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211 Cards in this Set
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- Back
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Chemotherapeutic drugs that damage DNA by crosslinking
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Cyclophosphamide
Cisplatin |
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Chemotherapeutic drugs that damage DNA by strand breakage
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Bleomycin
Doxorubicin |
Doxorubicin also freezes topoisomerase II
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Reduces cystitis side effect of Cyclophosphamide by inactivating its metabolites
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MESNA
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Cyclophosphamide: major side effect and cell cycle phases of activity
(cancer drug) |
Bone marrow suppression.
Active in all cycle phases |
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Cisplatin: major side effect and cell cycle phases of activity
(cancer drug) |
Renal toxicity.
Active in all cycle phases |
Loading with saline reduces toxicity
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Bleomycin: major side effect and cell cycle phases of activity
(cancer drug) |
Pulmonary toxicity.
Most active in M and G2 phases |
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Doxorubicin: major side effect and cell cycle phases of activity
(cancer drug) |
Cardiac toxicity (congestive heart failure) and bone marrow suppression.
Active in all cycle phases. |
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Chemotherapeutic drugs that are structural analogues (interferes with a cell pathway)
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Methotrexate
Fluorouracil Mercaptopurine |
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Chemotherapeutic drug that is a FOLIC ACID ANALOGUE. It blocks pyrimidine, purine, glycine and methionine production.
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Methotrexate
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Drug that is given with high doses of Methotrexate to rescue normal cells (in treatment of non-Hodgkin's lymphoma and osteosarcoma)
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Leucovorin
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also a folic acid analogue
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Chemotherapeutic drug that is a PYRIMIDINE ANALOGUE; induces strand breaks and and endonuclease to cleave DNA. Also has effects on RNA.
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Fluorouracil
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only used on solid tumors
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Chemotherapeutic drug that is a PURINE ANALOGUE; induces strand breaks and decreases purine levels.
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Mercaptopurine
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Methotrexate: major side effect and cell cycle phases of activity
(cancer drug) |
Bone marrow suppression.
Synthesis phase |
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Fluorouracil: major side effect and cell cycle phases of activity
(cancer drug) |
Bone marrow suppression.
Phase non-specific (active in all phases). |
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Mercaptopurine: major side effect and cell cycle phases of activity
(cancer drug) |
Bone marrow suppression.
Synthesis phase |
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Chemotherapeutic drug that stabilizes microtubule formation, inhibits mitosis.
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Paclitaxel
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Paclitaxel: major side effect and cell cycle phases of activity
(cancer drug) |
Neutropenia.
Mitosis phase (arrests cells in M or G2) |
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Chemotherapeutic drug that is a humanized monoclonal Ab against HER2 gene product.
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Herceptin
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HER2 is a receptor on breast tumor cell.
drug is used in combinations. |
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Herceptin: side effects
(cancer drug) |
Allergic rxn
Cardiac failure (congestive heart failure) LV ejection lowered |
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Chemotherapeutic drug that is a specific inhibitor of bcr-Abl, kit, PDGF tyrosine kinase. (binds ATP site)
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Gleevec
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given orally. substrate of P450s (3A4, 2C9, 2D6).
Used for CML --chronic myeloid leukemia. |
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Gleevec: side effects
(cancer drug) |
mild.
causes fetal harm. |
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Chemotherapeutic drug that inhibits EGFR and HER2. (binds ATP site)
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TYKERB
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Used in breast cancer.
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TYKERB: side effects
(cancer drug) |
Hepatotoxicity
Decrease in LV ejection fraction Causes fetal harm. |
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Chemotherapeutic drug that binds receptor to prevent estrogen binding. It is anti-estrogenic on breast and estrogenic on bone & uterus.
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Tamoxifen
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breast cancer treatment
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Tamoxifen: major side effects
(cancer drug) |
Fetal harm.
Risk of endometrial cancer in post-menopausal women. |
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Chemotherapeutic drug that binds estrogen receptor. It is anti-estrogenic on breast & uterus and estrogenic on bone.
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Raloxifene
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breast cancer treatment
lowers risk for endometrial cancer. Fetal toxicity an issue. |
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Chemotherapeutic drug that inhibits cholesterol to pregnenolone; prevents adrenal androgen production.
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Aminoglutethimide
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prostate cancer treatment.
must be given with steroid hormones. Causes lethargy. |
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Chemotherapeutic drug that is a synthetic estrogen, feedback inhibition of FSH and LH.
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Diethylstibestrol (DES)
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prostate cancer treatment
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Diethylstibestrol (DES): major side effects
(cancer drug) |
gynecomastia
impotence |
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Chemotherapeutic drug that is a GnRH superagonist, desensitizes receptor; inhibition of FSH and LH.
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Leuprolide
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prostate cancer treatment
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Leuprolide: major side effects
(cancer drug) |
Loss of libido
Gynecomastia Thromboembolism |
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Chemotherapeutic drug that is an androgen competitive inhibitor; it blocks their binding to receptor.
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Flutamide
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prostate cancer treatment.
used in conjunction with Leuprolide. has a secondary undesired effect of decreasing feedback inhibition of FSH and LH secretion. |
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Flutamide: major side effects
(cancer drug) |
Osteoporosis
Gynecomastia Loss of libido Hepatic toxicity |
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Chemotherapeutic drug that is a synthetic glucocorticoid; binds receptor and activates caspases to cause apoptosis.
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Prednisone
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Treats lympholytic anemias, Hodgkin's disease, and non-Hodgkin's lymphomas.
No bone marrow suppression. Major side effect: hyperadrenocorticism. |
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Chemotherapeutic drug that is an estrogen receptor antagonist; downregulates the receptor.
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Fulvestrant
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treats breast cancer.
used in post-menopausal pts. |
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Fulvestrant: major side effects
(cancer drug) |
Fetal toxicity
Hot flashes, GI issues |
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Chemotherapeutic drug that blocks aromatase from converting androgen to estrogen; competitive inhibitor.
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Letrozole
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treats breast cancer
only works in post-menopausal pts. |
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Letrozole: major side effects
(cancer drug) |
Fetal toxicity
Osteoporosis |
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Class of antimicrobial drugs with beta lactam ring & thiazoline ring; interact with PBPs and act as pseudo-substrates to inhibit enzymes needed to develop cell walls (transpeptidases).
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Penicillins.
(bactericidal, but only on actively growing bacteria) |
oral or IV. absorbed in upper bowel.
Highest concentration in kidney. Renal filtration/active tubular secretion. |
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Penicillins and special consideration with diabetics
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all beta lactams will have lower plasma levels in diabetic patients.
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Penicillins and pregnancy
Penicillins and CSF penetration |
Class B pregnancy risk: readily crosses placenta, gets into breast milk.
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Small amounts in CSF; there's greater permeability with inflamed meninges.
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Bacterial mechanisms of resistance to Penicillin drugs.
