Flashcards in L71 – Drugs Used in the Treatment of Pulmonary Infections Deck (92):
Symptom of tonsilitis?
Local infection of tonsils = red, swollen with exudate on the surface
What are some upper respiratory tract infections?
Sinusitis and otitis media
What is acute bronchitis? Symptoms? Pathogen?
Inflammation of bronchi
fever, cough, wheezing and "noisy chest“
Respiratory syncytial virus (RSV), parainfluenza virus, adenovirus
What is acute BRONCHIOlitis? Symptoms? Pathogen?
Inflammation and narrowing of terminal bronchioles
fever first and followed by
respiratory distress and wheezing
RSV, parainfluenza virus
Some general symptoms of pneumonia? Type of pathogens?
fever, respiratory distress and cyanosis
Primary community-acquired: bacterial infections are more prominent
Name all the classes of antibiotics used to treat primary community-acquired pneumonia (bacteria)?
1) Cephalosporins (3rd gen)
2) Penicillins +/- B-lactamase inhibitor
When is Fluoroquinolone used for primary community -acquired pneumonia?
For severe gram -ve bacterial infection
Give the bacterial component target for all classes of antibiotics used for primary comminity=acquired pneumonia?
B-lactams - cell wall peptidoglycan synthesis
Tetrcyclines - 30s inhibitor
Fluoroquinolones - Nucleic acid synthesis
Macrolides - 50s inhibitor
Is B-lactams bactericidal or static?
What is the MoA of B-lactams?
Cross bacteria cell wall > bind to penicillin-binding-protein > inhibit these transpeptidase enzymes > cannot make peptidoglycan cross links between NAM subunits
Activate autolysins in bacteria to destroy existing cell wall > cell burst through osmotic pressure
Compare the entry of B-lactams in gram +ve and-ve bacteria?
Gram +ve: no outer membrane, no porin channel >> antibiotics go in by diffusion >> less resistance
Gram -ve: if porin channel is impaired >> antibiotic cannot go in
What are some resistance mechanisms specific for gram -ve bacteria against B-lactams?
1. Loss of porins
2. Efflux pump
What are some resistance mechanisms used by both gram+ve and -ve bacteria?
Altered/ Modified PBP, penicillin binding protein (e.g. mecA)
What are the 4 classifications of penicillins?
1) Narrow spectrum, B-lactamase-SENSITIVE
2) Narrow spectrum, B-lactamase- RESISTANCE
3) Extended spec. AMINOpenicillins
4) Extended spec. ANTI-PSEUDOMONAL penicillins
What are some limitations of penicillin G?
Short duration of acid
Poor penetration into CNS
Unstable in stomach acid
Useless against B-lactamase
Allergy for some
What are some COMMON adverse effects of Penicillin G?
Seizures (esp. in epileptic patients)
What are some RARE adverse effects of Penicillin G?
Low toxicity > allergy
Acute interstitial nephritis
How can antistaphlyococcal penicillin resist B-lactamase?
BULKY SIDE GROUPS can block B-lactamases that hydrolyzes the B-lactam ring
Resist acid degradation
Name some antistaphlyococcal penicillin (B-lactamase-resistant penicillins)? which one is highly nephrotoxic?
methicillin (highly nephrotoxic)
When is antistaphlyococcal penicillin used and what is one disdavantgae?
Used to B-lactamase resistant STAPHYLOCOCCAL infections
Harder to penetrate cell membrane due to bulky side chain> less effective
Extended spectrum aminopenicillins are effective against which bacteria?
Gram +ve and Gram –ve cocci, Gram –ve
Not effective against Pseudomonas spp.
When is Extended spectrum aminopenicillins used?
Excellent oral agent for bacterial sinusitis, bronchitis
What are the advantages and disadv. of Extended spectrum aminopenicillins ?
Advantages: Acid stable, good oral bioavailability (amoxicillin > ampicillin)
Disadvantage: Do not resist B-lactamases
Name 2 Extended spectrum aminopenicillins?
Name 2 classes and 3 examples of extended spectrum antipseudomonal penicillins?
Carboxypenicillins (e.g. carbenicillin, ticarcillin)
Ureidopenicillins (e.g. piperacillin )
What are some advantages and disadvantages of extended spectrum antipseudomonal penicillins?
