Pharm cancer fungal anesthetics

1. A 37-year-old man complained of anorexia, nausea, enlargement of his breast and impotence. The man, recently diagnosed with pulmonary coccidioidomycosis, has been receiving an antifungal treatment for two weeks. Which of the following drugs most likely caused these adverse effects?

Amphotericin B

Nystatin

Ketoconazole

Flucytosine

Griseofulvin

Terbinafine

C is the correct answer. Coccidioides immitis is sensitive to amphotericin B and to antifungal azoles. Amphotericin B is the drug of choice for severe systemic coccidioidomycosis, but antifungal azoles are often preferred in case of mild infection because they are orally active and much less toxic. Ketoconazole is an azole antifungal drug that can inhibit the cytochrome P450 system in mammalian cells. This inhibition blocks the synthesis of adrenal and gonadal steroids in mammalian cells. Therefore, the drug can cause gynecomastia, impotence and infertility in males. The newer azoles appear to have greater affinity for fungal cytochrome enzymes and less interference with mammalian enzymes, so the above mentioned adverse effects are seen less frequently.

Explanation

C is the correct answer. Coccidioides immitis is sensitive to amphotericin B and to antifungal azoles. Amphotericin B is the drug of choice for severe systemic coccidioidomycosis, but antifungal azoles are often preferred in case of mild infection because they are orally active and much less toxic. Ketoconazole is an azole antifungal drug that can inhibit the cytochrome P450 system in mammalian cells. This inhibition blocks the synthesis of adrenal and gonadal steroids in mammalian cells. Therefore, the drug can cause gynecomastia, impotence and infertility in males. The newer azoles appear to have greater affinity for fungal cytochrome enzymes and less interference with mammalian enzymes, so the above mentioned adverse effects are seen less frequently.

2. A 37-year-old woman with AIDS has been recently diagnosed with systemic candidiasis due to Candida cruzii, and an IV antifungal treatment has been prescribed. Four days later the following lab results were obtained: serum creatinine 5.9 mg/dL (normal: 0.6-1.5), BUN 53 mg/dL (normal 7-30), plasma potassium 2.3 mmol/L (normal 3.5-5.3). Which of the following drugs was most likely prescribed?

Fluconazole

Amphotericin B

Griseofulvin

Flucytosine

Micafungin

B is the correct answer. The lab results indicate that the patient is suffering from renal insufficiency. Amphotericin B is the drug of choice for most systemic mycoses, but the drug can cause a serious, dose-dependent renal dysfunction due to direct damage of renal tubules. Azotemia, renal tubular acidosis, and K+ wasting are the most prominent symptoms. These other antifungal drugs do not cause renal toxicity.

Explanation

B is the correct answer. The lab results indicate that the patient is suffering from renal insufficiency. Amphotericin B is the drug of choice for most systemic mycoses, but the drug can cause a serious, dose-dependent renal dysfunction due to direct damage of renal tubules. Azotemia, renal tubular acidosis, and K+ wasting are the most prominent symptoms. These other antifungal drugs do not cause renal toxicity.

3. A 31-year-old homosexual male with AIDS presents to the emergency room with fever (102.3 °F), headache, confusion, muddled thinking and vomiting. Physical examination reveals nuchal rigidity, diplopia, and loss of vision. An agglutination test of the spinal fluid for capsular polysaccharide antigen is positive suggesting infection with the organism Cryptococcus neoformans. The patient is started on IV amphotericin B in combination with another drug which functions by disrupting fungal nucleic acid synthesis. Which of the following drugs is being used in conjunction with amphotericin B?

Caspofungin

Ciclopirox

Nystatin

Flucytosine

Tolnaftate

Terbinafine

D is the correct answer. The history, symptoms, and signs of the patient strongly suggest the diagnosis of cryptococcal meningitis. In fact after toxoplasmosis, cryptococcosis is the most common CNS infection associated with AIDS. Cryptococcus neoformans is a yeast that is characterized by a thick polysaccharide capsule. During infection the capsular polysaccharide is solubilized in spinal fluid and can be detected by an agglutination test which is diagnostic of cryptococcosis. Cryptococcus neoformans is sensitive to amphotericin B, flucytosine and antifungal azoles. The current treatment recommended for acute cryptococcal meningitis is amphotericin B plus flucytosine. Synergism between the two drugs has been demonstrated in vitro and in vivo. It may be related to enhanced penetration of flucytosine through the amphotericin-damaged fungal cell membrane.

