Term
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Definition
MOA: Binds to Ergosterol in fungal cell wall, creates channels, and compromises cell wall stability. This eliminates membrane's ability to be a selective barrier. Administered IV. Infiltration into CSF is extremely low.
Target Organisms: Histoplasma, blastomycosis, coccidioidomycosis, aspergillus, mucormycosis
Risks: Toxicity limits use. Can cause Cytokine Storm (drug elicits release of tumor necrosis factor-alpha and Interleukin-1 causing fever, chills, rigor, hypotension within first hours after administration. Also can cause renal toxicity and hepatic toxicity. |
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Definition
MOA: Binds to Ergosterol in fungal cell wall and compromises cell wall stability. This eliminates membrane's ability to be a selective barrier. Administered topically.
Target Organisms: Candidiasis of skin, vaginal mucosa, and oral mucosa. |
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Term
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Definition
The Fungins. First line therapy against esophageal candidiasis. Administered ONLY IV.
MOA: Inhibits beta-glucan synthase which creates beta-glucan, a pivotal component of fungal cell membrane. Inhibits cell wall synthesis.
Drugs: Caspofungin, micafungin, anidulafungin
Target Organisms: Candida and Aspergillus. |
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Term
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Definition
MOA: Binds to microtubule-associated proteins. Disrupts mitotic spindle. This keeps cell from dividing and growing making it Fungistatic. It also binds tightly to keratin meaning it attaches to new cells and inhibits fungal growth so it takes forever to work.
Target Organisms: Tineas (Dermatophytes) NOT yeast. Used in peds, but does have s/e.
Risks: Headache, lethargy, hepatotoxicity, vertigo, blurred vision, leukopenia.
Induces cytochrome p450. |
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Term
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Definition
| TB Medication. MOA: Inhibits synthesis of mycolic acids (essential to cell wall of mycobacterium). Promotes excretion of pyridoxine (Vitamin B6). Given in combination with rifampin and others for active TB. Given as a single dose for latent TB x 9 months? Supplement with 50g of pyridoxine qd |
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Term
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Definition
Drug-induced hepatitis (occurs more frequently in patients with alcohol dependence, pregnancy, and postpartum), peripheral neuropathy (up to 20% of patients will develop this)
Seizures? |
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Term
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Definition
MOA: Binds to beta-subunit of bacterial DNA-dependent RNA polymerase and thereby inhibits RNA synthesis. Human RNA polymerase does not bind to rifampin.
Side Effects: Red/orange color to urine, sweat, tears (soft contacts may be stained), Strong inducer of cytochrome p450 |
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Term
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Definition
| MOA: Disrupts mycobacterial cell membrane metabolism and transport functions. Used with INH and rifampin Side Effects: N/V, hyperuricemia (Peeing out purines elevates urase which may precipitate gout), hepatotoxicity. |
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Term
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Definition
Aminoglycoside.
MOA: Binds to 30S ribosomal subunit and halts protein synthesis. |
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Term
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Definition
| Anti-TB. MOA: Inhibits DNA-dependent RNA polymerase in susceptible strains of Mycobacterium tuberculosis but does not affect mammalian cells. Side Effects: Hepatotoxicity, hypersensitivity reactions, red/orange discoloration of urine, sweat, tears. C. diff. Avoid in patients with porphyrias. |
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Term
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Definition
MOA: Inhibits mycobacterial arabinosyl transferases (essential element of cell wall)
Reduce dose by half if renal failure. Not good CSF penetration. Always given in combination with other drugs.
Side Effects: Retrobulbar neuritis (loss of visual acuity and results in red-green color blindness) Must check visual acuity/colorblindness testing is recommended. Don't use in children who are incapable of differentiating red-green colorblindness. |
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Term
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Definition
MOA: Disrupts mycolic acid synthesis.
Activity against TB and Leprosy.
Side Effects: N/V, hepatotoxicity, hypothyroidism, gynecomastia.
Pregnancy category X |
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Term
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Definition
20% of people with previously treated TB have MDR TB.
9% have XMDR (India, China, Russia)
Requires resistance to at least 2 drugs (usually INH and Rifampin) |
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Term
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Definition
Isoniazid, Rifampin, ethambutol may be used.
Preventative tx recommended in following patients: Pregnant women with a positive tuberculin skin test result who are HIV seropositive or who have behavioral risk factors for HIV infection but who decline HIV testing
Pregnant women with a positive tuberculin skin test result who have been in close contact with a patient who is smear-positive for pulmonary TB
Pregnant women who had a documented tuberculin skin test conversion during the previous 2 years |
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Term
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Definition
Isoniazid and Rifampin x 6 months
Pyrazinamid for the first 2 months if the culture from the source case is fully susceptible.
