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71 Cards in this Set
- Front
- Back
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Drugs that fall into this category
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Antibiotics
Antifungals Antivirals Antiprotozoals |
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Effective Anti-microbial Therapy
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1. Accurate diagnosis
2. Appropriate drug choice (selective toxicity) 3. Appropriate treatment strategy 4. Informed follow up |
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Appropriate drug choice considerations
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1. Identify likely organism (empirically and maybe lab$$)
2. The site of infection - route of admin - mode of admin - inflammation can reduce "natural barriers" 3. Drug safety profile (toxicity and allergies) 4. Cost |
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The principles of selective toxicities
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- based on differences between bacterial and mammalian cells and cellular activity
1. CW 2. CM 3. Ribosome size 4. Internal synthesis of folic acid 5. DNA gyrase |
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"cidal" agents vs "static" agents
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static
- less potent - used for minor/mod infections Cidal - more potent - only used in critical conditions |
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Anti-bacterial resistence.
What is it. How? |
- represents a physiological adaptation
- by mutation or transfer via plasmid |
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Transfer of antibiotic resistance
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Transformation
Conjugation Transduction |
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Mechanism of antibiotic resistance
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1. Enhance exit or block entry
2. Degrade drug 3. Inactivate drug by blocking its active site |
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Majority of the antibiotics available today
a. Spectrum b. gental/aggressive why? |
a. extended spectrum, if not broad
b. aggressive; also pt must be compliant to eliminate resistance |
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Anti-bacterial Product Selection
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1. Clinical presentation guides the diagnosis
2. Selective Toxicity and Resistance (spectrum of activites, lieklihoods of susceptability and resistance) 3. Allergy (most common ADR and reason for premature tx termination) 4. Route/mode of admin - solution and susp for conjunctiva and cornea - ointment for external lids/lid margins - oral for internal lid infections 5. Others - amt of discharge |
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Anti-bacterial resistence.
What is it. How? |
- represents a physiological adaptation
- by mutation or transfer via plasmid |
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Transfer of antibiotic resistance
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Transformation
Conjugation Transduction |
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Mechanism of antibiotic resistance
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1. Enhance exit or block entry
2. Degrade drug 3. Inactivate drug by blocking its active site |
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Majority of the antibiotics available today
a. Spectrum b. gental/aggressive why? |
a. extended spectrum, if not broad
b. aggressive; also pt must be compliant to eliminate resistance |
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Anti-bacterial Product Selection
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1. Clinical presentation guides the diagnosis
2. Selective Toxicity and Resistance (spectrum of activites, lieklihoods of susceptability and resistance) 3. Allergy (most common ADR and reason for premature tx termination) 4. Route/mode of admin - solution and susp for conjunctiva and cornea - ointment for external lids/lid margins - oral for internal lid infections 5. Others - amt of discharge |
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Evaluating Effectiveness of Antibiotic Agents
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1. Sensitivity of organism to drug by MIC 90 (minimum inhibitory concentration to inhibit its growth); measure of potency
2. Concentration of drug at site of infection 3. Kill rate 4. Inhibitory Quotient (IQ) - integrates potency and tissue penetration to predict effectiveness of antibiotic against a particular infection |
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Mechanism of Action of Antibacterial Agents
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1. Inhibit CW
2. Inhibit CM 3. Inihbiti protein synthesis 4. Inhibit folic acid synthesis (metabolism) 5. Inhibit DNA synthesis |
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Drugs that affect CW synthesis
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Penicillin
Cephalosporins Bacitracin Vancomycin |
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Drugs that affect CM
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Polymyxin B
Gramicidin - act as detergent |
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Drugs that affect protein synthesis
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Aminoglycosides -30s
Tetracyclines -30s Macrolides -50s Chloramphenicol -50s Clindamycin -50s |
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Drugs affecting Folic Acid Synthesis
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Sulfonamide - competitively inhibit the conversion of PABA (no good if in pus --> lots of PABA)
Pyrimethamine Trimethorpim |
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Drugs affecting DNA synthesis
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Fluoroquinolones
- inhibit DNA gyrase to interfere with DNA synthesis |
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Penicillin
a. Acquired resistence b. ADR |
a. Production of penicillinases and B-lactimases
Staph resistnece is near absolute (MRSA) b. hypersenstivity, GI disturbances |
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Drugs that can counter microbes resistant to penicillin
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Dicloxacilin - penicillinase resistant
Augmentin (amoxicillin with clavulanate) Methicillin |
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Cephalosporins
a. Resistance b. ADR |
a. less susceptible to activation by b-lactimases but penicillinase inactivation still prevalent
b. cross-hypersensitivities with penicillin |
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Cephalosporin drug examples and compare.
