Anti bacterial drugs cell wall synthesis inhibitors 2 Flashcards
discuss the characteristics of Cephalosporins
They are similar to penicillin but are more stable to many bacterial beta lactamase and thus have a broader activity spectrum.
They are semi synthetic antibiotics
Which bacteria is resistant to all cephalosporins
Enterococci
Cephalosporin general rules
First generation is most effective against against gram positive
Fourth generation is similar to first generation and effective against gram negative
through chemical modification of the basic cephalosporins structure ,there is an increase in effectiveness of suceeding generations against gram neg aerobic organisms
How do bacteria develop resistance ?
- No cell wall
- Decreased permeability
- Bacteria do not grow
- Alterations in binding proteins
- β-Lactamase production
The pharmacokinetics of cephalosporins
Variable T1/2
• Ceftriaxone → 40% hepatic elimination
• Excretion → via kidney (can use probenecid to
increase t1/2 except ceftriaxone) (Drugs that block tubular secretion eg probenecid may increase serum levels ,thats why patients with impaired renal functions must be given i small doses
• Third generation → Penetrates well into CSF
Cephalosporins side effects
- Hypersensitivity reaction (anaphylatic shock ,fever ,skin rash ,nephritis ,granulocytopenia and hemolytiv anemia
Cephalosporins side effects
- Hypersensitivity reaction (anaphylatic shock ,fever ,skin rash ,nephritis ,granulocytopenia and hemolytiv anemia )
* .Chemical structure differes enough from penicillin so that some people can tolerate them
* Occurance of hypersensitivty occurs in 2% of population - Some can also cause alcohol intolerance (cefamandole)
- Effectiveness of combined with contraception
- Nephrotoxicity ( co- administered with aminoglycosides or vancomycin)
- Phlebitis can occur via IV
- Neurotoxicity can occur at high doses
How does cephalosporin interact with other substances ?
- Alcohol ( with some cephalosporins)
- Warfarin
- NSAIDs
- Combined with oral contraceptives pills
- probenecid
- Cephalosporins and aminoglycosides in same container may chemically inactivate each other .
- Ceftriaxone ( not to be administered at the same time as calcium solutions for more than 48 hrs
Cautions/Contraindications
- Anaphylatic shock (PENICILLIN)
- ALLERGY
- Ceftriaxone contraindicated in hyperbilirubinemia neonates ( premature infants)
What are the characteristics of carbapenems?
They have a broad spectrum ( gram pos and neg anaerobic bacteria
Not active against methicillin resistant staphylococus
List the drug examples of Carbapenems
Imipenem + cilastatin (enzyme inhibitor that blocks renal metabolism) • Meropenem • Ertapenem (narrower spectrum) • Doripenem (withdrawn in Europe)
What is the mechanism of action of carbapenems?
Bactericidal , same as penicillin
Uses of carbapenems
- Imipenem: Severe nosocomial infections ( septicemia, endocarditis and lower reparatory infection, GUT ,intra-abdominal,bone , skin, joints, and soft tissue infection )
- Meropenem: Alternative treatment for bacterial meningitis,it can penetrate the CSP
- Ertapenem : Single dose daily via IV
What are the side effects of carbapenems
1.Similar to other beta lactams (hypersensitivity reaction ,GIT effects ,haematological abnormalities ,CNS effects (seizures at high dosages of imipenem)
Increased liver enzymes
Increased serum creatinine and blood urea
- Red discoloration of urine in children(imipenem)
- IV : pain ,erythema and thrombophlebitis
Cautions and contradictions
1.Allergy
2 CNS disorders or seizures
3.Renal impairment
Give an example of monobactams
Aztreonam
Give the mechanism of action of monobactams
Bactericidal ,same as penicillin
What is the spectrum of monobactams?
Their spectrum is limited to aerobic gram negative bacteria eg E.coli and p. Aeruginosa
How are monobactams administered
IV or IM
What are the side effects of monobactams?
- Injection site reaction
- Rash
- Rarely toxic epidermal necrolysis
- Gastrointerstinal side effects
- Drug induced eosinophilia
Give an example of glycoprotein antibiotics
Vancomycin and Teicoplanin and fosfomycin
What is the spectrum of vancomycin
- It is active against gram positive only
- It is a antibiotic reserved for treatment of life threatening infections
- It is an alternative treatment for endocarditis (in penicillin allergic patients)
Use of vancomycin
Use is restricted to cloxacillin resistant staphylococci and penicillin resistant enterococci
How is vancomycin administered
- In gastrointestinal tract infections (orally) and
2. No cross resistance with other anti biotics
Action of mechanism of vancomycin
- bactericidial
- Inhibits cell wall synthesis
- Transglycosylation between side chains thus peptidoglycan cross-linkage does not form resulting in a weakened cell wall , eventually the bacterium lyses
Discuss the Pharmacokinetics vancomycin
- Poorly absorbed when administered orally
- IM administration is painful
- The drug is only administered by IV infusion slowly
- It administered orally for pseudomembranous colitis
- Half life is 4 to 11 hours
- Excreted 80-90% unaltered via glomerular filtration in the urine
What are the side effects of vancomycin
- fever and skin rashes
- When administered rapidly ,it causes histamine release ,causing blushing of the neck and face known as red man syndrom
- Ototoxic and nephrotoxic ,rare
- Nephrotoxic in geriatric
- Therapeutic drugs monitoring essential in elderly , children and impaired renal function
Drug interaction of vancomycin
Ototoxic and nephrotoxic drugs eg aminoglycosides
Cautions/Contraindications of vancomycin
- Renal Impairment
- Elderly patients
- Neonates/young infants
- Hearing abnormalities
- Pregnancy
What are the mechanism of action of teicoplanin
- Similar to vancomycin
1. bactericidial
2. Inhibits cell wall synthesis
3. Transglycosylation between side chains thus peptidoglycan cross linkage does not form resulting in a weakened cell walll ,eventually the bacterium lyses
Discuss the pharmacokinetics of teicoplanin
1.IM (painful)
Usually administered via IV
2.Half life is 45 to 70 hr ,thus give one dose a day
what are the side effects of teicoplanin?
Same as vancomycin, lower
incidence of “red man” syndrome, allergy
(cross sensitivity with vancomycin)
what is the spectrum of Fosfomycin
It is active against gram pos and gram neg ( broad spectrum
What are the actions of mechanisms for the fosfomycin
- bactericidal
2. Inhibits early stages in bacterial cell wall synthesis
What causes fosfomycin in resistance in bacteria
Inadequate transport of drug into cell
Discuss pharmacokinetics of Fosfomycin
1.when administered orally ,absorption is delayed by food (takes two hours before meal)
2. Excreted in breast milk
Excreted in urin (30 to 60%)
Uses of Fosfomycin
Uses:
1. Single-dose therapy for acute uncomplicated
lower urinary tract infections (sensitive E. Coli)
2. Prophylaxis in diagnostic and surgical
transurethral procedures
what are the side effects of fosfomycin
GIT disturbances, skin rashes
Drug interaction of fosfomycin
Metoclopramide → ↓ serum & urinary
concentrations of fosfomycin (avoid)
Cautions/Contraindications of fosfomycin
C/I in renal failure
2. Caution → pregnancy & lactation
