Antibiotics Flashcards
What is the difference between Gram + and Gram - bacteria?
Gram + = purple
1 inner lipid membrane + thick peptidoglycan layer
Gram - = pink
2 lipid membranes + thin peptidoglycan layer
What do antibiotics target?
- Cell wall synthesis
- Protein synthesis
- Nucleic acid synthesis
- Folate metabolism
- Cell membrane
What is the therapeutic index?
Difference between effectiveness + toxicity
What is the therapeutic spectrum?
Bacteria antibiotic effective against - narrow + extended
What’s the difference between pharmacokinetics and pharmacodynamics?
Pharmacokinetics = movement of drugs in body Pharmacodynamics = what drug does to body
What are the cell wall synthesis inhibitors?
- Penicillins
- Co-amoxiclav
- Cephalosporins e.g Cefotaxime
- Vancomycin (MRSA)
What are the protein synthesis inhibitors?
- Clarithromycin (Chlamydia)
- Gentamicin
- Oxytetracycline
What are the DNA/RNA synthesis inhibitors?
- Ciprofloxacin
- Nitrofurantoin (UTI)
- Metronidazole
- Rifampicin
Name a folate antagonist
Trimethoprim
Which group are the beta lactam antibiotics?
Penicillins + Cephalosporins
How do beta lactam antibiotics work?
- Binds to PBP via beta lactam ring, inhibiting transpeptidase + preventing cross linking of peptidoglycan layer
- Penicillin binding protein (PBP) = normally causes cross linking of peptidoglycans in cell wall
How do protein synthesis inhibitors work?
- Target ribosomes structurally different enough from human ribosomes
= Selective toxicity
How do DNA & RNA synthesis inhibitors work?
- Selective toxicity for bacterial enzymes involved in replication
- Narrower therapeutic index than cell wall synthesis inhibitors
How do folate synthesis inhibitors work?
- Humans take up folate through food, bacteria have to make it themselves
- Trimethoprim = enzyme inhibitor of this folate synthesis metabolic pathway
- Combined with sulphonamides to act synergistically to reduce folate synthesis
When are folate synthesis inhibitors not effective?
Presence of pus as it contains dead bacteria +. neutrophils that the bacteria can take their building blocks from
Why are there so many different antibiotics?
- antibiotic may not be able to reach target
- may cause side effects
- bacteria resistance
What are the routes of administration for antibiotics ?
- oral
- topical
- IV
- intramuscular
- intrathecal
What chemical properties affect the distribution of drugs?
- Lipid soluble - well absorbed + widely distributes, can lead to accumulation
- Polar - extracellular, low vol of distribution, pKa/pH dependent
- Protein binding - limits distribution, displaces other drugs
What are difficult targets for drugs to reach?
- BBB
- Prostrate
- Eye
- Intracellular bacteria
What are easy targets for drugs to reach?
- Inflammation - due to increased vasodilation + vasc permeability
- Pregnancy + breastfeeding
Why is it hard for dugs to cross the BBB?
- Tight junctions + active pumping mechanisms
Which antibiotic can penetrate the BBB?
Chloramphenicol
What affect do inflamed meninges have on antibiotic penetration?
More permeable to penicillin = rapid penetration of drug into CSF
Which antibiotics are used for intracellular bacteria?
- Macrolides - Azithromypcin + Clarithromycin
- Fluroquinolones - Ciproflaxcin
Are Neisseria Gonorrhoea intracellular bacteria?
No
Chlamydia IS
How is Gonorrhoea treated?
Azithromycin often used in combination with Cephalosporins as…
- co-infection with Chlamydia
- prevention of development of resistance to Cephalosporins
How are antibiotics eliminated?
- Liver + Kidneys
- UTI = renal impairment = accumulation toxicity
- Elderly patients = reduced kidney function
What are the types of ADR’s in patients?
Type A: - predictable - dose-related - gentamycin - contra indicated in renal dysfunction + elderly Type B: - unpredictable - immune mediated - penicillin allergy (IgE antibody against penicillin) - rash - anaphylactic shock
What are the ADR’s of Tetracycline?
Ca binding: in children affect bone + teeth growth
What are the ADRs of Chloramphenicol?
- Lipophilic so can easily penetrate mitochondria
= interferes with mitochondrial protein synthesis = Grey baby syndrome = under developed hepatic function
Describe the antibiotic spectrum
- Narrow: only few bacteria respond
- Extended: wider range
- Broad: v. wide range - risk of damage to commensal flora = superinfection
What is a superinfection an d what causes it?
= after killing of commensal flora
- Tetracycline e.g. candida
- Clindamycin or Penicillins = C.diff infection = pseudomembranous colitis
What is polypharmacy?
Interference with breakdown of other drugs via competition/inhibition/activation
e.g. Warfarin, Oral contraceptives, Prednisone
What is the effect of competition of drugs on liver function?
- competition for same metabolic pathway
- shortage of enzymes
- slower metabolism
- longer half life
What is antibiotics inhibit metabolism?
Fluorquinolones + Macrolides
Longer half life e.g. warfarin = bleeding
What antibiotics enhance metabolism?
Rifampicin - reduces half life of oral contraceptives by increasing metabolic activity of Liver
What factors should you consider when prescribing antibiotics?
Status of patient:
- Neonates - under developed haptic function
- Children - bone + teeth (tetracyclines) + cartilage growth (fluoroquinolones)
- Preg + breast feeding - drugs cross placenta
- Elderly - renal function + polypharmacy
- Allergies - Beta lactam antibiotics
- Poor perfusion - diabetes
Which people are more susceptible to infections?
- immune deficiencies
- immunosuppressive drugs
- anti-cancer drugs
- age
- diabetes
- alcoholism
- malnutrition
- immune-privileged sites (brain, placenta, testis, eyes)
What is the difference between bacteriostatic and bactericidal antibiotics?
- Bacteriostatic: stops growth
- Bactericidal: kills
For patients more susceptible to infection - increase the dose/duration or use bactericidal
Proper functioning IS - bacteriostatic enough but bacteria would start to grow again in immune-compromised
Why are combination of antibiotics used?
- prevents resistance
- in serious infection
- infection with 1+ microorganism
- unknown microorganism
- enhances efficacy: synergism
What is synergism?
Most favourable combination of antibiotics
e.g. cell wall synthesis inhibits weaken ell wall + facilitate entry of ahminoglycosides + fluoroquinolone which can’t penetrate cell wall
How does antibiotic resistance work?
Penicillin resistance:
- Bacteria have B-lactamases which cleaves beta-lactam ring of some penicillins + cephalosporins = inactivation
Quinolone resistance:
Bacteria have mutated tropoisomerases that antibiotic can’t bind to and/or Qnr plasmids
How do B-lactamase inhibitors work?
e. g. clavulanic acid
- Block action of B-lactamase by acting as substrate
- No antibacterial activity itself
