Pharmacology Of ABx Part 2

Question 1

List the types of antibiotics that inhibit protein synthesis, and state the general mechanism of action.

Answer 1

Tetracyclines
Aminoglycosides
Macrolides and streptogramins
chloramphenicol

All affect prokaryotic ribosomes.

Question 2

What is the mechanism of action of tetracyclines?

Answer 2

Bind reversibly to the 30s ribosomal subunit to block tRNA binding.
Bacteriostatic.

Question 3

What is the mechanism of action of aminoglycosides?

Answer 3

Bind irreversibly to the 30s ribosomal subunit and cause incorrect reading of mRNA.
Have a concentration-dependent bactericidal effect.

Question 4

What is the mechanism of action of macrolides and streptogramins?

Answer 4

Bind to the 50s subunit and inhibit translocation.

Question 5

What is the mechanism of action of chloramphenicol?

Answer 5

Binds to the 50s subunit and prevents the activity of peptidyltransferase (responsible for transpeptidation).

Question 6

Describe the spectrum of tetracyclines.

Answer 6

Broad spectrum. Effective against:
Atypical bacteria (eg chlamydia, Rickettsia, Mycoplasma), some gram positive and some gram negative bacteria, some protozoa (malaria).

Question 7

What is the main use of tetracyclines?

Answer 7

Treatment of community-acquired pneumonia and pelvic inflammatory disease. Because of their anti-inflammatory effects, they are often used to treat skin conditions such as acne.

Question 8

What is the preferred tetracycline of use, and what is it used for?

Answer 8

Doxycycline. Acts as a blood schizontocide for treatment of malaria in combination with other drugs, and also for malaria prophylaxis.
Is also the preferred tetracycline for renal impairment and can be used in normal doses.

Question 9

Describe minocycline and the limitations of its use.

Answer 9

Active against some tetracycline-resistant bacteria (including staph). Its use is limited by the incidence of:
benign intracranial hypertension
vestibular adverse effects
skin pigmentation (rare)
Can also cause autoimmune hepatitis, drug-induced erythematosus and abnormal pigmentation of mucosa and tissue.

Question 10

What are some side effects of tetracyclines?

Answer 10

GI upset (can be minimised by taking after food, and with a full glass of water). Patient must remain upright for 30 mins.
Photosensitivity

Question 11

What are the contraindications of tetracyclines?

Answer 11

Children under 8 (effects tooth development) –> grey or yellow teeth
Safe in the first 18 weeks of pregnancy, after which the drug may affect the development of the fetuses teeth.
Rare occurrences of hepatic necrosis in pregnancy.
Breastfeeding women should have short course (10 days).

Question 12

Describe the spectrum of tigecycline and the reason for this.

Answer 12

Very broad spectrum due to glycylamido group, which prevents efflux by bacteria, and modifies the ribosomal subunit.
Active against all 4 major groups of bacteria.
NOT active against P aeruginosa or Proteus species.

Question 13

What are the side effects or contraindications of tigecycline?

Answer 13

Due to structural similarity to the tetracyclines, it may have similar side effects. New drug, and so other previously unrecognised reactions may occur. Its safety and efficacy in children has not yet been established.

Question 14

Describe the spectrum of macrolides.

Answer 14

Wide spectrum covering G+ cocci, G- cocci (some Neisseria) atypical bacteria (e.g. Legionella, Mycoplasma and Chlamydia, and both G+ and G- anaerobes.
NOT enteric G-ve rods.

Question 15

How do macrolides work against Legionella spp.?

Answer 15

Macrolides have intracellular activity against Legionella. Also have excellent lung tissue penetration and are therefore used to treat many pulmonary infections including leigionaire’s disease.

Question 16

What is the major indication of macrolides?

Answer 16

Community acquired respiratory infections such as Bordatella.

Question 17

Describe the use of macrolides in dermatology.

Answer 17

Erythomycin is used both topically and systemically to treat acne and rosacea.
Roxythromycin can be a useful alternative due to better absorption, tolerability and lower potential for drug interactions.

