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Antimicrobial Pharmacology Flashcards

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1
Q

What bugs does amoxicillin / ampicillin cover?

A

HELPS
-> remember we have extended gram negative and anaerobe coverage (especially with beta lactam inhibitors paired)

Hemophilus, H. pylori
E. coli / Enterococcus
Listeria
Proteus mirabilis - UTI's
Salmonella / Shigella

+ Lyme disease (robin of Ixodes)

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2
Q

How do nafcillin and ampicillin differ with regards to resistance?

A

Ampicillin - still penicillinase sensitive, just wider spectrum. Needs to be combined with a Beta-lactamase inhibitor to retain activity

Nafcillin - Penicillinase resistant, narrower spectrum. Works by having a bulky R group which is not cleaved by penicillinases, but MRSA is still resistant due to altered penicillin-binding protein.

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3
Q

What drug is used for prophylaxis in patients at high risk for endocarditis undergoing surgical (i.e. cystoscopy) or dental procedures?

A

Amoxicillin - think of the guy’s teeth getting punched out in sketchy.

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4
Q

Are piperacillin / ticarcillin susceptible to beta-lactamases? What are they good for?

A

YES! They are in the amoxicillin / ampicillin sketch.

However, they are the pipers in the tiger suit charming mona lisa, in gas masks.

They are good against P. aeruginosa and anaerobes, but they MUST be paired with a Beta-lactam inhibitor (i.e. tazobactam / sulbactam)

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5
Q

What is the main use for 1st generation cephalosporins? And name a few.

A

Surgical prophylaxis + PEK UTIs -> proteus, E. coli, Klebsiella. More gram + coverage than other cephalosporins.

Think of General “Lex” flexing and his fez

Cephalexin, Cefazolin

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6
Q

What is the main use for 2nd generation cephalosporins? And name a few.

A

Cefotetan (tea), Cefoxitin (general fox), cefuroxime (furious)
HENS - Hemophilus, Enterobacter, Neisseria, Serratia
Pretty low yield overall

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7
Q

What is the main use for 3rd generation cephalosporins and name a few.

A

Great CNS penetration -> Ceftriaxone, cefotaxime (used in neonates so no biliary sludging), cefpodixime

Used for treatment of common meningitis, and better gram negative coverage than 1st two generations: Neisseria, Hemophilus, and Streptococcus pneumoniae.

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8
Q

What 3rd generation cephalosporin is most useful for nosocomial pneumonia?

A

If you have to cover for Pseudomonas -> Ceftazidime - general Taz’s wife is Mona Lisa.

Ceph TAZ for pseudomone-AZZ

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9
Q

What is usage of the 4th generation cephalosporin and what is it called?

A

Called Cefepime (general prime) -> know that it is broad spectrum and also next to the Mona Lisa poster -> covers Pseudomonas

Also wearing meningitis helmet -> good coverage for meningitis.

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10
Q

What is the usage of the 5th generation cephalosporin and what is it called? Does it have Pseudomonas coverage?

A

Think of General Tara knocking over the emperor -> only cephalosporin to have MRSA coverage

NO Pseudomonas coverage -> not next to the poster.

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11
Q

What are the mechanisms of resistance to cephalosporins?

A
  1. Altered PBPs

2. Extended spectrum beta lactamases - (they are generally resistant to normal beta lactamases due to side changes)

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12
Q

What is the only monobactam and what is its spectrum of activity? Why is it notably useful?

A

Aerobic gram negatives only -> think of the bellows. Mona Lisa stands by and is covered by this drug.

Notably useful because it has no side chain -> no cross-reactivity with penicillin. Think of the penicillin pencil sticking out of the robot, who is still being treated.

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13
Q

What is imipenem always administered with and why?

A

Also given with cilastin, an inhibitor of dehydropeptidase 1, which is a renal tubular enzyme which normally breaks down imipenem.

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14
Q

What is the primary clinical use of carbapenems in general and what is the side effect of concern?

