Antibiotics Flashcards
What are the 6 main groups of Antibiotics?
- Penecillins
- Cephalosporins
- Aminoglycosides
- Flouroquinolones
- Tetracyclines
- Macrolides
Which are the two most comply prescribed set of antibiotics?
Beta lactams and quinolones
Describe the mechanism of action of Beta- Lactams/ glycoprotein antibiotics?
–Act by inhibiting synthesis of bacterial cell walls
What is the main type of Beta- Lactam?
Penicillins
- Used to treat Gram Positive microorganisms
- Distribution to the eye, brain, CSF and prostatic fluid is low
-Clavulanate, Sulbactam and Tazobactam:
Beta Lactamase Inhibitors
- Used in conjunctions with other antibioitcs to make commercial drugs
- Clavulanate is under investigation as a NAALADase inhibitor (beta- lactamase inhibitor) with aphrodisiac & anti-depressant properties
What is the mechanism of action of Cephalosporins?
-Used to treat urinary tract infections (usually not in high concentrations in the CSF)
–use is dependent on it’s 1-4 generations.
1st generation- moderate spectrum agents (affinity for gram positives)
2nd generation- have a greater gram negative affinity
3rd generation- Broad spectrum of activity- high affinity for gram negative microorganisms
4th generation- extended spectrum drugs with affinity for gram positive microorganisms, similar to the first generation. Greater resistance to beta lacatamases than third generation cephalosporins
-Effective in treating Meningitis
Imipenem/ Citastatin
Carbapenems
- Class of Beta- Lactam antibiotics that are HIGHLY resistant to beta- lactamases
- broad spectrum of antibacterial activity
- *Imipenem/ Citastatin
Aztreonam:
- Only commercially available Monobactam
- Beta lactam antibiotics where the beta lactam in singular (not fused to another ring)
- Sensitive to Gram- Negative bacteria
- NOT useful against Gram Positive bacteria
True or False:
Beta- Lactams are bactericidal.
True (under most conditions)
Bacitracin:
Glycoprotein antibiotic
Topical agent to treat Gram Positive and certain Gram negative microorganisms
Vancomycin:
Glycoprotein antibiotic
-Primarily active against Gram Positive bacteria
What is the different between beta lactams and glycoproteins?
- Glycoprotiens don’t have a beta- lactam nucleus
- They are still a bactericidal cell wall inhibitor
- Beta lactams are receptive to resistance (last resort drug)
Tetracyclines:
–Bind to the 30S ribosome and prevent the binding of aminoacyl-tRNA to it’s acceptor site
- Enter Gram Positives by an energy dependent process
- Enter gram negatives by diffusion
Erythromycin and Ketolides (Telithromycin):
-Macrolides
Therapeutic Uses of Tetracyclines:
- Rocky Mountain Spotted Fever; Typhus; mycoplasma pneumoniae, chalmydia pneumoniae, Lyme disease and Brucellosis.
- Used to treat plague and pelvic anti-inflammatory disease
- Can also be used as a low dose acne medication
Erythromycin:
- Macrolide/ Bacteriostatic
- Used to treat mycoplasma pneumoniae
- Used for streptococcal group A (GAS) & upper respiratory tract infections to patients allergic to penicillins
- Legionella infection
- Can also be used to treat Lyme disease and Chlamydia infection
- Can also be used to treat syndromes such as bacterial bronchitis, ear infections with sulphonamide, and topically for acne
- Can also be used for large bowel surgery and oral surgery
Name 3 main Aminoglycosides:
- Bactericidal
- Streptomycin, Gentamycin and Neomycin
- Streptomycin was the first effective drug for treating TB
- Mostly inactive against fungi and anaerobic bacteria
- Administered IV or IM
Chloramphenicol:
-Bacteriostatic antimicrobial agent
-VERY inexpensive (used in 3rd world countries)
AE’s: Can cause Aplastic Anemia (BAD)
What is the most common form of resistance among Aminoglycosides?
The most common form of resistance in ahminoglycosides is modifications of the enzymes through enzyme- catalyzed phosphorylation- acetylation and adenylation
-Resistance can also occur through altering the ribosomes, as well as inadequate transport of the drug within the cell.
Resistance Mechanisms to Tetracyclines:
- Drug efflux due to new protein
- Alteration of the outer membrane due to mutations in chromosomal genes
- The ribosomal binding site is protected due to the presence of the plasma- generated protein that binds ribosomes.
True or False:
-Inhibition of folic acid synthesis is a direction for selective antibiotic development.
True
Sulfmethoxazole:
- Sulfonamide
- Inhibits dihydropteroate synthesis (competitive inhibition)
Trimethoprim:
-Dihydrofolate
Reversible inhibition of dihydrofolate reductase
Main Therapeutic Uses of Sulphonamides:
- Prophylaxis
- Urinary tract infections
- -The most common adverse effects are gastrointestinal disturbances and allergic risk reactions
Resistance of Sulphonamides:
- Inhibition of sulphonamides can be REVERSED by purines, thymidines, methionine and serine
- Resistance to sulphonamides is widespread, and its incidence continues to increase among all bacterial pathogens.
Which class of drugs act to inhibit or damage bacterial DNA?
