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Pharmacology
Test 3
| Question | Answer |
|---|---|
| What is the mechanism of action of the polyene antifungals? | Bind to ergosterol in cell membrane and allow leakage of small particles |
| Is amphotericin B fungistatic or fungicidal? | fungicidal |
| Is nystatin fungistatic or fungicidal? | It depends on the concentration, pH, and nature of infecting organism. |
| How common is resistance to the polyene antifungals? | Rare - only occurs in some candida species (not albicans) |
| What ions leak out of the pores created by polyene antifungals? | Mg++ and K+ |
| What is the least expensive and therefore the preferred formulation of amphotericin B | Deoxycholate |
| What form of amphotericin B is preferred in renally impaired patients? | One of the three lipid forms |
| How is amphotericin B metabolized? | It is not! |
| How is amphotericin B eliminated? | Slow release to urine and bile |
| What are the distribution characteristics of amphotericin B? (Sp. protein binding) | It is greater than 90% bound to beta-lipoproteins |
| What characteristic does the high protein binding of amphotericin B give it? | It is slowly and continuously released into the body over long periods of time (type of CR) |
| What is the dose-limiting factor of amphotericin B? | nephrotoxicity |
| What increases the nephrotoxicity associated with amphotericin B? | Na+ depletion |
| Why are lipid forms of amhotericin B less toxic than deoxycholate or other forms? | Lower blood levels of the drug are achieved |
| Can normal kidney function be regained once it is inhibited by admin of amphotericin B? | Yes, it normal function is usually re-gained upon suspension of treatment |
| What are the signs of nephrotox associated with amphotericin B? | Creatinine clearance drops and K+ is lost |
| Concomitant nephrotoxic drug use can worsen what condition? | azotemia |
| What can prevent the fevers and chills associated with amphotericin B administration? | Prophylactic admin of steroids or anti-pyretics |
| What can help bring down a fever that has started in response to admin. of amphotericin B? | meperidine |
| What drug interaction might amphotericin B have? | It may potentiate the action of doxorubicin |
| What are the three other adverse effects associated with amphotericin B? | thrombophlebitis, hypersensitivity, and shock-like hypotension |
| What are the therapeutic uses of amphotericin B? | Candida albicans (systemic), histoplasmosis, cryptococcus, aspergillus, blastomyces |
| Why is amphotericin B the preferred treatment for deep fungal infections in pregnant women? | The azoles are teratogenic |
| What caveat is associated with amphotericin use in pregnant women? | Should not be used unless there is no other treatment available and there is strong clinical indication |
| Why is nystatin never given parenterally? | unacceptable systemic toxicity |
| If any nystatin is absorbed, how is it excreted? | renally |
| What is the absorption of nystatin like from the GI tract, mucous membranes, etc.? | negligible |
| What are the two main adverse effects associated with nystatin? (not serious) | GI disturbances after PO admin, foul taste |
| What are the therapeutic uses of nystatin? | Candidal infections of the mucosa, skin, or intestinal tract |
| What is the only anti-malarial drug active against the exoerythrocytic stage? (Bugs are in schizant stage) | primaquine |
| What stage of malaria is chloroquine active against? | Erythrocitic |
| What stage of malaria is quinine active against? | Erythrocitic |
| What stage of malaria are the diaminopyrimidines active against? | Erythrocitic |
| What stage of malaria is mefloquine active against? | Erythrocitic |
| What 4 factors influence the choice of anti-malarial agent? | 1. species of plasmodia 2. resistant/sensitive plasmodia 3. infection in blood or liver? 4. use for prophylaxis or infection? |
| what is the MOA of chloroquine? | not really known, but believed to involve the inhibition of nucleic acid synthesis |
| What is the one mechanism of resistance against chloroquine? | P-glycoprotein efflux pump that pumps drug out |
| Characterize the oral absorption of chloroquine | Very rapid and complete |
| How does the wide distribution and extensive tissue binding of chloroquine affect its dosing? | A loading dose is needed to achieve effective plasma concentrations |
| What types of cells (cells containing ______) does chloroquine bind best to? | Cells containing melanin |
| Where is chloroquine metabolized and what is its primary metabolite? | Liver to desethylchloroquine |
| What is the half life of chloroquine? | 6 to 7 days |
| What significant AEs does chloroquine have when blood levels are kept low? | NONE |
| Which external body parts can high blood levels of chloroquine adversely affect? | skin, hair, eyes (also affects blood) |
| Why does chloroquine show the potential to impair vision? | Binds to melanin-containing areas of the eye |
