Antibacterial Agents targeting metabolism Flashcards by Dylan Hall

What are the gram negative Aerobes?

-1s, Escherichia coli (E. Coli), Klebsiella, Morganella, (found in GI and urine)

-2, Neisseriam Moraxella, Proteus (HEMAPHOLIS)
Found in respiratory tract

3, SPE (Enterobacter, Citrobacter, Serratia
4, Acinetobacter
5, Pseudomonas

The lower the number means the harder it is to treat

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What are the Gram Positive Aerobes

Streptococcus species (found on the skin and in the respiratory tract)
Staphylococcus aureus
1. MSSA (susceptible)
2. MRSA (resistant)
Enterococcus (VRE, Vanco resistant Enterococcus)

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What are the Obligate Anaerobes? (Gram positive)

Clostridum Difficile (c. Diff)

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What are the obligate anaerobes (gram negative)

Bacteroidies fragility (B. fragilis)

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What are the atypicals?

Chlamydia

Mycoplasma

Legionella

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What are the spirochetes

Treponema pallium ( T pallium)

Borelia burgdorferi. (B burgdorfei)

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What are the Mycobacterum? (AFB)

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Which drugs are Bacteriostatic?

Macrolides

Tetracyclines

Clindamycin

Sulonamide

Trimethroprim

Chloramphenicol

MTC-STC

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What drugs are bactericidal?

Aminoglycosides (torbamycin, gentamicin, akiacin)

Beta-lactams

Vancomycin

Quinolones

Rifampin

Metronidazole

ABV QRM

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What are the Nitromididazoles? And what is their MOA?

Metronidazole (Flagyl)

Inhibitor of nuclei acid synthesis, by disrupting the DNA structure of susceptible bacteria

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What are the drugs for Fluoroquinolones and their MOA?

Norfloaxcin

Ofloxacin

Ciprofloxacin (Cipro)

Levofloxacin (Levaquin)

Moxifloaxin (Avelox)

Gemifloxacin (Factive)

Delafloxacin (Baxdela)

MOA: Inhibitor of nuclei acid synthesis by inhibiting

DNA topoisomerase II (gyrase)
DNA toposiomerase IV

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What are the Folic acid antagonists and their MOA?

Sulfamethoxazole

Trimethoprim

Sulfa = inhibits dihydropteroate synthase

Trimethoprim = Dihydrofolate reductive

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What are the Rifamycins and their MOA?

Rifampin

Rifaximin

MOA: DNA-dependent RNA polymerase (ie. RNA transcription, later in the process)

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How does oxygen play a role when it comes to metronidazole?

Flagyl

It only works to break down the DNA when it is NOT in the presence of oxygen!!!

This is why it is so good at killing anaerobic bacteria such as: Bacteroides fragilis (B fragilis, and C diff)

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What is the distribution and oral bioavailability for metronidazole?

Distributes well to most tissues

Bioavailability is greater than 99%!!!!! VERY GOOD!!

Gets eliminated in the kidney and fecal

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What are the side effects for Metronidazole as well as drug interactions?

Flagyl

GI- N/V, diarrhea

METALLIC TASTE (DYSGUSIA)!!!!

Drug interactions

Alcohol (disulfiram-like) will have headache flushing and fell very sick

Also have to watch with Warfarin due to the fact that we get Vit K from out gut bacteria and this will kill that so it affects it (all antibiotics can do this)

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What’s interesting about metronidazole in terms of drug resistance?

Drug resistance is very uncommon!!!! Less than 5%

ALso it comes as PO, IV, topical

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What is the 2nd generation of fluroquinolones?

Ciprofloxacin (cipro)

What are the 3rd and 4th gen of fluoroquinolones and what are they good at treating?

They are the respiratory FQ (meaning they are good for respiratory bugs, remember cipro gets to the lungs but does not kill the bugs that cause those)

Levofloxacin (levaquin)

Moxifloxacin (Avelox)

Gemifloxacn (Factive)

Delafloxcin (Baxdela)

What does FQ get into gram (-) as well as get into gram (+) bacteria?

It can get thro gram (-) using proins and then it can get thro gram (+) by going thro the cell membrane

What are some resistance mechanisms that are there for FQ?

A gram (-) can decrease the amount of proins so less of the drug can get in. They can also increase the amount of efflux pumps which will push more of the bacteria out.