A

Used broad spectrum for all types of infections, especially against organsms making extended-spectrum beta-lactamases (think of rainbow beta-lactamase guys crawling over the wall). -> ESBLs

Side effect of concern - seizures, especially imipenem. Also cause Rash and GI distress (think of robot getting covered in poop / poopy rash)

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15
Q

What is the mechanism of Vancomycin / why is does it work where beta-lactams don’t?

A

Does not bind to PBPs, instead binds directly to what PBPs are binding, the D-ala-D-ala motif.
-> beta-lactamases and altered PBPs will have NO effect, since vancomycin doesn’t interact with this.

Resistance mechanism is just switching to D-ala-D-lac

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16
Q

Why is vancomycin added to meningitis regimens?

A

To cover penicillin-resistant Strept pneumo. (i.e. altered PBPs).

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17
Q

What are the side effects of vancomycin?

A

Nephrotoxicity - renally excreted so be careful
Ototoxicity - broken ear
Thrombophlebitis - vines coming up
Red man syndrome

DRESS syndrome may also occur

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18
Q

What is the mechanism of resistance to tetracycles?

A

Think of the efflux bike pump. Can also modify the 30S ribosome

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19
Q

How are tetracyclines eliminated, and why are expired ones an issue?

A

Eliminated fecally, so safe to use in renal failure -> think of the colonic poop tube in the back.

Expired ones are hella problematic cuz they can cause Fanconi syndrome (proximal absorption defect, including a Type II RTA).

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20
Q

What are the side effects of macrolides?

A

Increased GI motility
Prolonged QT
Cholestatic hepatitis (failure to excrete bowel, think of the Gi soldier’s yellow face)
CYP inhibition

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21
Q

What is the most commonly tested indication for Clindamycin?

A

Aspiration pneumonia -> since it has good coverage against gram positives of the mouth, as well as anaerobes

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22
Q

What is a common treatment regimen for severe polymicrobial infections of the female genital tract (i.e. endometritis)?

A

Clindamycin + gentamicin -> think of the karate lady doing Pec fly’s with the ovaries while having psi’s in her pockets

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23
Q

Give four other indications for clindamycin than aspiration pneumonia and female GU infections.

A

Trainer with MRSA tattoo holding pie:

  1. MRSA
  2. Group A strept

Guy who has falling and perforated his pants:
3. Clostridium perfringens

Plants all around the front:
4. Gardnerella vaginosis (Metronidazole can also be used)

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24
Q

What are the indications for chloramphenicol?

A

Used to treat meningitis in developing countries (kid with helmet hitting ball)

Also used to treat Rickettsia ricketsii infection of pregnant mothers (doxycycline contraindicated in pregnancy)