-Flouroquinolones and Nitrofurans
Ciprofloxacin, Norfloxacin, Levofloxacin, Gatifloxacin and Moxcifloxacin
Flouroquinolones
- Act by inhibiting Topoisomerases
- Act by binding to and trapping the DNA synthesis and cell growth- has a lethal effect
Mutations in DNA Topoisomerases are the main reason for most bacterial resistances of quinolones, as well as active efflux of the drug.
Nitrofurantione
Nitrofurans
- Not used anymore due to carcinogenicity and mutagenicity (banned in Canada)
- Used to treat Urinary Tract Infections
- At high concentrations, nitrofuration is bactericidal
Colistin (Polymixin E) and Polymyxin B:
- Polymyxin
- Administered by IM injection
- Used to treat pseudomonas, aeruginosa & Acinetobacter baumannii
- Can also be used topically for the treatment of eye and ear infections
Polymyxins:
- Branched chain cyclic decapeptides
- Not absorbed well by the GI tract
- Used only in patients with Cystic Fibrosis because of Toxicity
- Lipophilic and Lipophobic groups interact with phospholipids & disrupt bacterial cell wall membranes
Actinobacteria:
Mycobacteria is a type of Actinobacteria which can lead to severe disease such as TB and Leprosy, as well as soft tissue infections after trauma or surgery
Drugs to Treat Tuberculosis:
First line drugs:
Isoniazid, Rifampin, Rifabutin, Rifapentine, Pyrazinamide and Ethambutol
Second line drugs:
Flouroquinolones, Streptomycin, Kanamycin, Amikacin, Capreomycin, Ethionamide, p-Aminosalicyclic acid (PAS), and Cycloserine
Rifampin:
A mycobacterial DNA- dependent RNA polymerase inhibitor
-These drugs bind to the beta subunit of DNA dependent RNA polymerase and inhibit RNA synthesis
Isoniazid:
Drugs which inhibit protein synthesis:
-Aminoglycosides, streptomycin, kanamycin and amikacin
p-Aminosalicyclic Acid:
Affect THF synthesis by competitive inhibition with p-aminobenzoic acid
Pyrazinamide (PZA):
Disruptions of plasma membrane by targeting of fatty acid synthesis
-Has the ability to kill M. tuberculosis
Thalidomide:
- Immunomodulatory drug
- Never to be taken in pregnant women
Anti- Leprosy Drugs:
-Rifampin, Dapsone and Clofazimine
Rifampin for Leprosy:
-Acts by inhibition of m. Leprae DNA dependent RNA polymerase
Dapsone for Leprosy:
-Acts as an inhibitor of dihydropteroate synthetase in folate synthesis to produce a bacteriostatic effect.
True or False: Active TB can be treated with one drug.
False.
NEVER treat active TB with only one drug- requires multi drug therapy
Why can’t antibiotics be used to treat Fungi’s?
-Fungi’s have different ribosomes, possess a discrete nuclear membranes and their cell walls have different components.
Capsofungin:
-Kills fungi
Blocks the synthesis of major fungal cell wall components (1-beta-D-glucan)
Triazoles (Fluconazole, Itraconazole and Voriconazole):
- Kills fungi
- Inhibits fungal cytochrome P450 enzyme 14-alpha-demthylase resulting in inhibition of ergosterol synthesis
Ketoconazole (Imidazoles):
- Kills fungi
- Inhibits ergosterol synthesis
Amphotericin (polyene):
- Kills fungi
- Associates with ergosterol to inhibit fungal cell wall synthesis
Terbinafine (allymines):
-Inhibits ergosterol biosynthesis via inhibition of squalene epoxidase
Griseofulvin:
- Inhibits fungal mitosis through interaction with polymerized microtubules
- Inhibits mitosis
Flucytosine:
- Disruption of essential proteins of fungi or inhibition of fungal DNA synthesis
- Replaces uracil with 5-flurouracil in fungal RNA
Azoles:
-Inhibits the synthesis of ergosterol by blocking the action of 14-alpha-demethylase
Nystatin:
- Polyene anti-fungal
- Minimal side effects
- Bad tase & can produce nausea
- Not allergic on the skin
Amphotericin B:
- IV administration of Amphotericin B may cause many adverse effects.
- headache, chills, high fever, general discomfort, nausea, and hypertension may develop
- Anemia with hematocrits between 22-35%
- Leads to reduced eythromoiesis
- Some degree of renal toxicity
- Hepatotoxiticy has also been reported
Mechanism of action of Polyenes (Amphotericin B and Nystatin):
- Polyenes bind to sterols in the cell membrane, forming channels allowing K+ and Mg2+ to leak out.
- The polyenes become integrated into the membrane & bind ergosterol
- ->Polyenes only work in fungi’s which have ergosterol in their cell membranes
Ideal Therapeutic Index Ratio:
- Therapeutic Index= Lethal Dose (LD)/ Effective Dose (ED)
- Safer drugs have a higher therapeutic index, while drugs that easily cause toxicity have a low TI.
MIC
Minimal Inhibitory Concentration:
-The lowest concentration of anti-microbial agent that prevents visible growth of 18-24 hours of incubation
MBC
Minimal Bactericidal Concentration:
-The minimal concentration of antimicrobial agent that kills 99.9% of cells
Ideal selective toxicity values for MIC/ MBC and TI:
Low MBC and a high TI
- High lethal dose compared to effective dose
- Low bactericidal concentration
Penicillin Drugs:
Amoxicillin, Penicillin, ect.
-Target Gram Positive bacteria
