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85 Cards in this Set

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EXAM-praziquantal
(worm drug)

opens Ca++ channels to cause muscle tetany
==>tegmental damage
==>activates host imm sys
EXAM-albendazole
(worm drug)

inhibits synthesis of microtubules req for glucose uptake
==>decr [glycogen] & [ATP]
==>death

mneum: Peg Bundy complains that "AL" Bundy won't have sex with her, so they can't synthesize (conceive) the little microtubules they need (kids w/food stamps) they need to get glucose (food stamps)
EXAM-thiabendazole
(worm drug)

inhibits mictochondrial fumurate reductase
EXAM-ivermectin
Tx:
*onchocerciasis (Onchocerca volvulus)
*strongyloidasis (threadworm)
*ectoparasites

MOA:
releases GABA and incr GABA binding
==>open Cl chann in NMJ (remember: Cl- channels are GABA-mediated)
==>flaccid paralysis

-may also cause tonic paralysis in musculature of nematodes (roundworms) d/t Glu-gated Cl chann found only in invertebrates
Rx for Cestodes
(Cestodes=tapeworms)

DOC=niclosamide (mneum: niclo sounds like nickel, and worms are flat like a nickel)

also, praziquantal, mebendazole
Tx Ascaris lumbricoides
(Ascaris lumbricoides=roundworm)

AlBENDazole
MeBENDazole
Pyrantel pamoate
Piperazine

(mneum: "worms BEND")
Tx Enterobius vernicularis
(Enterobius vernicularis=pinworm:
"A safety PIN ENTERs your body painfully")

-Mebendazole (mneum: a safety pin has a bend in it)
-Pyrantel pamoate
Tx Necator americanus
(Necator americanus=hookworm)

Albendazole
Mebendazole

"Me and Al say, "There's nothing american about a hookworm."
Tx Trichuris trichiura
(Trichuris trichiura=whipworm:
imagine a whip making the swift noise "trich trich" and BENDing as it hits its victim)

alBENDazole
meBENDazole

"ME and AL love whips!"
Tx Strongyloides stercoralis
(Strongyloides stercoralis=threadworm:
"Thread is strong")

mneum: "thread is strong"

DOC=ivermectin
(mneum: We need IVER (~Ivan), the "strong" Viking, to break the strong thread.)

albendazole
thiabendazole
Tx Trichinella spiralis
(Trichinella spiralis=trichinosis:

ridic p. 253:
-from raw pork
-in sm int, encysted larvae leave their cysts and mature into mating adults
==>female adults penetrate sm int mucosa and produce thousands of larvae
==>larvae enter bloodstream and spread to organs and SkM
(muscle aches)


Albendazole
Mebendazole
Tx Filariae
*Wucheria bancrofti (elephantiasis)= diethylcarbamazine
--Ridic p. 256 picture

*Onchocerca volvulus=Ivermectin (DOC):
-Ridic p. 255:
Onchocerca (transmitted by black flies; Africa & Central/South America) causes river blindness, so "I VER" ("I see") w/IVERmectin
-Black flies (flies are near river==>"river blindness") transmit larvae (microfilariae) to humans.
-Larvae develop into adults, which coil up in subcutaneous nodules
==>skin thickens d/t papular lesions (intraepithelial granulomas) and can appear rough ("lizard skin").
-Adults produce larvae, which can travel to eye==>"river blindness"
Tx Wucheria bancrofti
diethylcarbamazine

(ridic p. 256, pic)
Tx Onchocerca volvulus
DOC=Ivermectin

ridic simple p. 255:
-found in Africa & central/sotuh america
-transmitted via black flies
-AKA "river blindness"

mneum: "iVER"= "i see" (Spanish) b/c Tx river blindness
pt passes tape worm segments (proglottids).
-what is most likely tapeworm?
-how Tx?
Taenia saginata (beef tapeworm) or
Diphyllobothrium latum (fish tapeworm--from sushi)

Tx:
*DOC=niclosamide ("tapeworms are flat like a nickel")
-praziquantel
what does Diphyllobothrium latum do?
Diphyllobothrium latum (fish tapeworm) eats up B12 in gut [Goljan]
==>megaloblastic anemia
Tx cysticercosis
albendazole
Tx tapeworm (and don't know identity)
DOC=praziquantel
baby with pruritis and + "cellophane tape" test.

