DRUGS - Nucleic Acid Synth Inhibitors [Wk 4 FOM] Flashcards
Identify the 1) Mechanism of inhibition, 2) Spectrum of activity, 3) Mechanism of resistance, and 4) Adverse effects associated with the following agent(s):
Rifamycin
• MECHANISM
Binds bacterial RNA polymerase at the active center (Beta-subunit) blocking the elongation of mRNA
• SPECTRUM
Gram +/- (e.g. Mycobacteria tuberculosis)
• RESISTANCE
Intrinsic: the drug is unable to bind to the beta-subunit of polymerase
Acquired: the strain acquires mutations in rpoB gene, which prevents drug binding
• SIDE EFFECTS
- GI side effects
- Hypersensitivity – Fever
- Hepatotoxic (caution in pt w/ chronic liver disease)
- Turns body fluids orange/red
Identify the 1) Mechanism of inhibition, 2) Spectrum of activity, 3) Mechanism of resistance, and 4) Adverse effects associated with the following agent(s):
Fidaxomicin
• MECHANISM
Inhibits RNA polymerase by binding to the sigma subunit; (better at preventing recurrent infections of C. diff)
• SPECTRUM
Narrow: Gram + anaerobes (e.g. C. diff)
*note: Spares many of the gut flora
• RESISTANCE
Point mutation in RNA polymerase has been observed in vitro
• SIDE EFFECTS
Low absorption
Nausea, vomiting
Identify the 1) Mechanism of inhibition, 2) Spectrum of activity, 3) Mechanism of resistance, and 4) Adverse effects associated with the following agent(s):
Fluoroquinolones Class
- Ciprofloxacin
- Levofloxacin
- Moxifloxacin
• MECHANISM
Inhibit DNA replication by binding bacterial DNA topoisomerase:
- Gram neg. = topoisomerase II, prevents relaxation of supercoiled DNA
- Gram pos. = topoisomerase IV, interferes with sepearation of replicated chrom DNA
• SPECTRUM
Broad: Gram +/- and atypical organisms like Mycoplasma
• RESISTANCE
Active efflux of the drug
Mutations in topoisomerases
• SIDE EFFECTS
- GI side effects
- confusion
- photosensitivity
- Tendon rupture
- Contraindicated in pregnant women
- Prolongation of QT interval
Identify the 1) Mechanism of inhibition, 2) Spectrum of activity, 3) Mechanism of resistance, and 4) Adverse effects associated with the following agent(s):
Sulfonamides Class
- -Sulfamethoxazole
- -Sulfisoxazole
- -Sulfadiozine
• MECHANISM
Para-aminobenzoic acid (PABA) analog and acts as a competitive inhibitor of dhidyropteroate synthetase
• SPECTRUM
Folate Antagonist: Bacteria & Fungi that synthesize their own dihydrofolic acid
• RESISTANCE
- Change in dihydropteroate synthetase
- Increased efflux
- Increased production of PABA
• SIDE EFFECTS
- Hypersensitivity (Rash, ^ T cells)
- Stevens-Johnson Syndrome
- Cross reaction to other drugs containing sulfonamide moieties
- Crystalluria -> acute renal failure
Identify the 1) Mechanism of inhibition, 2) Spectrum of activity, 3) Mechanism of resistance, and 4) Adverse effects associated with the following agent(s):
Trimethoprim
• MECHANISM
Inhibits bacterial dihydrofolate reductase
• SPECTRUM
Folate Antagonist: Bacteria and fungi that synthesize their own dihydrofolic acid
• RESISTANCE
- Altered dihydrofolate reductase
- Increased amounts of dihydrofolate reductase
- Alternative metabolic pathways
• SIDE EFFECTS
- Bone marrow suppression
- Hyperkalemia
Identify the 1) Mechanism of inhibition, 2) Spectrum of activity, 3) Mechanism of resistance, and 4) Adverse effects associated with the following agent(s):
Trimethoprim/ Sulfamethoxazole [TMP-SMX]
• MECHANISM
Sequential blockage of the folate synthesis pathway
• SPECTRUM
- Broad treatment of UTIs
- Shigella
- Salmonella
- Pneumocystis
• RESISTANCE
• SIDE EFFECTS
Identify the 1) Mechanism of inhibition, 2) Spectrum of activity, 3) Mechanism of resistance, and 4) Adverse effects associated with the following agent(s):
Metronidazole
• MECHANISM
Activated form generates free radicals leading to DNA strand breaks and cell death; *Also blocks aldehyde dehydrogenase, inhibiting oxidation of acetaldehyde
• SPECTRUM
- Protozoa
- Anaerobic bacteria including C. diff
- NOT AEROBES (only metabolized to the active form in anaerobes)
• RESISTANCE
RARELY
• SIDE EFFECTS
- Nausea
- diarrhea
- headache
- metallic taste
- Avoid during pregnancy
- Disulfiram-like reaction w/ alcohol (hang over feeling)
Identify the 1) Mechanism of inhibition, 2) Spectrum of activity, 3) Mechanism of resistance, and 4) Adverse effects associated with the following agent(s):
Nitrofurantoin
• MECHANISM
Reduced by bacterial flavoproteins to reactive intermediates, which inactivated or alter bacterial ribosomal proteins and other macromolecules. This leads to an inhibition of the synthesis of DNA, RNA, cell wall, and protein
• SPECTRUM
Broad spectrum; Rapidly excreted in the urine in an active form
*note: Only reach high conc. in the urine
• RESISTANCE
Lack of bacterial resistance since the drug interferes with a variety of processes
• SIDE EFFECTS
- Vomiting
- Pulmonary toxicity
Which NA Inhibitors are used for UTI infections?
- Fluoroquinolones
- TMP-SMX
- Nitrofurantoin (PREFERRED TREATMENT; ineffective for infections outside the lower urinary tract)
Name three special precautions regarding treatment with Fluoroquinolones
- Chelate cations (don’t take w/ Ca, Fe, Al, and Zn)
- Avoid dairy products or calcium-fortified juice
- Adjust for renal dysfunction for all agents except moxifloxacin (not secreted into the urin)
What is Kernicterus, and with which NA Inhibitor class is it associated?
Kerniticus = accumulation of bilirubin in the brain, leading to encephalopathy.
Sulfonamides
Sulfonamides can compete for binding to albumin leading to kernicterus in infants and complications with drugs like warfarin
What happens when G6PDH deficient patients are (X-linked recessive) treated with Sulfonamides?
Hemolysis
Name the two bacteriostatic Nucleic Acid Inhibitors
- Sulfonamides class
- Trimethoprim
If mismanaged, which Nucleic Acid Inhibitor can lead to organ rejection/loss of seizure control, and how does this happen?
Rifamycin
Induction of cytochrome p450 enzymes can induce metabolism of other medicines leading to organ rejection/loss of seizure control
What is unique about the treatment protocol for Mycobacteria tuberculosis
Mycobacteria tuberculosis must be treated with 4 different antibiotics due to the high rate of resistance