Bactrim (Sulfamethoxazole/Trimethoprim)

MOA

MOA

-gives sequential block in THF synthesis by microorganisms

-Sulfamethoxazole inhibits Folic acid synthase

-Trimethoprim inhibits DHF reductase

Primaxin (Imipinem/Cilastin)

MOA

MOA

-inhibitor of polymer crosslinking

-B-lactams inhibit transpeptidase by forming a covalent (dead end) acyl enzymre intermediate

-Cilastatin is a dehydropeptidase inhibitor that prevents renal metabolism of Imipinem by dehydropeptidase

Vancocin (Vancomycin)

MOA

MOA

-inhibits synthesis of cell wall by binding to d-alanyl-d-alanine terminus of cell wall precursor units

(is a dephosphorylation inhibitor which binds to d-alanyl-d-alanine end of park nucleotide to prevent polymerization of n-acetylglucosamine (NAG) and park nucleotide to make the 1st strand  and elongation of peptidoglycan)

-is bacteriocdal

-Stage 2 Inhibitor

Cycloserine (Seromycin)

MOA

MOA

-Inhibits reactions in which d-alanine is involved in bacterial cell-wall synthesis

(-  inhibitor of d-alanine-d-alanine synthase in the production of park nucleotide step in stage 1)

-Cycloserine and d-alanine are structural analogues of each other

-Stage 1 inhibitor

MOA

-fluoroquinolone

-inhibit prokaryotic type II topoisemerases (inhibitor of topoisomerase II (dna gyrase))

(inhibits DNA-gyrase (topoisomerase II) to inhibit relaxation of supercoiled DNA and promotes breakage of DNA strands. DNA gyrase is essential for DNA replication and transcription)

-at therapeutic levels is bacteriocidal by causing dissiociation of the top topoisemerases from nicked DNA, leading to double-stranded DNA breaks and cell death

Penicillin G

Spectrum

Spectrum:

Gram + cocci: staph, strep

gram -cocci: Neissera species

Gram + Bacilli: Bacillus anthracis, Clostridium species

Spirochetes: treponema pallidum (syphillis)

Sulfonamides

Spectrum

Spectrum

Broad

Gram +:

-Strep pyogenes

-Strep pneumoniae

-Bacillus anthracis

-Corynebacterium diphtheria

Gram -

-Hemophilus ingluenza

-Vibrio cholerae

Other

-Chlamydia trachomatis

-Nocardia

Azactam (Aztreonam)

Adverse Effects

Adverse Effects

1. Phlebitis, injection site rxns, rash

2. Supra Infection

-not wide spectrum, narrow spectrum

-but b/c it affects many bacteria residing in the stomach, it can cause infection in GI (enteric organism)

3.Hypersensitivity

4. GI (NVD) nausea, vomiting, diarrhea

5. BMD (bone marrow depression)

-anemia, thrombocytompenia, leukopenia

Vancomycin (Vancocin)

Adverse Effects

Adverse Effects

1. Red Man syndrome

2. Nephrotoxic

3. Ototoxic-balance and hearing

4. Hypersensitivity

5. Some neutropenia and bone marrow depression

6. Neurotoxic effect in small extent

Carbapenems

Compare and contrast ADME

Penicillins

( in terms of their route of administration, plasma protein binding, susceptibility to the actions of Beta-lactamase I )

Compare and contrast

-IV, IM, Per os (erratic absorption)

-Repository (Benzathine, Procaine-never admin IV, IM only)

-When given PO take on empty stomach

-Excreted renally

*Piperacillin is the least protein bound of all penicillins

Absorption:

-Pen G-incomplete GI absorption

-Pen V-better GI absorption

-Food interfer with enteric absorption of penicillin so administer 1/2 hr before or 2-3 hrs after a meal

-Also absorbed from IM injection site (very painful)

-Better to give the repository preparation IM (e.g. Procaine penicillin G; Benzathine penicillin G)

Distribution:

-widely but not uniformly distributed

-does not readily enter CSF (cerobrospinal fluid). Penetrates better when meninges are inflamed

-about 65% is protein bound

Excretion:

Mainly through the kidney. Rapid

-Filtered and secreted (effect of Probenecid). Probenecid, 1gram, 30 minutes before administering Penicillin, will inhibit excretion of Penicillin into renal tubules.

