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What are 4 wrongs of pen G?
- 1. Narrow spectrum
- 2. Acid sensitive
- 3. Beta lactamarase sensitive
Oral form of pen G
herpes virus infection indicaiton?
If staph aureus is resistant to methicillin what do you use instead?
- Extended spectrum (include gram-)
- Ampicillin, amoxilcillin
- Nitrogen group allows it to penetrate gram- cell wall
What do you use tx pseudomonas?
- Carboxypen (cabenicillin, ticarcillin)
- Ureidopenicillin (piperacillin, azlocillin, mezlocillin)
- But these are sensitive to beta lactamase so must combine with b-lactamase inhibitors (clavulanic acid, sulbactan, tazolbactam
Beta latamase inhibitor?
- Clavulanic acid
What do you use to tx staph aureus?
- Isozazyolyl pen
- Addition of bulky R group makes it resistant to beta lactamase
Mechanism of pen?
- *Binds to PBP (pen binding protein) or transpeptidase and inhibit cell wall synthesis
- *creating pores in membrane; collapse of mem potential
- --> eventual cell lysis
How pen blocks cell wall synthesis?
- Stereochem similarity
- B-lactam ring CO-N bone is very similar to bacterial CO-N bond In cell wall --> so prevent cross linking
Slow release form of pen?
Which pen has to be given by IV?
- Pen G
- Antipseudomonals (mezlocillin, piperacillin)
Inhibits tubular secretion and so can be used to elevate blood level
Adverse effect of pen
- - Allergic rxn (hypersensitivity rxn - most common) (high with ampicillin)
- - acute anaphylactic rxn (tx with epi)
- - superinfection
- - hyperkalemia (possible arrythmia or cardiac arrest)
Mechanism of resistance of pen
Change in PBP (important in g+; s aureus resistnace to methicillin, pneumococcus
Presence of pen triggers b lactamase production?
Use of pen in dentistry
- Amoxicillin orally
- Ampicillin parenterall
- 6membered dihydrothiazine ring + beta lactam ring
1st gen of Cephalosporins
- Cephalex (oral)
- Greayest activity vs g+
2nd gen of Cephalosporins
- Cafaclor (oral)
- Cefoxitin (actice vs bacteriodes fragilis, serratia marcescens)
- Extended spectrun (gram-) due to increase in
- affinity to PBP
- Penetration to g- cell wall
- Resistance to b-lactamase
Third gen of Cephalosporins
- Cafriaxone (vs pseudomonas)
- Caftazidime (vs pseudomonas)
- Cefpodoximine proxetil (oral)
Useful for menigitis by g-
Addition of AMINOTHIZOKE MOIETY to beta lactam increased the activity va g-
Fourth gen of cephalosporins
Active vs pseudomonas
Cafepime is ZWITTERION and has enhanced activity to penetrate the porin in g-
Adverse effect of cephalosporin
- MTT (cafamandole, cafotetan, cafoperazone, cafopnicid)★★★
- Interferes with vK formation -clotting problem
- 5-10% ppl allergic to pen also allergic to this
Monocyclic lactam - unique spectrum (aerobic g-) (pseudomonas)
Mechanism: sulfonic acid group binds to PBP3
im or iv
Alternative when allergic to pen
What can you use when pt is allergic to pen?