-what do they have?
-Tx?
(pruritis=anal itching)

-they have pinworm: Enterobius vermincularis (pic in Ridic simple p. 255)

Tx:
mebendazole
pyrantel pamoate
pt with mixed infxn: cestode + trematode
(cestode=tapeworm)
(trematode=fluke)

Tx w/praziquantel
metronidazole
Tx--
DOC for:
-Giardia (beaver fever, campers fever),
-Trichomonas
-C. dif (obligate anaerobe)

Also Tx obligate anaerobes:
-Entamoeba histolytica (amebiasis)
-Clostridium dif (repeat from above)
(pseudomemebraneous colitis)

Ridic p. 236, picture:
"METRO-rail" train goes down the tracks, as protozoa scream, "I know it's DIFFICult (c. DIFFICil), but GET (Giardia, Enteromoeba, Trichomonas) out of his way!")

S/E:
-teratogenic
-disulfiram-like rxn with EtOH:
H/A
N/V
flushing
person has infxn and taking a Rx. He goes to wine-cheese party and gets b/v.

-What drug is he on?
Metronidazole
Pentamidine isethionate
-2nd line drug for PCP (if person can't take trim-sulfa)
Tx PCP
DOC= trim-sulfa

-if person can't take trim-sulfa, give Pentamidine isethionate
organisms that cause typical pneumonia?
Strep pneumo
H flu
M cat (Moraxella cat)--"the MCAT gave me pneumonia"
organisms that cause atypical pneumonia?
Legionella
Chlamydia
Mycoplasma
antimalarial drugs
-prophylaxis
-Treatment
-S/e of drugs
"--quine": mneum--Dr Quinn, medicine woman, worked in Africa and had to Tx malaria
(chloroQUINE, mefloQUINE, primaQUINE)

-Malaria is caused by 4 diff protozoa. All are Plasmodium:
P. falciparum (the worst),
P. malariae,
P. ovale
P. vivax

I. PROPHYLAXIS for travelers:
-If traveleing to chloroquine-sensitive area
==>Use chloroquine
--S/E: tinnitus, H/A
--MOA: block DNA/RNA syn

-If traveling to chloroquine-resistant area
==>DOC= MefloQUINE
(can also use doxycycline)


II. TREATMENT:

*P. malaria, P. ovale, & P. vivax are all susceptible to Chloroquine. Pushovers!

*But P. ovale & P. VIVAx have exo-erythrocytic life cycles in the liver ("VIVA in the liver!"), so they are resistant to chloroquine while in the liver. So Tx with PRIMaquine while in the liver:

ridic p. 243: "PRIMaquine is the PRIMe drug to kill P. vivax & P. ovale in the liver"
--S/E of Primaquine: acute hemolysis d/t Glucose-6-phosphate Dehydrogenase deficiency

--Chloroquine-resistant P. falciparum areas:
*most of Af (except n. Af)
*S Amer
*S & SE Asia

(Chloroquine-sensitive P. falciparum areas:
*Central Amer
*N. Af
*Middle East)


D. Sulfadoxine-pyrimethine
--DOC for chloroquine-resistant strains b/c has diff MOA than chloroquine.
(can also use mefloquine)
-Like trim-sulfa, it inhibits bacterial THF formation via 2 steps:

i. MOA of sulfadoxine=(-)dihydropteroate synthase
(like sulfa drug in trim-sulfa: sulfa drug substitutes for PABA==>cannot form THF)

ii. MOA of pyriMETHamine= (-) DHF reductase (~triMETHaprim in trim-sulfa)
==>cannot regenerate THF
==>megaloblastic anemia
Acyclovir
Tx HSV (esp. HSV encephalitis)