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25
What are the side effects of chloramphenicol?
1. Dose-dependent anemia - deflated RBCs 2. Aplastic anemia - gray bone 3. Gray baby syndrome
26
What is gray baby syndrome?
Gray baby syndrome - hypothermia, flaccidity gray color, and shock since infants have low UDP-glucuronyltransferase activity needed to properly inactivate the drug
27
What is the activity / usage of Linezolid?
Gram + infections, especially MRSA and vancomycin-resistant enterococcus
28
What are the side effects of linezolid?
1. Peripheral neuropathy - glove and stocking of crime investigator 2. Optic neuropathy - snapped camera cord 3. Thrombocytopenia most commonly, even pancytopenia 4. Serotonin syndrome - weak MAOI
29
What is the general indication of aminoglycosides? Mechanism of action? What are they used with?
severe AEROBIC gram NEGATIVE infections (sepsis). Usually combined with a cell wall active drug (esp. beta lactams or vancomycin) to enhance penetration. They are then uptaken thru the cell membrane in an oxygen-dependent transport method They are 30S ribosome bacterioCIDAL (think of the assassin killing the dude).
30
What two luminal aminoglycoside agents are used for bowel prep before surgery or treating intraintestinal parasites? (Aminoglycosides have poor oral absorption and are usually given IV)
Neomycin - think of neo at the ditch Paromomycin - i guess it's not actually paramycin lol
31
What aminoglycosides are generally used against pseudomonas?
TAG Tobramycin Amikacin Gentamicin -> this one is used for a lot of gram negative septicemia
32
What is the role of aminoglycosides in treating enterococcus infection?
Often used to treat enterococcus endocarditis -> good activity against this gram positive bug with the help of vancomycin.
33
What are the mechanisms of resistance against aminoglycosides?
1. Bacterial acetylation enzymes, or other transferase enzymes i.e. phosphorylation, adenylation - think of the enterococcus throwing shurikens at the tobramycin cobra 2. Porin mutation -> which brings the aminoglycosides into the cell 3. Modification of ribosome binding sites
34
What are the adverse effects of aminoglycosides?
1. Nephrotoxicity - Acute Tubular Necrosis - Killing is max concentration dependent so try to keep the troughs low 2. Ototoxicity / Vestibulotoxicity 3. Neuromuscular blockade - contraindicated in myasthenia gravis due to severe weakness 4. Teratogenicity - deafness in the newborn - tarantula on gong
35
What drug can be used as a monotherapy against latent TB?
ISOniazid - think of the lone ranger next to the sleeping guy.
36
What is the mechanism of action of isoniazid (INH)? How is it activated / how do you get resistance to it?
Inhibits synthesis of mycolic acids (think of the fuchsia cacti on the horizon) It is a prodrug converted by Kat-G (Catalase-peroxidase in mycobacterium, think of the tiger leaping at the isolated ranger in sketchy) -> resistance is via downregulation of KatG
37
What patients are at greatest risk for toxicity from isoniazid? How does it interact with other drug levels?
Slow acetylators - metabolism occurs in liver initially by N-acetyltranferase It is a CYP inhibitor (while rifampin is a CYP inducer)
38
What are the most common adverse effects of isoniazid therapy?
INH Injures Nerves - peripheral neuropathy due to increased B6 wasting -> give with pyridoxine Hepatocytes - hepatitis is common adverse effect, must monitor liver function tests -> think of the cow liver spot (all RIPE drugs) and LFT flag held up by slow acetylator Also causes drug-induced lupus -> wolf next to lone ranger MUDPILES - metabolic acidosis
39
What derivative of rifampin is preferred for patients taking protease inhibitors? Why?
Rifabutin, induces CYP only about half as much as rifampin, which is useful in maintaining therapeutic drug concentrations
40
What is the P of RIPE and what its major side effects? Mechanism of action?
Pyrazinamide (think pyro) - mechanism unknown Side effects: 1. Nausea and vomiting which is significant 2. Dose dependent hepatotoxicity - like all RIPE drugs 3. Hyperuricemia - think of the guy knitting
41
What drugs are used for the treatment of Mycobacterium avium complex?
1. Macrolide - Clarithromycin or azithromycin 2. Ethambutol - Think Ethyl the Sheriff with her AIDS ribbon 3. Rifabutin - think "Buttes" - mesas, a drug related to rifampin but less problematic for CYP induction in patients already being treated for HIV
42