Explanation

D is the correct answer. The history, symptoms, and signs of the patient strongly suggest the diagnosis of cryptococcal meningitis. In fact after toxoplasmosis, cryptococcosis is the most common CNS infection associated with AIDS. Cryptococcus neoformans is a yeast that is characterized by a thick polysaccharide capsule. During infection the capsular polysaccharide is solubilized in spinal fluid and can be detected by an agglutination test which is diagnostic of cryptococcosis. Cryptococcus neoformans is sensitive to amphotericin B, flucytosine and antifungal azoles. The current treatment recommended for acute cryptococcal meningitis is amphotericin B plus flucytosine. Synergism between the two drugs has been demonstrated in vitro and in vivo. It may be related to enhanced penetration of flucytosine through the amphotericin-damaged fungal cell membrane.

4. A 48-year-old woman presented to her physician complaining of pain, abdominal distension, and changes in her bowel habits. Abdominal and pelvic ultrasound revealed a 10-15cm pelvic mass and her serum CA125 antigen level was significantly elevated. She was diagnosed with epithelial ovarian cancer, advanced stageIII. Her tumor was considered too large for initial surgery; systemic rather than intraperitoneal neoadjuvant chemotherapy was instituted to shrink her tumor prior to debulking surgery. She received 6 cycles of combination chemotherapy with paclitaxel and carboplatin. Which of the following statements correctly describes the mechanisms by which the drug combination sends a higher proportion of neoplastic cells into apoptotic mode?

Paclitaxel inhibits purine synthesis; carboplatin inhibits microtubular protein polymerization

Paclitaxel blocks thymidylate synthase: carboplatin blocks dihydrofolate reductase

Paclitaxel inhibits telomerases; carboplatin is toxic to topoisomerases

Paclitaxel inhibits microtubule disassembly; carboplatin disrupts DNA

Paclitaxel is toxic to cells in Go phase; carboplatin is specifically toxic to cell in S phase.

PACLITAXEL stabilizes microtubules and as a result, interferes with the normal breakdown of microtubules during cell division
Paclitaxel is a mitotic inhibitor used in cancer chemotherapy

Explanation

PACLITAXEL stabilizes microtubules and as a result, interferes with the normal breakdown of microtubules during cell division
Paclitaxel is a mitotic inhibitor used in cancer chemotherapy

5. A 26-year-old man, presents with a painless swelling in his left testicle. On examination an indurated mass was located in the lower pole of the left testicle. Blood tests show: alfa fetoprotein (AFP) 300ng/ml (normal<40); beta human chorionic gonadotrophin (beta-hCG) <5 IU/L. He is referred to an urologist who performs an orchiectomy followed by a retroperitoneal lymph node dissection. The pathologist's report reveals embryonal carcinoma, and four positive nodes. A combination chemotherapy regimen was designed. In preparation for this regimen, appropriate baseline tests were done: pulmonary function tests; an audiogram; and a 24h creatinine clearance; and plasma electrolytes, CBC and differential platelet counts. The patient was hydrated with IV sodium chloride, prior to receiving combination chemotherapy. A 21day cycle of treatment was implemented (x4.) In the light of the tests ordered to establish baseline functioning of specific organs, what is the most likely combination of drugs used to treat this cancer?

Leuprolide and finasteride

Bleomycin, vinblastine and cisplatin

Paclitaxel and cyclophosphamide

Cyclophosphamide, methotrexate and 5-fluorouracil

Concept: Tests for baseline functioning of specific organs to monitor cumulative dose-limiting toxicity of specific drugs

Explanation

Concept: Tests for baseline functioning of specific organs to monitor cumulative dose-limiting toxicity of specific drugs

6. A 7-year-old girl is brought to the physician by her mother because she has several small hairless patches in her scalp. Upon close physical examination, the patches look like black dots in the skin surface. Microscopic examination reveals a dense sheath of spores around the hair. Which of the following drugs, given orally, would be an appropriate treatment for this patient?