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1) beta lactamase enzymes
2) porins 3) eflux pumps 4) altered PBPs 5) L-form bacteria, quiescent bacteria, tolerant bacteria |
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Penicillin class of drugs: side effects
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Hypersensitivity reactions
CNS toxicity at high levels GI disturbance; Nephritis Thrombophlebitis with repeat IV Suprainfection (C. difficile colitis) |
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Natural penicillins (2) and their spectrums
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Penicillin G --IV mainly, also IM
Penicillin V --oral |
gram +/- cocci.
gram + bacilli. spirochetes anaerobes |
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Beta-lactamase resistant penicillins (4) and their spectrums
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Methicillin --oral (not used anymore due to interstitial nephritis)
Cloxacillin, Dicloxacillin, Oxacillin --oral (best on empty stomach) |
primarily for Staph infections (gram +)
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Aminopenicillins (2)
[spectrum is broad gram +/-. Useful in ear & respiratory infections in kids; H. influenzae] |
Ampicillin --IV/IM, oral
Treats acute bacterial meningitis due to Listeria. Combination use with Sulbactam. |
Amoxicillin --IV/IM, oral
Combination use with clavulanic acid |
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Antipseudomonal Penicillins (3) and their spectrums
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Piperacillin
Ticarcillin and Carbenicillin |
gram - respiratory tract infections and Pseudomonas.
not good for gram + |
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Class of antimicrobial drugs that are beta lactam ring & dihydrothiazolidine rings; act to disrupt cell wall synthesis and development.
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Cephalosporins.
(are more stable to pH and temp changes compared to Penicillin) |
most given IV/IM. wide distribution in body. poor CNS penetration.
kidney tubular secretion. |
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Bacterial resistance to Cephalosporins
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1) beta lactamases
2) altered PBPs |
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Cephalosporins: side effects
(antimicrobial) |
Antigenic properties (cross sensitive with penicillins)
Nephrotoxic other side effects of penicillins |
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1st generation cephalosporins (2)
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Cephalexin --oral
Cephazolin --IV (given preoperatively) |
gram + cocci except Enterococci and most E. coli, P. mirabilis, K. pneumoniae.
does not reach effective conc. in CNS to treat meningitis |
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2nd generation cephalosporins (3)
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Cefaclor --oral
more active against gram - than 1st gen. Treats pneumonia and throat infections this drug and Cefuroxime are active against Staph compared to 1st gen. |
Cefoxitin --IV/IM
more active against anaerobes. B. fragilis commonly. |
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3rd generation cephalosporins (3)
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Ceftriaxone and Cefotaxime --IV/IM (penetrates CNS, treats meningitis)
Ceftazadime (effective against Pseudomonas) |
more gram - activity seen.
excellent against Enterobacteriaceae. Ceftriaxone: gram + cocci, Pseudomonas. Cefotaxime: H. influenzae, meningococci, enterobacteriaceae (meningitises) |
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4th generation cephalosporin
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Cefepime --IV
comparable to 3rd gen. but more resistant to beta lactamase |
very broad spectrum activity against gram + cocci, Pseudomonas, many Enterobacteriaceae. used to treat meningitis.
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Beta lactamase inhibitors (3)
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Clavulanic Acid
Sulbactam Tazobactam |
no antimicrobial activity on its own but enhances activity of beta lactam antibiotics.
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another class of beta lactam antimicrobial drugs. These are highly resistant to beta lactamases and have broad specificity, reserved for treatment of bacteria resistant to other antibiotics.
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Carbepenems class
drugs --> Imipenem and Meropenem |
No oral forms.
Most are effective against Pseudomonas. |
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another class of beta lactam antimicrobial drugs. These have the lactam ring by itself structurally, have a narrow range against aerobic gram - bacteria only.
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Monobactams class
drug --> Aztreonman |
No oral forms.
Effective against Pseudomonas. |
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Class of antimicrobial drugs that inhibit bacterial protein synthesis by binding to 30S ribosomal subunit. Also has a secondary effect of causing misreading of mRNA template and structural changes in bacterial membranes.
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Aminoglycosides
(Bactericidal) |
Highly polar polycationic compounds so poorly absorbed. Given IV/IM or topically.
Generally does not cross into CNS. Distribute primarily in extracellular fluid. Kidney is King! Glomerular filtration. |
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Aminoglycosides transport into the bacterial in two ways
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Phase I: low affinity binding that is energy dependent (so oxygen dependent)
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Phase II: high affinity, rapid uptake. also energy dependent.
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Bacterial resistance to Aminoglycosides
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bacterial inactivation by enzymes
1)adenyltransferase: adenylate an OH group 2) acetyltransferase: acetylation of amino group 3) phosphotransferase: phosphorylation of OH group |
Pseudomonas can show adaptive resistance --permeability barrier.
Often combined with beta lactams to treat S. aureus infection. Infective endocarditis due to enterococci are resistant. |
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Aminoglycosides: side effects
(antimicrobial) |
Major toxicity: Nephrotoxicity.
Ototoxicity (Vestibular and Auditory) Neuromuscular blockade. Allergic skin reactions. |
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Aminoglycoside drugs (7)
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Streptomycin
Gentamicin Tobramycin Kanamycin Amikacin Neomycin Netilmicin |
drugs able to treat Gram - bacilli on their own.
Gram + cocci and bacilli need to use in combination with a Penicillin drug |
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Streptomycin (IV/IM)
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Enters CNS with inflamed meninges.
Treats Tuberculosis (2nd line drug) |
Used in combination with Penicillin to treat Bacterial endocarditis, Tularemia, Bubonic plague, Brucellosis, Pseudomonas.
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Streptomycin: side effects
(aminoglycoside) |
Hypersensitivity
Vestibular toxicity Peripheral neuritis |
less nephrotoxic than other aminoglycosides.
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Most commonly used aminoglycoside drug, the "workhorse".
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Gentamycin (IV/IM)
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Works on many gram - and used to treat Pseudomonas, Klebsiella, Serratia.
Strep, Pneumococci, Anaerobic bacteria & fungi are resistant |
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Gentamicin: side effects
(aminoglycoside) |
Ototoxicity, more vestibular.
Most nephrotoxic of the systemically used aminoglycosides |
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Combination drugs:
Aminoglycoside and a Penicillin are used to treat these infections (6) Aminoglycoside and Cephalosporin are used to treat this infection (1) |
1) Gentamicin and Penicillin/Ampicillin for Strep. faecalis UTI
2) with Carbenicillin to treat Pseudomonas pneumonia 3) with Ampicillin to treat E. coli or Proteus pneumonia 4) with Penicillin/Ampicillin to treat Strep. agalactiae meningitis 5)with Ampicillin to treat Listeria meningitis 6) with Penicillin/Ampicillin to treat Strep. faecalis endocarditis |
Gentamicin with Cephalosporin to treat Klebsiella pneumonia.
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Tobramycin (IV/IM)
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aminoglycoside drug that's similar to Gentamicin but more expensive
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Greater effect on Pseudomonas; treats pneumonia, bacteremia, osteomyelitis.
Resistant bacteria: attacked by 7 enzymes |
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Tobramycin: side effects
(aminoglycoside) |
Ototoxic.
less nephrotoxic than Gentamicin. |
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The aminoglycoside drug that is given orally to suppress intestinal flora before surgery. And this drug is no longer available in the USA.
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Kanamycin (topical, oral)
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treats gram - infections but much resistance so has limited use now.
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The aminoglycoside drug that is used to sterilize bowel prior to surgery. It is too toxic for systemic use and was previously used to treat burn patients as a topical application.
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Neomycin (topical, oral)
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Neomycin: side effects
(aminoglycoside) |
Severe oto- and nephrotoxicity if taken systemically.