| Is a loss of vision associated with chloroquine reversible? | NO |
| Extremely high doses of chloroquine can result in what 3 AEs? | Otoxicity, myopathy, and peripheral neuropathy |
| What is the most versatile drug used against plasmodia? | Chloroquine |
| In which plasmodium species is the usfulness of chloroquine declining? | P. falciparum has begun to show significant resistance |
| Why is chloroquine not a good DOC for intestinal amoeba infections? | It's completely absorbed - too little drug reaches the intestine |
| What is the MOA of quinine? | Binds DNA and inhibits nucleic acid synthesis |
| Which of the following does quinine act as: tissue schizonticide, blood schizonticide, gametocide, or hypnozoitocide? | Blood schizonticide |
| Quinine will kill the gametes of which 2 plasmodium species? | Vivax and malariae |
| Which species of plasmodium gametes will quinine NOT kill? | falciparum |
| Between chloroquine and quinine, which drug is more effective if the bug is sensitive to both? | chloroquine |
| Between chloroquine and quinine, which drug is less toxic? | chloroquine |
| What drug when given parenterally is useful in the treatment of drug resistant strains of P. falciparum? | quinine |
| How good is the oral absorption of quinine? | Very good |
| Is quinine well distributed throughout the body? | YES |
| Does quinine build up in body tissues (i.e. chloroquine)? | NO |
| Where is quinine metabolized? | liver |
| Does quinine undergo slow or rapid metabolism? | rapid |
| Will decreased liver function affect the concentration of quinine in the plasma? | YES it increases plasma levels |
| How is quinine excreted? | Rapidly by the kidneys |
| Of all the anti-malarials, which drug has the worst therapeutic index? | Quinine |
| High doses of quinine may cause the patient to develop a condition known as cinchonism, what are its symptoms? | Tinnitus, blurred vision, nausea, Headache, and decreased hearing acuity |
| What effect does quinine have on vascular smooth muscle and myocardium? | depressive effect on myocardium and a dilatory effect on vascular smooth muscle |
| Why would quinine treatment be avoided in pregnant women? | can cause contraction of uterus |
| What is the one significant drug interaction associated with quinine? | rifampin (cyp inducer) - accelerates the metabolism and clearance of quinine |
| What drug should ALWAYS be tried BEFORE quinine? | chloroquine |
| Quinine is a prototype blood ________ (Schizonticide, gametocide, or hypnozoiticide)? | schizonticide |
| What drug is the d-isomer of quinine? | quinidine |
| Quinidine is gametocidal to which species of plasmodia? | vivax and malariae, NOT falciparum |
| Quinine or quinidine, which is more active against falciparum? | quinidine |
| Since it is more active than quinine against some species, what does this mean about the dosing of quinidine? | Lower dose needed to be effective |
| Is quinidine oraly bio-available? | YES |
| How well distributed is quinidine in vivo? | very well, except to the brain |
| In what 3 parts of the body does quinidine accumulate? | heart, liver, and skeletal muscle |
| Where is quinidine metabolized? | liver - mostly |
| Alkalinization of the urine will (increase or decrease?) the excretion of quinidine? | decrease |
| What is the main AE of quinidine? | it has an anti-cholinergic effect |
| What precautions does quinidine have as a result of its major AE? | may interfere with anti-hypertensive therapy |
| What contraindication does quinidine have as a result of its major AE? | Pts with AV block should avoid |
| What are the two indications for quinidine? | Life-threatening P. falciparum AND arrhythmias (quinidine is an anti-arrhythmic) |
| What anti-malarial drug is also an anti-arrhythmic? | quinidine |
| What is the MOA of mefloquine? | not well established - probably the same as quinine |
| Is mefloquine orally bio-available? | YES |
| In what cells does mefloquine accumulate? | RBCs |
| Is the protein binding of mefloquine significant? | YES - about 98% protein bound |
| What is the T1/2 of mefloquine? | LONG - 21 days |
| What is the main route of excretion of mefloquine? | biliary |
| What are the main AEs associated with mefloquine? | CNS effects(insomnia and nightmares), vertigo, visual disturbances, GI effects |
| Due to its CNS effects, in what patients is mefloquine contraindicated? | Patients with a history of seizures or nuropsychiatric disorders |
| Patients on which type of anti-hypertensive/cardiac therapy should probably avoid mefloquine? | Patients on beta-blockers |
| Which anti-malarial is active only agianst asexual erythrocytic stages? | halofantrine |
| What is the MOA of 5-flucytosine? | It is an antimetabolite that inhibits thymidylate synthase and DNA synthesis |
| Is 5-flucytosine fungicidal or fungistatic? | Depends on the dose |
| What is the toxic metabolite of 5-flucytosine? | 5-flurouracil |
| What anti-fungal is flucytosine usually used in combo with? | amphotericin B |