Mode of admin |
1st gen
Keflex (cephalexin)L - G+ effective - contrain: hypersensitivity - overuse: assoc with superinfec. Duricef (cefadroxil): - great for staph species Ceclor (cefaclor) 2nd gen - G+, some G- 3rd gen Broad Spectrum - G+, more G- 3rd gen pseudomonal ceph - pseudomons, G-, poor G+ Mode of admin: oral or parenteral |
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Bacitracin
a. mechanism of action b. formulation c. common use |
a. similar to b-lactom
b. ung only, combined with other products to give broad spectrum c. bacterial blepharitis |
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Common properties of drugs affecting bacterial CM
a. mechansim b. resistance c. formulation d. targets what type of microbe? |
a. cationic detergent/surfactant that disrupt with the phosopholipid membrane
cellular contents leak out and lysis b. resistance is rare c. common drug used in combination formation and extensive G- coverage |
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Example of a drug affecting bacterial CM and diagram
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Polymyxin B
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Aminoglycosides
a. static/cidal b. target c. examples |
a. cidal
b. G-, aerobes only c. neomycin, gentamycin, tobramycin |
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Drugs affecting Folic Acid Synthesis
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Sulfonamide - competitively inhibit the conversion of PABA (no good if in pus --> lots of PABA)
Pyrimethamine Trimethorpim |
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Drugs affecting DNA synthesis
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Fluoroquinolones
- inhibit DNA gyrase to interfere with DNA synthesis |
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Penicillin
a. Acquired resistence b. ADR |
a. Production of penicillinases and B-lactimases
Staph resistnece is near absolute (MRSA) b. hypersenstivity, GI disturbances |
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Drugs that can counter microbes resistant to penicillin
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Dicloxacilin - penicillinase resistant
Augmentin (amoxicillin with clavulanate) Methicillin |
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Cephalosporins
a. Resistance b. ADR |
a. less susceptible to activation by b-lactimases but penicillinase inactivation still prevalent
b. cross-hypersensitivities with penicillin |
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Evaluating Effectiveness of Antibiotic Agents
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1. Sensitivity of organism to drug by MIC 90 (minimum inhibitory concentration to inhibit its growth); measure of potency
2. Concentration of drug at site of infection 3. Kill rate 4. Inhibitory Quotient (IQ) - integrates potency and tissue penetration to predict effectiveness of antibiotic against a particular infection |
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Mechanism of Action of Antibacterial Agents
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1. Inhibit CW
2. Inhibit CM 3. Inihbiti protein synthesis 4. Inhibit folic acid synthesis (metabolism) 5. Inhibit DNA synthesis |
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Drugs that affect CW synthesis
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Penicillin
Cephalosporins Bacitracin Vancomycin |
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Drugs that affect CM
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Polymyxin B
Gramicidin - act as detergent |
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Drugs that affect protein synthesis
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Aminoglycosides -30s
Tetracyclines -30s Macrolides -50s Chloramphenicol -50s Clindamycin -50s |
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Components of Polymyxin B and characteristics
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Polysporin/polycidin
- broad coverage and safe for eyes -soln or ung Polytrim - choice for bacterial conjunctivis esp kids - soln only Neosporin - soln or ung - rarely used bc contact dermititis |
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Aminoglycosides
a. cidal/static b. target c. example |
a. cidal
b. G-, aerobes only c. neomycin, gentamycin and tobramycin |
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Mechanism of action of AG
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susceptible organism have an O2 dependent system that transports the antibiotic into the bacterium
Once inside, AG inhibits protein synthesis by binding to 30S ribosome --> inhibits biding of tRNA --> misread genetic code --> premature termination of mRNA from ribosome --> inhibit assembly of ribosomes |
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Ophthalmic Aminoglycosides
a. formulation b. toxicity |
a. 0.3% soln or ung
b. common; neomycin (allergic reations of the lids> gentamicin>tobramycin |
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Topical macrolide
Name a. formulation b. uses c. toxicity |
Erythromycin
a. ung only b. preesure patching corneal abrasions, nocturnal antibiosis and lubrication |
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Systemic Macrolides
a. uses (incl ophthalmic) b. common examples |
a. 2nd line drugs to penicillin and cephalosporins
b. erythromyicn - 2nd line for intectious internal hordeola; otherwise limited ophthalmic use Azithromycin (Zitrhomax) drug of choice for chlamydial infections; convenient one dose qd and ok preg clarithromycin (Biaxin) --> not as effective as zithromax |
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Tetracycline
a. Mechanism b. Resistance c. indication |
a. bind to 30s
b. ineffective against Staph and pseudomonas c. ung for neonatla prophylaxis against gonococcal infections; oph use |
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Oral tetracyclines
a. impt ophthalmic use |
a. acne rosacea, some RCE, chlamydial conjunctivitis and meibomian gland dysfunction (posterior blepharities)