*MOA: acyclovir (acycloguanosine) is converted to acyclovir-monophosphate (acyclo-GMP) by thymidine kinase. Other enzymes convert it to acyclovir-triphosphate (acyclo-GTP), which inhibits viral DNA polymerase.
-Acyclovir is not toxic to host cells b/c mammalian cells phosphorylate acyclovir at much lower rate than the rate of HSV, and acyclovir is much less active at inhibiting mammalian DNA poly than viral DNA poly
-HSV can develop resistance to acyclovir if thymidine kinase is mutated
Tx HSV encephalitis
acyclovir
Tx: keratoconjunctivitis caused by HSV
trifluridine (trifluorothymidine)
Gangciclovir
Tx: CMV

MOA: phosphorylated to triphosphate, which competes with deoxyguanosine triphosphate (dGTP), which is the compound normally used for DNA
==>inhibits DNA poly
==>stops DNA chain elongation
==>inhibits DNA synthesis
Tx immunocompromised pt w/CMV
gangciclovir
Idoxuridine
Tx: HSV keratitis (keratitis=inflamed cornea)

[mneum: Tx "EYE" with "I"doxuridine"]

MOA: inhibit DNA poly (it's a thymidine derivative)
[this is true for both idoxURIDINE and triflURIDINE]
==>thus, if resistant to idoxuridine, also resistant to trifluridine
Tx HSV keratitis
idoxuridine
Amantadine
Tx:
*Influenza A, Rubella
*prophylaxis to prevent Influenza A infxn

MOA:
~inhibits viral uncoating by inhibiting membrane coat ion channel that allows acid-mediated dissociation of ribonucleoprotein complex early in repliation
==>prevents transfer of viral RNA into cyto of mammalian cell
Tx Influenza A
amantadine
Tx rubella
amantadine
prophylaxis against Influenza A
amantadine
zanamivir
Tx: flu

MOA: inhibit viral neuraminidase

(ridic p. 172, picture)
zidovudine
AKA AZT=AZidoThymidine

Tx: HIV
MOA: converted to active triphosphate which either:
~inhibits DNA poly (RT)
~incorporated into DNA in the place of thymidine (T) to stop DNA elongation

S/E: BM depression & anemia
saquinavir
HIV protease inhibitor

MOA: inhibits HIV aspartic proteast, which converts polyproteins into functional core proteins and viral enzymes
interferons
Tx: viruses

MOA: initiate protein synthesis:

A. 2,5 Adenine Synthetase-
makes adenylate oligomers, which activate RNAse to degrade viral RNA

B. protein kinase-
phosphorylates Elongation Facotr 2 (EF2) to prevent viral peptide chain elongation

C. PDEase-degrades terminal nucleotide of t-RNA to inhibit viral peptide chain elongation

Net effects:

*interferes w/viral penetration, uncoating, assembly, and release
*interferes w/viral mRNA syn
*interferes w/viral mRNA translation
Amphotericin B
*Ridic-p. 156 picture

Tx Fungus:
*DOC for Coccidioides immitis
(Ridic p. 147, pic 148: AIDS pts in sw US: AZ, NM, SoCal)
*DOC for Aspergillus
*Candida

MOA:
*binds ergosterol in fungal cell membranes
==>makes pores in cell membranes
==>cell contents (ions and macromcs) leak out

*enhances binding of other anti-fungal Rx like flucytosine

*Resistance d/t decr ergosterol in membranes or ergosterol has altered structure

S/E:
*neprotoxicity ("Amphoterrible")
==>cell necrosis in renal tubules

*"renal tubule acidosis" (bicarb cannnot be reabs in PT or DT
==>hyperchloremic metabolic acidosis (retain Cl- because not enough HCO3-)

*avoid renal toxicity by giving mannitol to induce high rate of renal flow
("the solution to pollution is dilution")
Tx Coccidioides immitis
DOC=Amphotericin B
Tx Aspergillus
DOC=Amphotericin B
Tx candidiasis
Ketoconazole (on surface)

Amphotericin B (systemic)
ketoconazole
Tx:
Candida
Coccidioides immitis

MOA (for all "--conazoles"):
inhibits fungal CYP450
==>prevents demethylation of lanosterol to ergosterol
==>blocks cell wall syn