What is the first line agent to use in treating leprosy? What is its mechanism of action and two important side effects?
Dapsone - deputy - Similar to sulfonamides -> inhibits dihyDROPterate synthase 1. Hemolysis in G6PD deficiency - eating watermelon 2. Agranulocytosis - hourglass
43
What other drug is used to treat leprosy other than dapsone? What is added for the lepromatous form?
Rifampin Added for lepromatous form - think of the guy with the leonine face cleaning his rifampin rifle with a cloth -> clofazimine Mechanism of action of clofazimine is nebulous, inhibiting bacteria growth probably by binding guanine in DNA. Low yield.
44
Is TMP/SMX teratogenic?
Yes! It antagonizes folate synthesis -> think of the tarantulas climbing down the walls. -> neural tube defects
45
Why does TMP/SMX cause a Type IV RTA?
Trimethoprim is a competitive inhibitor of ENaC -> hyperkalemia Decreased reuptake of K via the H/K antiporter leads to acidosis.
46
What are the consequences of TMP/SMX's interaction with albumin?
Displacement of unconjugated bilirubin in newborn -> kernicterus - candy korn Displacement of warfarin from albumin binding -> increased INR and bleeding events - blood all over mom snapping photosensitivity photo
47
Which fluoroquinolones are useful for treating pseudomonas and when are these drugs indicated for the treatment of UTIs? Pyelo?
Think of Mona Lisa elevating and sipping her UTI cup -> Levofloxacin and Ciprofloxacin, but NOT moxifloxacin Cipro / Levo good for complicated UTIs or prostatitis. First line is TMP / SMX. Think of the kidney canteen spilling out -> FQs are 1st line in the empiric treatment of pyelonephritis
48
Are Salmonella / Shigella treated and how?
Think of the salmon in the center of the table, along with intestines Shigella - routinely treated with FQs, much like Campylobacter and ETC. Salmonella - prolongs course generally, do NOT treat unless infection is severe or patient is immunocompromised.
49
What are the contraindications of fluoroquinolones?
1. Children < 10 and pregnant women - cartilage damage / teratogen 2. Susceptible elderly patients and those on longterm glucocorticoid therapy - tendon / cartilage rupture.
50
Are fluoroquinolones active against Strep pneumoniae?
Yes - the respiratory FQs including levofloxacin and moxifloxacin have good gram positive coverage Includes Legionella and Mycoplasma pneumonia as well
51
What drug can be used in place of amoxicillin in triple antibiotic therapy? What's the usual regimen?
Metronidazole - think of the helicopter outside!!!!!!!! Normal regimen: Amoxicillin + clarithromycin + PPI
52
What is the classic infusion reaction of Amphotericin B?
"Shake and Bake" - Fever and Chills
53
What are the consequences of renal toxicity of amphotericin B?
1. Type 1 renal tubular acidosis - Distal RTA with hypokalemia -> Think of 1 acidic test tube, slipping on banana peel 2. Hypomagnesemia - should supplement. Remember that very low magnesium and can lead to low PTH -> hypocalcemia 3. Anemia -> broken kidney leads to decreased erythropoieitin synthesis 4. Prerenal azotemia - from pores formed in kidney and volume loss. Always give with saline.
54
What is the mechanism of action of flucytosine and how is it activated?
Converted from cytosine analog by cytosine deaminase (C-> U being tipped) to become 5-fluorouracil analog. Inhibits DNA / RNA biosynthesis, thus protein synthesis. Used in combination with amphotericin for cryptococcal infections.
55
What is the mechanism of action of the azoles in general?
Think "Lane Closed" They inhibit the CYP450 which converts lanosterol to ergosterol for the fungal cell wall.
56
What are the side effects and indications of voriconazole?
Think of the dimly lit vortex portion of the sketchy with light flashes - > Causes photopsia and blurry vision 1. Aspergillosis - think of vortex in aspergillus sketch 2. Candidal infections - i.e. AIDS esophagitis - think of Canada flag
57
What are the uses of fluconazole?
Think of flying monkeys wearing helmets Has REALLY good CNS penetration - Cryptococcal meningitis + maintenance - Candidal infections of all types
58
What is itraconazole used for?
ITraconazole - for fungi with two ITerations Dimorphic fungi including Histo, Blast, Coccidiodo, Sporothrix
59
What azoles are used to treat tinea infections?
Think of the lion next to the tin man holding a pinecone and getting his hair cut Close trim - Clotrimazole My cone - Miconazole
60
What are the side effects and uses of ketoconazole?
