
|
Ethambutol: Applications
|
Ethambutol [Myambutol]is active only against mycobacteria. The drug is bacteriostatic, not bactericidal. Ethambutol is an anti-tuberculosis drug that is always employed as part of a multi-drug regimen.
|
|
|
Ethambutol: Adverse effects
|
The most significant adverse effect is optic neuritis, though allergic reaction and hyperuricemia may also occur.
|
|
|
Second line anti-tuberculosis drugs...
|
Second line anti-tuberculosis drugs are generally less effective and more toxic than the first-line drugs. They are used to treat infection caused by organisms that are resistant to first-line drugs. The second-line drugs include streptomycin, para-aminosalicylic acid, ethionamide, cycloserine, capreomycin, kanamycin, amikacin, and fluoroquinolones
|
|
|
Combination chemotherapy offers three advantages:
|
Combination chemotherapy offers three advantages: 1) suppression of drug resistance, 2) increased cancer cell kill, and 3) reduced injury to normal cells.
|
|
|
Major toxicities of cancer chemotherapy include:
|
Bone marrow suppression (Neutropenia, thrombocytopenia, anemia)
Digestive tract injury (stomatitis and diarrhea) Nausea and vomiting Alopecia Hyperuricemia Local injury from extravasation of vesicants Reproductive toxicity Carcinogenesis |
|
|
The most important factors predicting the outcome of chemotherapy are:
|
The general health of the patient (assessed with the Karnofsky Performance Scale)
The responsiveness of the type of cancer the patient has |
|
|
Alkylating agents: Therapeutic effects and applications
|
Alkylating agents are highly reactive compounds that have the ability to transfer an alkyl group to a variety of cell constituents. Cell kill results from alkalization of DNA, specifically the nitrogen atom in guanine. Alkylating agents are able to bind to DNA in two places to form cross-links. These bridges may be formed within a single strand of DNA, or between parallel DNA strands.
Because alkylation reactions can take place at any time during the cell cycle, alkylating agents are considered cell-cycle phase nonspecific. Most of these drugs are more toxic to proliferating cells than to cells in G0. |
|
|
Alkylating agents: Drug resistance
|
Drug resistance is common. A major cause of resistance is increased production of enzymes that repair DNA. Resistance may also result from decreased uptake of alkylating agents and from increased production of nucleophiles (compounds that act as decoy targets for alkylation)
|
|
|
Nitrogen mustards:
|
Nitrogen mustards such as cyclophosphamide [Cytoxan] are bifunctional alkylating agents that are active against a broad spectrum of cancers. Indications include Hodgkin’s disease, Non-Hodgkin’s lymphomas, multiple myelomas, and solid tumors of the head, neck, ovary, and breast. Adverse effects include bone marrow suppression, nausea, vomiting, and alopecia.
|
|
|
Nitrosoureas:
|
Nitrosoureas such as carmustine [BiCNU, Gliadel] are alkylating agents that are able to cross the blood-brain barrier and access the CNS. Gliadel is a wafer implant that may be placed in a cavity created by surgical removal of a tumor. Streptozocin [Zanosar] is a nitrosourea that is indicated for metastatic islet cell tumors
|
|
|
Busulfan:
|
Other alkylating agents include busulfan [Myleran], a bifunctional agent whose effects are limited almost exclusively to the bone marrow. Busulfan is the drug of choice for chronic myelogenous leukemia
|
|
|
Platinum compounds:
|
Platinum compounds are very similar to the alkylating agents and are often classified as such. The platinum compounds produce cross-links in DNA, and hence are cell-cycle phase nonspecific.
|
|
|
Cisplatin:
|
Cisplatin [Platinol-AQ] is a platinum compound that is indicated for testicular cancer. The major dose-limiting toxicity is kidney damage. Cisplatin is highly emetogenic. Other adverse effects include neurotoxicity, bone marrow suppression, tinnitus
|
|
|
Carboplatin:
|
Carboplatin [Paraplatin] is a platinum compound that is an analog of cisplatin. The drug’s only indication is ovarian cancer. Carboplatin has adverse effects that are similar to those of cisplatin, but are less severe.
|
|
|
Oxaliplatin:
|
Oxaliplatin [Eloxatin] is a platinum compound with actions similar to those of carboplatin. It is approved only for colorectal cancer. The major toxicity is peripheral sensory neuropathy (numbness and tingling).
|
|
|
Antimetabolites:
|
Antimetabolites are structural analogs of important natural metabolites. They disrupt critical metabolic processes. Antimetabolites are effective only against cells that are active participants in the cell cycle.
|
|
|
Methotrexate: Applications
|
Methotrexate (Rheumatrex) and pemetrexed [ALIMTA] are folic acid analogs. Methotrexate inhibits dihydrofolate reductase, a necessary enzyme for the production of folic acid. Folic acid is required for production of DNA, RNA, and proteins. Methotrexate may be administered orally, by IV, IM, or intrathecally. • Methotexate is curative for women with choriocarcinoma, non-Hodgkin’s lymphomas, acute lymphocytic leukemia of childhood (ALL), and sarcoma. It has also been used to treat non-cancerous diseases such as rheumatoid arthritis, Crohn’s disease, psoriasis, and abortion.
