Pharm - Drugs for Infections II
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- Penicillins
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- weaken cell wall
- causes bacteria to take up excessive water & rupture
- BACTERICIDAL - Types of allergic reactions
-
1. Immediate: 2-30 mins
2. Accelerated: 1-72 hours
3. Late: days or weeks - Anaphylaxis Reactions:
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- Laryngeal EDEMA (swelling)
- bronchoCONSTRICTION
- severe HYPOTENSION (low blood pressure) - Treatment for penicillin allergies
-
1. Benedryl (Diphenhydramine)
2. Epinephrine
3. Respiratory support
4. Prevention - skin testing
**caution with cephalosporins (also risk of being allergic) - Vancomycin, Erythromycin, Clindamycin - Most widely used group of antibiotics:
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Cephalosporins
- beta-lactam antibiotics
- similar to penicillin structure
- bactericidal
- broad spectrum
- usually given parentally
- low toxicity (less allergies than penicillins) - Cephalosporins have same MOA as penicillins
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- binds to PBP's (penicillin-binding proteins)
- disrupt cell wall synthesis & activate AUTOLYSINS to cut cell walls
- cell death results from lysis - Penicillin G (Benzylpenicillin)
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- IV, IM ONLY (acid instability)
- distributed to most tissues (INFLAMMATION = distribution to joints & meninges)
- Toxicity risk: KIDNEY disease (leaves kidneys unchanged)
- NARROW spectrum
- penicillinase sensitive
- inhibits TRANSPEPTIDASES (enzyme that makes peptidoglycan strands stronger by cross-linkage)
- activates bacterial AUTOLYSINS
- bactericidal to gram positive - 3 factors that cause bacterial resistance to penicillins:
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1. inability of penicillins to reach their target's (PBPs)
2. Inactivation of penicillins by bacterial enzymes
3. Production of PBPs that have a low affinity for penicillins (MRSA) - Penicillin G (Benzylpenicillin) Uses:
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Gram Positive Cocci causing:
- pneumonia
- meningitis
- pharyngitis
- Staph. Aureus
- gas gangrene
- tetanus
- syphilis
- PREVENTATIVE for BACTERIAL ENDOCARDITIS - Difference between Penicillin salts
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1. Potassium Pen G (rapid absorption)
2. Procaine Pen G
3. Benzathine Pen G (low levels that last weeks: only useful against highly sensitive organisms) - Penicillin Allergies
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Types:
Intermediate (minutes)
Accelerated (hours)
Late (day or weeks)
- no prior exposure necessary - Anaphylaxis adverse reactions to Penicillin
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1. Laryngeal EDEMA (swelling)
2. BRONCHOconstriction
3. HYPOTENSION (severe) - low BP - How to treat penicillin allergies (or cephalosporin)
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- benedryl (diphenhydramine)
- EPINEPHRINE (stabilize mast cells & causes bronchodilation)
- respiratory support
- prevention (skin testing) - Penicillin V
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- similar to Pen G
- can be given ORALLY (greater acid stability than Pen G)
- take with food (reduces irritation to gut)
- CAUSES: DIARRHEA (poorly absorbed)
- NARROW spectrum - Broad Spectrum Penicillins (AMINOPENICILLINS)
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1. Ampicillin
2. Amoxicillin - What are the uses for Ampicillin?
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- E. Coli
- Salmonella
- Shingella
- H. Influenzae
- enterococcus faecalis - What are the side effects of Ampicillin?
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- Rash
- Diarrhea
***Occur more frequently with Ampicillin than any other penicillin - What are the routes for Ampicillin & Amoxicillin?
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Ampicillin = IV (acid instability)
Amoxicillin = PO (greater acid stability) - What are the uses for Amoxicillin?
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SAME as ampicillin
- E. Coli
- Salmonella
- Shingella
- H. Influenzae
- enterococcus faecalis - What are the side effects of Amoxicillin?
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***AMOXICILLIN is absorbed more
- LESS diarrhea compared to ampicillin
- Extended-Spectrum Penicillins
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ANTIPSEUDOMONAL penicillins:
1. Piperacillin
2. Ticarcillin - Piperacillin (ANTIPSEUDOMONAL penicillin)
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- IM/IV ONLY (not absorbed orally)
PRIMARY TARGET: PSEUDOMONAS AERUGINOSA
- often used in IMMUNOCOMPROMISED patients
- difficult to eradicate
- What drug is Piperacillin (Antipseudomonal) often combined with?