- Tricyclic glycopeptide
- Used to tx SERIOUS RESISTANT TO STAPH ENTEROCOCCUS AND STREPH INFECTION or pen allergy
Adverse effect: red man or red neck syndrone, ototoxic -permanant hearing loss
Resistance: replace D-ala with D-lactate
- Imipenem/cilastatin given together★★
- A carbon instead of sulfur
Pulmonary intra ab and soft tissue infection
- Meropenem (imipenem) is resistant to degradation by dehydropeptidase 1
- So it must be given with cilastatin (competitive dehydropeptidase1 inhibitor)
Iv or im
- Bactericidal vs g+
- Use it only as topically bc too toxic
Inhibit cell wall synthesis by blocking formation kf n-acetylmuramic acid
To tx TB that is resistant to first line choices
- Toxic - not the First line drug
- Inhibit alanine ligase or alanine racemase
- Wk base supplied as hydrochloride salt
- Doxycyclune most used now
Borrelia burgdorferi - lyme dz - carried by tick - amoxicillin or tetracycline
Inhibit protein synthesis (30S)
- Best under acidic condition
- Impaired by milk products (chelastion, increase in PH)
During formation of bone, dentin, enamel of unerupted teeth: discoloration
- Adverse effects: discolored band, growth inhibition, photosensitization
- Contraindicated in pregnancy
Resistance: increase efflux
Broad spectrum (only for SERIOUS INFECTION: meningitis, typhoid fever when others don't work)
Adverse effects: toxic bone marrow depression, Aplastic anemia, gray baby syndrome
Gray baby syndrome
Red neck or redman syndrome?
Synergistic action with pen to tx enterococcal endocarditis
Tx penumonia cause by pseudomonas!!
- Neomycin for topical infection of skin
- Neosporin (neomycib, polymyxinB, bacitracin)
30S - BACTERIOCIDAL!! Conc dependent
Basic so may react with pen (acidic) or cephaloporin in high conc
- Adverse effects:
- 1.renal damage (nephrotoxicity)
- 2.ototoxicity (destruction of vestibular (headache) or cochlear (tinnitus) sensory cells)
- 3.fetal exposure in pregnancy
- 4.respiratory paralysis
- Acetyltransferase, phosphotransferase, adenyltransferase
Ab distention, vomiting, cyanosis, hypothermia, irregular respiration, vasomotor collapse from chloramohenicol
Gray baby syndrome
Macro - many rings
- Erythromycin (alternative for pen)
- Azithromycin (acid stable)
- Peptic ulcer dz (helicobacter pylori)
- Clarithromycin + omeprazole + amoxicillin
- Legionella pneumonia
- Azithromycin bc
- 1.excellent activity
- 2.Sup tissue conc
- 3.easy admin as single daily dose
- 4.Better tolerability
- 5.Longer half life
- Chlamydia trachomatis (trachoma, urethritis) - eye dz, inflammation
- Azithromycin and erythromycin can be used during pregnancy
Erythromycin best absorbed under alkaline condition - acid sensitive
- Adverse effects:
- Cholestatic hepatitis (mainly by erythromycin)
- Inhibit P450 isoenzyme
- Production of methylase enzyme - modify ribosomal target. Can no longer inhibit protein synthesis
Anaerobic g- : used in dentistry
- Lung and pleural infection
- No predictable for brain access as poor penetration into CSF
Flavored suspension for peds use
- Adverse effects:
- PSEUDOMEMBRANEOUS COLITIS due to superinfection with chlostridium difficile
(Bc its free radical wipe off all chlostridium; not selective)
Combined with beta lactams for serious infection
Adverse effect of clindamycin?
Enters abcess!! Important for dentists
- Free radicals
- Conc dependent killers - diffuse into cells and nitro grouo is reduced to metabolites that damages DNA leading to cell death★
Adverse effects: disulfiram rxn with ethanol (nausea and flushing) -inhibit alcohol metabolism★
- Use in dent?
- Progressive periodontitis with combination of beta lactam
Sulfonamide & trimethiprim
- Sulfa in names
- (Except mefanide)
- Co-trumoxazole: Trimethiprim combined with sulfamethoxazole
- Useful for peumocystis carinii infection in AIDS pts★
Alleric rxn, skin rash, serum sickness★
what is the mechanism of sulfonamides and trimethoprim?
inhibition of folic acid production
which of the followin gdoes not inhibit dihydrofolate reductase?