| What is a flucytosine/amphotericin B combo used to treat? | systemic mycoses and meningitis caused by cryptococcus neoformans and Candida |
| Why is flucytosine used in combo with amphotericin B? | The combo is synergistic - Amp B may increase permeability of flucytosine |
| Does resistance against flucytosine develop rapidly or slowly? | Rapidly (another reason to use in combo) |
| What are the 3 main mechanisms of resistance against flucytosine? | 1. lack of permease. 2. defective or decreased cytosine deaminase. 3. deficient UMP pyrophosphorylase |
| How good is the oral absorption of flucytosine? | It is well absorbed orally |
| What is the distribution of flucytosine like? Does it penetrate the CNS? Protein binding? | Widely distributed to many organs. Penetrates into the CNS and shows a low amount of protein binding. |
| What is the route of elimination of flucytosine? | glomerular filtration |
| Should the dosing of flucytosine be reduced with renal failure? | YES |
| One of the AEs associated with flucytosine is hematological toxicity. What is this? | potentially lethal, dose-related bone marrow toxicity |
| What drugs should be used with caution in patients who have suffered from hematological toxicity? | radiation or chemo drugs that depress bone marrow |
| Is the neutropenia and thrombocytopenia associated with hematological toxicity reversible or irreversible? | It is reversible |
| If a patient becomes hepatically dysfunctional while taking flucytosine, can that be reversed? | YES |
| What is a symptom of hepatic dysfunction as a result of flucytosine? | elevated hepatic enzymes |
| Co-administration with amphotericin B will (reduce or increase?) the rate of clearance of flucytosine | reduce |
| In which specific fungal infection is flucytosine the preferred agent? | candida esophagitis |
| In which fungal infection is flucytosine used in combo with amphotericin B? | cryptococcus |
| Which fungal infection is flucytosine used to prevent in immunocompromised patients? | candida albicans |
| What is the MOA of the imidazole anti-fungals? | block the synthesis of ergosterol by inhibiting the methylation of ergosterol precursors |
| Are the imidazoles fungistatic or fungicidal? | fungistatic at low concentrations and fungicidal at high concentrations |
| Do the imidazoles have a narrow spectrum or a broad spectrum as a class? | broad spectrum |
| Rank the imidazoles in order of Cyp450 inhibition - starting with the one with the most inhibition | voriconazole > itroconazole = ketoconazole >> fluconazole |
| What are the 4 mechanisms of resistance to azole anti-fungals? | 1. Change in sterol components of plasma membrane 2. genetic changes in demethylase enzyme 3. alterations in other enzymes in ergosterol biosynthesis. 4. increased efflux of drugs |
| How do cells change their demethylase enzyme to gain resistance to azole antifungals? | alter binding site and overproduction of enzyme |
| Are the azoles well absorbed orally? | YES |
| Characterize the distribution of fluconazole. | distributes into most tissues INCLUDING CSF |
| What is one advantage fluconazole has over ketoconazole? | lack of endocrine side effects |
| What is the half-life of fluconazole? | 22 hrs |
| What is the main route of excretion of fluconazole? | renal |
| Should the dose of fluconazole be reduced with decreased renal function? | YES |
| What are the two main AEs associated with fluconazole? | GI distress and possible teratogenic |
| What is the DOC for local candidal infection? | fluconazole |
| What are the therapeutic uses of fluconazole? | candidiasis, coccidiomycosis, cryptococca meningitis (2nd line), supression in immunocompromised pts. after initial amp. B and flucytosine therapy |
| What drugs if co-administered with itroconazole can decrease absorption? | H2 blockers and antacids |
| Characterize the absorption of itraconazole. | variable - increased in acid environment |
| Does the presence of food increase or decrease absorption of itraconazole? | increases absorption |
| Describe the distribution of itraconazole. Does it penetrate the CSF? | Distributes into most tissues, but NOT the CSF |
| Where is itraconazole metabolized? | liver |
| What is the excretion route of itraconazole? | mostly bile |
| Should the dose of itraconazole be reduced with renal failure? | NO |
| What are the 3 main AEs of itraconazole? | GI distress, hepatic tox, and reported CHF |
| As a result of its AEs, in what patients should itraconazole therapy be avoided? | Pts. with ventricular dysfunction |
| What are the therapeutic uses of itraconazole? | histoplasmosis, blastomycosis, aspergillus, cryptococcus, fluconazole resistant C. glabrata |
| What is the DOC for blastomycosis? | itraconazole |
| Which of the azoles may be given PO or IV? | voriconazole |
| characterize the distribution of voriconazole. | extensive to tissues |
| Which of the azoles' metabolism is affected by a genetic polymorphism? | voriconazole |