Think of the key locking the witch in Tin man has boobs - Gynecomastia, from blocking androgen synthesis Blocking of 17,20-desmolase in adrenal cortex -> first step in cholesterol synthesis Blocks androgens / estrogens -> used in PCOS to reduce androgenic symptoms Also used in treatment of Cushing's disease -> blocks cortisol overproduction
61
What is Griseofulvin's interaction with the CYP system?
Induces CYP! | -> think of greasing a car's engine to make it a well-oiled machine
62
How does caspofungin and other echinocandin's differ greatly from other antifungal medications? Indication?
They act at the fungal cell WALL, not cell membrane, diminishing synthesis of Beta 1,3 glucans. Indicated for Candidal esophagitis and other systemic infections (given IV) + Aspergillus (scare crow)
63
What are the two main adverse effects of NRTIs as a class?
1. Mitochondrial toxicity leading to LACTIC ACIDOSIS -> mitochondrial table with spilled milk on it 2. Lipodystrophy - particularly stavudine and zidovudine (think of the horse)
64
What NRTI does not require a phosphorylation before becoming active?
Tenofovir - think T for nucleoTide -> already has the phosphaTe
65
What drug is commonly used in the treatment of HBV which is a NRTI and what's its main side effect? What other drugs in class also have this side effect?
Lamivudine - think Sir Lancelot -> peripheral neuropathy (gloves and stockings) Other drugs: Stavudine - Steve Didanosine - Dan
66
What are the side effects of zidovudine?
1. Myelosuppression -> bone dish. Which leads to: 2. Anemia - think of her white dress (no red anymore) 3. Agranulocytosis - think of hourglass she's holding 4. Lipodystrophy - horse Basically just pancytopenia + lipodystrophy
67
Which NRTI causes pancreatitis?
Didanosine
68
What type of hypersensitivity is it to Abacavir?
Type IV / delayed type hypersensitivity in those with HLA-B57-01
69
What is the unique side effect of emtricitabine?
Hyperpigmentation of palms and soles -> think of Arthur's "excalibur" and the gloves he's wearing
70
What are the three NNRTI's you should know for the exam? Which can be safely used in pregnancy?
1. Nevirapine - only one which can be safely used in pregnancy "never gonna fk up ur baby" 2. Efavirenz 3. Delavirdine - Lady Delavir - WATCH OUT! Sounds like the name of an NRTI
71
What are the important class side effects of NNRTIs?
1. Hepatotoxicity - seen in all - think of the horse with the liver spot 2. SJS / rash - think of the SJS mask on the left side of the picture
72
What side effects if Efavirenz known for?
CNS / psychiatric symptoms - think of Queen Efavir holding her head and freaking out while looking at the moon -> vivid dreams and insomnia
73
What gene is mutated to become resistant to protease inhibitor? Integrase inhibitors? Reverse transcriptase inhibitors?
Pol gene - think of Paul's black smith. Pol gene encodes for protease, reverse transcriptase, and integrase ALL the same!
74
Main side effects of Protease inhibitors? One specific on for indinavir?
1. Hyperglycemia - candy 2. Lipodystrophy - horse 3. Hyperlipidemia - butter Indinavir - indigo lady -> Nephrolithiasis
75
What protease inhibitor is used as a booster in many protease regimens?
Think of the kids high fiving eachother "Right on!" as they collapse the CYP450 cart -> Ritonavir, raises drug concentrations of other protease inhibitors Remember to use rifabutin instead of rifampin if you need to treat TB or prophylaxis for Neisseria / Hemophilus
76
What is the mechanism of action of maraviroc?
Blocks CCR5 - inhibits gp120 binding to this receptor on T cells / monocytes in susceptible strains
77
What drug is a fusion inhibitor and what protein does it target?
Targets the protein responsible for fusion of the virion with the cell -> gp41 (interacts after gp 120 has bound CD4 + CCR5/CXCR4) Drug: EnFUvirtide
78
What is the major side effect of integrase inhibitors and give an example of one? What is used as a booster?
Elevated creatine kinase / rhabdomyolysis -> think of chicken next to guard who is supposed to be guarding against HIV DNA integration into the genome Example: ElviTEGRavir Booster: Cobicistat - Pogue notes, low yield but might come up.
79
What are the indications for interferon alpha?
1. Hepatitis A and B 2. Hairy cell leukemia - hairy brown ball 3. Malignant melanoma - black ball 4. Kaposi sarcoma - Kate's Posie's roses on the side 5. Condyloma accuminata - HPV - jar which sits on table 6. Renal cell carcinoma - claw machine nearby shaped like kidney