One thing they both do but is big for gram (+) (they don’t have the proins or efflux pumps) is they change the binding site on the DNA gyrase or topoisomerase

***this can be really bad because just one change can result in the WHOLE class not being functional to the bacteria (only takes 1 DNA base pair change)

Which FQ is not going to be used for UTI? Also how is the oral bioavailability for the FQ?

Remember they are alll good for UTI EXPECT MOXIFLOXACIN (AVELOX)

This one does not build up enough concentration in the urine to be effective for treating UTI

Oral bio for all of the is good

Which FQ can treat Pseudomonas?

Ciprofloxacin (Cirpo)

Levofloxacin (levaquin)

Delafloxacin (Baxdela)

Chris

Loves

Dylan

What FQ are good for gram negatives?

All of them

What FQ work for Gram positive aerobes

Delafloxacin (Baxdela) Moxifloxacin (Avelox) Gemofloxacin Levofloxacin (levaquin)

What FQ can work for MRSA?

Delafloxacin (Baxdela)

Which FQ work for Gram negative anaerobes?

Moxifloxacin (Avelox) Delafloxacin (Baxdela)

Which FQ work for Gram positive anaerobes?

NONE!

What are the black box warning for FQ

1. Tendinitis and tendon rupture (Kobe effect) 2. Peripheral neuropathy 3. Exacerbation of muscle weakness in patients with myasthenia gravis 4. CNS effects - Convulsions / Seizure - Psychoses (AMS) - Increased intracranial pressure

What are the side effects of FQ?

A LOT OF THEM 1. Insomnia, dizziness, headache 2. Hepatotoxicity (inc AST/ALT) 3. QTc prolongation of ECG (increased risk of arrhythmia) 4. Inc risk for aortic aneurysm (AAA) 5. Phototoxicity 6. Hematologic (Agranulocytosis, thrombocytopenia) 7. GI = N/V diarrhea 8. CDAD

What are some drug interactions that you have to worry about when it comes to FQs?

Have to to watch for cations Mg and calcium - will reduce GI absorption due to it binding and forming a precipitant - Antacids (Ca & Mg) - milk **also warfarin cuz it can increase your INR which will lead to an increased risk of bleeding

What’s the main reason why you want to combine sulfamethoxazole and trimethoprim

When added together they work very well and turn the individual agents which are static into cidial drugs

What does sulfamethoxazole and trimethoprim do in order to kill bacteria (what do they block in terms of production)

They block their things which leads to the blocking of Purine bases (G, A) as well as Thymine (T) and Methionine (MET) **these are needed in order for the bacteria to create DNA and replicate. It will no longer be able to do so without these

What are the different sulfonamides and how are they used?

Sulfamethoxazole (SMZ) - used systemically Sufladiazine - used topically (wound or burn pts) and systemically for toxoplasmosis Sulfadoxine - used for malaria Sulfasalazine - not used an antibiotic

What is the ratio that for sulfamethoxazole and trimethoprim combo?

It’s bactrim and the ratio is always 5:1 Bactrim = 400:89 Bactrim DS = 800:160

What are the pharmacokinetics for sulonamides and trimethoprim ?

Good oral availability Metabolized by CYP3A4 - so drug interactions are a lot Cleared in the kidney ; avoid in pts on dialysis

What are the side effects fo rFolic acid antagonists?

SMX-TMP 1. Hypersensitivity (allergic rxn, anaphylaxis) 2. Skin rashes, photo toxicity 3. Bone marrow suppression (dose-dependent; uncommon but significant) 4. Hepatotoxic 5. Renal toxicity - acute kidney injury (AKI) 6. Hyperkalemia **drug interaction with warfarin = inc INR so more bleeding

What are the rifamycins and their MOA?

Rifampin, Riabutin, riapentine MOA: inhibitor of transcription by inhibiting the RNA polymerase

What are the pharmacokinetics of the rifamycins?

Good oral bioavailability ***These are potent enzyme inducer and have to watch for drug interactions

What are the uses for rifamycins ?

TB and it is cidial Mycobacterium infections (TB, MAC)

What are the adverse effects of rifamycins?

1. Red color body fluids (will cause you to turn red, like your sweat, and urine) 2. Rash, N/V, anorexia, abdominal pain 3. Thrombocytopenia 4. Hepatotoxicity

What are the clinical used for rifaximin (Xifaxan)?

1. Travelers diarrhea | 2. C. Diff

What is fidaxomicin (dificid), what is used for?

It is used for CDAD MOA: inhibition of RNA polymerase of the sigma submit Adverse effects: GI- N/V and abd pain