| What is the major route of excretion of voriconazole? | "via hepatic metabolism" |
| What is an indication of hepatic toxicity associated with voriconazole? | elevated LFTs |
| What drug should only be given orally if creatinine clearance is below 50 ml/min? | voriconazole |
| What are the 4 major AEs associated with voriconazole? | visual disturbance, hepatic tox, rash, photosensitivity (hallucinations have occurred) |
| With what drugs is voriconazole contraindicated? | drugs that induce P450 enzymes |
| What are the therapeutic uses of voriconazole? (4) | invasive aspergillosis, scedosporium, fusarium, invasive fluconazole-resistant candida |
| A Cyp2C19 deficiency will result in increased levels of which anti-fungal? | voriconazole |
| Characterize the absorption of ketoconazole. | well-absorbed from GI tract |
| Does ketoconazole distribute to the CSF? | NO |
| Where is ketoconazole primarily metabolized? | liver |
| What is the primary route of excretion of ketoconazole? | bile |
| Which of the azoles inhibits steroid biosynthesis? | ketoconazole |
| What are the common AEs associated with ketoconazole? | GI effects - N/V, anorexia |
| Which of the azoles may be used alternatively to inhibit the excesive production of glucocorticoids? | ketoconazole |
| Which of the azoles is suitable for the treatment of ringworm? | miconazole |
| Which 2 azoles are indicated in the treatment of mucocutaneous fungal infections? | miconazole and clotrimazole |
| What is the one AE associated with miconazole and clotrimazole? | skin irritation after topical application |
| Which of the azoles may be formulated as troches for the treatment of oral candidiasis? | clotrimazole |
| What is the MOA of caspofungin? | inhibits synthesis of 1,3 D-glucan, an integral component in the fungal cell wall |
| What is the route of admin of caspofungin? | IV infusion |
| What is the dominant mechanism of plasma clearance of caspofungin? | distribution |
| What anti-fungal shows little metabolism in the first 30 hrs after it is given and is slowly metabolized then excreted via feces and urine? | caspofungin |
| What are the main AEs associated with caspofungin? | mild hepatic tox, histamine-mediated symptoms, embryotoxic |
| What are the therapeutic uses of caspofungin? | invasive aspergillus (when amp. B and itroconazole aren't effective) and invasive candida |
| What is the MOA of terbinafine? | interferes with fungal ergosterol biosynthesis by inhibiting squalene epoxidase |
| In what parts of the body does terbinafine concentrate? | hair and nail beds (concentrates in keratin) |
| What is the main route of excretion for terbinafine? | urine |
| Does terbinafine show a high degree of protein binding? | YES - 99% |
| What are the most frequent AEs associated with terbinafine? | HA & GI disturbances, occasional taste disturbance |
| What are the rare but serious AEs associated with terbinafine? | symptomatic hepatobiliary disfunction including cholestatic hepatitis |
| What is the one therapeutic use of terbinafine? | onychomycosal fungal infection (ringworm of the nail) |
| What is the MOA of griseofulvin? | disrupts mitotic spindle structure of fungal cell by interacting with microtubules |
| In what cells is griseofulvin deposited? | keratin precursor cells |
| Is griseofulvin fungistatic or fungicidal? | fungistatic |
| What increases the absorption of griseofulvin? | fatty meal |
| To which cells does griseofulvin distribute? | keratin precursor cells ONLY |
| What is the route of metabolism of griseofulvin? | liver |
| What is the route of excretion of griseofulvin? | kidney |
| Continuing griseofulvin therapy will (worsen or decrease) AEs associated with its use. | With continued use, AEs decrease |
| What are the common AEs associated with griseofulvin? | HA, GI upset, photosensitivity |
| What is the main therapeutic use of griseofulvin? | dermatophytes |
| Which of the anti-fungals is used against dermatophytes? | griseofulvin |
| What is the main drug interaction associated with griseofulvin? | Cyp P450 inducer - accelerates metabolism of other drugs |
| What 3 factors make TB so tough to treat? | 1. multiplies slowly. 2. survives in protected intracellular location. 3. propensity to develop resistance |
| What is the MOA of isoniazid? | interferes with mycolic acid synthesis which disrupts cell wall synthesis |
| Is isoniazid bacteriostatic or bactericidal? | cidal for rapidly dividing bacilli, static for slower growing |
| Would isoniazid be bacteriostatic or bacteriocidal in closed caseous lesions? | static |
| Would isoniazid be cidal or static in extracellular cavitary lesions? | cidal |
| What are the major mechs. of resistance against isoniazid? (3) | 1. inability to take up drug. 2. alteration in target enzyme. 3. overproduction of target enzyme |
| Why should isoniazid never be used as monotherapy against TB? | resistance develops too rapidly |
| Can isoniazid be admin'd IM? | YES |