- AMINOGLYCOSIDE (Gentamicin)
- 1st Generation Cephalosporins
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- Most common PRE-OPERATION drug
- Used for GRAM POSITIVE infections
- Mild penicillin allergy
- LOW access to CSF
- HIGH sensitivity to beta-lactamases - 3rd Generation Cephalosporins
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- most common for NOSOCOMIAL infections
- used for GRAM NEGATIVE infections
- HIGH access to CSF
- high RESISTANCE to beta-lactamases - Antimicrobial Uses (1st generation to 4th generation)
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- increasing activity against gram-negative
- increasing resistance to destruction by beta-lactamses
- increasing ability to reach CSF - Adverse effects of Cephalosporins:
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- DISULFIRAM-like reaction (*unpleasant effects when ALCOHOL is consumed - vomiting/GI distress)
- bleeding (interferes with Vitamin K)
- thrombophlebitis at IV site - Vancomycin Uses:
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- pseudomembranous colitis (C. diff)
- MRSA
- streptococcus and staphylococcus
- serious infections
- used as "last resort" - Vancomycin
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- only used for serious infections and if patient is allergic to penicillins
- DOES NOT contain beta-lactam ring (therefore, it does not bind with PBP's)
- binds to molecules that are precursors for cell wall biosynthesis - Vancomycin Adverse Effects:
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OTOTOXICITY (toxic to hair cells in inner ear)
- toxicity risk: kidney disease (leaves kidneys unchanged; same as Pen G & V)
- thrombophlebitis
**give SLOWLY by IV ONLY - MOA Aminoglycosides (Gentamycin)
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bind to 30S ribosomal subunit which blocks initiation of protein synthesis and terminates synthesis (causes misreading of genetic code)
- synthesis of faulty proteins (bactericidal) - Uses of Aminoglycosides (Gentamicin)
-
- Serious infections of ANAEROBES
- gram negative
- NARROW SPECTRUM
- E. Coli
- pseudomonas
- CANNOT KILL ANAEROBES (need O2 to cross cell wall) - Which aminoglycoside can be given pre-op GI surgery?
- Neomycin
- How should doses of Aminoglycosides (Gentamicin) be given?
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better to give ONCE-DAILY dose than divided doses
*divided doses can cause washout because of frequent low levels - Monitor serum blood levels when giving Aminoglycosides (Gentamicin)
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- timing is important
- peak levels (highest blood level achieved from a dose - should be within therapeutic range) - 30 mins after IM injection or right after 30 min IV infusion)
- trough levels (lowest blood level achieved before giving the next dose should be low enough to achieve washout of kidneys & hair cells of cochlea in ear) - if divided doses, check blood levels just prior to next dose; if once-daily, draw sample, 1 hour prior to next dose
****NOTE: if trough is too high, next dose may become toxic!!
- Adverse effects of Aminoglycoside (Gentamicin)
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1. OTOTOXICITY (damage to hair cells within cochlea of inner ear which disrupts balance, causes tinnitus, and hearing impairment)
- due to excessive trough levels
2. NEPHROTOXICITY
injury to proximal renal tubules leads to ACUTE TUBULAR NECROSIS (ATN) causing high levels of BUN (uric acid) & creatinine (kidney becomes unable to concentrate or filter urine - dilute; with proteinuria)
- due to excessive trough levels (tight prolonged binding of drug to renal tissue)
* drugs are not metabolized (excreted intact) - Determinants of risk for wound infection
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1. number of bacteria at the surgical site at the time of surgery (pre-op shaving, pre-op baths using antiseptic, GI or GU surgery)
2. Pre & Intraop factors: (length of hospital stay prep, duration of surgery, surgeon's skill in minimizing tissue trauma)
3. Patient factors (nutritional status, infection at other sites, diabetes, use of immunocompromised drugs)
4. Improving tissue oxygenation (controlling pain, reducing stress, reducing caffeine, eliminating nicotine, ensuring adequate circulatory volume)
5. Providing adequate nutrients
6. Managing Diabetes - Wound Care Products
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1. Normal Saline
2. Povidone-Iodine
3. Hydrogen Peroxide - Normal saline as a wound care product
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- Benefits: mechanical cleanser (won't damage new cells or good bacteria)
- Risks: None - Povidone-Iodine as wound care product
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- Benefits: slowly release iodine; antiseptic
- Risks: toxic to FIBROBLASTS, WBCs, MICROBES *can cause iodine toxicity & for use on intact skin only - Hydrogen peroxide as wound care product
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Benefits: weak antiseptic; effervescent action - mechanical cleanser
Risks: can break up new clots - Vitamin C for the common cold
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- Vit C is important in collagen synthesis
- strong collagen may impede virus entry into cells
- no evidence that it prevents cold
- Vit C can decrease length & severity of a cold
- antioxidant (may decrease inflammatory effects of free radicals) - Combining cold remedy products
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- increases risk of side effects
- increase inappropriate usage
- use single specific preparations - Antipyretic cold remedy, actions, effect and problems
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Acetaminophen:
Action: hypothalamus heat-regulating centre
Effect: decrease discomfort & complications
Problems: decreased monitoring mechanism - Decongestant cold remedy, action, effect and problems
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Dristan - pseudophedrine
Action: stimulates alpha receptors which cause vasoconstriction
Effect: decreased nasal edema, congestion, post-nasal drip, and cough
Problems: sympathomimetic (increased HR, BP) and increased rebound congestion - Antihistamine cold remedy
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Benadryl
Action: H1 receptor antagonist
Effect: drowsiness and dry mouth
Problems: Not indicated - Expectorant cold remedy
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Guaifenesin
Action: reflex outflow of respiratory fluids
Effect: increased amount & fluidity of secretions
Problems: increased inappropriate use (fluids work best) - Dextromethorphan cold remedy
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Robitussin
Action: suppresses cough reflex in the CNS - opioid derivative
Effect: suppresses cough
Problems: only if DRY & irritating; if losing sleep - Nyquil
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dextromethorphan (cough suppressant)
decongestant
acetaminophen
alcohol
sugar