Week 1 - Day 4 notes

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Mechanism of Penicillin: Inhibits transpeptidase enzyme of both gram - and + bacteria.
Are penicillin bacteriacidal: yes
What are the mechanism of resistances found for penicillin?: 1. Altering of porin (in g-)
2. Beta - lactamase (g -, +). Cleaves the C-N bond. e.g Penicillinase
3. Altering the transpeptidase (e.g Methicillin resistant staphy. aureus)
What do all penicillian have as an adverse effect?: Anaphylactic rxn (allergic)
IgE mediated.
What are the GI effects of penicillin: Lead to diarrhea due to *clostridium difficile* overgrowth (due to destroyed natural GI flora)
Name the 5 types of penicillin?: 1. Penicillin G (1941)
2. Aminopenicillin (g-)
3. Penicillinase resistant penicillin
4. Anti - Pseudonomas penicillin
5. Cephalosporins
Penicillin G - name the oral form: Penicillin V
Penicillin G is very sensitive to beta-lactamase. what can it be used against: Group A hemolytic streptococcus
Name the Aminopenicillins? what is their coverage? and are they inhibited by penicilinase? Any notable combos?: 1.Ampicillin, Amoxicillin
2. g- and g+ enterococcus(ecoli, proteus, salmonella,shigella)
3. yes (pencillinase senstive)
4. Amp-gent (ampicillin and genatmycin)
Name 3 IV administed Penicillinase resistance penicillin? what is the primary bug they kill?: 1. Methicillin, nafcillin and oxacillin
2. IV
3. Staph aureus - cellulits,endocarditis,sepsis
Name the orally administed Penicillinase resistance penicillin?: 1. Cloxacillin, dicloxacillin
continue at page 117 of micro (start with Anti-pseudonomal penicillin): incomplete
Penicillin is bacteri (-cidal / -static): bactericidal
How do the penicillins work? What method of inhibition is used?: competitive inhibition of transpeptidase enzyme that crosslinks peptidoglycan
One mechanism of resistance employed only by gm - bacteria: alter porins to prevent entry of drug
What is the mechanism employed by MRSA?: mutated transpeptidase so that beta-lactam will not be able to bind.
Acid stable form of penicillin: Penicillin V
Drug of choice for beta-lactamase neg H. influenza. (hint: HELPS kill ------): amoxicillin