1. sulfonimides2. trimethoprim3. methotrexate4. pyrimthamine
- answer: sulfonimides
- sulfonimides inhibits dihydrofolate synthase
- cliprofloxacin (cipro) - choice for post-exposure prophylaxis of inhalation anthrax ***
- (floxacin in names)
mechanism: inacativate DNA gyrase
(g-) and topoisomerase IV (g+) and promote DNA trand break
contraindicated in pragancy
adverse effects of sulfonamides and trimethoprim?
- kernicterus in infants
- (displacement of bilirubin)
kernicterus in infants?
sulfonamides and trimethoprim
- aminosalicyic acid
peripheral neuritis - more common in slow acetylators; protecdt with pyridoxine
reduce rate of emergence of resistance if used in combination
- inhibits DNA dependent RNA polymerase
- Binds to (b subunit) and inhibit DNA-dependent
- RNA polymerase of mycobacteria and other microorganisms.
- inducer of cytochrome p450
orange red brown color?
optic neuritis with decrease in visual acuity and loss of ability to discrimate colors
- used in resistant cases
- very good for treating TB
- mechanism of action**
- interfere with the synthesis of folic acid by acting as competitive inhibitors of dihydrofolate synthetase
(structurally similar to sufonamides obviously)
- advers effect: methemoglobinemia
- adverse effect*
- color urine, feces, sputum, sweat red*
- amphotericin B
- pneumocadins and papulocandins
binds to sterols (ergosterol - fungal cholesterol) in cell membrane forming pores or channels
you dont want to use amphotericin B with imidazoles
candidal infection of the oral cavity (oral moniliasis, thrush, denture stomititis)
combined with amphotericinB for cryptococcal meningitis in AIDS pts
most broad spectrum ABX?
- imidazole (2Ns): systemic candidiasis
- triazoles (3Ns): topical
- mecahnism of actionazole inhibit the synthesis of ergosterol by inhibiting sterol 12-a-demethylase, a cytochrom p450 dependent enzyme system
- adverse effects:hepatotoxicity and increase in liver enzyme
- fetal hepatic necrosis
- ketoconazole causes gynecomastia and menstrual irrecularities by lowering steroid biosynthesis ***
- spectrum of actionuse liumited to infection of the skin, hair, and nails
fungal infection of skin, nail, hair?
what do you treat with?
Pneumocandins and papulocandins
inhibit cell wall synthesis by inhibiting b-1,3-glucan synthetase (not in human cells - safe)
effective vs azole resistant C albicans
Agents to treat AIDS!
- neucleoside reverse transcriptase inhibitors1. zidovudine (retrovir)
- 2. didanosine
- 3. zalcitabine
- 4. stavudine
- 5. lamivudine
- 6. abacavir
- non-neucleoside reverse transcriptase inhibitors(these directly inhibit RT w/o being incorporated into the DNA)
- 1. nevirapine
- 2. delavirdine
- 3. efavirenze
- HIV protease inhibitors1. saquinavir
- 2. ritonavir
- 3. indinavir
- 4. nelfinavir
- 5. amprenavir
what is the adverse effect of using HIV protease inhibitors?
HIV protease inhibitors1. saquinavir2. ritonavir3. indinavir4. nelfinavir5. amprenavir
buffalo humps - fat deposit and redistribution
VIRAL respiratory infections (influenza)
- mechanism of action
- - prevent viral replication- prevent fusion of viral memebrane with host cell membrane - interfere with release of new virus
- (neuraminidase inhibitor)
- Converted to triphosphate with viral-specific thymidine kinase. Triphosphate selectively inhibits virus DNA-polymerase and thus inhibits viral DNA replication
herpes virus infection indicaiton?
ganciclovir useful for CMV retinitis in imunnocompromised pt
- Initial and recurrent herpes genitalis,
- Herpes simplex encephalitis, mucocutaneous
- infections in immunocompromised
- patients. Useful in Herpes zoster infections (shingles)
- aminoglycosides (bacteriocidal)