|
|
|
Leucovorin rescue:
|
• A technique known as leucovorin rescue can be employed to enhance the effects of methotrexate. Some neoplastic cells are unresponsive to the effects of methotrexate because they lack the transport system required for uptake of the drug. Extremely high concentrations of methotrexate may be given to force the drug into these unresponsive cells, but when this puts normal cells at risk of toxicity. To save them, leucovorin is given
|
|
|
Methotrexate: Adverse effects
|
The usual toxicity is bone marrow suppression
|
|
|
Methotrexate: Resistance
|
• Resistance to methotrexate can be acquired from three forms: 1) decreased methotrexate uptake, 2) increased dihydrofolate reductase synthesis or 3) synthesis of a modified form of dihydrofolate reductase.
|
|
|
Pyrimidine analogs:
|
Pyrimidine analogs are antimetabolites that have structural similarity to the bases cytosine, thymine, and uracil. These bases are required for biosynthesis of DNA and RNA.
|
|
|
Cytarabine:
|
Cytarabine [Cytosar-U] is also known as cytosine arabinoside. It is a pyrimidine analog. Cytarabine is converted to its active form – ara-CTP – within the body. As ara-CTP, the drug becomes incorporated into DNA and inhibits synthesis. Cytarabine is highly S-phase specific. The principle indication for cytarabine is acute myelogenous leukemia. Adverse reactions include bone marrow suppression, nausea and vomiting, stomitis, liver injury, and conjunctivitis
|
|
|
Fluorouracil:
|
Fluorouracil [Adrucil]is a fluorinated derivative of uracil (FdUMP). It is a pyrimidine analog. The drug is employed extensively to treat solid tumors. FdUMP inhibits thymidyate synthetase, thereby depriving cells of thymidyate needed to make DNA. The usual toxicities are bone marrow suppression and oral/GI ulceration. Other adverse effects include palmar-plantar erythrodysesthesia (tingling, burning, redness, flaking, and blistering), alopecia, hyperpigmentation, and neorologic deficits
|
|
|
Purine analogs:
|
Purine analogs have structural similarity to the bases adenine, guanine, and hypoxanthine. These bases are required for biosynthesis of DNA and RNA.
|
|
|
Mercaptopurine:
|
Mercaptopurine [Purinethol] is a purine analog. It is a prodrug that undergoes conversion to its active form within cells. Once activated, the drug can interfere with purine biosynthesis. The principle indication for mercaptopurine is indicated for acute lymphocytic leukemia. Mercaptopurine is administered orally and absorbed drug is administered widely (but not to the CNS). The usually toxicities include bone marrow suppression, hepatic dysfunction, oral and intestinal ulceration, nausea and vomiting. Mercaptopurine is mutagenic, and should not to be used during pregnancy
|
|
|
Antitumor antibiotics:
|
Antitumor antibiotics are cytotoxic drugs that were originally isolated from cultures of Streptomyces. Because of their poor GI absorption, they are all administered parenterally (usually IV). All of these drugs injure cells through direct interaction with DNA. The may be anthracyclines or nonanthracyclines.
|
|
|
Anthracyclines include:
|
Doxorubicin
Daunorubicin Epirubicin Idarubicin Mitoxantrone |
|
|
Nonanthracyclines include:
|
Dactinomycin
Bleomycin Mitomycin |
|
|
Doxorubicin:
|
Doxorubicin [Adriamycin] (antitumor antibiotics) is active against a broad spectrum of neoplastic disease, but its utility is limited by cardiotoxicity. The drug imparts a harmless red color to tears, sweat, and urine. Doxorubicin is employed to treat solid tumors, Hodgkin’s and non Hodgkin's lymphomas, acute lymphoblastic and myeloblastic leukemias, and sarcomas of soft tissue
|
|
|
Daunorubicin:
|
Daunorubicin and liposomal daunorubicin [DaunoXome] (antitumor antibiotics) is designed to increase delivery of the drug to tumor cells and decrease uptake by normal cells
|
|
|
Epirubicin:
|
Epirubicin [Ellence] (antitumor antibiotics) is an analog of doxorubicin that may be used for adjuvant therapy of breast cancer after surgery
|
|
|
Idarubicin:
|
Idarubicin [Idamycin] (antitumor antibiotics) is indicated for acute myelogenous leukemia
|
|
|
Mitoxantrone:
|
Mitoxantrone (antitumor antibiotics) is a structural analog of doxorubicin and daunorubicin, but is less toxic than those drugs. Principle applications are prostate cancer and acute nonlymphocytic leukemias.