Question 18

Describe clarithromycin and its use.

Answer 18

Macrolide with a microbiologically active metabolite. Used in combination with other drugs for Mycobacterium avium complex, and the eradication of H pylori. Both of these are gram negative.

Question 19

Describe azithromycin and its use.

Answer 19

Activity against a few G-, some anaerobes, nanotuberculous mycobacteria (inc MAC) and some parasites (toxoplasma gondii).
Less active than erythromycin against G+ pathogens)

Question 20

Describe the benefits of the newer macrolides.

Answer 20

More reliable absorption and longer half lives which allows less frequent dosing. Attain high intracellular concentrations which are advantageous against for intracellular pathogens.

Question 21

Which macrolides inhibit the cytochrome P450 (CYP3A4) system? What is the consequence of this?

Answer 21

Erythromycin and clarithromycin are potent inhibitors of this system, resulting in significant drug interaction.
Eg coadministration of colchine and clarithromycin or erythromycin is associated with increased risk of fatal bone marrow toxicity.

Question 22

What is a significant adverse effect of macrolides? Which macrolides are responsible?

Answer 22

Erythromycin and clarythromycin have the potential to prolong the QT interval and cause potentially fatal arrhythmia. Other macrolides have been associated with case reports.

Question 23

What is the effect of erythromycin in babies less than 1 month old?

Answer 23

Pyloric stenosis.

Question 24

What is a risk of using erythromycin in pregnancy?

Answer 24

may increase foetal cardiac abnormalities.

Question 25

What is the mechanism of action of aminoglycosides?

Answer 25

Inhibit protein synthesis by irreversibly binding to the 30S subunit and causing cell membrane damage. Has a concentration-dependent bactericidal effect.

Question 26

What are amino glycosides used to treat?

Answer 26

Most rapidly bactericidal drugs available for treatment of G- sepsis. Also given in lower amounts with cell wall-active agents to treat G+ bacteria.

Question 27

Why aren’t amino glycosides active against anaerobes?

Answer 27

Oxygen is required for the transport of the amino glycoside into the bacterial cell.

Question 28

What should the use of amino glycosides depend on?

Answer 28

Local susceptibility patterns.

Question 29

What are the adverse effects of amino glycosides, and which patients are most likely to experience them?

Answer 29

All amino glycosides are potentially ototoxic and nephrotoxic, so renal, auditory and vestibular function should be monitored. also TDM.
Respiratory depression due to neuromuscular blockade (treat with IV calcium gluconate)
Most likely n elderly, renal impairment, hearing loss or vestibular impairment.

Question 30

Describe gentamicin and its spectrum.

Answer 30

Aminoglycoside. Broad G- spectrum, inc P aeruginosa. 95% of aerobic G- remain susceptible, and is amino glycoside of choice. Also active against G+ enterococci.
Can cross placental barrier and cause hearing loss in new-borns.

Question 31

Describe tobramicin, including spectrum and compare to gentamicin.

Answer 31

Aminoglycoside. Slightly more active in vitro than gentamicin against P aeruginosa. Tobramicin use should be restricted, but may have a role in treatment of pseudomonal sepsis. Not active against enterococci.

Question 32

Describe amikacin and its use.

Answer 32

Aminoglycoside, most resistant to enzymatic inactivation. Reserved for treatment of resistant bacteria. Considerably more expensive than other amino glycosides, and not active against enterococci.

Question 33

Describe framycetin.

Answer 33

Topical aminoglycoside for superficial eye and ear infections. Long term use not recommended.

Question 34

Describe neomycin.

Answer 34

Topical aminoglycoside active against a range of G- organisms. Most nephrotoxic and ototoxic, which prohibits parenteral use. Topical use may induce sensitisation.

Question 35

Describe the frequency of administration of amino glycosides.

Answer 35

Once daily: efficacious, cheaper and less likely to cause toxicity than divided daily doses. Recommended for those with normal renal function. Once-daily dosing not used for patients with unconventional kinetics.

Question 36

Describe the counselling for amino glycosides.