Also
H.Flu,E.coli, Listeria monocytogenes, Proteus, Salmonella and Enterococci

HELPS kill Enterococci
Ampicillin and amoxicillin have a broader spectrum against ------- --------- bacteria.: gram negatives due to better penetrance and binding.
The aminopenicillins are also one of the few drugs still effective against the gram pos ------ (a relative of strep).: enterococci
Name three penicillinase-resistant beta-lactam drugs given IV for S. aureus infections.: methicillin, nafcillin, and oxacillin
Drug of choice for serious S. aureus infections such as cellulitis, endocarditis, and sepsis. Given IV.: nafcillin
What are the three anti-pseudomonal penicillins?: carbenicillin, piperacillin, and ticarcillin
Are the anti-pseudomonal penicillins penicillinase resistant?: no. They are susceptible to penicillinase.
Name three beta-lactamase inhibitors.: clavulanic acid, sulbactam, tazobactam
With each new generation of cephalosporins, the drugs are able to kill an increasing spectrum of gram ------ bacteria.: gram negative.
Which generation of cephalosporins are most effective against the gram-positives?: first generation
T/F. Cephalosporins can be used to treat enterococcal infections.: False.
A cephalosporin that has great gm - coverage, but also has good coverage of gm + and Pseudomonas: fourth generation
Tx of choice for gonorrhea: ceftriaxone, a 3rd generation cephalosporin
What kind of reaction will result in a combination of cephalosporins with EtOH?: disulfiram-like reaction
Magic bullet for gram neg aerobes: aztreonam
How do you characterize aztreonam's activity against gm + and anaerobes?: no effect on either
Drug for MRSA: vancomycin
From Pharm Card
Given the use, give the appropriate generation of cephalosporins
the appropriate generation of cephalosporins in pneumonia, COPD, peritonitis, diverticulitis, mixed-aerobic-anaerobic infections: second
the appropriate generation of cephalosporins for surgical prophylaxis, cellulitis: first
Main clinical uses for third and fourth generation cephalosporins: efficiently crosses BBB --> meningitis, sepsis
Is it ok to give someone who has had a mild allergy to penicillin a cepholosporin?: yes. Only 10-15% have cross reaction.
Is it ok to give someone who has had a and anaphylactic response to penicillin a cepholosporin?: no. very bad.
best cephalosporin generation for anaerobic infections: second
First line drug for meningitis in neonates, children, and adults: ceftriaxone
Beta-lactam drug associated with seizures, especially in those with renal dysfunction: imipenem
Drug given IM for gonorrhea: ceftriaxone
the broadest spectrum of antibacterial activity of any antibiotic known.: imipenem
Is imipenem sensitive to beta-lactamases?: no.
Normal kidney has a dihydropeptidase that breaks imipenem down, so a selective enzyme inhibitor called ------- is given with imipenem.: cilastatin
Name the four drugs that are 50S inhibitors: chloramphenicol, clindamycin, linezolid, and erythromycin
Name the two drugs that are 30S inhibitors: tetracylcine and aminoglycosides
The class of anti-ribosomal antibiotics that cannot be absorbed orally: aminoglycosides
Name the two effects of chloramphenicol on bone marrow (one is reversible, the other is not): dose dependent suppression (reversible). Irreversible damage to marrow--> aplastic anemia
What is clindamycin good for?: gram positives and anaerobes (incl. bacteroides fragilis)
Must not take this antibiotic with milk, antacids, or iron-containing compounds: tetracycline
Only group of anti-ribosomal antibiotics that are bactericidal: aminoglycosides
Drug of choice in pregnant women with rocky mountain spotted fever who cannot take tetracycline because of its effects on the fetus.: chloramphenicol
Drug of choice for community acquired pneumonia that does not require hospitalization.: erythromycin
Used along with an aminoglycoside for penetrating wound infections of the abdomen.: clindamycin
Used to treat bacterial meningitis when the organism is not yet known and the pt has severe rxn to penicillins, incl. cephalosporins.: chloramphenicol
Chelates with cations in milk and milk products, aluminum hydroxide, Ca2+, and Mg+, so it is not absorbed. Doxycycline is one of these drugs, but chelates poorly and is better absorbed with food.: tetracycline
Drug classically associated with pseudomembranous colitis.: clindamycin
What is the Tx for pseudomembranous colitis?: vancomycin or metronidazole
(remember the pic with the Van and Metro chasing Clostridium difficle in the GI)
Drug associated with gray baby syndrome (vasomotor collapse, abdominal distention, cyanosis= ashen gray color): chloramphenicol
Causes irreversible eighth cranial nerve toxicity: aminoglycosides
Premature babies lack what enzyme that makes them susceptible to gray baby syndrome?: UDP-glucuronyl transferase
Why is tetracycline not given to pregnant women?: their babies will have depressed bone growth due to tetracycline's chelation to calcium of teeth and bone. Also fatty liver in the pregnant women
Used to kill aerobic gram negative enterics, incl Pseudomonas. Gentamycin and tobramycin are members of this class: aminoglycosides
Aminoglycosides can be combined with ------ to treat nosocomial infections.: penicillins
What is the spectrum of Chloramphenicol?What clinical senario is it used and why?: 1. Kills most bugs (g+,g-,anaerobes)
2. Bacterial Meningitis - H.flu, N.meningitidis, Strep. pneumonaie. Especially if the diagnosis is unknown.
3. Excellent CSF penetration
4. For Rocky Mountain spotted fever for women and young children(normally Tetracycline is used but Tetracycline is bad for this group)
What are the adverse effects of Chloramphenicol?: 1. Bone Marrow suppression(2main efxs)
a. Anemia (reversible)
b. Aplastic anemia (irreversible,rare)

2. Gray Baby Syndrome (poor conjugation by babies-toxic efxs)
1.What causes Gray baby syndrome? 2.How? 3.What are the Si/Sx?: 1. Chloramphenicol
2. Toxicity (due to poor conjugation by liver to be excreted by kidney)
3. Vasomotor collaspe (shock), abdominal distentions, cyanosis ->gray ashen color
1.What is the clinical use of Clindamycin? 2. Name the physicians that love using this drug?: 1. Anaerobic infection (not useful in general for g- below the diaphram)

Bacteriodes and Clostridium perfringens

2. Surgeons (with aminoglycoside for aerobic g- enterics)
Name the 2 drugs Surgeons love to use? List their coverage?: 1. Clindamycin - Bacteriodes and Clostridium perfringens

