Pharm-Part 3

Front 1

EXAM-praziquantal

Back 1

(worm drug)

opens Ca++ channels to cause muscle tetany
==>tegmental damage
==>activates host imm sys

Front 2

EXAM-albendazole

Back 2

(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)

Front 3

EXAM-thiabendazole

Back 3

(worm drug)

inhibits mictochondrial fumurate reductase

Front 4

EXAM-ivermectin

Back 4

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

Front 5

Rx for Cestodes

Back 5

(Cestodes=tapeworms)

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

also, praziquantal, mebendazole

Front 6

Tx Ascaris lumbricoides

Back 6

(Ascaris lumbricoides=roundworm)

AlBENDazole
MeBENDazole
Pyrantel pamoate
Piperazine

(mneum: "worms BEND")

Front 7

Tx Enterobius vernicularis

Back 7

(Enterobius vernicularis=pinworm:
"A safety PIN ENTERs your body painfully")

-Mebendazole (mneum: a safety pin has a bend in it)
-Pyrantel pamoate

Front 8

Tx Necator americanus

Back 8

(Necator americanus=hookworm)

Albendazole
Mebendazole

"Me and Al say, "There's nothing american about a hookworm."

Front 9

Tx Trichuris trichiura

Back 9

(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!"

Front 10

Tx Strongyloides stercoralis

Back 10

(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

Front 11

Tx Trichinella spiralis

Back 11

(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

Front 12

Tx Filariae

Back 12

*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"

Front 13

Tx Wucheria bancrofti

Back 13

diethylcarbamazine

(ridic p. 256, pic)

Front 14

Tx Onchocerca volvulus

Back 14

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

Front 15

pt passes tape worm segments (proglottids).
-what is most likely tapeworm?
-how Tx?

Back 15

Taenia saginata (beef tapeworm) or
Diphyllobothrium latum (fish tapeworm--from sushi)

Tx:
*DOC=niclosamide ("tapeworms are flat like a nickel")
-praziquantel

Front 16

what does Diphyllobothrium latum do?

Back 16

Diphyllobothrium latum (fish tapeworm) eats up B12 in gut [Goljan]
==>megaloblastic anemia

Front 17

Tx cysticercosis

Back 17

albendazole

Front 18

Tx tapeworm (and don't know identity)

Back 18

DOC=praziquantel

Front 19

baby with pruritis and + "cellophane tape" test.

-what do they have?
-Tx?

Back 19

(pruritis=anal itching)

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

Tx:
mebendazole
pyrantel pamoate

Front 20

pt with mixed infxn: cestode + trematode

Back 20

(cestode=tapeworm)
(trematode=fluke)

Tx w/praziquantel

Front 21

metronidazole

Back 21

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

Front 22

person has infxn and taking a Rx. He goes to wine-cheese party and gets b/v.

-What drug is he on?

Back 22

Metronidazole

Front 23

Pentamidine isethionate

Back 23

-2nd line drug for PCP (if person can't take trim-sulfa)

Front 24

Tx PCP

Back 24

DOC= trim-sulfa

-if person can't take trim-sulfa, give Pentamidine isethionate

Front 25

organisms that cause typical pneumonia?

Back 25

Strep pneumo
H flu
M cat (Moraxella cat)--"the MCAT gave me pneumonia"

Front 26

organisms that cause atypical pneumonia?

Back 26

Legionella
Chlamydia
Mycoplasma

Front 27

antimalarial drugs
-prophylaxis
-Treatment
-S/e of drugs

Back 27

"--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

Front 28

Acyclovir

Back 28

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

Front 29

Tx HSV encephalitis

Back 29

acyclovir

Front 30

Tx: keratoconjunctivitis caused by HSV

Back 30

trifluridine (trifluorothymidine)

Front 31

Gangciclovir

Back 31

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

Front 32

Tx immunocompromised pt w/CMV

Back 32

gangciclovir

Front 33

Idoxuridine

Back 33

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

Front 34

Tx HSV keratitis

Back 34

idoxuridine

Front 35

Amantadine

Back 35

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

Front 36

Tx Influenza A

Back 36

amantadine

Front 37

Tx rubella

Back 37

amantadine

Front 38

prophylaxis against Influenza A

Back 38

amantadine

Front 39

zanamivir

Back 39

Tx: flu

MOA: inhibit viral neuraminidase

(ridic p. 172, picture)

Front 40

zidovudine

Back 40

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

Front 41

saquinavir

Back 41

HIV protease inhibitor

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

Front 42

interferons

Back 42

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

Front 43

Amphotericin B

Back 43

*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")

Front 44

Tx Coccidioides immitis

Back 44

DOC=Amphotericin B

Front 45

Tx Aspergillus

Back 45

DOC=Amphotericin B

Front 46

Tx candidiasis

Back 46

Ketoconazole (on surface)

Amphotericin B (systemic)

Front 47

ketoconazole

Back 47

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

Front 48

why is ketoconazole X-ind in pts taking amphotericin B?