*X-ind in pt tx w/ampho B b/c ketoconazole BLOCKS antifungal actions of ampho B
(ampho B binds ergosterol to form pores to fungal membranes)

S/E:
*inhibits CYP450==>incr plasma conc of other drugs, esp cyclosporine in transplant pts; (fluconazole also incr [cyclosproine] by unknown MOA)

*inhibits adrenal 17α hydroxylase & scc CYP450's
==?adrenal insufficiency & decr [test] & [estradiol]
==>males: gynecomastia & decr libido
==>females: menstrual irreg
why is ketoconazole X-ind in pts taking amphotericin B?
b/c ketoconazole BLOCKS antifungal actions of ampho B
flucytosine
Tx: fungus

MOA: converted to fluouracil, which inhibits thymidylate synthase==>inh DNA syn
(mneum: "FU-TS in a dump",
FU=FluoroUracil, TS=Thymidylate Synthase)
-selectively toxic to fungal cells b/c mammalian cells unable to catalyze the deamination of fluCYTOSINE to fluoroURACIL [cytosine and uracil are both nucleic acids])

S/E: BM depression (limits clinical use)
-Give with ampho B b/c:
--1. fungal resistance to flucytosine develops quickly
--2. Amph B enhances the penetrance of flucytosine (synergistic)
which drug is selectively toxic to fungi b/c mamalian cells cannot catalyze its deamination?
flucytosine
(mammalian cells cannot catalyze deamination of flucytosine to fluorouracil, which is what inhibits thymidylate synthesis to inhibit DNA synthesis)
(+) silver stain means what dz?

-tx?
PCP

Tx:
DOC=trim-sulfa
if allergic to trim-sulfa, give pentamidine
Griseofulvin
Tx:
*DOC for ringworm
*DermatoPHYTES w/hyphae:
--TrichoPHYTON
--EpidermoPHYTON
--Microsporum

MOA: disrupts mitotic spindle by interacitng iwth polymerized microtubules
==>inh fungal mitosis
Tx athlete's foot?
miconazole

MOA: inhibit fungal CYP450 to block synthesis of ergosterol

("--CONAZOLES" [i.e. miCONAZOLE and ketoCONAZOLE] have same MOA)
Penicillin (PCN)
MOA:
Ridic p. 114:
-PCN bind bacterial PCP's (AKA transpeptidases), which are req to cross-link peptides to form bact cell wall
==>no cell wall
==>bact die (thus, Penicillin=bacteriCIDAL)

-eliminated by renal tubular secretion; Probenacid incr half-life of PCN by inhibiting its renal excretion

*Clavulanate, sulBACTAM, and tazoBACTAM inhibit bacterial beta-lactamases (major form of bacterial resistance)

*PCN's resistant to B-lactamase (i.e. beta-lactamase producting Staph):
--acid-labile: methcillin, nafcillin
--acid-stable (thus can take po): OXACILLIN, clOXACILLIN, diclOXACILLIN

*imipenem/cilastatin:
--imipenem is resist. to beta-lactamase
--cilastatin inhibits renal tubular dihydropeptidases (which metabolize/elim imipenem)==>incr half-life of imipenem


S/E:
***Hypersensitivity (Many ppl are allergic to penicillin)
EXAM--Cephalosporins
*same MOA as penicillins

Ridic p. 114:
-PCN bind bacterial PCP's (AKA transpeptidases), which are req to cross-link peptides to form bact cell wall
==>no cell wall
==>bact die (thus, Penicillin=bacteriCIDAL)
pt has gonorrhea. tx with PCN for 8 wks. Pt returns with similar Sx, but no diplococci in urine. How Tx?
(no diplococci in urine==>no longer has gonorrhea)

Pt has chlamydia. Tx with Tetracycline unless pt is a pregnant femlae, then Tx w/macrolide (eryTHROMYCIN, clariTHROMYCIN, aziTHROMYCIN)
man has Strep infxn and is allergic to PCN. How Tx?
Tx w/macrolides:

eryTHROMYCIN,
clariTHROMYCIN, aziTHROMYCIN
How is MRSA resistant to PCN?
altered PBP's