2. Aminoglycoside - g- aerobic enterics
(pseudonomas, E.Coli)
What are the adverse effect of Clindamycin? Due overgrowth of what bug?: 1. Pseudomembranous Colitis
2. Overgrowth of Clostridium difficle
How do you treat Pseudomembranous colitis?: Metronidazole(cheap) or Vancomycin (expensive)
1.What group is erythromycin part of? 2.Why is erythromycin best used for g+? 3. Name the g- it can cover: 1. Macrolides (others azithromycin, clarithromycin)
2. Absorbs 100x better in g+
3. Mycoplasma, Neisseria, Legionella and Chlamydia

used in g+ bugs, if patient is allergic to pencillin.
What are clinical conditions - can we use Erythromycin?: 1. URI
2. Pneumonia
3. STD's
Name the 3 community acquired pneumonia causing bugs that can be treated with Erythromycin?: 1. Strep pneumonia
2. Mycoplasma
3. Chlamydia trachomatis (strain TWAR)
How safe is erythromycin? What are the side effects?: 1. One the safest antibacterial drugs
2.
.Common and dose dependent abdominal pain (GI irritation)
.Cholestatic hepatitis (rare)
What drug is an alternative to doxocycline for the treatment of (chlamydial) non-gonorrheal urethritis?: Azithromycin (can also be used for community pneumonia)
Part of the Macrolide
1.What is the difference between Tetracycline and Doxycycline?: 1. Doxycycline is a tetracycline but doesnt chelate Ca2+, Mg2+ (ions in milk)
2. Due to this property: it gets better absorbed.

When Tetracycline is chelated it will pass thru GI without being absorbed
List the clinical uses of Tetracycline/Doxycycline? VACUUM you BedRoom.: 1. Vibro Chlorae
2. ACNE
3. Chlamydia
4. Ureaplasma Urealytica
5. Mycoplasma (alt. for erythromycin)

6. Borrelia
7. Rickettsia
What are the adverse effects of tetracycline?: 1. GI distress (common)
2. Phototoxic dermatitis
3. Renal and hepatic toxicity
4. Discolored teeth and depressed bone growth (due to the chelation properties)

This soldier with bad teeth b4 war - had GI problems.During the war, a bomb explode and the light burnt is face. The sharpnels hit his liver and kidney.
What are the bugs that Aminoglycoside are used for? Name some Aminoglycoside?: 1. g- aerobic bacteria -mainly the enterics and pseudonomas
2. Gentamycin, Streptomycin, Tobramycin,
Amikacin and Neomycin(skin, too toxic)
Netilmicin (great for GI surgery)
What are the toxic effects of Aminoglycosides?: 1. Ototoxity (irreversible) - esp with loop diuretics
2. Nephrotoxicity (reversible)-esp with cephalosporins
What does Aminoglycoside require for uptake? It is dangerous to fetus?: 1. oxygen
2. it is a teratogen
How do you treat a gonorrhea urethritis infection - if you have tried Ceftriaxone (IM shot)?: remaining choices are
1. Quinolones
2. Spectinomycin(alt for penicillin and tetracycline)

But still always give doxycycline for Chlamydia
Name the Drugs used for treating TB? Name the 3 that are liver toxic?: 1. Isonaizid -
2. Rifampin
3. Pyrazinamide
I SAW a Red PYRe-burning the liver
4.Ethambutol
5.Streptomycin

1-3 are liver toxic
Risk factor for isoniazid induced liver-injury?: 1. Age (>50 - 2.3%)
2. Alcohol use
How does INH (Isoniazid) work?: It inhibits the synthesis of mycolic acid - part of the cell wall of Mycobacterium.
What are the toxic effects of Isoniazid(NIH) and How?: 1. Hepatoxicity -
ETOH increases risk of hepatitis and decrease therapeutic efx (due to increased metabolism of INH)

2.B6 deficiency - needed for nerve function. INH increases excretion of B6 in Urine
What is the mechanism of Rifampin(red) in the Tx of TB? Weird but not harmful side-effect?: 1. it is a DNA dependent RNA polymerase inhibitor

2. Red- makes Urine, Tears, Feces, Saliva, Sweat all look a BRIGHT ORANGE color
What is the major side effects of Rifampin? What a key drugs to avoid or monitor?: 1. Activates the P450 pathway in liver (microsomal oxidase system)
it decreases the T1/2 these drugs below:

a. Coumadin
b.Oral contraceptive
c.Oral hypoglycemics and Corticosteroids
d. Anticonvulasants e.g Phenytoin