Back 48

b/c ketoconazole BLOCKS antifungal actions of ampho B

Front 49

flucytosine

Back 49

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)

Front 50

which drug is selectively toxic to fungi b/c mamalian cells cannot catalyze its deamination?

Back 50

flucytosine
(mammalian cells cannot catalyze deamination of flucytosine to fluorouracil, which is what inhibits thymidylate synthesis to inhibit DNA synthesis)

Front 51

(+) silver stain means what dz?

-tx?

Back 51

PCP

Tx:
DOC=trim-sulfa
if allergic to trim-sulfa, give pentamidine

Front 52

Griseofulvin

Back 52

Tx:
*DOC for ringworm
*DermatoPHYTES w/hyphae:
--TrichoPHYTON
--EpidermoPHYTON
--Microsporum

MOA: disrupts mitotic spindle by interacitng iwth polymerized microtubules
==>inh fungal mitosis

Front 53

Tx athlete's foot?

Back 53

miconazole

MOA: inhibit fungal CYP450 to block synthesis of ergosterol

("--CONAZOLES" [i.e. miCONAZOLE and ketoCONAZOLE] have same MOA)

Front 54

Penicillin (PCN)

Back 54

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)

Front 55

EXAM--Cephalosporins

Back 55

*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)

Front 56

pt has gonorrhea. tx with PCN for 8 wks. Pt returns with similar Sx, but no diplococci in urine. How Tx?

Back 56

(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)

Front 57

man has Strep infxn and is allergic to PCN. How Tx?

Back 57

Tx w/macrolides:

eryTHROMYCIN,
clariTHROMYCIN, aziTHROMYCIN

Front 58

How is MRSA resistant to PCN?

Back 58

altered PBP's

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

Front 59

Tx MRSA

Back 59

in-pt: Vanc

out-pt:
T-S
clindamycin
doxycycline

Front 60

Vancomycin

Back 60

=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)

Front 61

trimethoprim-sulfamethoxazole

Back 61

("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

Front 62

Tetracyclines

Back 62

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

Front 63

lincosamides

Back 63

=clindamycin
*bacteriostatic

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

Front 64

clindamycin

Back 64

*bacteriostatic

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

Front 65

Tx pt with clindamycin, and he develops pseuedomembranous colitis. how tx?

Back 65

(pseudomembranous colitis caused by C diff)

Tx with oral metronidazole or oral vancomycin

Front 66

EXAM-Macrolides

Back 66

*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

Front 67

erythromycin

Back 67

*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

Front 68

clarithromycin

Back 68

*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

Front 69

azithromycin

Back 69

*bacteriostatic

Macrolides=
eryTHROMYCIN
clariTHROMYCIN
aziTHRYOMYCIN

Front 70

Tx TB

Back 70

"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

Front 71

Nalidixic acid

Back 71

inhibits DNA gyrase (forms negative DNA supercoils)

Front 72

flouroquinolones

Back 72

"--FLOXACIN::
-ciproFLOXACIN
-levoFLOXACIN
-gemiFLOXACIN
-moxiFLOXACIN

MOA: inhibit DNA gyrase (which forms negative DNA supercoils (req for bact DNA))

Front 73

protein synthesis inhibitors

Back 73

"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

Front 74

bacteriocidal vs bacteriostatic drugs

Back 74

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

Front 75

Resistance to β-lactams

Back 75

-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.

Front 76

B-lactams

Back 76

-B-lactams=
*PCN
*cephalosporins
*monobactams
*carbapenems

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

Front 77

resistance to Vancomycin

Back 77

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

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Resistance to Flouroquinolones

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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.)

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Resistance to aminoglycosides

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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

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Resistance to macrolides

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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]

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Resistance to clindamycin

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Same as resistance to macrolides (eryTHROMYCIN, clariTHROMYCIN, aziTHROMYCIN):

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

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Resistance to tetracyclines

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[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).

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Resistance to trim-sulfa

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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

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Resistance to rifampin

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("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

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Resistance to chloramphenicol

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bacterial plasmid produces acetyltransferases which inactivate the drug