Ethambutol is avoided in young children from risk/difficulty monitoring visual acuity and color perception. |
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Term
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Definition
Nucleic acid synthesis inhibitor!
Converts to 5-Fluorouracil then 5-fDUMP (which disrupts DNA synthesis) and 5-FUTP (which disrupts RNA synthesis). For really sick people! Used in combo with amphotericin B to treat systemic mycoses (candidiasis, cryptococcis) Often used in HIV/AIDs patients. Excellent penetration into the eye, CNS, and urinary tract. When used alone, resistance develops rapidly.
s/e: Bone marrow suppression (leukopenia, thrombocytopenia), N/V/D, hepatic dysfunction.
Contraindicated in pregnancy. |
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Term
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Definition
Ergosterol pathway disrupter. Inhibits 14-a sterol demethylase. Affects lanosterol to zimosterol step.
Target Organisms: (Broad Spectrum) Histoplasma, cryptococcus, coccidioides, dermatophytes, candida.
Drugs: Ketoconazole, miconazole, clotrimazole, econazole, butoconazole, oxiconazole, sertaconazole, sulconazole (topical).
s/e: Drug-Drug interactions, N/V. Do not use if taking H2 blockers, or Proton Pump Inhibitors. |
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Term
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Definition
| An imidazole antifungal. Poor penetration into CSF. most non-specific (azoles metabolized via fungal CYPs BUT also have some affinity for human enzymes; keto has more human CYP interactions, hence more potential drug-drug interactions) and is no longer used systemically in US |
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Term
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Definition
| Itraconazole, fluconazole, voriconazole, terconazole (topical), posaconazole. |
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Term
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Definition
| Anti-fungal. PO and IV. Targets: Aspergillosis, blastomycosis, histoplasmosis s/e: hepatotoxicity |
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Term
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Definition
| Ergosterol pathway disrupter (Triazole). PO and IV. Widely distributed into CNS, sputum, urine, and saliva. Excreted by kidneys. DRUG OF CHOICE for systemic candidiasis and cryptococcal/coccidioidal meningitis. s/e: drug-drug interactions, N/V/D |
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Definition
PO and IV.
Targets: Aspergillosis and Candida.
Used in Bone Marrow Transplant pts.
s/e: hepatotoxicity, photophobia, do not use in renal failure. |
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Term
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Definition
Targets: Candida, Cryptococcus, Trichosporon.
Used for invasive fungal infections. |
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Term
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Definition
An allylamine antifungal. Oral and Topical.
Targets: Onychomycosis, tinea.
s/e: Oral can cause Stevens-Johnson syndrome! Do not use in pregnancy, renal, or hepatic failure. LFTs must be monitored during oral tx. Careful with other CYP (P-450) inhibitors/inducers. |
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Term
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Definition
A benzylamine anti-fungal.
Topical. Good against dermatophytes. |
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Term
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Definition
Antiprotozoal. Free radical when it enters the cell. Forms a nitrogen free radical, binds to DNA, and destroys it.
Activity is directly related to the presence of pyruvate-ferredoxin oxidoreductase (PFOR) [which is Pyruvate Synthase]. Eukaryotes lack PFOR, but protozoa have it, so Metronidazole is toxic to them. It can be activated in poorly oxygenated tissues (gut).
Targets: trichomonads, giardia, intestinal parasitic infections, C. diff, H. pylori.
s/e: Metallic taste! Disulfram-like effect (inhibition of ethanol metabolism)
Be careful with anti-coags. Many are poteniated. Dilantin?? |
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Term
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Definition
| Antiparasitic. Similar to metronidazole. Targets: Giardiasis, amebiasis, vaginal trichomoniasis. s/e: Similar to metronidazole. Do NOT use in first trimester of pregnancy Do NOT use in children <3 years old or in breastfeeding. |
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Term
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Definition
| Anti-parasitic. MOA unknown. SECOND line tx for pneumocystis jiroveci pneumonia (aerosolized) Also used in African Sleeping Sickness (Trypanosoma brucei gambiense) |
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Term
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Definition
| Chloroquine, Mefloquine, Primiquine, atovaquone/proguanil |
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Term
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Definition
Caused by protozoa Plasmodium
Transmitted by anopheles mosquito. Infects RBCs.
Five disease causing species: P. falciparum, P. vivax, P. ovale, P. malariae, P. knowlesi |
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Term
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Definition
Anti-malarial. Tx and Prophylaxis for malaria.
