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Antibiotic Selection
- Patient history
- site of infection
- Likely causative agent (get culture)
- Lab results (WBC level, etc.)
- Isolation and Identification (gram stain; culture from sputum, wound, urine, blood, stool)
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Bactericidal
chemical substances that KILL microorganisms
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bacteriostatic
chemical substances that SUPPRESS growth of microorganisms
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Major principles
- -kill the bugs, not the host is the idea
- -select the narrowest spectrum agent possible
- -Less impact on the good/beneficial bacteria in the body
- -Killing everything leads to antibiotic resistance (those partially killed will evolve or things normally beneficial may become pathological)
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Two major categories of drugs
- Work over time: dosing around clock, must keep even concentration of drug over several days, and needed for "thick cell" (Gram +) bacteria
- Concentration dependent: Need enough to destroy DNA of bacteria; can be a once or twice daily dosing
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Administration
- Oral most common
- IM when shorter term administration (deltoid or gluteus for best absorption and least irritation)
- IV for most serious infections (must be given w/in 1/2 hour of designated due time (imp to keep specific level in blood)
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Superinfections
- those that occur during or after admin of antimicrobial therapy
- most common w/ broad spectrum antibiotic that also affects normal flora
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Penicillins
- Prototypes: penicillin G and V, methicillin, ampicillin
- Action: act on developing bacterial cell wall making it susceptible to osmotic pressure and it explodes
- -most effective against gram + bacteria
- -contain a beta-lactam ring that is essential to its antibiotic abilities (B-lactam group)
- Side effects: allergic rxns (<5%) like hives, fever, chills, GI: N/V/D, Renal
- PCN is easily excreted from kidneys; If given w/ Probenecid (drug that increases uric acid excretion in the urine), excretion of PCN is blocked (HELPFUL interaction!)
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Aminopenicillins
- Prototope: Ampicillin amoxicillin
- Indications: Useful in selected gram-neg bacteria so broader spectrum but not penicillinase (enzyme produced by bacteria that inactivate penicillin) resistant
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Cephalosporins
- chemical modifications of the penicillin structure (inhibits cell wall synthesis)
- Divided into 4 generations
- SE: GI, superinfections, allergic rxn, candidiasis, rash, edema
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Macrolides
- Prototypes: erythromycin, azithromycin (Zithromax), clarithromycin (Biaxin)
- Inhibit protein synthesis (bacteriostatic)
- Indications: oral and topical, drug of choice for many respiration infections; one of least toxic and few allergies
- SE: GI symptoms
- Foods can decrease absorption (but have to b/c people get queasy)
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Vancomycin (Vancocin)
- Binds to cell wall precursors, leads to cell lysis (bactericidal)
- Used for serious staph infections of bone, joint, septicemia, MRSA strains, prophylaxis for endocarditis
- SE: N/V, metallic taste, "red neck" syndrome (histamine flush) if IV admin too rapid
- -peak and trough med
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Aminoglycosides
- SE: nephrotoxicity, ototoxicity (kills sensory cells of inner ear)
- Overdose: Neuromuscular blockade; CHECK drug levels (peak and trough at certain times) by drawing blood for levels... results determine when next dose will be administered
- Gentamicin is an aminoglycoside antibiotic, used to treat many types of bacterial infections, particularly those caused by Gram-negative organisms.
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Tetracycline
- Prototype: tetracycline & doxycycline
- Inhibits protein synthesis (bacteriostatic)
- Indications: Chlamydia, Lyme disease, Acne
- Oral ONLY.. do NOT mix with milk, antacids, or iron supplements
- Contraindications: pregnant and breastfeeding women, children under 8 (permanent staining of teeth and decreases growth)
- SE: most common is GI tract (local irritation and oral candidiasis and Oral candidiases), Photosensitivity
- Class very useful in RARE things (Plague, Cholera, Atypical bacteria, rabbit fever)
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Fluoroquinolones
- Prototype: ciprofloxacin (Cipro)
- synthetic, broad spectrum, bactericidal by altering bacterial DNA
- Wide distribution in body (used for pseudomonas, anthrax)
- Popular for UTIs, but not anymore.. saving for bigger problems
- Makes tendons rupture, weaker, ache, pain
- Can't take with Ca, Zn, Fe, Al, or Mg
- Never given to pregnant patients of children!
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Sulfonamides
- Prototype: TMP-SMX (Bactrim)
- Synthetic
- interfere with bacterial enzymes
- Bacteriostatic
- Interferes with folic acid metabolism
- good absorption, take on empty stomach
- Indications: used for UTIs and MRSA
- *A lot of people are genetically allergic to sulfa drugs.
- SE: GI, bone marrow toxicity, allergic rxns common, hematologic effects if long-term therapy, Steven's Johnson Syndrome
- Must drink a lot of water with sulfa drugs
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Antiviral drugs
- Used alone or in combination
- Indications: Herpes simplex 1 (cold sore), herpes zoster (shingles), genital herpes (herpes simplex ll), varicella, influenza, RSV, HIV
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Herpes and Varicella
- Prototypes: acyclovir (Zovirax), famciclovir (Famvir)
- Action: interferes with DNA replication
- Use: needs to be initiated w/in 24 hrs of onset of s/s
- available in PO, IV, and topical forms
- Poor absorption PO, so you're taking a lot more than being used at cellular level
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Influenza
- Prototype: amantadine
- Action: Blocks uncoating of the influenza A (not B or swine or chicken flus) virus and the release of viral nucleic acid into host cell
- Rapid absorption, wide distribution (crosses BBB)
- Viruses have gotten smart and now resistant to this med... now have tamiflu.
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Oseltamivir (Tamiflu)
- In news as Bird Flu drug
- Start as early as possible (probably wont' work)
- Take even if feel better
- NOT a substitute for a flu shot
- May decrease length of illness by a day
- now last year's flu and bird flu are resistant
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HIV
- composed of RNA which is translated to DNA by reverse transcriptase enzyme in order to reproduce
- Integrated DNA then becomes part of the cell's DNA and produces proteins for assembly of new HIV
- Cannot be cured.. only suppress symptoms
- Drugs used: reverse transcriptase and protease inhibitors
- Ongoing HIV replication leads to immune system damage and progression to AIDS
- Plasma HIV RNA levels (viral load) indicate magnitude of HIV replication and its rate of CD4 T-cell destruction (CD4 counts tell us extent of damage); some cocktails may make viral load = 0, but will come back if stop meds
- At minimum therapy begins when CD4 count <500 or plasma HIV RNA levels >5,000-100,000
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SE of HIV medication
- Lactic acidosis: can be fatal - N & V
- Lipodystrophy syndrome (fat distribution, hepatotoxic, peripheral neuropathy, pancreatitis, fatigue)
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Drugs used in treatment of Opportunistic infections
- Anti-TB meds (anti-virals make you more susceptible to TB)
- Anti-fungal meds (thrush, severe vaginitis, severe rashes)
- anti-herpes drugs
- chemotherapy (more likely to get cancer on HIV drugs)
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