NOT via B-lactamase. Methicyllin is b-lactamase resistant, so MRSA must have some other form of resistance (altered PBP's)
Tx MRSA
in-pt: Vanc

out-pt:
T-S
clindamycin
doxycycline
Vancomycin
=bactericidal
=a glycopeptide

Ridic p. 141, picture:

Tx: ALL G+ BUGS!!!
-MRSA
-multi-resistant Staph epi (indwelling IV catheters)
-Enterococcus (Strep faecalis)
-endocarditis caused by Strep and Staph in PCN-resistant pts

MOA (Ridic):
-bind D-ala D-ala
==>cannot form peptidoglycan cell wall

MOA (Keeton):
-blocks cell wall synthesis by blocking sugar-glycan pentapeptide linked to a phospholipid in the cell wall
-(can't work via PCP's b/c MRSA have altered PCP's)

-If C. diff occurs w/iv Vanc, po vanc will still cure it (b/c Vanc not absorbed orally, so it cruises down the GI tract unabsorbed, and kills C. diff in intestine!)

S/E:
"red man syndrome" (non- allergic release of histamine==>red rash of torso and itching skin)
trimethoprim-sulfamethoxazole
("trim-sulfa")

DOC for PCP in AIDS pts

-MOA:
*blocks sequential steps (see flowchart on "Part 3," p. 6).

Ridic Simple p. 141: good explanation
Both sulfa and trim block bacterial THF synthesis, but at different steps.
1. (Bacteria normally use PABA to make THF.) Sulfa drugs look like PABA, so bacteria uses sulfa drug instead of PABA→no THF made

(Thus, sulfa drugs inhibit the step in which (PABA+pteridine)→dihydropteroic acid via enzyme=dihydropteroate synthase.)

2. TriMETHOprim (=MOA of METHOtrexate, Tim’s mneumonic) blocks DHF-R→cannot regenerate THF

*Sulfa drugs don't harm humans b/c we don't have this process; humans don't make THF, we get it from our diet (leafy veggies have folate)

*Trim is much more active against bacterial enzyme vs mammalian enzyme

S/E:
-sulfonamides can displace bilirubin from plasma protein binding sites==>kernicterus in neonates
-sulfonamides can cause hemolytic anemia
Tetracyclines
Tetracyclines ("Tet offensive soldier"--GREAT pic in Ridic Simple p128)
*Doxycycline
*Minocycline

*bacteriostatic

Tx:
*G+ and G-
--Ricketssiae (tick)
--Mycoplasma (walking pneumonia)
--Chlamydia
--amoebas

MOA: binds 30S subunit
==>blocks aminoacyl tRNA binding to acceptor site

*not used for pneumococcal pneumonia (tx w/PCN, ceph, erythromycin)

S/E:
-severe rash with sunlight
-liver and kidney stoxicity
-chelates Ca++
==>adverse effect on formation of bones and teeth (bad for fetus and babies)
==>bioavailability decreased by milk and food in GI tract
lincosamides
=clindamycin
*bacteriostatic

MOA: binds 50S subunit, preventing aminoacyl translocation of peptide chain
clindamycin
*bacteriostatic

MOA: binds 50S subunit,
preventing aminoacyl translocation of peptide chain
Tx pt with clindamycin, and he develops pseuedomembranous colitis. how tx?
(pseudomembranous colitis caused by C diff)

Tx with oral metronidazole or oral vancomycin
EXAM-Macrolides
*bacteriostatic

Macrolides=
eryTHROMYCIN
clariTHROMYCIN
aziTHRYOMYCIN

DOC=CAP (community-acquired pneumonia); CAP refers to any pneumonia (whether typical or atypical) that is acquired in community, rather than in a hospital (nosocomial pneumonia)

G- pneumonia
==>probly atypical bug
==>Tx with macrolides

-G+ pneumonia
==>it's probly Strep pneumo
==>Tx with ceph

-erythromycin can be used to incr stomach motility in DM pts w/diabetic gastroparesis (erythromycin stimulates gastrin receptrs)

S/E: erythromycin causes stomach cramping b/c stimulates motilin receptors in stomach
erythromycin
*bacteriostatic