Hypersensitivity with topical. Suprainfection of bowel. |
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The aminoglycoside drug that is a derivative of kanamycin, specifically modified to be less vulnerable to resistant bacterial enzymes (only attacked by 2 of 9 enzymes). It is reserved for resistant gram - strains in hospital.
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Amikacin.
is more costly. Side effects... |
Oto- and nephrotoxicity.
(Auditory) |
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Netilmicin
NO LONGER AVAILABLE IN USA |
similar to gentamicin.
used to treat infections with Enterobacteria and aerobic gram - bacilli. effective against gentamycin resistant organisms. |
oto- and nephrotoxicity like the others, but may be less so
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Class of antimicrobial drugs that reversibly inhibits protein synthesis by binding 30S ribosomal subunit.
Is bacteriostatic. |
Tetracyclines (all taken orally)
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absorption impaired by food, divalent cations, dairy/antacids, alkaline pH.
Biotransformed and renal excretion. Enterohepatic circulation. ENTERS FETUS AND CSF |
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Tetracycline uptake into bacteria occurs in two ways
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Passively: diffusion through outer membrane. Extent of uptake dependent on lipophilic nature of tetracycline.
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Actively: energy dependent pump to get through inner plasma membrane of Gram - and plasma membrane of Gram +. Dependent on drug binding to bacterial transporter protein.
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Tetracycline: side effects
(antimicrobial) |
Phototoxicity: UV causes skin to turn red/purple.
Liver toxicity: jaundice, acidosis, shock. Hypersensitivity: rash, hives, exfoliative dermatitis, anaphylaxis rare Kidney toxicity: kidney failure GI upsets |
Brown discoloration of teeth: long term oxidation of Calcium-tetracycline complex. Pregnant women or infants/kids up to 7yrs.
Suprainfection by resistant organisms (most susceptible are leukemia, lymphoma, lupus erythematous pts) |
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Chlortetracycline, Oxytetracycline, Tetracycline (oral, IV/IM)
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short acting tetracyclines
Gram +/- activity. Bacteroides, Chlamydia, M. pneumonia, Rickettsia. |
Side effects are GI, rash, deposition in bone/teeth, hepatotoxicity
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Demeclocycline (oral)
tetracycline |
intermediate acting tetracycline
Gram +/- activity. M. pneumonia, Chlamydia |
Major side effect is phototoxicity
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Minocycline (oral)
tetracycline |
long acting tetracycline
Gram +/- activity. Mainly for Chlamydia. |
Major side effect is phototoxicity
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Doxycycline (oral)
tetracycline |
long acting tetracycline
Gram +/- activity. Chlamydia, M. pneumonia. |
almost exclusively excreted in feces as an inactive conjugate, unlike other tetracyclines.
side effects like other tetracyclines. |
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Antimicrobial drug that is bacteriostatic. It acts by binding 50S ribosomal subunit to inhibit binding of aminoacyl-tRNA and so inhibit protein synthesis.
It is bactericidal on H. influenzae. It can inhibit mitochondrial protein synthesis in euk. |
Chloramphenicol (oral, because very well absorbed. levels are about the same as when given IV/IM)
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distribution into all body fluids (including breastmilk) readily enters CSF and concentrates in brain tissues.
Glucuronidation inactivates it; drug inhibits P450s. Renal excretion |
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Chloramphenicol and drug interactions
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Inhibits hepatic P450s so prolongs half life & serum conc. of Phenytoin, Tobutamide, Chlorpropamide, Warfarin.
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Also attenuates action of bactericidal drugs (penicillin, aminoglycosides)
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Chloramphenicol: side effects
(antimicrobial) |
Irreversible aplastic anemia --SERIOUS
NEONATAL TOXICITY --gray baby syndrome |
Other side effects of chloramphenicol : Hypersensitivity, Reversible anemia, GI upsets, Suprainfection of bowel.
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Infections treated by chloramphenicol (5)
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1) typhoid fever by S. typhi
2) meningitis by H. influenzae, N. meningitidis, Strep. pneumoniae 3) Abscesses by B. fragilis 4) RockyMountainSpottedFever by Rickettsia 5) Brucellosis |
can also be used topically to treat infections due to ability to permeate ocular tissue and aqueous tumor
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Class of antimicrobial drugs that is wide spectrum and bacteriostatic. It is a chemical analogue of PABA, competitively inhibiting dihydropteroate synthetase, disrupting the synthesis of dihydrofolic acid.
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Sulfonamides (oral)
IV forms available but not commonly used. Also topical and eye drops. Free para NH2 group on benzene is essential for antimicrobial activity. |
Gets to all tissues including CSF and FETUS, breastmilk.
Metabolized by liver, major route of excretion is renal glomerular filtration. |
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Bacterial Resistance to Sulfonamides (3)
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1) decrease cell permeability
2) overproduce PABA to outcompete drug 3) altered form of dihydropteroate synthetase with lower affinity |
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Sulfonamide: side effects
(antimicrobial) |
Hypersensitivity
Interstitial nephritis Steven's Johnson Syndrome: cell death by epidermal layer separating from dermal layer. |
Renal crystalluria
Hemolytic anemia (esp. with G6PD), Aplastic anemia, Thrombocytopenia, Eosinophilia Contraindicated in G6PD deficiency (increase risk of kernicterus in newborns) |
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Sulfonamide: drug interactions
(antimicrobial) |
anticoagulants, anticonvulsants, hypoglycemic agents increase availability of sulfonamides.
Antacids inhibit GI absorption. |
Drug solutions are incompatible with calcium or other polyionic-containing fluids
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Sulfonamide drugs (5)
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Sulfadiazine
Sulfisoxazole Sulfamethoxazole Sulfacetamide Sulfasalazine |
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Sulfadiazine (oral)
(sulfonamide) |
primarily treats UTI.
use with pyrimethamine to treat Toxoplasma gondii in immunocompromised. |
not as soluble so more potential for crystalluria
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Silver Sulfadizine (topical)
(sulfonamide) |
antibiotic ointment that treats/prevents infections of 2nd and 3rd degree burns.
also used in surgery |
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Sulfisoxazole (oral, topical)
(sulfonamide) |
good solubility, less likely for crystalluria.
Treat UTI, otitis media, an alternate amoxicillin therapy in children |
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Sulfamethoxazole
(sulfonamide) |
often used in combination with Trimethoprim to treat UTI, otitis media, long-lasting recurrent bronchitis.
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Sulfacetamide (eye drop, topical)
(sulfonamide) |
treat common eye infections --bacterial conjunctivitis
ointment for rosaceae |
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Sulfasalazine
NOT technically a sulfonamide because the para NH2 is not free. |
reduces the synthesis of inflammatory mediators. Used to treat Crohn's disease or colitis.
Drug is active at lower bowel sites due to poor absorption. Hydrolysis of drug leads to 5-amino salicyclic acid which is active. |
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Antimicrobial drug that is a dihydrofolate reductase inhibitor; a structural analogue; prevents folic acid synthesis. It is combined with Sulfamethoxazole to create a synergistic therapy --both drugs target steps in folic acid synthesis.
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Trimethoprim (oral, IV)
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distribution to all tissues including CNS.
excreted in urine. |
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Trimethoprim: side effects
(antimicrobial) |
similar to sulfonamides.
Rash and Neutropenia high in immunocompromised. |
Pancytopenia in pts at risk for folate deficiency due to drug.