Miconazole

Tolnaftate

Amphotericin B

Flucytosine

Griseofulvin

E is the correct answer. The microscopic examination of the hair strongly suggests the diagnosis of ‘black dots’ tinea capitis, a cutaneous mycosis cause by Trichophyton tonsurans. Cutaneous mycoses are caused by fungi (mainly dermatophytes) that infect only the superficial keratinized tissues. Dermatophytes are sensitive to griseofulvin, terbinafine, antifungal azoles and amphotericin B, but the first two agents are the drugs of choice in cutaneous mycoses since they are deposited in newly forming skin where they bind to keratin, so protecting the skin from the infection. Oral itraconazole, not miconazole, is the antifungal azole of choice for tinea capitis. Tolnaftate is not taken orally and is generally not used for tinea capitis. Amphotericin B is given only topically in cutaneous mycoses. Flucytosine is a systemic antifungal drug, but is not effective against dermatophytes.

Explanation

E is the correct answer. The microscopic examination of the hair strongly suggests the diagnosis of ‘black dots’ tinea capitis, a cutaneous mycosis cause by Trichophyton tonsurans. Cutaneous mycoses are caused by fungi (mainly dermatophytes) that infect only the superficial keratinized tissues. Dermatophytes are sensitive to griseofulvin, terbinafine, antifungal azoles and amphotericin B, but the first two agents are the drugs of choice in cutaneous mycoses since they are deposited in newly forming skin where they bind to keratin, so protecting the skin from the infection. Oral itraconazole, not miconazole, is the antifungal azole of choice for tinea capitis. Tolnaftate is not taken orally and is generally not used for tinea capitis. Amphotericin B is given only topically in cutaneous mycoses. Flucytosine is a systemic antifungal drug, but is not effective against dermatophytes.

7. A 32-year-old woman presents to her gynecologist with a 4 days history of perineal pruritus and a non-malodorous, thick, cheesy vaginal discharge. The only medication the woman is taking is an oral contraceptive. A wet preparation of vaginal secretion shows budding yeast cells and pseudohyphae. Which of the following drugs, given locally, would be appropriate for this patient?

Miconazole

Amphotericin B

Fluconazole

Anidulafungin

Griseofulvin

A is the correct answer. The symptoms of the patient and the lab results strongly suggest that she is suffering from genital candidiasis, the most common opportunistic mycosis of genital tract in women taking oral contraceptives. Other predisposing factors include pregnancy, menstruation, diabetes mellitus, and use of broad-spectrum antibiotics, corticosteroids, or immunosuppressive drugs. Budding yeast cells and pseudohyphae of Candida albicans (the most common candida species causing candidiasis) can be detected by microscopic examination of biologic specimens. Candida albicans is sensitive to most antifungal drugs, but for genital candidiasis a vaginally administered azole derivative is the treatment of choice. B is incorrect because the patient’s condition does not warrant the potential toxicity that can be caused by amphotericin B. C is incorrect because fluconazole is normally administered orally and by IV. D is incorrect because anidulafungin is given by IV. Griseofulvin is not effective against Candida albicans.

Explanation

A is the correct answer. The symptoms of the patient and the lab results strongly suggest that she is suffering from genital candidiasis, the most common opportunistic mycosis of genital tract in women taking oral contraceptives. Other predisposing factors include pregnancy, menstruation, diabetes mellitus, and use of broad-spectrum antibiotics, corticosteroids, or immunosuppressive drugs. Budding yeast cells and pseudohyphae of Candida albicans (the most common candida species causing candidiasis) can be detected by microscopic examination of biologic specimens. Candida albicans is sensitive to most antifungal drugs, but for genital candidiasis a vaginally administered azole derivative is the treatment of choice. B is incorrect because the patient’s condition does not warrant the potential toxicity that can be caused by amphotericin B. C is incorrect because fluconazole is normally administered orally and by IV. D is incorrect because anidulafungin is given by IV. Griseofulvin is not effective against Candida albicans.