MOA: Heme metabolism. Poisons parasite by inhibiting the ability of the parasite to detoxify toxins produced by hemoglobin catabolism.
Risks: Lethal at very high doses (used worldwide in suicide)
Ineffective against P. falciparum in Africa, Asia, and South America. |
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Term
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Definition
MOA unknown, but appears to disrupt erythrocytes in malarial parasites.
s/e: Nausea, prolongation of QT interval, arrhythmias, neuropsych (vivid dreams, hallucinations) |
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Term
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Definition
Inhibits plasmodial electron transport.
Attacks only the hepatic form of malaria caused by P. vivax and P. ovale.
Induces hemolytic anemia in pts with G6PD (must be screened) |
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Term
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Definition
Malarone!
Atovaquone is an inhibitor of plasmodial electron transport.
Proguanil is a dihydrofolate reductase inhibitor.
They are synergistic in anti-malarial activity.
DOC for prophylaxis for all malarias.
Can be used in treatment of Chloroquine resistant P. falciparum. |
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Term
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Definition
Depends on country of origin (P. falciparum resistance to Chloroquine)
Parts of the world that can be treated with Chloroquine: Central America west of Panama, Haiti/DR, Middle East |
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Term
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Definition
| An aminoglycoside antibiotic used for luminal amoebas. |
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Term
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Definition
| Inhibit tubulin polymerization. Disrupts nematodal motility and DNA replication. |
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Term
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Definition
Targets: Strongyloidiasis (roundworm) due to nematode parasite strongyloides stercoralis.
MOA: binds selectively and with high affinity to glutamate-gated chloride ion channels which occur in invertebrate nerve and muscle cells. (No mammalian analogs).
This leads to an increase in the permeability of the cell membrane to chloride ions with hyperpolarization of the nerve or muscle cell, resulting in paralysis and death of the parasite. |
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Term
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Definition
| Bacteria, unable to pick up folic acid from the environment, synthesize it with PABA, pteridine, and glutamate. Sulfa drugs are PABA analogues that competitively inhibit dihydropteroate synthesis and prevent synthesis of folic acid with bacteria. Lack of folic acid prevents synthesis of numerous proteins and results in cessation of bacterial growth. Therefore, sulfa drugs are usually bacteriostatic. |
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Term
| Two types of sulfa drugs? |
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Definition
Sulfonamides: Lots of resistance to sulfonamides due to: Excessive production of endogenous PAPA, mutated PABA binding sites, or decreased membrane permeability towards sulfonamides.
Sulfones |
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Term
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Definition
Usually given with trimethoprim or pyrimethamine.
Sulfonamides compete with billirubin for binding sites on serum albumin which can cause kernicterus (markedly elevated unconjugated free billirubin) in newborns. Pregnancy category D. Do not use in first two months of newborn's life. Can use in breastfeeding, but best to wait until after first 2 months of life. |
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Term
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Definition
Many strains of formerly susceptible species to sulfonamides, including meningococci, pneumococci, streptococci, staphylococci, and gonococci, are now resistant.
The fixed-drug combination of trimethoprim-sulfamethoxazole (Bactrim®, Septra®) is the drug of choice for infections such as Pneumocystis jiroveci pneumonia, toxoplasmosis, and occasionally other bacterial infections i.e. MRSA for super uncomplicated. |
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Term
| Sulfonamide Used in Treatment |
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Definition
Sulfadiazine in combination with pyrimethamine is first-line therapy for treatment of acute toxoplasmosis
Sodium sulfacetamide ophthalmic solution or ointment is effective in the treatment of bacterial conjunctivitis and as adjunctive therapy for trachoma
Silver sulfadiazine (Silvadene) is a topical sulfonamide and is used for prevention of infection in burn wounds |
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Term
| Cross-reactivity in Sulfa drugs. |
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Definition
Historically, drugs containing a sulfonamide, including antimicrobial sulfas, diuretics, and the sulfonylurea hypoglycemic agents, were considered to be cross-allergenic.
However, recent evidence suggests cross-reactivity is uncommon and patients who are allergic to non-antibiotic sulfonamides may safely receive sulfonamide antibiotics. |
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Term
| Common Adverse Effects of sulfonamides |
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Definition
Fever, skin rashes, exfoliative dermatitis, photosensitivity, urticaria, nausea, vomiting, diarrhea.
Stevens-Johnson syndrome, although relatively uncommon (< 1%), is a particularly serious and potentially fatal type of skin /mucous membrane eruption associated with sulfonamides.