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Examples of oral tetracyclines
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Tetracycline HCl
- prototype (min use) Doxycycline - drug of choice minocycline - disadv to doxy because of side effects (dizzy, vertigo) |
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1. Contraindications and b. warnings for tetracyclines
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Contra:
a. - hypersensitivities - preganancy, nursing kids <8 bc tooth discolouration - renally impaired b. - photosensitivity - Mg2+, Ca2+, Fe impair absorption - allow time gap between - reduces OCP's efficacy |
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Chloramphenicol
a. general opinion in NA b. ADR |
a. not used when less toxic agents are available and equally effective
b. aplastic anemia --> no risk factors to predict occurence, result of drug metabolite |
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Sulfonamide
a. cidal/static b. spectrum c. use d. resistance e. ADR f. warning |
a. static
b. broad (G+,-, toxo and chlamydia) c. limited d. staph and pseudomonas are resistent e. allergies are common - cross sensitivity with other common systemic drugs (CAI), stining drop f. anestheitcs that are esters of PABA act as antagonist of sulfonamide |
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Mechanism of action of sulfonamide
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- structural analogue of PABA
- competitive inhibition of PABA (makes folic acid --> essential substrate of purine and component of pus) |
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Sulfonamides
a. sodium sulfacetamide b. sulfisoxazole |
a. mostly 10% and may be in comb with steroids to decrease inflammation
b. 4% soln or ung |
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Trimethoprim
a. use b. formulation c. spectrum |
a. minor infections
excellent for bacterial conjunctivitis in children and adults b. combination in Polytrim (0.1% trimethoprim and polymyxin B) c. broad |
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Fluoroquinolone family tree
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0 all are derivatives of nalidixic acid
2nd generation - norfloxacin, ofloxacin Ocuflox, ciprofloxacin Ciloxan 3rd generation - levofloxacin Quixin, Iquix 4th gen - gatifloxacin Zymar, moxifoxacin Vigamox |
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2 fluoroquinolones approved for treatment of bacterial corneal ulcers
b effectiveness c resistance d how many drops needed e approved for what age |
Ocuflox (ofloxacin)
Ciloxan (ciprofloxacin) b. almost effective c. staph and strep resistance is emerging d. depends on severity of the clinical presentation e. >1 year, ung >2 year |
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Mechanism of action of fluroquinolone
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- inhibit DNA gyrase
- required for replication of DNA msg |
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Ofloxacin 0.3% (Ocuflox)
Use |
bacterial conjunctivitis and corneal ulcers
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Fluoroquinolone 3rd vs 4th gen
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3rd --> enhance spectrum (G-)
4th --> also G+ and anaerobes improved PK and PD inhibit BOTH topoisomerase II and III rather than 1 only - harder to develop resistance |
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4th gen Fluoroquinolone is in approval for a.
b. dosage |
a. tx of keratitis
- superior efficacy based on bioavailability b. less freq and shorter duration |
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Generally which one wins in these categories re Fluoroquinolone
a. Staph aureus b. Coagulase -ve Staph c. Pneumoniae and Strep vividans d. Serratia marcescens |
a, b, c, d --> moxifoxacin
e --> ciprofloxacin |
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2 classes of thought re: Fluoroquinolone
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1. milder infections --> tobramycin/polytrim
Mod to severe infections --> quinolones 2. use quinolones and treat aggressively |
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Which quinolone drug is an ophthalmic spin-off from a highly effective oral antiobiotic Levaquin?
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levofloxacin (Quixin)
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gatifloxacin (Zymar)
characteristics |
- 1st topical opth 4th gen
- approved in 2003 for conjunctivities only |
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moxifloxacin (Vigamox)
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- approved for conjunctivitis (2003)
- first self-preserved agent easier (1gt tid for 7 days) |
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Likely cause of resistance for Fluoroquinolone
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heavy oral use
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Most recent orals for fluoroquinolone
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Trovaflocacin (Trovan)
- broad spectrum (esp staph, strep, H. infuenze and chlyamydia species) Ciprofloxacin (Cipro) Ofloxacin (Floxin) |
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Fluoroquinolones ADRs
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tearing and photophobia
allergic, GI, drowsiness with oral |
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Resistance with the new Fluoroquinolone
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Gatifloxacin and moxifloxacin are less prone to resistance as a result of single step topoisomerase mutations
max. tissue concentration relative to MIC therefore less likly to develop resistance |
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Trovan (trovofloxacin)
a. What is it? b. Use? c. Characteristic |
a. newest floroquinolone in trial
b. tx bacterial endophthalmitis and bacterial keratitis c. in vitro potency, favourable pharmacokinetics, in vivo efficacy |