8. A 68-year-old woman with a history of breast cancer came to her physician complaining of back pain. 7 years previously she had a lumpectomy in her left breast followed by localized radiotherapy. At that time her tumor was documented as positive for both estrogen and progesterone receptors; she received 5 years of daily oral tamoxifen, which finished 2 years ago. As there is now radiographic evidence of bony metastases, it was decided to initiate combination of endocrine therapy, together with a bisphosphonate. Which of the following paired drugs may be identified as representatives of these two classes of therapeutic agents?

Tamoxifen and zoledronic acid

Fulvestrant and pamidronate

Anastrozole and finasteride

Finasteride and trastuzumab

FULVESTRANT is a drug treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy. It is an ESTROGEN RECEPTOR ANTAGONIST with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor

Explanation

FULVESTRANT is a drug treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy. It is an ESTROGEN RECEPTOR ANTAGONIST with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor

9. A 56-year-old obese woman went to her doctor with complaints of episodes of long, heavy ,vaginal bleeding and lower abdominal pain. On questioning , it was established that she was post menopausal and she had vaginal bleeding for over 6 months. After further tests, she was diagnosed with endometrial carcinoma for which she had an abdominal hysterectomy. Adjuvant chemotherapy was instituted with doxorubicin and paclitaxel. Unfortunately, within eight months there was recurrent disease. Which is the most likely explanation for drug therapy failure?

Mutations in beta tubulin isoforms

Overexpression of multidrug resistance gene(MDR1)

Enhanced activity of enzymes which reseal DNA breaks

Changes in receptor affinity characteristics

Increase in the production of drug-inactivating enzymes

Concept: mechanisms of resistance which minimize chemotherapeutic efficacy

Explanation

Concept: mechanisms of resistance which minimize chemotherapeutic efficacy

10. A 46-year-old man complains of dizziness, blurred vision, a pounding headache, perioral tingling, and a metallic taste. The patient is currently undergoing a surgical procedure on his shoulder that required administration lidocaine to induce a brachial plexus block. Which of the following is the most likely reason why lidocaine is inducing these adverse effects in this patient?

Lidocaine was injected directly into a nerve

Lidocaine was rapidly broken down

Lidocaine was injected intravascularly

Lidocaine was administered together with epinephrine

Lidocaine was inappropriately used as a regional anesthetic

C is the correct answer. The two most common causes of lidocaine CNS toxicity is inadvertent intravascular administration and administration of an excessive dose.

Explanation

C is the correct answer. The two most common causes of lidocaine CNS toxicity is inadvertent intravascular administration and administration of an excessive dose.

11. A 73-year-old man presents to his doctor with blood in his urine and complains that his shoulder is hurting. He had been taking finasteride to treat benign prostatic hypertrophy and his PSA levels had been < 4.5. His PSA now is 35.7ng/L. After various tests and evaluations, he is diagnosed with prostatic carcinoma, Gleeson score 9 with positive perineural invasion. He has metastatic, androgen-dependent, hormone-sensitive disease, with skeletal metastases involving skull and right shoulder. Which one of the following drugs would be part of a neoadjuvant androgen –deprivation therapy?

Anastrozole

Mifepristone

Flutamide

Oxandrolone

Spironolactone

Concept: Combined antiandrogen therapy is favored in the treatment of advanced metastatic prostate cancer.

Explanation

Concept: Combined antiandrogen therapy is favored in the treatment of advanced metastatic prostate cancer.

12. A 32-year-old woman undergoing a minor gynecological surgical procedure undergoes spinal anesthesia by administration of bupivacaine. If the final level of motor anesthesia achieved by bupivacaine in this patient is at the T10 dermatome, what would most likely be the final level of sensory and sympathetic anesthesia achieved in this patient by this drug?

U

V

W

X

Y

Z

B is the correct answer. Typically in spinal anesthesia, the final level of motor anesthesia will average two dermatomal levels below the final level of sensory anesthesia, while the final level of sympathetic anesthesia will average two dermatomal levels above the final sensory levels.

Explanation

B is the correct answer. Typically in spinal anesthesia, the final level of motor anesthesia will average two dermatomal levels below the final level of sensory anesthesia, while the final level of sympathetic anesthesia will average two dermatomal levels above the final sensory levels.