Combo Trimethoprim and Sulfamethoxazole is CONTRAINDICATED IN PREGNANCY |
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Trimethoprim: clinical use/spectrum
[Trimethoprim-Sulfamethoxazole] |
most gram +/- activity. does not work on anaerobes.
Treat uncomplicated infections: all types of UTI (chronic, recurrent, etc.) |
also treat prostate infection, H. influenza upper respiratory infection, Listeria, Pneumocystis.
Not useful against Pseudomonas. |
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Class of antimicrobial drugs that binds bacterial DNA and perturbs structure. Distortion recognized by Topo II increases DNA breaks. Also inhibits DNA gyrase.
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Quinolones
Fluoroquinolones inhibit gyrase and topo IV |
presence of food may delay absorption; also delay with metals.
Gets to all tissues including CSF and FETUS. Renal excretion mainly. phase I metabolism then glucuronic acid conjugation. |
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Moxifloxacin
3rd/4th generation fluoroquinolone |
hepatic metabolism and biliary excretion unlike other quinolones with renal excretion.
Added anaerobic coverage; poor Pseudomonas activity. should not be used for UTI. |
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2nd Generation, Fluoroquinolones (2)
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Ciprofloxacin and Ofloxacin
increased gram - activity; some gram + activity. Treats UTI, GI, STD, skin infections. particularly Pseudomonas. Good penetration into bone to treat gram - osteomyelitis |
biliary excretion also important for ciprofloxacin
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Quinolones/Fluoroquinolones: side effects
(antimicrobial) |
Not recommended for prepubertal kids or pregnant women due to possible arthropathy (cartilage toxicity).
Potentiation of warfarin, C. difficile colitis, CNS effects (dizziness, mood change, delirium, seizure) |
may inhibit theophylline metabolism leading to possible toxicity (Ciprofloxacin)
Fluoroquinolones can cause phototoxicity with UVA. Tendonitis/tendon rupture (avoid in pts on steroids or with renal failure) Contraindicated in pts with or at risk for QT prolongation too. |
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1st Generation Quinolone (1)
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Nalidixic acid.
narrow gram - spectrum. Restricted to treatment of UTI |
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3rd and 4th generation, Fluoroquinolones (2)
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Levofloxacin and Gatifloxacin
expansive gram+/- coverage; also treats atypical pathogens (mycoplasma and chlamydia). Targets streptococci, treats H. influenzae meningitis. |
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Antiprotozoan drug that forms free radicals leading to cell destruction. Is the drug of choice for Trichomoniasis, Giardiasis, Systemic E. histolytica infections.
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Tinidazole (oral)
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Distribute to all tissues including CSF.
metaolized by CYP3A4 and excreted in urine. is a mixed amoebicidal drug that is best to treat Active Intestinal and Systemic infections |
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Tinidazole: side effects
(anti-protozoan) |
well tolerated; GI upsets.
Metallic/bitter taste in mouth, anorexia. Rarely may get seizures, peripheral neuropathy, leukopenia, neutropenia. |
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Tinidazole and drug interactions
(anti-protozoan) |
Alcohol potential for disulfiram reaction (Tinidazole inhibits aldehyde dehydrogenase).
CYP3A4 inducers may decrease drug serum conc. while CYP3A4 inhibitors may increase conc. |
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Antiprotozoan drug that is an alternative to Tinidazole for treating Giardiasis. This drug has a similar mechanism but more GI distress than Tinidazole.
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Metronidazole
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Antiprotozoan drug that inhibits protein synthesis by binding to the 30S ribosomal subunit. It is used to treat luminal trophozoites and is the drug of choice for Asymptomatic Luminal Ambebiasis.
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Paromomycin (oral)
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poor absorption hence why this is used to eradicate trophozoites from the lower GI tract. Often given after a course of Tinidazole.
Excreted unchanged in feces. |
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Paromomycin: side effects and drug interactions.
(anti-protozoan) |
GI upsets, anorexia, cramps, epigastric pain.
Rarely can get headache & vertigo, oto- and nephrotoxicity |
Paromomycin decreases Digoxin serum conc. by 30-82% (a cardiac disease drug)
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Antiprotozoan drug that is now a second choice for treatment of Intestinal/Luminal Amebiasis due to rare adverse effects of optic atrophy and blindness.
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Iodoquinol
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Antiprotozoan drug that disrupts the energy metabolism of trypanosomes to kill them. This is the drug of choice for African Trypanosomiasis aka African Sleeping Sickness, but only in its early stages before CNS involvement.
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Suramin (IV)
given in combination with Pentamidine |
Does not get into CSF well. poor absorption hence the IV.
local tissue necrosis and inflammation keeps it from being IM. strong protein binding so it stays in the system for a long time. |
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Suramin: side effects
(anti-protozoan) |
significant toxicity from GI upset, urticaria, to photophobia and peripheral neuropathy.
Less common is kidney damage, blood dyscracias, shock |
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Antiprotozoan drug that functions by binding DNA or by inhibiting Topo II. It is used to treat T.b gambiense infections of African Trypanosomiasis aka African Sleeping Sickness, in its early stages without CNS involvement. It can also be used as an aerosol for prophylaxis against Pneumocystis in AIDS pts.
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Pentamidine (IV)
sometimes aerosols Given in combination with Suramin |
poor absorption, does not get to CNS.
70% protein bound in serum |
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Pentamidine: side effects
(anti-protozoan) |
50% --headache, dizziness, breathlessness, tachycardia.
24% --renal function impaired. Also can cause hypoglycemia/hyperglycemia, development of insulin dependent diabetes. |
NOT USED DURING PREGNANCY due to risk of spontaneous abortion.
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Antiprotozoan drug that reacts with sulfhydryl groups to inactivate enzymes, in particular, trypanothione reductase needed by trypanosomes to make trypanothione. This is the drug of choice for African Trypanosomiasis with CNS involvement.
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Melarsoprol (IV)
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Well absorbed, crosses to CNS.
renal excretion. mammals inactivate this drug faster hence the selectivity. |
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Melarsoprol: side effects
(anti-protozoan) |
extremely toxic!
encephalopathy, phlebitis, peripheral neuropathy, hypersensitivity to 2nd injections, hypotension, myocardial damage. |
hemolytic anemia in G6PD deficient pts.
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Melarsoprol resistance and secondary usage on Trypanosomes
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T.b. rhodesiense relapse can be treated again with this drug.
T.b. gambiense not cured the first time rarely will respond to a 2nd treatment. |
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Antiprotozoan drug that irreversibly inhibits ornithine decarboxylase, needed for DNA synthesis in trypanosomes. This is an alternate drug for the late stage of African Trypanosomiasis, with CNS involvement.
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Eflornithine (oral, IV)
*not effective on T.b. rhodesiense |
crosses to reach CSF, well absorbed.
Renal excretion. |
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Eflornithine: side effects and drug interactions
(anti-protozoan) |
anemia and leukopenia common.
diarrhea, thrombocytopenia, seizures, hearing loss less so. |
additive bone marrow suppression with marrow suppressant drugs.
additive ototoxicity with aminoglycosides. |
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Antiprotozoan drug that acts by producing free radicals to kill tryptomastigotes. It is the drug of choice for American Trypanosomiasis aka Chagas disease. Cures most cases of acute disease.
