Antimicrobials

Question 1

Protein synthesis inhibitor MOA

Answer 1

Inhibit target bacterial ribosome growth
- reduces uptake by bacterial as well and deactivates bacterial enzymes related to protein synthesis

Are broad spectrum and bacteriostatic
- a few can be bacterialcidal

Requires high level of host immune system
(Don’t use on immunosuppressive patients)

Question 2

Tetracycline and aminoglycoside MOA

Answer 2

Bind to 30S subunit and prevent binding of incoming tRNA

Question 3

Macrolides, clindamycin and chloramphenicol specific MOA

Answer 3

Bind to the 50S subunit and block peptide bond formation

Question 4

Aminoglycosides specifics

Answer 4

“ANGST” drugs
- amikacin, neomycin, gentamicin, streptomycin, tobramycin

Broad spectrum bacteriostatic/cidal agents

Bind to 30S subunit and prevent initiation of protein synthesis causing RNA misreading.

Is both bacterial static and cidal due to producing abnormal proteins that are toxic

Used primarily gram (-) bacilli

Can only be administered parenterally (injection) and is toxic to kidneys/inner ear
- used sparingly because of this (especially neomycin and streptomycin)

Question 5

ADRs of aminoglycosides

Answer 5

Ototoxicity (inner ear toxicity), kidney toxicity and neurotoxicity

Neurotoxicity occurs via bloackade of presynaptic release of acetylcholine at NMJ

Hypersensitivity reactions

Question 6

Contraindications for aminoglycosides

Answer 6

Myasthenia gravis

Pregnancy

Kidney failure

Question 7

Tetracyclines specifics

Answer 7

Doxycycline, tigecycline, minocycline, tetracycline

tigecycline is often used for MRSA and other resistance

Broad-spectrum against wide variety of gram +/- bacteria (better against (+))

Bind irreversibly to 30s subunit specifically to bacteria preventing tRNA binding

Question 8

Ways for tetracycline resistance to occur

Answer 8

Acquire effusion pathways

Produce protein blocking tetracycline binding

Enzymes unregulated to inactivate drug

Question 9

Types of agents to use tetracyclines

Answer 9

MSSA and MRSA

H. Pylori infections

Lyme disease/cholera/Rocky Mountain spotted fever

Protozoa and mycobacteria

Acne and chlamydial infections

Question 10

tetracycline pharmacokinetics

Answer 10

Are given PO (excluding tigecycline) however all food impairs its absorption
- this is especially true with metal ion foods (calcium, magnesium, iron, etc.)

Are hepatically metabolized and are bound to serum proteins quite high 40-80%

Question 11

Tetracycline ADRs

Answer 11

Hypersensitivity reactions
- especially phototoxicity

nausea, vomiting, diarrhea

Discoloration of teeth and increased bone break down (binds to calcium very well)

Question 12

Contraindications of tetracycline

Answer 12

Pregnancy

Children under age 8

Liver or kidney failure patients

Question 13

Macolides specifics

Answer 13

Azithromycin, clarithromycin, erythromycin

Bacteriostatic agents that bind to 50S subunit and inhibits peptide growth
- can be bacterialcidal at high doses

Most widely effective antibiotic, however not used often anymore since resistance is beginning to grow

Question 14

Macrolide ADRs

Answer 14

Liver and ototoxicity
- especially azithromycin

Cardiotoxicity via QT prolongation and arrthymia

DDIs with agents using CYP450 metabolization

Question 15

Streptogramins specifics

Answer 15

Quinupristin/dalfopristin (only used together via IV dose)

Bind to 50S ribosomal subunit at separate sites further stimulating ribosomal blocking

Bacterialcidal again gram-positive cocci
Bacterialstatic agaisnt enterococcus fascium species (VRE strains as well)

Normally only used in very high resistance bacterial in factions and atypical pneumonia species

Question 16

Streptogramins ADRs and contraindications

Answer 16

Venous irritation

Hyperbilirubinemia (25% incidence)

Arthralgia and myalgia

DDIs via combination with other CYP 3A4 agents

dont use in liver failure patients

Question 17

Oxazolidinones specifics

Answer 17

Linezolid

Binds to 23S ribosomal RNA of the 50S ribosomal subunit
- prevents generation for he 70S ribosomal complex

Is bacteria static, but bacterialcidal against streptococci species

Used only for drug-resistant, aerobic, gram-positive organisms
- often alternative for VRE species

Question 18

Oxazolidinones ADRs, Contraindications and pharmacokinetics

Answer 18

Renal and liver metabolized

ADRs

• neurotoxicity (blindness and peripheral neuropathies)
• GI distress, nausea, diarrhea, thrombocytopenia

Can produce serotonin syndrome when taken with large quantities of tyramine-containing foods

Question 19

Chloramphenicol specifics

Answer 19

Broad spectrum antibiotic against almost all species except pseudomonas aeruginosa

Is not used often due to super high toxicity via self cells uptaking the drug and accumulating in mitochondrial ribosomes

ADRs
gray baby syndrome: genetically cant conjugate the drug often fatal
- produces gray coloration, abdominal distention, vomiting, hypothermia and vasomotor collapse
bone marrow depression and aplastic anemia: fatal

Question 20

Lincosamides specifics

Answer 20

Clindamycin

Bacteriostatic affective for gram (+) organisms

Binds to the 50S ribosome site

• used to treat MRSA, streptococcus and anaerobic bacteria
• especially good for B-lactam allergies*

100% orally bioavailable

can also cause C. Difficile superinfections

Question 21

Fluoroquinolones

Answer 21

Ciprofloxacin, moxifloxacin

Broad spectrum bacterialcidal agent

• Inhibit DNA gyrase and topoisomerases resulting in inhibition of DNA replication
• ONLY CLASS OF AGENT TO INHIBIT DNA REPLICATION*

Question 22

Flouroquinolone ADRs and contraindications

Answer 22

Used to treat the following

• anthrax
• UTIs
• anaerobic infections
• resistant respiratory infections
• GI infections

ADRs:

• nausea, vomiting, headache dizziness
• phototoxicty
• cardiotoxicity (prolonged QT interval)
• DDIs via CYP 1A2 and 3A4

Question 23

Folic acid (folate) antagonists

Answer 23

Cotrimoxazole (sulfamethoxazole + trimethoprim)

Broad spectrum agent that is bacteriostatic
- does not affect mammalian cells since folate metabolisms are different from bacteria

Used against gram-positive cocci and gram-negative bacilli, actinomycetes, chlamydia and Protozoa.