-Also excreted in bile, human milk, and saliva

1^st generation and 2^nd generation Fluoroquinolones 

( in terms of their effectiveness against Gram-positive aerobic cocci, absorption and frequency of administration)

Compare and Contrast

Penicillin

Drug to Drug Interaction

Drug to Drug Interaction

1. "static" antibiotics (e.g. Erythromycin, Tetracycline) may decrease penicillin's "cidal" activity

2. Probenecid blocks renal tubular secretion of penicillin

3. Mixing penicillin with amionoglycosides in parenteral solutions may result in substantial inactivation of aminoglycosides

4. Oral contraceptive failure and breakthrough bleeding in patients taking penicillin

Sulfamethoxazole

Drug to Drug Interaction

Drug to drug interaction

-Local anesthetics (e.g. Procaine)-esters of PABA

-The most important is with oral anticoagulants, the oral sulfonylurea hypoglycemic agents, diuretics, and the hydantoin anticonvulsants. Sulf increases effects of these drugs.

-Synergism with the DHFR Inhibitor  ***DHFR is species specific, Trimethoprim and Pyrimethermine can inhibit the DHFR only in small organisms, it does not effect the DHFR in humans

-Asprin & Indocin can displace the sulfonamides from the ppb sites

Cipro

Drug to Drug Interaction

Drug to Drug Interaction

Decrease Cipro absorption

Antacids, Carafate, Zinc, Iron, Pepto-Bismol, Maalox, DDI (dideoxyiocin)

Decrease Cipro elimination

Tagamet, Probenecid

*Cipro decreases clearance of theophylline (very serious and fatal reactions may occur)

Cipro 

Counseling

Counseling

• Complete entire course of antibiotic
• May reduce oral contraceptive efficacy (use other contraceptive)
• Avoid taking divalent and trivalent cations (take them 2 hours before or after taking the Cipro)

Bactrim

Counseling

Counseling

i.Hypersensitivity - drug fever - anaphylactic shock, rash, itching, serum sickness

ii.Very rarely  you can see a hepatic effect - an elevation of hepatic enzymes - drug induced hepatitis

iii.Hemotologic effects - Agranulocytosis, anemia (may be the hemolytic type), thrombocytopenia

iv.Crystalluria - crystals in the renal system - may lead to tubular necrosis - can lead to death if not taken care of due to blockage in nephron(must counsel to take plenty of water) 

v.Photosensitivity 

vi.CNS effects - HA, hallucinations, dizziness, peripheral neuritis (neuopathy) - nerve pain, Kernicterus (typically in children) - brain damage. When you have a lot of unconjugatied bilirubin going to the CNS. The sulfonamides tend to bind to the albumin, and then they compete with bilirubin. Now you have a lot of unconjugated bilirubin going to the brain.  

vii.Skin - Production of Stevens-Johnson Syndrome, TEN (toxic epidermal necrolysis) - very serious (worse than a third degree burn) where the skin peels off the skin, even while taking off clothes. Most serious skin condition around.  

Amoxicillin

Counseling

Counseling

i.Complete the full course of therapy

*Take with food

*Notify physician if rash, hives or severe diarrhea occurs

ii.May decrease oral contraceptive  effectiveness

iii.Hypersensitivity - Sneezing, wheezing, itching,, hives, swelling in face and hands and the worse form is anaphylaxis shock - could lead to death

iv.Blistering, peeling, red skin rash

v.GI - Non-specific (NVD) - stomatisis (inflammation of the oral mucousa - corners of the mouth), abdominal pain

vi.Black furry tongue

vii.BMD - anemia, thrombocytopenia - increase in bleeding can lead to hemorrhagic episodes - mostly seen in ESPs though), leukopenia, agranulocytosis

viii.Renal - nephritis (oliguria - scanty urine formation) (proteinuria - wasting of protein in urine) - mostly seen in Methocillin