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Nifurtimox (oral)
*not effective on the amastigotes of the chronic stage of Chagas |
well absorbed, wide distribution.
Hepatic excretion. |
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Nifurtimox: side effects and drug interactions
(anti-protozoan) |
anorexia, vomiting, weight loss, ataxia, nystagmus, insomnia, dementia, seizure.
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alcohol may enhance the drug's CNS effects
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Antiprotozoan drug that inhibits energy metabolism, interfering with glycolysis and fatty acid oxidation to reduce the amt of ATP generated. This drug is the drug of choice for cutaneous and kala azar Leishmaniasis.
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Sodium stibogluconate (IV)
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must be administered repeatedly parenterally.
excreted in urine. |
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Sodium stibogluconate: side effects
(anti-protozoan) |
thrombophlebitis, abdominal pain, GI upsets, anorexia, myalgia, arthralgia, headache.
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Antimalarial drug that is a weak base, accumulating in acidic food vacuole and inhibiting polymerization of heme. Individual heme are membranolytic. Drug of choice for treating Malaria during the Erythrocytic phase.
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Chloroquine
*not effective for liver parasites like P. ovale and P. vivax. |
well absorbed and rapid distribution to tissues. Retained in liver, kidney, spleen.
Renal excretion. Can be used as prophylaxis during pregnancy. |
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Chloroquine: side effects and drug interactions.
(anti-protozoan) |
headache, vomiting, pruritus, skin eruptions, alopecia, exfoliate dermatoses.
Increase in QTc interval. Increase incidence of hemolytic anemia with the G6PD deficient. |
P. falciparum strains are becoming resistant.
Auminum and magnesium salts decrease absorption. Any drugs prolonging QTc may result in additive prolongation. |
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Antimalarial drug that accumulates in acidic food vacuoles and inhibits heme polymerization, leading to lysis, but is not a weak base. It is the drug to treat Chloroquine-resistant strains of P. falciparum in the erythrocytic stage of Malaria.
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Mefloquine
*not effective in exo-erythrocytic stage |
well absorbed, widely distributed including to CSF.
Hepatic excretion. |
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Mefloquine: side effects and drug interactions
(anti-protozoan) |
GI upsets, abdominal pain, dysphoria, dizziness.
50% --CNS effects like ataxia, alterations in motor function. Extrasystole, sinus bradycardia. Hemolysis with G6PD deficiency |
Additive suppression of cardiac conduction with certain drugs.
Avoid giving with other drugs that prolong QTc. Contraindicated in psychiatric and epileptic pts due to vivid dreams, acute psychosis, seizures. |
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Combination of two drugs used to treat Chloroquine resistant strains of Malaria in its erythrocytic stage.
One inhibits dihydrofolate reductase and the other inhibits dihydropteroate synthase. Same folic acid synthesis pathway is being blocked. Synergistic effect. |
Pyrimethamine (reductase inhibitor) and Sulfadoxine (synthase inhibitor)
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both well absorbed, metabolized in liver, renal excretion.
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Pyrimethamine and Sulfadoxine: side effects and drug interactions
(anti-protozoan) |
folic acid deficiency with megaloblastic anemia and pancytopenia.
hemolytic anemia (increased in G6PD), leukopenia, thrombocytopenia, allergic reaction, anorexia, GI upsets, headache, dizziness, insomnia Stevens Johnson Syndrome due to sulfonamide. |
Additive bone marrow suppression can occur with concurrent use of other drugs.
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Combination of two drugs that have synergistic effects to treat the erythrocytic cycle of Malaria. One is a selective inhibitor of parasite mitochondrial electron transport and the other is a dihydrofolate reductase inhibitor.
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Malarone --made up of Atovaquone (mitochondrial) and Proguanil (reductase inhibitor).
*proguanil is a prodrug metabolized to active cycloguanil metabolite. |
Both are given orally. Atovaquone is excreted in feces; Proguanil excreted in urine.
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Malarone (Atovaquone and Proguanil): side effects and drug interactions
(anti-protozoan) |
GI upsets, abdominal pain, anorexia, headache, dizziness.
NOT recommended for pregnant pts. |
Atovaquone levels decrease 40% with coadministration of Tetracycline, Rifampin, Metoclopramide.
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Antimalarial drug that interferes with pyrimidine synthesis and mitochondrial electron transport chain. Drug of choice for the Exo-erythrocytic cycle of Malaria. Treats P. ovale and P. vivax which have hepatic hypnozoites.
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Primaquine (oral)
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Metabolized by liver. Renal excretion.
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Primaquine: side effects and drug interactions
(anti-protozoan) |
hemolytic anemia in G6PD.
Neutropenia and Leukopenia incidence higher with a higher dose. Also GI upsets., abdominal pain. |
Additive bone marrow suppression if given with bone marrow suppressants
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Combination drugs for treatment of Chloroquine-resistant strains of Malaria. These two drugs are often given in conjunction with other anti-malarial drugs like Quinine.
These inhibit protein translation by binding 30S ribosome subunit, and are normally used to treat bacterial infections. |
Tetracycline and Doxycycline.
*doxycycline is also used as short term prophylaxis for travelers; is contraindicated for pregnant women and kids under 8 yrs. |
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Class of antimicrobial drugs that reversibly bind 50S ribosomal subunit and inhibit translocation of peptidyl tRNA. These are good against respiratory infections. Active against Strep sp. (gram + cocci), M. avium complex, H. influenza & Bordetella (gram - bacilli).
Not active against anaerobes, Enterococcus, Staphylococcus. |
Macrolides (oral, IV)
--Clarithromycin, Azithromycin |
wide distribution but poor CNS penetration.
Clarithromycin Renal and Fecal excretion. Azithromycin Hepatic excretion. |
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Clarithromycin: side effects and drug interactions
(antimicrobial) |
Macrolide!
GI upsets. |
it is metabolized in liver and inhibits P450 enzymes.
RESISTANCE: methylase modifies target sites on ribosome, increased efflux, esterase action on drug itself. |
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Azithromycin: side effects and drug interactions
(antimicrobial) |
Macrolide!
GI upsets, may increase QTc interval. No drug interactions since it does not interfere with P450 metabolism of other drugs. |
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This drug is Bacteriostatic in action, binding 50S ribosome subunit. It is active against most gram+ aerobic and anaerobic except Enterococcus, gram- anaerobes, MRSA, serious infections due to B. fragilis.
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Clindamycin (oral, IV, topical)
*use with aminoglycosides to treat infection from fecal spillage, like from a surgery... |
food does not interfere with absorption. Widely distributed including bone, NOT CSF.
Hepatic excretion through bile. |
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Clindamycin: side effects and drug interactions
(antimicrobial) |
AAPMC (C. difficile colitis) and neuromuscular blockade
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Use with neuromuscular blockers can increase apnea and respiratory paralysis.
RESISTANCE: methylase like macrolides. bacteria resistant to macrolides and chloramphenicol also resistant to clindamycin. |
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Called Synercid, the combination of these two drugs is synergistic and bactericidal. One binds to 50S ribosome subunit like macrolides while the other binds 50S at a nearby site.
Used to treat gram+ aerobic bacteria. Use is reserved for treating multi-resistant organisms like VRE; treats MRSA bone infections. |
Quinupristin (active site) and Dalfopristin (nearby site).