| Characterize isoniazid's absorption from GIT | Rapidl absorption |
| Characterize the distribution of isoniazid | all tissues and fluids |
| Can isoniazid enter the CSF? | therapeutic levels can be achieved if meninges are inflamed |
| Will isoniazid cross the placenta and into breast milk? | YES to both |
| What is the mechanism of metabolism of isoniazid? | acetylation via N-acetyl transferase |
| What effect does chronic liver disease have on the metabolism of isoniazid? | decreases metabolism |
| Which of the TB agents may need dose adjustment based on the rate of acetylation of the patient? | isoniazid (conc. affected by slow and fast acetylators) |
| What is the main route of excretion of isoniazid? | urine |
| Burning or prickling sensation in hands and feet is symptomatic of what AE associated with isoniazid treatment? | peripheral neuropathy |
| What is the cause of a peripheral neuropathy associated with isoniazid use? | competition b/w isoniazid and pyridoxal phosphate |
| What is used to treat a peripheral neuropathy associated with isoniazid use? | B6 supplementation |
| In which patients is a peripheral neuropathy associated with isoniazid use more frequent? | malnourished, diabetic, and alcholic patients |
| Which of the AEs associated with isoniazid is related to the dose? | hepatotox |
| What drugs decrease absorption of isoniazid when given concurrently? | antacids with Al+++ salts |
| What class of drugs decreases the efficacy of isoniazid when used concurrently? | corticosteroids |
| Which P450 enzyme does isoniazid inhibit? | the one that metabolizes phenytoin |
| How does food affect the absorption of rifampin? | impairs absorption |
| What might decrease the absorption of rifampin? | food or para-aminosalicylic acid |
| What is theh % of protein binding exhibited by rifampin? | 75 - 85 % |
| Does rifampin cross into the CSF? | YES |
| Where is rifampin mainly metabolized? | liver |
| What is the primary route of excretion of rifampin? | bile |
| Is a dose adjustment of rifampin necessary with renal failure? | no |
| What are the AEs associated with rifampin? | discolors body fluids, GI disturbance, fever and chills, hepatotox |
| In what subset of patients is hepatotoxicity more of a concern with rifampin treatment? | slow acetylators and alcoholics |
| What is the most significant drug interaction associated with rifampin? | It is a potent Cyp inducer |
| What is the primary use of rifampin? | mycobacterium tuberculosis |
| What are some secondary uses of rifampin? | MRSA and Staph. epidermidis in combo w/ vanc or gent |
| What are some prophylactic uses of rifampin? | household members exposed to meningitis cause by h. flu or meningococci |
| What is the most potent anti-leprosy drug available? | rifampin |
| What is the MOA of rifampin? | binds RNA Pol beta subunit and inhibits RNA synthesis |
| Is rifampin bactericidal or bacteriostatic? | bactericidal |
| What is the main mechanism of resistance against rifampin? | RNA Pol doesn't bind the drug |
| Why is rifampin never used as a single agent? | Resistance emerges too rapidly |
| What is the spectrum of rifampin? | intra or extracellular mycobacteria |
| What is the MOA of ethambutol? | believed to inhibit RNA synthesis |
| Is ethambutol static or cidal? | static - possibly cidal at high levels |
| In order for ethambutol to be effective, what must bacilli be doing? | actively dividing |
| Does resistance to ethambutol develop quickly or slowly? | slowly |
| With what drugs does ethambutol show cross resistance? | NONE |
| Can ethambutol cross into CSF and achieve therapeutic levels? | YES - if meninges are inflamed |
| Does ethambutol cross placenta and into breast milk? | YES |
| What are the routes of metabolism and excretion of ethambutol? | metabolism - liver; clearance - renal |
| Which 2 TB drugs have hyperuricemia associated with their use? | ethambutol and pyrazinamide |
| What is the dose related AE of ethambutol? | optic neuritis |
| What are the symptoms of optic neuritis associated with ethambutol use? | decreased visual activity, loss of color discrimination, constriction of visual fields |
| Is the optic neuritis associated with ethambutol reversible? | YES - weeks to months after therapy |
| Can high enough pyrazinamide levels be achieved in the CSF to be therapeutic? | YES if meninges are inflamed |
| What are the routes of metabolism and excretion of pyrazinamide? | metabolism - hepatic; excretion - glom. filt. and renal |
| What AE of pyrazinamide is typically seen when large doses are given for long periods of time? | hepatotoxicity |
| Which TB drug may cause non-gouty arthralgias? | pyrazinamide |
| What is cycloserine generally used to treat? | active pulmonary and extrapulmonary TB, UTIs, Myco. Avium complex when nothing else works ( it is generally a 2nd line agent) |
| Against which bugs is pyrazinamide active? | tubercle bacilli in acid env. of lysosome and macrophage (intracellular bus w/ slow replication rates) |