Good: effective against many gram -ve bacilli and very effective against Pseudomonas aeruginosa (unlike aminopenicillins)
Bad: sensitive to B-lactamses, acid labile
What are B-lactamase inhibitors
= potent irreversible inhibitor of many β-lactamases producing bacteria, esp. in respiratory tract
1. Clavulanate (clavulanic acid)
What drugs is usually given with B-lactamase inhibitors and why?
normally formulated / combined
with a broad spectrum penicillin derivative
>> to protect them from enzymatic inactivation by β-lactamases
Name the 4 combo preparations of B-lactamase inhibitors?
Combo broad spectrum penicillin and B-lactamase inhibitor
Augmentin (amoxicillin + clavulanic acid = co-amoxiclav
Unasyn (ampicillin + sulbactam = sultamicillin)
Timentin (ticarcillin (= carboxypenicillin) + clavulanic acid)
Tazocin (piperacillin (= ureidopenicillins) + tazobactam)
Cephalosporin is effective against which bacteria? Bacteriocidal or static?
Broad spectrum (vs. Gram +ve, Gram –ve, some vs. anaerobes)
** improved activity against gram -ve bacteria **
Name some first, second, third, fourth, fifth gen cephalosporins?
What is 1st gen cephalosporin best used against?
community acquired enterobacter
What is 2nd gen cephalosporin best used against?
What is 3rd gen cephalosporin best used against?
Mainly against gram -ve
What is 4th adn 5th gen cephalosporin best used against?
4th: wide spectrum + B-lactamase resistant
5th: wide spectrum + MRSA active
Which cepahlosporins can be given orally unlike others that are given IV or IM dur to poor oral absorption?
Which gen cephalosporin has good CSF penetration?
All gens are shit except 3rd gen
What is the half-life and path of excretion for cephalosporins?
long half-life (e.g. 6-8hr)
Renal secretion (except ceftriaxone > bile excretion)
Adverse effects of cephalosporin? aside from being very expensive
Oral admin> GI irritation
Compare the spectrum between tetracyclines and macrolides?
Tetra = broad
Macrolides = Moderate
Difference between erthyromycin vs clarinthromycin and azithromycin?
Erythromycin (= prototype)
clarithromycin and azithromycin are new analogues >> improved pharmacokinetic properties, broader antibacterial
What is the MoA of macrolides?
Bind irreversibly to a site on 50S subunit
of the bacterial ribosome
>> inhibit translocation of the polypeptide chain from A-site to P-site catalyzed by peptidyltransferase
>> block movement of peptidyl tRNA from acceptor to donor site
>> incoming tRNA cannot bind to the still occupied acceptor site >> inhibit bacterial
When is erythromycin used?
Active vs. Gram +ve organisms (same as
>> narrow spectrum
For patients allergic to penicillins
When is Clarithromycin used?
Slightly greater activity than erythromycin
Higher activity vs. intracellular pathogens, e.g. Chlamydia, Legionella, Moraxella
Also has activity vs. Mycobacterium
leprae, Toxoplasma gondii, H.pylori
When is Azithromycin used?
Slightly less active than erythromycin
vs. Gram +ve
But enhanced activity vs. some Gram –ve organisms, e.g.Haemophilus
Rank the three macrolides antibiotics in terms of activity against gram +ve bacteria?
Clarithromycin > erythromycin > azithromycin
When is Telithromycin used?>
Different site of action >>
effective vs. macrolide-resistant strains
What is the difference in absorption between erythromycin and newer macrolides?
Newer macrolides are more acid stable (instead of labile in gastric acid) and better obsorbed
Are all macrolides orally absorbed?
Are all macrolides converted to an active metabolite?
All except Erthyromycin
Which of the 4 macrolides are extensively metabolised in body?
Erthyromycin and telithromycin
Which of the 4 macrolides are exreted in bile in an active form (undergo enterohepatic circulation)?
Erthyromycin and azithromycin
Which macrolide is metabolized to active 14-hydroxy metabolite and eliminated in urine?
What is the toxicity and therapeutic index of macrolifdes?
High therapeutic index, relatively non-toxic
What are some adverse effects of macrolides?
GI disturbances (due to stimulation of motilin receptors
High dose of ethromycin can cause deafness
Risk of arrhythmia
Drug interactions (except azithromycin)
What respiratory tract infections are treated by macrolides?
Upper and Lower, including pharyngitis and tonsilitis
Macrolides is the drug of choice for which type of pneumonia?
Caused by Mcoplasma and Legionella
Macrolides is used to replace which drug in case of allergy?
for infections caused by staph. Strep. or pneumococci
Macrolides is used as an empirical therapy for which diseases?
Early outpatient pneumonia or bronchitis
Macrolides cannot be used for which patients?
Those with Liver disease
What are the 3 bacteria mechanisms against macrolides?