Macrolides="ACE"
aziTHRYOMYCIN
clariTHROMYCIN
eryTHROMYCIN

DOC for CAP (community-acquired pneumonia)

*G(-) pneumonia
==>probly atypical bug
==>Tx with macrolides

*G+ pneumonia
==>probly Strep pneumo
==>Tx with ceph

-erythromycin can be used to incr stomach motility in DM pts w/diabetic gastroparesis (erythromycin stimulates gastrin receptrs)

S/E: erythromycin causes stomach cramping b/c stimulates motilin receptors in stomach
clarithromycin
*bacteriostatic

Macrolides=
eryTHROMYCIN
clariTHROMYCIN
aziTHRYOMYCIN

DOC=CAP (community-acquired pneumonia)
-Note: G- pneumonia:
==>probly atypical bug
==>Tx with macrolides
-Note: If pt has G+ pneumonia
==>it's probly Strep pneumo
==>Tx with ceph
-erythromycin can be used to incr stomach motility in DM pts w/diabetic gastroparesis (erythromycin stimulates gastrin receptrs)

S/E: erythromycin causes stomach cramping b/c stimulates motilin receptors in stomach
azithromycin
*bacteriostatic

Macrolides=
eryTHROMYCIN
clariTHROMYCIN
aziTHRYOMYCIN
Tx TB
"RIPE"
Rifampin
Isoniazid (INH)
Pyrazinamide
Ethambutol


S/E: (ridic: p. 134-5):
*RIP all cause hepatotoxicity!

"I SAW (Iso) a RED (Rifampin) PYRE (Pyrazinimide) BURNING THE LIVER"

*Rifampin
-"R"ifampin="R"NA: Rifampin binds prokaryotic RNA polymerase's beta-subunit

S/E:
1. induces CYP450, so speeds metabolism of:
--phenytoin==>seizures
--OCP's==>pregnancy
--coumadin (anticoagulant)==>not enough anticoagulation

2. "R"ifampin="R"ed:
turns body fluids (urine, feces, tears, sweat) a red color

*Isoniazid=INH
-peripheral neuropathy (b/c incr excretion of Vit B6 (pyridoxine)
-thus give Vit B6 supplement

*Pyrazinamide
--especially hepatotoxic

*Ethambutol
--Marjan: reversible, dose-dependent ocular toxicity:
-decr visual acuity w/central scotoma
-color vision loss
Nalidixic acid
inhibits DNA gyrase (forms negative DNA supercoils)
flouroquinolones
"--FLOXACIN::
-ciproFLOXACIN
-levoFLOXACIN
-gemiFLOXACIN
-moxiFLOXACIN

MOA: inhibit DNA gyrase (which forms negative DNA supercoils (req for bact DNA))
protein synthesis inhibitors
"buy AT 30, CELL at 50":

"AT" (30)
*A=Aminoglycodies (cidal) + spectinomycin (static) =
Tx PCN-resistant gonorrhea

*T=Tetracyclines (Doxycycline)

"CELL" (50)
C=Chlorampheticol
E=Erythromycin
L=Lincomycin
L=cLindamycin

Since chloramphenicol, clindamycin, & macrolides (erythromycin, clarimycin, and erythromycin) work at same site, do NOT use them together b/c interfere with each other
bacteriocidal vs bacteriostatic drugs
BACTERIOCIDAL
PCN’s, cephalosporins, aztreonam, imipenem
Vanc
Bacitracin
Cycloserine
Aminoglycosides (gentamicin, etc)
Methenamine
Polymixin, colistin
Rifampin
Isoniazid
Fluoroquinolones (norfloxacin, etc)
Nalidixic acid

BACTERIOSTATIC:
Spectinomycin
Chloramphenicol
Macrolides (eryTHROMYCIN, etc)
Lincomycin
Clindamycin
Tetracyclines (doxocycline, minocycline)
Nitrofurans = nitrofurantoin
Trim-sulfa
Resistance to β-lactams
-B-lactams=
*PCN
*cephalosporins
*monobactams
*carbapenems