| What is the MOA of cycloserine? | Blocks cell wall synthesis (structural analog of D-ala) |
| Is cycloserine cidal or static? | Depends on the concentration @ site of infection |
| Which TB drug shows good activity against resistant organisms and has no cross resistance w/ other TB drugs? | cycloserine |
| Characterize the distribution of cycloserine. | lungs, pleural fluid, synovial fluid, not highly protein bound, good dist. to CSF |
| What types of AEs are associated w/ cycloserine? | CNS effects |
| In whom is cycloserine contraindicated? | patients with a history of epilepsy |
| Are AEs associated with cycloserine use reversible once treatment is stopped? | YES |
| Is capreomycin static or cidal? | static |
| Is capreomycin orall bioavailable? | NO |
| What is the LAST LINE agent against TB? | capreomycin |
| Which TB drug may be useful when infection is resistant to many drugs? | capreomycin (always in combination w/ other TB drugs) |
| Primaquine is absorbed so rapidly from the GI tract that it may cause GI distress. What can be done to help this? | take with food |
| What AE may occur if IV primaquine is given? | marked hypotension |
| Why should long term primaquine use be avoided? | risk of toxicity and sensitization |
| G6PD deficient patients may develop what AE if given primaquine? | hemolytic anemia |
| Wha are the symptoms of hemolytic anemia associated w/ primaquine use? | dark urine, pallor, tiredness, fever, back pain |
| What is the MOA of pyrimethamine? | inhibits DHFR |
| In which bugs is pyrimethamine schizonticidal? | P. falciparum - NOT vivax |
| What drug should be used in combo with pyrimethamine? | sulfadoxine |
| What are the main mechanisms of resistance against pyrimethamine? | amino acid changes near DHFR binding site |
| In what cells does pyrimethamine concentrate? | blood cells |
| What anti-malarial can have single dose suppressive effects of up to 2 weeks? | pyrimethamine |
| With prolonged pyrimethamine treatment, what serious AE can occur? | megaloblastic anemia |
| Why would Fansidar (combo of pyrimethamine and sulfadoxine) not be used prophylactically? | severe AEs (i.e. Steven-Johnsons and epidermal necrolysis) |
| What is the MOA of flagyl? | Reduced intermediates disrupt DNA's helical structure which inhibits nucleic acid synthesis |
| On what organisms does flagyl exhibit cidal effects? | protozoans (amoeba, giardia, trichomonas) |
| Is flagyl more effective in dividing or non-dividing cells? | equal in both |
| What anti-protozoal agent is also one of the best drugs to treat an anaerobic bacterial infection? | flagyl |
| Characterize the distribution of flagyl | good to CSF, low protein binding, wide distribution to rest of body |
| In what patients is flagyl contraindicated? | patients with CNS disease |
| Are the AEs associated with flagyl usually sever enough to d/c use? | NO (HA, GI, metallic taste, **discolored urine) |
| What antiprotozoal agent shows disulfiram effect with alcohol? | flagyl |
| What are the 2 main drug interactions associated with flagyl? | Lithium tox and coumadin |
| What is the DOC for B. fragilis and C. difficile? | flagyl |
| What is the DOC for giardiasis? | flagyl |
| What is the DOC for amoebiasis? | flagyl |
| What is the MOA of atovaquone? | inhibition of mitochondria electron transport leading to pyrimidine synth. inhibition. |
| On what bug is atovaquone a cidal drug? | pneumocystis |
| Usually, is atovaquone cidal or static? | static (pneumocystis is exception) |
| Characterize the absorption of atovaquone. | poor and highly variable |
| What can increase oral absorption of atovaquone? | take with a high fat meal |
| Characterize the distribution of atovaquone. | 99% protein bound |
| What is the route of elimination of atovaquone? | fecal |
| Atovaquone is an anti-protozoal agent used in the treatment of what infections? | PCP, toxoplasmosis, amoebal, trichomonas, P. falciparum |
| What anti-protozoal agent MAY interfere with polyamine synthesis in trypanosomes? | pentamidine |
| What COULD the MOAs of pentamidine be? | DNA interference, Polyamine synthesis, Antifolate activity |
| What is the route of admin of pentamidine? | parenterally or inhalation |
| Does pentamidine penetrate the CNS? | NO |
| What are the positives and negatives of giving pentamidine via inhalation? | positive - decrease toxicity; negative - decrease distribution |
| The apparent half life of this anti-protozoal drug is 6 hours, but it can be detected 6 weeks later. What is it? | pentamidine |
| Which anti-protozoal agent shows toxicity in 50% of patients treated? | pentamidine |
| What are the AEs associated with pentamidine? | hypotension, hypoglycemia, blood dyscrasias, nephrotoxicity, and cardio toxicity |
| What is African sleeping sickness? | trypanosomiasis |
| What are the therapeutic uses of pentamidine? | PCP (alternative), leishmaniasis (alternative), trypanosomiasis (alternative) |