"Can make you become uncontrolled diabetic, bleed, pregnant and Seize"
Pyrazinamide is used for what disease? Mechanism? Adverse efxs? Good for Pregnancy?: 1. Tuberculosis
2. Unknown mechanism
3. Heptotoxic!!!
4. NO (unknown efx to fetus)
Ethambutol is used for what disease? Adverse efx?: 1. TB
2. Ocular toxicity (think of ethane-butane flame torch on the eye)
What are the combination treatment for Leprosy? For how long?: 1. Dapsone
2. Rifampin
3. Clofazimine

- 2 years for severe leprosy cases
Dapsone is part of what group of drugs? Mechanism? Used for what bug?: 1. Sulfones (e.g sulfoxone,sulfonamides)
2. PABA antagonist - inhibition of bacterial DNA synthesis.
blocking DHF (folate) synthesis
3. M. Leprae
How does Clofazimine work? (think of the clown in strips) Adverse effects?: 1. Binds to DNA of M. Leprae and has anti-inflammatory actions.
2. Red and black skin discolorations
Dapsone vs. Clofazime - which does resistance develop rapidly?: Dapsone>
Resistance to Clofazime is slowly
Mechanism of Fluroquinolones? List common drugs under this class? Which causes prolong Q-T? Which has the broadest coverage?(Trove): 1.Inhibit DNA gyrase
2.
Ciprofloxacin - g- (nosocomial,UTI,osteomyelitis true for all the fluoroquinolones)
Levofloxacin,Ofloxacin
3.Sparfloxacin - prolonged QT and photosensitivity