Effluc pump/ reduce permeability of cell membrane
Modify 50s subunit (methylases encoded by erm)
Release endogenous esterases to hydrolyse macrolides
Name 2 teracyclines? Which one it most popular?
Tetracycline spectrum and bacteriocidal or static?
Bacteriostatic > inhibit protein synthesis
MoA of tetracyclines?
Bind to 30s ribosome > prevent access of tRNA to -site on mRNA- ribosome complex
> block addition of amino acid to growing peptide
> peptide not transferred to amino acid receptor
What type of infections if tetracyclines used against and why?
Not against common infections (reduce resistance)
Treat uncommon infections (like Chlamydia, Mycosplasma, spirochetes infections)
Why can Doxycycline be used in renal impaired patients? *think absorption and excretion*
Exreted in bile and not accumulate in kidney
What is Glycylcyclines effective against and not?
Effective: multi-resistant Gram +ve pathogens, some gram -ve, anaerobic organisms
Ineffective: Protus and pseudomonas spp.
When is glycylcyclines used?
Treat complicated skin and soft tissue infections
complicated intra-abdominal infections
Excretion of Glycylcycline?
Why is IM injection avoided for tetracyclines?
Cause local tissue irritation
What are some adverse effects of tetracyclines?
discoloration in children
fatty liver esp in pregnant
Vestibular problems (e.g.
3 mechanisms in bacteria against tetracyclines?
Efflux pump/ impaired influx (porin)
Synthesis of blocking molecule to interfere binding to 30s ribosome
Production of tetracycline inactivating enzyme
Name the prototype quinolone and fluoroquinolone?
Quin = Nalidixic acid
Fluoro = Ciprofloxacin
What is the difference between 1st gen and 2nd, 3rd gen quinolones/ fluoroquinolones?
2nd gen = expanded activity:
against gram -ve
some gram +ve
What is the general improvement of generations of quinolones?
Improve coverage against more gram -ve, +ve, atypical, anaerobic coverage
Name one 1st, 2nd, 3rd, 4th gen quinolone/ fluoroquinolone?
1= nalidixic acid (urinary
2 = ciprofloxacin
3 = levofloxacin
4 = gemifloxacin
Spectrum and bactericidal or static for quinolones/fluoro--?
When is quinolone/ fluoro -- used? Which patients should not take it?
Treating lower respiratory tract infections
Contraindicated in children,
nursing mothers, pregnancy
(arthropathy >> potential: problem in joints)
What is the MoA for quinolones/ fluoro--?
Dual action: inhibit DNA gyrase and topoisomerase IV
form quinolone-DNA- gyrase
complex >> induce cleavage of DNA
Penetration, excretion of quinolones/ fluoro--?
High tissue penetration
Mainly excreted into the
3 mechanisms for resistance in bacteria against quinolones/ fluoro--?
Overexpress efflux pump
Reduce membrane permeability (less porin in gram -ve)
bacterial chromosomal mutations for genes that encode for bacterial DNA
gyrase, topoisomerase IV
Adverse effects of quinolones/ fluoro--?
CNS problems (e.g. confusion, dizziness)
Ruptured tendons in elderly
What drugs interact with quinolones/ fluoro--?
with cations (divalent and
What is the outpatient therapy for pneumonia?
1) Macrolides, doxycycline or oral, anti-pneumococcal B-lactam
2) Oral fluoroquinolone active against S. pneumonia for allergic patients or highly resistant infection
What is the inpatient therapy for pneumonia?
1) Parenteral B-lactam* + macrolide
*e.g. ceftriaxone, ampicillin-sulbactam, cefotaxime
2) Fluoroquinolone in some patients
S. pneumonia is highly resistant to which antibiotics?
erthromycin, tetracycline, co-trimoxazole
3 things recommended by CDC against pneumonia?
Only prescribe antibiotics when its beneficial
Use specific agent to target pathogen
Use appropriate dose and duration
Adv. and Disadv. of amoxicillin.
Adv. = high dose kills 60-96% s, pneumonia
Disadv. = cannot kill atypical or B-lactamase bacteria
Adv. and Disadv. of Augmentin (amoxicillin - clavulanate)?
Adv. = kill B-lactamase bacteria
Disadv. = cannot kill atypical agents
Adv. and Disadv. of Cephalosporins?
Adv = active against all H. influenzae and 75-85% S. pneumoniae
Disadv. = cannot kill atypical agents
Adv. and Disadv. of Macrolides.
Adv. = kill most common + atypical pthogens
Disadv. = drug resistance problem