-B-lactams work by binding PCP's on bacteria

Resistance to B-lactams in G+ bugs:
1. produce B-lactamases
(Methicillin, nafcillin, and oxacillin(& clOXACILLIN & diclOXACILLIN) are B-lactamase-resistant drugs that can kill staph aureus

Mneum (ridic p. 117, picture): i MET a NAsty OX w/a B-lactamase ring around its neck)

2. altered PCP's with decr affinity for B-lactams

*MRSA: altered PCP binding site
==>no B-lactam can bind
==>thus resistant to all B-lactams (PCN, ceph, imipenem, aztreonam)
==>Tx MRSA w/

(Inpt)
Vanc

(Outpt)
*clindamycin
*trim-sulfa
*doxycycline

Resistance to B-lactams in G- bugs:

1. produce B-lactamases (penicillinases), which may be inducible
2. Decr permeability:
β-lactams gain access to the periplasmic space (the site of the peptidoglycan wall in G- bugs, where PCP's are) by passing through channels (called porins) in the outer bacterial membrane. A mutation which decreases the number of porins reduces the entry of the β-lactams to their site of action. Thus a β-lactam could be resistant to β-lactamases, and yet not be able to inhibit bacteria growth because it could not reach the PBP's.
B-lactams
-B-lactams=
*PCN
*cephalosporins
*monobactams
*carbapenems

-B-lactams work by binding PCP's on bacteria
resistance to Vancomycin
Vanc works by binding to terminal D-ala of the nascent bacterial chain
==>inhibits trans-glycosylation
==>inhibits elongation and cross-linking of peptidoglycan

Resistance to Vanc:
*change the growing bacteria's terminal D-ala==>D-lactate
==>Vanc can no longer bind
Resistance to Flouroquinolones
a single point mutation
==>alters FQ's binding to active site of DNA gyrase

(DNA gyrase is a type of Topoisomerase II that introduces negative supercoils or relaxes positive supercoils.

[mneum: "gyrate"~think of Elvis gyrating (twisting) his hips.]

-Gyrase's can introduce negative supercoils
==>allows bacteria to have free negative supercoils.

-Gyrase can relax positive supercoils
==>allows DNA replication to occur.)
Resistance to aminoglycosides
Aminoglycosides= (Ridic p. 130 picture)
*gentaMICIN
*tobraMYCIN
*amikaCIN

"buy AT 30" (A=Aminoglycosides)

(MOA: AG binds to 30S subunit = interfere w initiation complex of peptide formation
==>misreadi mRNA and break polysomes into non-functional monosomes.)

*Some bacteria are resistant b/c their transferases (plasmid-mediated enzymes) alter the structure of AG (i.e. by acetylating amine groups, phosphorylating hydroxyl groups)
==>AG's can't bind bact
Resistance to macrolides
Macrolides="ACE":
*aziTHROMYCIN
*claryTHROMYCIN
*eryTHROMYCIN

Bacteria methylate 23S subunit of 50S ribosome, so that drug can't bind

[this is also mech of resistance to clindamycin]
Resistance to clindamycin
Same as resistance to macrolides (eryTHROMYCIN, clariTHROMYCIN, aziTHROMYCIN):

Bacteria methylate 23S subunit of 50S ribosome, so that drug can't bind
Resistance to tetracyclines
[TetraCYCLINE, eg. doxaCYCLINE, are pumped into bacteria by E-dependent transport system in their cellular membranes.]

Bacteria can become resistant by decreasing intracellular accumulation of drug or via efflux pumps (pump the drug out).
Resistance to trim-sulfa
The following is the same mech of Resistance for all Rx that inhibit folate synthesis.

Bacteria are resistant if they have a plasmid-coded gene that does not bind sulfonamides (the Rx) but still binds PABA (req for bact to make DNA, RNA, proteins)
==>bacteria can still make folate
Resistance to rifampin
("RIPE": Tx: TB)

(rifampin inhibits M. tb's DNA-directed RNA polymerase)

mutation causes single amino acid substitution in the B-subunit of the bacteria's DNA-directed RNA polymerase
==>reduces binding of rifampin
Resistance to chloramphenicol
bacterial plasmid produces acetyltransferases which inactivate the drug