Sulfonamides may precipitate in urine, especially at neutral or acid pH, producing crystalluria, hematuria, or even obstruction.
This is rarely a problem with the more soluble sulfonamides (eg, sulfisoxazole (Gantrisin©) |
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Term
| Other adverse affects of sulfonamides |
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Definition
hemolytic or aplastic anemia, granulocytopenia, thrombocytopenia, or leukemoid reactions.
may provoke hemolytic reactions in patients with glucose-6-phosphate dehydrogenase deficiency.
if taken near the end of pregnancy, can increase the risk of kernicterus in newborns |
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Term
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Definition
Dapsone: Used in treatment of leprosy and Pneumocystis jiroveci pneumonia.
s/e: Methemoglobinemia (typically patients are G6PD deficient) |
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Term
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Definition
| Folate analogue. Selectively inhibits DHFR (Dihydrofolate reductase). Used in combination with sulfamethoxazole to block sequential steps in pathway of tetrahydrofolate. Called a "Synergistic Sequential Blockade" |
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Term
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Definition
One double-strength tablet (each tablet contains trimethoprim 160 mg plus sulfamethoxazole 800 mg) given every 12 hours is effective treatment for susceptible UTIs and prostatitis.
For PJP it is dosed much higher and Q 6 hours IV
A single-strength tablet given three times weekly sometimes used as prophylaxis in recurrent UTI in women.
One double-strength tablet every 12 hours is effective treatment for infections caused by susceptible strains of shigella and salmonella.
The dosage for children treated for shigellosis, urinary tract infection, or otitis media is 8 mg/kg trimethoprim and 40 mg/kg sulfamethoxazole every 12 hours |
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Term
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Definition
| Antibiotic. Inactivates or alters bacterial ribosomal proteins. Caution in the elderly (risk of pulmonary toxicity and renal problems). Do not use if prolonged tx planned. Not effective if Creatinine Clearance < 60mL/min. Used for susceptible UTIs (E. coli, klebsiella) not used for systemic illness. |
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Term
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Definition
Can use in Peds > 1 month old.
Available in liquid form 5-7 mg/kg/day PO divided q6hr for 7 days
Typically used in pregnancy except at term
Risk of cholestatic jaundice or hepatic dysfunction
Do not use if breastfeeding |
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Term
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Definition
Macrocrystals (Macrodantin®, Furadantin®, and equivalents): 50-100 mg PO q6hr for 7 days or for 3 days after obtaining sterile urine
Monohydrate/macrocrystals (Macrobid® and equivalents): 100 mg PO q12hr for 7 days or for 3 days after obtaining sterile urine
Long-term prophylaxis/suppression: 50-100 mg macrocrystals PO HS for up to 12 months |
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Term
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Definition
2 billion people (1/3 of the world’s population) have TB
Socioeconomic issues surrounding TB: Substance Abuse, Nutritional Status, Environmental Factors, Systemic Disease |
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Term
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Definition
the most commonly reported behavioral risk factor among patients with TB in the United States
Drug use – homelessness, incarceration contribute to the high prevalence of TB among drug users.
Tobacco – Cigarette smoking = relative risk of 1.5 to 2.0 for the development of TB (has been found to be associated with risk of relapse and mortality).
Alcohol – The risk of active TB is substantially elevated in individuals who consume more than 40 g alcohol per day. |
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Term
| Nutritional Status and TB |
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Definition
Nutritional status —
Underweight –BMI <18.5 have increased risk for TB by a factor of 2.6 (1.2 to 4.8)
Vitamin D – Vitamin D plays an important role in macrophage activation and restriction of mycobacterial growth, and ↓ serum vitamin D levels appear to increase risk for TB infection
Iron status – Iron is an important growth factor for M. tuberculosis in macrophages and appears to play an important role in host susceptibility to TB infection |
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Term
| Environmental Factors and TB |
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Definition
Close living quarters (nursing homes, homeless shelters, correctional facilities, hospitals)
Birth in a TB-endemic area (Asia, Latin America, SSA)
Household contacts |
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Term
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Definition
| HIV/AIDS Other immunosuppression (glucocorticoids, TNF inhibitors, transplant patients) |
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Term
| TB Regiment in order of preference |
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Definition
Isoniazid, Rifampin, Pyrazinamide for 6 months
Isoniazid, Rifampin for 9 months
Rifampin, Ethambutol, Pyrazinamide for 6 months
Rifampin, Ethambutol for 12 months
Isoniazid, Ethambutol for 18 months
All others for 24 months |
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