13. A 26-year-old man undergoes local anesthesia with lidocaine for a minimally invasive medical procedure. Which of the following bio-macromolecules that is the primary drug receptor for lidocaine has the lowest affinity for this drug?

Resting Na+ channels

Inactivated Na+ channels

Activated K+ channels

Activated Na+ channels

Inactivated K+ channels

Na+/K+ ATPase

A is the correct answer. The primary drug receptor for local anesthetics are voltage-gated Na+ channels. Of the three possible states of these channels, the state with the lowest affinity for the local anesthetics is the resting state.

Explanation

A is the correct answer. The primary drug receptor for local anesthetics are voltage-gated Na+ channels. Of the three possible states of these channels, the state with the lowest affinity for the local anesthetics is the resting state.

14. Which of the following types of nerve fibers would most likely be the least sensitive to administration of a local anesthetic such as lidocaine?

Type A delta fibers

Type C sympathetic fibers

Type B fibers

Type C dorsal root fibers

Type A alpha fibers

E is the correct answer. Of the nerve fiber types listed in this question, Type A alpha fibers have the largest diameter. While several characteristics determine how sensitive a nerve fiber is to blockade by local anesthetics, the diameter of the fiber is probably the characteristic with the most influence on this effect.

Explanation

E is the correct answer. Of the nerve fiber types listed in this question, Type A alpha fibers have the largest diameter. While several characteristics determine how sensitive a nerve fiber is to blockade by local anesthetics, the diameter of the fiber is probably the characteristic with the most influence on this effect.

15. A 34-year-old woman presents to the emergency department with a 3-inch laceration on her left forearm caused by an accident while cleaning her yard. The physician injects lidocaine in several places within the lacerated tissue before proceeding to stitch up the wound. Which of the following terms most correctly identifies this specific clinical utilization of lidocaine?

Surface anesthesia

Epidural anesthesia

Local infiltration

Peripheral nerve block

Topical anesthesia

Central neuraxial block

C is the correct answer. Local infiltration is the extravascular injection of a local anesthetic in order to create a limited area of anesthesia in and around the area where the agent is injected.

Explanation

C is the correct answer. Local infiltration is the extravascular injection of a local anesthetic in order to create a limited area of anesthesia in and around the area where the agent is injected.

16. The now 30-year-old male from the previous question came to his doctor complaining of fatigue, easy bruising, bleeding, fever and infection. The results from blood smears and a marrow biopsy confirm a diagnosis of Acute Myelogenous Leukemia. His doctor notes that four years previously the patient was successfully treated for testicular cancer using bleomycin, etoposide and cisplatin. A mixture including vinblastine was also employed as a variant regime. Which of the agents used to treat his testicular cancer most likely caused the development of AML in this patient?

Cisplatin

Vinblastine

Etoposide

Bleomycin

Concept: An antineoplastic drug, toxic to bone marrow, eliminates one cancer, but may precipitate a different cancer

Explanation

Concept: An antineoplastic drug, toxic to bone marrow, eliminates one cancer, but may precipitate a different cancer

17. In 1957 Ethel Longoria was admitted into intensive care bleeding rapidly into the lining of her lungs. Three years previously she had an ectopic pregnancy. Now a tumor had grown out of the placental tissue surrounding the abnormal pregnancy; it had metastasized into her lungs, where the tumor hung in grapelike clusters bleeding profusely. Her oncologist, Min Chiu Li, stabilized her, measured her plasma levels of human chorionic gonadotropin, (hCG) and started treatment with an antifolate drug. After four cycles of chemotherapy, the lung tumors disappeared, the chest X-ray improved, and the hCG levels diminished but were still measurable. What is the most likely outcome if antifolate treatment is continued?

Lung toxicity

Proliferation of micrometastases

Severe anemia

CNS meningeal metastases

Concept: antifolate toxicity versus drug resistance
METHOTREXATE decreases WBC not RBC, and the rapid development of resistance may lead to micrometastases.

Explanation

Concept: antifolate toxicity versus drug resistance
METHOTREXATE decreases WBC not RBC, and the rapid development of resistance may lead to micrometastases.

Pharm Cancer Fungal Anesthetics