| Against what infection is pentamidine used prophylactically? | PCP |
| What is the MOA of eflornithine? | irreversible inhibition of ornithine decarboxylase and blocks polyamine synthesis |
| Is eflornithine orally bioavailable? | YES ~50% |
| What level of protein binding does eflornithine have? | NONE |
| Which of the following is eflornithine active against: West African trypanosomiasis, East African trypanosomiasis? | West African only! |
| What serious AEs are associated with eflornithine? | anemia, leukopenia, thrombocytopenia, convulsions, and alopecia |
| In what class of drugs is paramomycin? | AMGs |
| In what patients should paramomycin treatment be avoided? | Those with renal disease |
| What is the DOC for cryptosporidiosis in AIDS patients? | paramomycin |
| Are the AEs associated with eflornithine reversible once treatment is stopped? | YES - generally |
| The life cycle of what parasites require 2 hosts? | helminthics (parasitic worms) |
| Name the three classes of helminthics. | nematodes(roundworms), trematodes(flukes), cestodes(tapeworms) |
| Why is drug resistance not generally a problem in helminthics? | The parasites are generally long-lived with complex life cycles |
| What are the 3 primary targets of anti-helminthics? | NM coordination, Carbohydrate metabolism, microtubular integrity (affects eggs and larvae) |
| Name the 3 benzimidazoles used in anti-helminthic therapy. | Albendazole, Mebendazole, Thiabendazole |
| What is the MOA of the benzimidazoles? | affects tubulin and microtubular integrity |
| Rank the benzimidazoles in order of increasing oral absorption. | Thiabendazole, Albendazole, Mebendazole |
| Which of the benzimidazoles is highly protein bound? | mebendazole |
| Which of the benzimidazoles is available in a topical formulation? | thiabendazole |
| Which of the benzimidazoles is teratogenic in humans? | mebendazole |
| Which of the benzimidazoles has shown teratogenicity in animals? | albendazole |
| Which of the benzimidazoles has the fewest AEs? | albendazole |
| Which of the benzimidazoles interferes with the metabolism of xanthene derivatives? | thiabendazole |
| What are the DOCs for many nematodes includin: ascariasis, enterobius, and hook worm infection? | albendazole and mebendazole |
| How quickly do benzimidazoles work to kill and clear parasites from the GI tract? | SLOWLY |
| What is the MOA of pyrantel pamoate? | binds nicotinic receptors leading to paralysis and allowing for release of int. wall by worm |
| What AEs are associated with pyrantel pamoate? | mild GI, HA, dizziness, rash |
| Alternatively to mebendazole, what other drug may be used in the treatment of intestinal nematodes? | pyrantel pamoate |
| What is the MOA of ivermectin? | increase chloride permeability and inhibition of glu & GABA gated channels leads to hyperpolarization and paralysis |
| What is the DOC for strongiloidiasis (a nematode)? | ivermectin |
| What is the DOC for onchocerca (also known as river blindness)? | ivermectin |
| What are the symptoms of onchocerciasis? | tachycardia, edema, orthosatic hypotension |
| Which of the anti-helminthics shows rapid GI absorption, metabolism, and urine excretion? | diethyl carbamazine |
| What helminthic parasite causes a major host response when killed by anti-helminthic drugs? | microfillariae |
| What is the main therapeutic use of diethyl carbamazine? | lymphatic fillariasis |
| What is the MOA of praziquental? | increases calcium permeability (and other cations) increasing spasticity and paralysis and biochemical changes |
| What anti-helminthic drug has rapid oral absorption and has metabolites that are 100 times more concentrated than the parent drug? | praziquental |
| What is the only contraindication for praziquental? | ocular schistosomiasis |
| What is the DOC for liver, lung, or intestinal flukes? | praziquental |
| What type of helminth is praziquental "highly effective against"? | all species of schistosomes |
| What is the MOA of niclosamide? | inhibits respiration and glucose uptake AND anaerobic ATP production |
| What is cysticercosis? | tape worm is killed in vivo - releases viable eggs which develop into larvae which penetrate intestinal wall and move into lymph/rest of body |
| Which drug involves a risk of cysticercosis? | niclosamide |
| What is DOC for tapeworm infection? | praziquental |
| What is 2nd DOC for tapeworm infection? | niclosamide |
| Name 3 classes of RNA viruses (retroviridae). | Oncovirinae, lentivirinae, spumavirinae |
| 3 stages of HIV | primary infection (flu-like), asymptomatic phase, AIDS phase |
| Per 1993 CDC classification, pts in what HIV stage should be offered anti-retro viral therapy? | symptomatic (AIDS) phase |
| What does and HIV evalution consist of? | history & physical, CBC & chem profile, CD4+ and T-lymphocyte ct., and measure of HIV RNA |
| What type of antiretroviral drug is enfuvirtide? | fusion inhibitor |
| What is the MOA of enfuvirtide? | binds gp41 of viral envelope and impedes fusion of viral and host CM |