|
|
|
Dactinomycin:
|
Dactinomycin [Cosmegen] undergoes intercalation within DNA and blocks RNA synthesis
|
|
|
Bleomycin:
|
Bleomycin [Blenoxane](antitumor antibiotics) binds to DNA, causing chain scission and fragmentation. Bleomycin is unusual among the cytotoxic agents in that it causes very little bone marrow suppression. However, it can cause severe injury to the lungs (about 10% of patients experience lung toxicity). This toxicity may occur because the skin and lung lack the enzyme bleomycin hydrolase, which most tissues use to render the drug inactive
|
|
|
Mitomycin:
|
Mitomycin [mutamycin](antitumor antibiotics) is a prodrug that is converted to its active form within cells. Mitomycin is labed for disseminated adenocarcinoma of the stomach and pancreas.
|
|
|
Mitotic inhibitors:
|
Mitotic inhibitors are drugs that act during M phase to prevent cell division. There are two groups of drugs: vinca alkaloids and taxoids
|
|
|
Vinca alkaloids:
|
1) Vinca alkaloids are mitotic inhibitors that are derived from Vinca rosea (the periwinkle plant).
a. Vincristine [Oncovin] is a vinca alkaloid that disrupts microtubule assembly. Peripheral neuropathy (sensory and motor nerve injury) is the principle toxicity. In contrast to most anticancer drugs, vincristine causes little toxicity to bone marrow. As a result, the drug is especially desirable for combined therapy with other anticancer drugs. Indications for vincristine include Hodgkin’s and non-Hodgkin’s lymphomas, acute nonlymphocytic leukemias, Wilm’s tumor, rhabdomyosarcoma, Kaposi’s sarcoma, breast cancer, and bladder cancer. b. Vinblastine [Velban] is a structural analog of Vincristine. The major toxicity is bone marrow suppression c. Vinorelbine [Navelbine]is a semisynthetic vinca alkaloid. Vinorelbine can cause profound bone marrow suppression and well as local tissue necrosis |
|
|
Taxoids:
|
2) Taxoids are mitotic inhibitors that promote formation of stable microtubule bundles, thereby inhibiting cell division.
a. Paclitaxel [Taxol] is a widely used drug that acts during the late G2 phase to stabilize microtubules. In combination with cisplatin, the drug is a first-line therapy for ovarian cancer and non-small cell lung cancer. In addition, the drug is approved as second-line therapy for AIDS-related Kaposi’s sarcoma. Severe hypersensitivity reactions have occurred during paclitaxel infusion. Bone marrow suppression is also a major concern. b. Docetaxel [Taxotere] is similar to paclitaxel. Docetaxel can cause severe hypersensitivity reactions, manifested by hypotension and angioedema. Significant neutropenia develops in almost all patients. Other adverse effects include bradycardia, fatal myocardial infarction, alopecia, and GI reactions |
|
|
Topoisomerase inhibitors:
|
Topoisomerase inhibitors inhibit topoisomerase I, an enzyme that relieves torsional strain in DNA by creating reversible single-strand breaks (the enzyme breaks DNA and then fixes it). Topoisomerase II makes double-strand cuts to relieve strain.
|
|
|
Topotecan:
|
Topotecan [Hycamtin] inhibits topoisomerase I, thereby preventing repair of the strand breaks caused by the enzyme. Topotecan is indicated for small cell lung cancer and metastatic cancer of the ovary. The drug is administered via IV, and may cause bone marrow suppression. Neutrophenia often results.
|
|
|
Irinotecan:
|
Irinotecan [Camptosar] inhibits topoisomerase I and thereby impairs DNA replication. Irinotecan is approved for metastatic colorectal cancer (in combination with fluorouracil). The most common adverse effect is severe diarrhea (caused by excessive cholinergic stimulation of the GI tract)
|
|
|
Etoposide:
|
Etoposide [VePesid] is derived from a naturally occurring plant alkaloid. The drug inhibits topoisomerase II, and thereby prevents resealing of DNA strand breaks. Administration is PO and IV. Penetration to the CNS is low. Etoposide is approved only for refractory testicular cancer and small cell cancer of the lung. Major adverse effects include bone marrow suppression, alopecia, peripheral neuropathy, and GI disturbances
|
|
|
Asparaginase:
|
Asparaginase [Elspar] is an enzyme that converse asparagine (an essential amino acid) to aspartic acid. By converting asparagine to aspartic acid, the drug deprives cells of asparagine needed to synthesize proteins. Toxicity is limited to leukemic lymphoblasts, which are unable to manufacture their own aspaaragine (whereas normal cells can). Asparaginase is indicated only for acute lymphocytic leukemia. It may be administered parenterally via IM or IV. There are multiple adverse effects (but bone marrow suppression is NOT among them)
|
|
|
Mitotane:
|
Mitotane [Lysodren] is a structural analog of the insecticides DDD and DDT. The drug is selectively toxic to cells of the adrenal cortex. Mitotane is administered PO, and its only indication is inoperable adrenocortical carcinoma. Adverse effects include CNS depression, vomiting, and nausea
|
|
|
Miscellaneous cytotoxic drugs include:
|
Asparaginase
Mitotane |