Given IV only! |
IV to a central vein (internal jugular, subclavian, femoral veins).
Hepatic excretion. |
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Quinupristin and Dalfopristin: side effects and drug interactions
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Phlebitis at injection site, arthralgias and myalgias.
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inhibits P450 enzymes (CYP3A4) and so enhances toxicity of some drugs.
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Antimicrobial drug that binds 50S ribosome subunit to prevent formation of the whole 70S complex. Used on gram+ and reserved as an agent of last resort to treat MRSA, MRSE, VRE. Poor activity against gram-
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Linezolid (oral, IV)
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70% CSF penetration.
Renal excretion. oxidized metabolite or excretes unchanged. |
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Linezolid: side effects, drug interactions, resistance.
(antimicrobial) |
mild reversible thrombocytopenia, anemia, leukopenia.
No cross resistance to other drugs. Resistance through mutation of 50S binding site. |
Drug is a weak MAO, enhances drug effects of serotonergic agents to cause Serotonin Syndrome.
Could also increase risk of hypertensive crisis in pts taking sympathomimetic drugs. |
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Antimicrobial drug that is bactericidal, inhibits pyrophosphatase to prevent incorporation of peptidoglycan (inhibit cell wall synthesis).
It is used topically for conjunctivitis and infected corneal ulcer. Also used to prevent infection in minor cuts, scrapes, burns. |
Bacitracin (topical mainly)
*active on gram+ and spirochetes, also some gram- like H. influenzae, Neisseria sp. |
not absorbed in GI but rapid/complete via IM. Not ever IV due to severe thrombophlebitis.
Good CNS penetration. Renal excretion (oral is fecal excreted). |
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Bacitracin: side effects, drug interactions
(antimicrobial) |
severe nephrotoxicity, so rarely (almost never) used systemically.
topical effects are rare |
Given parenterally can increase neuromuscular block by non-depolarizing muscle relaxants like tubocurarine.
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Antimicrobial drug that is cationic detergeant, binding lipids and altering osmotic barrier of cell membranes. Is bactericidal.
Used topically for skin, mucous membranes, eye and ear infections. |
Polymyxins (topical mainly)
*active on gram- organisms including Pseudomonas. Actinobacter *Not good for anaerobes. |
poorly absorbed from GI. dose adjustment needed for renal impairment.
does not get to CNS through IM/IV. |
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Polymyxins: side effects
(antimicrobial) |
serious neprhotoxicity, so probably not used systemically often.
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Antimicrobial drug that binds bacterial membrane and causes depolarization and loss of membrane potential, stopping OXPHOS and production of ATP. Is bactericidal.
Used to treat skin infections, acute bacterial endocarditis and bacteremias due to MRSA. |
Daptomycin (IV, oral)
*active against aerobic gram+ including Staph, MRSA, VRE, E. faecium/faecalis. *does not work for pneumonia because it is inactivated if bound to surfactant. |
cannot give IM due to dose dependent muscle destruction.
Renal excretion (dose adjustment needed for impairment). Wide distribution but not into CNS. |
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Daptomycin: side effects, drug interactions
(antimicrobial) |
constipation, nausea, headache.
monitor serum creatine phosphokinase levels to detect potential muscle damage. |
not really used IV either due to dose dependent muscle damage.
Statins use is recommended to be stopped during Daptomycin therapy. |
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Antimicrobial drug that inhibits cell wall synthesis by binding D-ala-D-ala and inhibiting cross linking to build cell wall. It is bactericidal (log phase only) for gram+ but bacteriostatic for Enterococcus unless given with aminoglycosides. Used for Staph infections on pts that are allergic to beta lactam.
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Vancomycin (IV, oral)
*not effective against gram- because cannot get through outer membrane. *normally reserved for serious infections (MRSA, MRSE). |
poor absorption. IV distributes to all compartments.
Gets into CNS only if meninges are inflamed. Intrathecal may be needed for effective levels. Renal excretion (dose adjust for impairment). |
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Vancomycin: side effects, drug interactions
(antimicrobial) |
hypersensitivity, red neck syndrome, phlebitis and pain at the site of injection.
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increases nephrotoxicity of aminoglycosides and polymyxin B.
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Antiviral drugs that are guanosine/guanine analogues missing terminal 3' OH needed for DNA chain elongation. Are phosphorylated by thymidine kinase and cause chain termination.
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Acyclovir --HSV1,2 and VZV
Gancyclovir --CMV reactivation in immunodeficient |
Acyclovir derivatives are more bioavailable and must be cleaved to become active drug.
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Antiviral drug that is an adenosine analogue.
Treats HSV of eye and HSV, VZV reactivation in immunodeficient. Less effective and more toxic than acyclovir. |
Vidarabine (Ara-A)
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Antiviral drug that is a thymidine analogue, where the methyl is replaced by iodine. Replaces dTTP and used topically against herpes keratitis.
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Iododeoxyuride
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Antiviral drug that is a deoxyribonucleoside analogue (thymine, fake dTTP). The methyl of thymidine is replaced by 3 fluoride ions instead of H atoms in this drug.
Used to treat herpes keratitis and is too toxic for systemic use |
Trifluorothymidine
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Acyclic Nucleoside Phosphonates --ANPs (3)
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Cidofovir
Adefovir Tenofovir |
are monophosphates, needs 2X phosphorylation by cell kinase to be active.
Targets DNA polymerase and are chain terminators for DNA synthesis. |
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Antiviral ANP drug, analogue of cytosine. Treats CMV retinitis in AIDS, is stockpiled for smallpox/monkeypox. Is Nephrotoxic.
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Cidofovir
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Used off label against molluscum contagiosum, adenovirus, HPV, BK and JC viruses.
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Antiviral ANP drug, analogue of adenosine. Treats Hep B infections.
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Adefovir dipivoxil
(prodrug) |
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Antiviral ANP drug, analogue of adenosine that treats HIV infection in combination with a nucleoside analogue. Also used to treat HBV.
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Tenofovir dipivoxil fumarate
(prodrug) |
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Antiviral drug, guanosine analogue that works by 4 mechanisms: immune system is more favorable towards Th1 response, inhibits IMP dehydrogenase/depletes GTP pool, substrate for polymerase to terminate chains, mutagen when incorporated into viral genome.
Used to treat HCV in combination with interferon, treats Influenza infections and RSV infections |
Ribavirin
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Antiviral drug that is a noncompetitive inhibitor of some DNA polymerases. It binds pyrophosphate binding site of enzyme. It is used to treat Herpes, Hep B, HIV but because it is too toxic it's only used in life-threatening situations
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Phosphonoformic acid (Foscarnet)
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accumulates in bone.
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Antiviral drug, a humanized mouse monoclonal antibody specific to L glycoprotein of RSV.
It neutralizes virus and used to treat RSV infection in infants, premature babies, immunocompromised. |
Palivizumab
*usually given with Ribavirin. |
given as IV prophylaxis in high-risk children
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Antiviral drug, peptide corresponding to COOH terminal of HIV envelope protein gp41. Inhibits fusion of HIV envelope with the cell membrane --no viral entry.
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Enfuvirtide
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needs 2X injections daily and causes severe reactions @ injection site. Resistance also developing
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Antiviral drug, substrate analogue (thymidine) to inhibit reverse transcriptase. It is phosphorylated by thymidine kinase and terminates DNA chain 100X more effectively on HIV reverse transcriptase.