4.Trovafloxacin - g+,g- and anaerobes
Mechanism of Vancomycin ? Administered and Coverage? Adverse effects? Resistance?: 1. Inhibit g+ peptidoglycan.Ala-D Ala-D
2. IV, g+ (even MRSA + alot of resistant bugs)
3. Red man syndrome (rapid IV -->histamine release. Flushed, pruitic)
4. Vancomycin resistant enterococcus
Mechanism of Trimethroprim and Sulfamethoxazole? (TMP/SMX): Inhibit the formation of purines by
1. SMX is a PABA analog -
2. TMP inhibits DHF reductase
What is the coverage of the 1st cephalosporins? hint:PEcK: g+ , Proteus mirabilis, E.coli, Klebsiella
What is the coverage of 2nd gen cephlosporins? hint: HEN PEcKS: g+,
Haemophilus
Enterobacter aerogenes
Neisseria spp.
Proteus mirabilis
E.Coli
Klebsiella pneumoniae
Serratia marcescens
What is the enzyme inhibited by sulfonamides? What is the hypersensitivity rxn toxicity by these drugs? Other toxicities?: 1.Dihydropteroate Synthase
2. Hemolysis if G6PD deficient
3. Nephrotoxic (tubulointerstial nepritis), Kernicterus (infants)
drugs-albumin displacement(e.g warfarin)
Tx combo therapy of TMP-SMX for recurrent ---- ------ ------ -----?: 1. UTIs
2.Shigella
3. Salmonella
4. PCP pneumonia (given as a prophylaxis even)
Toxicity of Trimethoprim? Hint:TMP- treats marrow poorly.: 1. Megaloblastic anemia
2. Leukopenia and granulocytopenia
Give patient folate
Of the Aminoglycosides - which has the broadest coverage and good for nosocomial infections?: AmiKacin
------ ( a first line TB drug) is rapidly bacteriocidal to Mtb, but the risk of liver toxicity is too great if used for more than 2 months.: Pyrazinamide
In condsidering treatment for an asymptomatic PPD positive person, remember that advancing age and ----- ------ increase the risk of developing hepatitis from INH.: EtOH consumption
Under age ----- there is virtually no risk of developing hepatitis from INH.: 35
Toxicity common to INH, Rifampin, and pyrazinamide.: hepatotoxicity
Mechanism of action of INH: inhibits inhA subunit of fatty acid synthase II
Mechanism of action of pyrazinamide: inhibits FAS I
FAS is involved in ----- ----- synthesis: mycolic acid
The main side effect of ethambutol is dose dependent, reversible ------ -----.: ocular toxicity. Decreased acutity with central scotoma, color vision loss
First line TB drug that inhibits the 30 ribosomal subunit and stops protein synthesis.: Streptomycin, an aminoglycoside
Toxicities of streptomycin: ototoxic, nephrotoxic
Why should streptomycin be avoided in pregnant women?: can cause congenital deafness
Tx of leprosy.: dapsone, rifampin, clofazimine
How does clofazimine work?: it works by binding to the DNA of M. leprae and by anti-inflammatory properties
Anti mycobacterial drug that turns body fluids red: rifampin
how does rifampin work?: inhibits DNA dependent RNA polymerase (inhibits transcription)
Rifampin decreases the half life of what four classes of drugs,: coumadin, oral contraceptives, oral hypoglycemics and corticosteroids, anticonvulsants (phenytoin)
During treatment of leprosy, 50% of pts develop a leprosy reaction. What kind of reactin is type I?: delayed type hypersensitivity
What kind of reaction is type II leprosy reaction?: immune-complex mediated--> complement activation (type III hypersensitivity)
What is the treatment of choice for Type II leprosy reaction?: thalidomide
Name the fungus infections on the superficial layer of skin? Name cause and Appearence?: 1. Pityriasis - Malassezia furfur, multicolored (hypo or hyperpigmented)
2. Tinea nigra - Exophilala werneckii, black
Give three reasons that fluoroquinolones are good drugs.: safe, absorbed well orally, penetrate extremely well in to tissues
Fluoroquinolones result in the breakage of the bacterial DNA structure by what mechanism?: inhibit DNA gyrase
Resistance to FLQs results from a point mutation in --- ---.: DNA gyrase
Name three side effects of FLQs. Think of Achilles running to the bathroom: GI upset, cartilage damage, achilles tendonitis, rare CNS disturbances
Cipro has poor gram ----- coverage.: positive
However, cipro is active against what two gram positives in particular?: Staph aureus, and Bacillus anthracis
FLQs are most useful for treating what general group of organisms?: gram negatives
How is FLQ coverage of anaerobes like bacteroides?: poor
Pts with cystic fibrosis can be given FLQs to treat infection with what bug?: Pseudomonas
Name four enterics that can be treated with FLQs in the event that they cause traveller's diarrhea. (not anaerobes): E. coli, salmonella, shigella, campylobacter
What kind of UTIs can be treated with FLQs?: complicated (pseudomonas, etc)
Levofloxacin can be used to treat what general group of infections that Cipro cannot?: Community acquired pneumonia. This generation of FLQs have better coverage of gm +, particularly against S. pneumonia, E. fecalis, and S. aureus
Why are FLQs good to treat UTIs?: they achieve high renal concentrations
The FLQs are good for community acquired pneumonia because they also treat atypical pneumonias, including which three organisms?: legionella, mycoplasma, chlamydia
FLQs can prolong the QT interval, predisposing the pt to what particular type of arrhythmia?: Torsades de pointes
Aztreonam covers all gram negatives (aerobes only), while ----- covers all gram positives, even MRSA and enterococcus: vancomycin
What is the mechanism of action of vancomycin?: complexes with D alanines to prevent transpeptidation (one step earlier block than in penicillin mechanim)
Vancomycin is not absorbed orally, but this feature can be taken advantage of in what case?: C. difficile pseudomembranous colitis. Vancomycin cruises down the GI unabsorbed
What new drug can be given in case of vancomycin resistance?: Synercid (quinopristin/dalfopristin)
The sulfa drugs are ----- analogs.: para-amino benzoic acid
The sulfa drugs competitively inhibit the production of ---, which is needed for nucleotide and DNA formation.: TH4
TH4 gives up ----- to form purines and other metabolic building blocks.: carbons
After giving up a carbon, it become dihydorfolate (TH2) and must be reduced back to TH4 by the enzyme DHFR. ------ looks like DHFR of bacteria and competitively inhibits this reduction.: Trimethoprim
TMP/SMX is active against (gm- / gm+ / both gm-&gm+ / anaerobes): both gm- & gm+. Not anaerobes.
TMP/SMX is excreted in the ----- so it is good to treat ----: urine, UTIs
Giving TMP/SMX with ------ is very dangerous!: warfarin. Levels are increased and risk of bleeding is great
TMP/SMX is given prophylactically to AIDS pts with CD4+ counts less than 200-250 to prevent what dz?: PCP
TreeMouthPee / Syndrome : mneumonic to remember the uses of TMP/SMX: Respiratory tree (s. pneumo, H. flu); GI tract (enterics); Pee (GU infections)
What parasites are covered by TMP/SMX that AIDS pts might also get?: toxo, iospora belli

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