| What is the route of admin of enfuvirtide? | sub cu |
| does enfuvirtide exhibit a high degree or low degree of protein binding? | high degree |
| What is the mech. of metabolism of enfuvirtide? | proteolytic hydrolysis (no P450) |
| What AEs are associated w/ enfuvirtide? | hypersensitivity, pain @ inj. site, increased risk of bacterial pneumonia |
| What is the MOA of maraviroc? | chemokine R 5 antagonist - prevents viral uptake |
| What is the route of admin of maraviroc? | oral |
| What is maraviroc used in? | Tx of CCR5 tropic HIV-1 (NOT CXCR4) |
| With which drugs does maraviroc interact? | cyp 3a inducers and inhibitors |
| What is the MOA of NRTIs? | analogs of naturally occurring nucleosides - integration=chain termination |
| Of which nucleoside is zidovudine an analog? | T |
| Of which nucloside is lamivudine an analog? | C |
| Of which nucleoside is didanosine an analog? | A AND G |
| Of which nucleoside is abacavir an analog? | G |
| Of which nucleoside is stavudine an analog? | T |
| Of which nucleoside is emtricatibine an analog? | C |
| Are NRTIs better at preventing infection of susceptible cells or healing cells already infected? | prevention |
| What is the only NRTI shown to reduce perinatal HIV transmission? | zidovudine |
| What is the only mechanism of resistance against NRTIs? | mutations in reverse transcriptase @ level of specific codon |
| Only 2 of the NRTIs are metabolized, which two? | zidovudine and abacavir |
| Which NRTI should NOT be taken w/ meals? | didanosine |
| What are the common AEs associated w/ NRTIs? | GI distress, lactic acidosis w/ hepatic steatosis, lipodystrophy |
| What causes the hepatic steatosis associated w/ NRTI use? | mitochondrial toxicity |
| What NRTI shows higher levels of lactic acidosis, lipodystrophy, and can cause peripheral neuropathies? | stavudine |
| Peripheral neuropathy is associated w/ what NRTIs? | didanosine and stavudine |
| A pt. may be genetically pre-disposed to having an allergy against which NRTI? | Abacavir |
| Which NRTI may cause bone marrow depression? | zidovudine |
| What drug increases plasma [didanosine]? | ganciclovir |
| What drug decreases plasma [didanosine]? | methadone |
| What drugs may augment the neuropathy and pancreatitis associated w/ didanosine? | ethambutol, isoniazid, vincristine, cis-platin |
| What drug shows same drug interactions as didanosine? | stavudine |
| What drug increases plasma conc. of lamivudine? | septra |
| What drug significantly increases plasma conc. of abacavir? | ethanol |
| What is the main mech. of resistance against NRTIs? | mutations in reverse transcriptase |
| In what class of drugs is tenofovir? | NucleoTIDE RTIs |
| What is the difference b/w nucleotide RTIs and nucleoside RTIs? | Nucleotide RTIs only require two intracellular phosphorylation steps |
| Viruses resistant to which nucleoside RTI may also show resistance against tenofovir? | zidovudine (and possibly stavudine) |
| Which nucleotide does tenofovir mimic? | T |
| Which AIDS drug should be seperated by 1 - 2 hrs from tenofovir admin? | didanosine |
| What will increase oral BA of tenofovir? | taking w/ food |
| Name the 3 NNRTIs listed. | delavirdine, nevirapine, efavirenz |
| What are the indications for NNRTIs? | HIV-1 only! |
| What is the MOA of NNRTIs? | induce conformational change in reverse transcriptase |
| What are the advantages of NNRTIs over NRTIs? | don't require intracellular phosphorylation |
| Why have 3 different NNRTIs all w/ same MOA? | each selects for different mutations of RT gene |
| Which NNRTI is a cyp3A4 inhibitor? | delavirdine |
| Which 2 NNRTIs are cyp3A4 inducers? | efavirenz and nevirapine |
| What is a common AE associated w/ all NNRTIs? | maculopopular rash |
| Which NNRTI causes bad dreams and shows teratogenicity in non-human primates? | efavirenz |
| Which NNRTI may cause life-threatening hepatotox? | nevirapine |
| What is the MOA of reltegravir? | inhibits HIV-1 integrase |
| What suffix indicates the drug is a protease inhibitor? | -navir |
| What drugs are the most potent anti-retrovirals? | Protease inhibitors |
| Which cells are PIs active in that NRTIs and NNRTIs are not active? | monocytes and macrophages |
| What is one downfall of the PIs? | does not affect early stages of HIV-1 replication cycle |
| Characterize the distribution of the PIs? | Bind extensively to plasma proteins |
| What drug interactions do the PIs have? | potent cyp 3A4 inhibitors |
| What 5 serious AEs are associated w/ the PIs? | hyperlipidemia & lipodystrophy, insulin resistance & diabetes, elevated LFTs, possible increased bleeding in hemophiliacs |
| Ritonavir may cause _______ at high doses. | hepatotox |
| What PI should pts drink @ least 2 L/day if using? | indinavir |
| Jaundice - a sign of hyperbilirubinemia may occur in pts. taking what PI? | atazanavir |
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zdelaney
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