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Azidothymidine (AZT)
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Toxic to bone marrow. Also causes headache, nausea, insomnia.
Resistance due to mutations in RT gene. |
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Nucleoside Reverse Transcription inhibitors (2) --these target the active site of RT as competitive inhibitors. Incorporation into cDNA and then chain termination.
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dideoxycytidine ddC
dideoxyinosine ddI |
No cross resistance with AZT.
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Antiviral drug that binds and causes conformational change in reverse transcriptase to inhibit activity. It's an allosteric inhibitor.
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Non-nucleoside Inhibitors of RT
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Antiviral drugs that are peptidomimetic HIV protease inhibitors. They mimic the transition state formed by hydrolysis of peptides. Prevents polyprotein cleavage in HIV, so virus does not replicate.
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Saquinavir
Indinavir |
potentially active against all viruses with essential protease
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Antiviral drug that is a non-peptidomimetic HIV protease inhibitor. It is active against strains resistant to other protease inhibitors. This drug binds to the active site of HIV protease.
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Tipranavir
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This is a small molecule inhibitor of HIV integrase; HIV cDNA is not intergrated into cellular DNA.
This drug is used in combination therapy for pts with resistance to other HAART drugs. |
Raltegravir
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Resistance develops quickly if used as monotherapy.
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This is a common first line treatment drug for HIV infection. It is a combination drug, combining different mechanisms into one pill...
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Atripla
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Antiviral drugs (2) that are ion channel blockers. These block M2 of the influenza A virus preventing H ions from entering the virion. This blocks HA-mediated fusion of viral envelope with endosome membrane.
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Amantadine
Rimantadine |
Resistance with mutations in M2.
Does not work on Influenza B because B does not have M2 channel. |
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Antiviral drugs that are neuraminidase inhibitors (2), treating influenza.
These bind/plug active site of neuraminidase to prevent release of virion buds from host cell surface and from each other. |
Zanamivir (Relenza, inhaled)
Oseltamivir (Tamiflu, oral) *reduces severity and duration of symptoms |
these are effective for both Influenza A and B.
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This antiviral drug is not virus specific. It is produced from a signal transduction pathway and then activates Jak/STAT to activate antiviral genes.
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Interferon alpha/beta.
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antiviral proteins: Protein kinase R inhibits protein synthesis and 2-5A synthetase activates RNaseL to degrade RNA.
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Most common/important use of Interferon
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Combination treatment with Ribavirin for HepC.
*IFN is usually pegylated for longer half-life and better pharmacokinetics. |
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Antiviral drugs (2) targeted to HCV protease. To be used with pegylated IFN + Ribavirin.
These are specific for HCV type 1 and increase cure rate by 20% |
Telaprevir
Bocceprevir |
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Antihelminthic drug that inhibits uptake of glucose and uncouples OXPHOS. It binds beta-tubulin and blocks microtubule polymerization to immobilze and expel dead parasites from GI.
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Mebendazole (oral)
*drug of choice for T. trichiura, A. duodenale, N. americanus, A. lumbricoides. |
poor absorption, feces excretion.
side effects = abdominal pain, diarrhea also effective for GI phase of T. spiralis and for E. vermicularis |
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Antihelminthic drug that acts to inhibit uptake of glucose and uncouples OXPHOS. It bind beta-tubulin. It is an oral drug and needs a fatty meal in order to absorb. It can enter CNS.
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Albendazole (oral)
*drug of choice for A. duodenale and N. americanus (hookworms), GI phase of T. spiralis, A. lumbricoides. *drug of choice for T. solium cysticercosis |
Renal excretion.
It is increased with concurrent use of Dexamethasone or use of Praziquantel. |
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Albendazole: side effects
(anti-helminthic) |
Short term: GI upsets, dizziness, headache, abdominal pain
Long term therapy: increase in serum amino transferases (ALT, AST) and rarely see jaundice & cholestasis. |
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Antihelminthic drug that is a depolarizing neuromuscular blocking agent. Acts as agonist to cause persistent activation of nicotinic ACh receptors.
Worms are paralyzed and expel from GI. |
Pyrantel pamoate (oral)
*drug of choice for E. vermicularis *also used on A. lumbricoides and the hookworms. |
Feces excretion.
Cannot give with Piperazine (GABA agonist) because this drug is opposite in action; antagonistic! |
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Pyrantel pamoate: side effects
(anti-helminthic) |
GI intolerance, headache, insomnia, hypersensitivity.
Very high doses, >1g, can cause neuromuscular blockade in host. |
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Antihelminthic drug that sensitizes the worm to phagocytosis by fixed macrophages of reticuloendothelial system. Used to treat systemic helminth infections: O. volvulus and W. bancrofti (combo with Albendazole). Also treats infections of skin and lymphatics.
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Diethylcarbamazine (oral)
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Renal excretion.
Toxicity may increase with decreased renal clearance in alkaline urine caused by alkalinizers = sodium lactate, sodium bicarbonate |
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Diethylcarbamazine: side effects
(antihelminthic) |
Serious inflammatory reaction to released proteins from phagocytosed filarieae: Mazzotti reaction.
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O. volvulus = chorioretinitis, pruritus, fever, wheezing, hypotension, tachycardia
W. bancrofti = swelling or nodules may develop along lymphatics, transient lymphedema. |
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Antihelminthic drug that activates glutamate gated and GABA gated chlorine channels to cause tonic paralysis of muscle. Used to treat W. bancrofti (combo with Albendazole), O. volvulus, S. stercoralis.
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Ivermectin (oral)
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give on empty stomach.
Hepatic excretion. |
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Ivermectin: side effects
(antihelminthic) |
Mazzotti reaction: pruritus, hypotension, fever, bone and joint pain.
High doses or a damaged brain barrier could result in CNS toxicity: tremors, ataxia, lethargy |
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Antihelminthic drug that increases permeability of membrane to cations (calcium) to cause severe muscular contractions.
It directly kills schistosomes; treats Schistosomiasis (systemic). It does not kill cestodes but dislodges them from their residence in the GI tract; treats cestodes in the GI tract. |
Praziquantel (oral)
*effective against T. solium, T. saginata, D. latum, H. nana, all schistosomes. *alternative for T. solium cysticercosis |
metabolized by P450 (dose adjust for depressed liver function).
Renal excretion. Contraindicated for pts with ocular cysticercosis (needs surgery). |
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Praziquantel: side effects and drug interactions
(antihelminthic) |
Best to avoid during pregnancy.
Dizziness, headache, drowsiness, GI upsets. |
Macrolides and HIV protease inhibitors increase serum conc.
Phenytoin, Rifampin, Nevirapine, Phenobarbital, Carbamazepine, Efavirenz may decrease serum conc. |
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Antifungal drug that binds ergosterol in cell wall, forms pores in membrane, and allow electrolytes to leak causing death. Fungicidal.
Drug of choice for most systemic fungal infections. |
Amphotericin B (IV, topical)
*major side effect is Nephrotoxicity --monitor creatine |
Does not enter CNS. Intrathecal injection needed for fungal meningitis.
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Oral and topical antifungal used to treat Candida, cutaneous mycoses --oral or vulvovaginal candidiasis.