80
What are the side effects of interferon alpha?
1. Flu-like symptoms - think of guy passes out on the machine 2. Bone marrow suppression - Shape of game board
81
What are the main indications of interferon beta and gamma?
IFN-beta - Multiple sclerosis | IFN-gamma - Chronic granulomatous disease - increase macrophage activation
82
What is the mechanism of action of ribavirin and how is it activated?
Guanine nucleoside analog - > must be phosphorylated three times (three pepper shakers by ribs) before becoming active - > inhibits RNA synthesis as well as DNA synthesis (via inhibiting IMP dehydrogenase
83
What are the two main side effects of ribavirin to remember? One of these "side effects" is broadly similar to a concern of griseofulvin.
1. Dose-dependent hemolytic anemia - think of the rupturing tomatoes 2. Teratogenic!!!! - just like griseofulvin
84
What is the mechanism of action of sofosbuvir?
Chain terminator -> inhibits HCV RNA-dependent RNA polymerase -> think of the sofa with the chain next to it, must be terminated. Used in combination with ribavirin / IFNalpha
85
What is the mechanism of action of simeprevir? Main side effect?
Think of the guy simmering some food in his back, next to his machete -> Machete in tree = protease inhibitors. Protease, like in HIV, cleaves the polyprotein precursor for viral maturation. Side effect - flashing camera = photosensitivity
86
What is the first step in activation of acyclovir and why is this important?
The guanosine (think gucci bag) analog is phosphorylated by Hermes (VIRALLY encoded thymidine kinase) - > important because initial phosphorylation step only occurs in virally infected cells, which allows for interference. - > only HSV/VZV has the thymidine kinase, it is not present in CMV / EBV -> acyclovir ineffective in these cells
87
What is the mechanism of action of Cidofovir? What drug is similar?
NucleoTide analog which does not require viral activation -> along with Foscarnet, can directly target polymerases with kinase activation of any kind Think of Cid dragging his car in to turn off the polymerase
88
What is the mechanism of action of foscarnet?
inorganic pyro"fos"phate compound, inhibits DNA polymerase, RNA polymerase, and HIV reverse transcriptase
89
When is foscarnet used and what are its big side effects?
Only for CMV when ganciclovir is not available Side effects: Nephrotoxicity (think of barrel of kidney beans falling over), CNS effects -> boy seizing, potential chelator of divalent cations in blood -> hypocalcemia, hypokalemia, hypomagnesemia
90
What is the spectrum for cidofovir and when is it used?
HSV, VZV, CMV Used for CMV (esp. retinitis) when CMV is resistant to ganciclovir / foscarnet -> works against these cuz thymidine kinase is not needed
91
What is the mechanism of action of ganciclovir?
Same as acyclovir in HSV / VSV In CMV: Activated by kinase phosphotransferase (Rather than thymidine kinase), then same steps -> drug of choice for CMV
92
What is the major side effect associated with ganciclovir?
Bone marrow suppression -> VERY COMMON, bad since immunosuppressed need this drug. Really bad since AIDS patients on zidovudine (think of lady eating off bone marrow suppression tray) will have additive bone marrow suppression Also has renal toxicity similar to acyclovir
93
What is the best drug to use for herpes zoster?
Famciclovir
94
What is the mechanism of foscarnet-induced electrolyte disturbance? Include how hypomagnesiemia causes hypokalemia?
Pyrophosphate analog -> binds free calcium -> hypocalcemia Hypomagnesemia -> decreased GI absorption Magnesium is required to decrease the activity of ROMK in the kidneys. Hypomagnesemia -> hypokalemia.
95
What is the main toxicity of cidofovir and how do you reduce this?
Nephrotoxicity -> reduce by giving with probenecid -> think of the probation officer keeping cid away from the shelf of kidneys Also give IV saline to keep hydration up (like amphotericin) Giving probenecid reduces the renal excretion of cidofovir, preventing high tubular concentration and subsequent kidney damage.
96
What is the mechanism of resistance to foscarnet and cidofovir?
Mutations in the DNA polymerase, since they interact with it directly (no phosphorylation required).
97
What are the best antibiotics to use against anaerobic infections?
1. Piperacillin/tazobactam - or another similar regimen 2. Clindamycin 3. Metronidazole #1198

Step 1 Miscellanous (40 decks)

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