It is toxic if given IV. A polyene like Amphotericin B |
Nystatin
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Antifungal that is a prodrug. It enters cells through permease, converted to 5-FU by cytosine deaminase which is not found in human cells, and inhibits fungal DNA synthesis. It is effective against systemic mycoses like Candida, Cryptococcus, Aspergillus.
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5-fluorocytosine (5-FC) --oral drug
*used with amphotericin B because monotherapy results in high resistance |
Side effects: elevated hepatic enzymes, bone marrow suppression, hemotological, GI disturbance.
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Antifungal drug class that inhibits the reaction Lanosterol to Ergosterol.
Two types... |
Azole class.
Imidazoles include Ketoconazole, Miconazole and Clotrimazole (too toxic for systemic, only topical) Triazoles include Fluconazole, Voriconazole, Itraconazole, Posaconazole |
all azoles ...
Are metabolized by and affect CYP enzymes. many drug reactions! Should be avoided during pregnancy. Cause hepatic dysfunction. |
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Ketoconazole (oral, topical): spectrum and side effects
(antifungal) |
Does not penetrate CNS.
Broad spectrum against Histoplasma, Blastomyces, Dermatophytes, Coccidioides, Paracoccidioides. Candida, Cryptococcus. |
Side effects include ...
Gynecomastia Inhibit testosterone & cortisol production. Gi distress. |
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Fluconazole (oral, IV): spectrum and side effects
(antifungal) |
Penetrates CNS.
Effective against Candida. Cryptococcus, Coccidioides, Histoplasma. Given to AIDS pts to prevent relapse of meningitis. |
Headache, Nausea, Rash.
no steroid metabolism interference. P450 interactions |
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Voriconazole (oral, IV): spectrum and side effects
(antifungal) |
Drug of choice for Aspergillus.
Penetrates CNS. also effective for Candida. |
Visual disturbances, hepatotoxicity, skin rash.
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Itraconazole: spectrum
(antifungal) |
the one Triazole that does not penetrate the CNS.
Effective for Histoplasma, Sporothrix, Aspergillus. |
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Antifungal drug that inhibits cell wall biosynthesis by inhibiting beta (1,3)-glucan synthesis. Very costly though.
Effective against Aspergillus and Candida. |
Echinocandins like Caspofungin.
(also Micafungin, Anidulafungin) *relatively few side effects |
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Antifungal drug that inhibits microtubule function so prevents mitosis. It accumulates in keratin of skin and hair, making them resistant to fungal infections.
Effective against dermatophytes; used in a variety of tinea infections. |
Grisans like Griseofulvin (oral)
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major side effects: hepatotoxic, headache, bone marrow suppression, GI irritation.
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Antifungal drug that inhibits squalene epoxide needed in ergosterol synthesis. Fungicidal.
Used in treatment of tinea infections, particularly onychomycoses. |
Allylamines like Terbinafine aka Lamisil (oral and topical)
others include Butenafine, Natilafine. |
Side effects are rare: GI upset and headache.
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Antimycobacterial drug that targets fatty acid synthase II to inhibit synthesis of mycolic acid that's needed in cell wall. Is bactericidal during the log phase of growth and bacteriostatic in resting organism.
Used to treat M. tuberculosis, M. kanasaii |
Isoniazid (oral)
*also used as prophylaxis but not for those over 35 or with liver disease |
given daily. is acetylated so polymorphisms exist in the population (fast vs. slow acetylators).
Diffuses to all fluids including CSF. Renal excretion. |
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Isoniazid: side effects
(antimycobacterial) |
Jaundice and Hepatic injury = hepatotixicity increases with age.
Can also cause peripheral neuritis if Pyridoxine B6 is not given concurrently. |
Alcohol and Rifampin increases hepatotoxicity risk.
Resistance from mutation of catalase-peroxidase decreasing drug activity. |
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Antimycobacterial drugs (2) that function by inhibiting DNA dependent RNA polymerase. They block the initiation of RNA chain.
Treatment of M. tuberculosis, M. kansasii, M. avium complex, M. leprae, M. marinum. Also bactericial against gram+/- and can treat MRSA. Also treats asymptomatic carriers of N. meningitidis. |
Rifampin and Rifabutin (both oral)
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Gets into CNS. metabolized by liver
Rifampin hepatic excretion Rifabutin renal excretion Resistance: mutation of enzyme is high if used as monotherapy. |
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Rifampin and Rifabutin: side effects, drug interaction
(antimycobacterial) |
imparts orange-red color to body fluids coming out.
anemia, fever, thrombocytopenia Rifampin causes hepatitis in pts getting isoniazid or who are alcoholics/have a history of liver disease. |
Rifampin is a substrate and potent inducer of CYP3A4, also induces other CYPs.
Rifabutin is used in HIV pts instead to decrease the CYP inducing. Decreases efficacy of oral contraceptives, glucocorticoids, anticoagulants like coumarin, methadone, HIV protease inhibitor. |
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Antimycobacterial drug that may inhibit mycolic acid incorporation. It is effective for M. tuberculosis, M. kansasii, M. avium complex, M. marinum.
Is a bacteriostatic drug, does not distribute to the CNS (unless meninges inflamed) |
Ethambutol (oral)
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metabolism in liver and renal excretion (dose adjust for renal impairment)
Use with Ethionamide may increase adverse effects. |
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Ethambutol: side effects
(antimycobacterial) |
Optical Neuritis! visual acuity and red-green discrimination need to be tested.
Could also get acute attacks of gout due to inhibition of uric acid excretion. |
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Antimycobacterial drug that targets fatty acid synthase I involved in mycolic acid synthesis. It is bactericidal. This drug is not used as monotherapy because resistance is too fast. It is used to treat M. tuberculosis.
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Pyrazinamide (oral)
*similar to isoniazid) |
good CSF penetration. Renal excretion.
Metabolized to active metabolite pyrazoic acid in liver. Ethionamide may increase hepatotoxicity. |
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Pyrazinamide: side effects
(antimycobacterial) |
Major hepatotoxicity so use is recommended for short term (max 6 mo.).
Not given to pts with hepatic function impairment. Frequent mild polyarthralgias and hyperuricemia |
Occasional GI intolerance and gout.
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Antimycobacterial drug that binds DNA and intercalates to inhibit DNA template function. Is bactericidal for some. used to treat M. leprae.
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Clofazimine (oral)
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Gets into CNS. Hepatic excretion. Unabsorbed drug is feces excreted.
NOT RECOMMENDED FOR PREGNANCY, esp. in 1st trimester. Drug also comes out with breastmilk. |
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Clofazimine: side effects, drug interactions
(antimycobacterial) |
Pink to brown discoloration of skin, cornea, retina, urine.
Dry skin and GI upsets |
Aluminum and magnesium containing antacids may decrease absorption.
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Antimycobacterial drug that is a sulfonamide type. It inhibits dihydropteroate synthase activity and blocks synthesis of tetrahydrofolate. Used to treat M. leprae.
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Dapsone (oral)
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Hepatic metabolism and Renal excretion.
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Dapsone: side effects, drug interactions
(antimycobacterial) |
like sulfonamides. Hemolysis with G6PD, Steven Johnson's syndrome. GI upsets.
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Rifampin decreases serum levels.
Primaquine increases hemolytic risk for G6PD deficient. Dapsone decreases effectiveness of oral contraceptives. |