Answer 36

IV: if using for more than 7-10 days, may reduce kidney function while undergoing therapy.
May affect hearing and balance. Some permanent hearing loss may occur. Tell doctor if hearing becomes worse or you become dizzy.

Question 37

What are the practice points for amino glycosides?

Answer 37

Calculate creatinine clearance before starting treatment.
To minimise toxicity, use short-duration treatment, dose once daily, TDM, keep hydrated, monitor for ototoxicity and nephrotoxicity.
Can enhance the effects of depolarising neuromuscular blocking drugs, e.g. suxamethonium.

Question 38

Describe the spectrum of chloramphenicol.

Answer 38

Broad spectrum: G+ and G-, rickettsiae and chlamydia, S typhi, H influenzae and Bacteroides fragilis (G- anaerobe).

Question 39

What are the adverse effects of chloramphenicol?

Answer 39

Reversible dose-dependent bone marrow hyperplasia and rare, irreversible dose-independent aplasia (may be fatal).
Aplastic anaemia is not dose dependent. High mortality rate, and may lead to development of leukaemia.
Grey baby syndrome in neonates due to reduced renal elimination.

Question 40

Describe the use of chloramphenicol.

Answer 40

Should only be given systemically when there is no other suitable alternative.
Topically used for eye and ear infections.
Used for life threatening infections (H influenza and S typhi).

Question 41

Describe counselling points for chloramphenicol.

Answer 41

Tell doctor if you get pale skin, sore throat, fever, tiredness or weakness, unusual bleeding or bruising in the months after stopping treatment.

Question 42

What are the practice points for the use of chloramphenicol?

Answer 42

Obtain complete blood picture before and during treatment.
Consider stopping treatment if haematological changes occur, or if peripheral neuropathy or optic neuritis occurs.
Has variable activity against vancomycin-resistant enterococci.

Question 43

Describe lincosamides.

Answer 43

bacteriostatic. bind to the 50S subunit to inhibit protein synthesis.
Used for staphylococcal bone infections (e.g. osteomyelitis) and as prophylaxis for endocarditis.
Second-line therapy in those intolerant to conventional therapy.

Question 44

Describe the spectrum and use of clindamycin and lincomycin.

Answer 44

both Active against G+ aerobes (Staph and Strep) and most anaerobes, and some protozoa (e.g. Toxoplasma gondii).
Clindamycin is active against Proprionbacterium acnes.
Community-acquired MRSA.
Adjunct therapy in TSS.

Question 45

What are the side effects of lincosamides?

Answer 45

antimicrobial-assosciated diarrhoea with systemic admin.
Cardiovascular effects following rapid IV infusion.
C difficile colitis in 0.1-10% of patients.

Question 46

Describe the administration of lincosamides.

Answer 46

Oral and IV formulations available. No oral paediatric clindamycin available in Aus.
IV doses should be administered slowly to avoid serious arrhythmias.
Clindamycin used topically in acne and rosacea, and for intravaginal treatment of bacterial vaginosis.

Question 47

Describe counselling points for clindamycin.

Answer 47

Take with full glass of water.
Stop taking medication if you develop diarrhoea.
Check with doctor or pharmacist before taking any antidiarrhoeal medications.

Question 48

Describe streptogramins including mechanism of action, spectrum, and use.

Answer 48

Include IV quinupristin and dalfopristin. Inhibit protein synthesis.
Synergistic combination used for staph (inc MRSA), enterococcal or other G+ infections.
Effective against most enterococcus faecium.
Poorly active against Enterococcus faecalis (superinfection may occur)

Question 49

What are the adverse effects of quinupristin + dalfopristin?

Answer 49

arthraligias and myalgias.
elevation of bilirubin and liver enzymes
injection site reactions
QT interval prolongation, risk of ventricular arrhythmias
extremely expensive

Question 50

Describe oxazolidinones, including mechanism of action, spectrum and side effects.

Answer 50

Linezolid inhibits early step in bacterial protein synthesis.
effective against G+ (inc MRSA, VRE and penicillin-resistant strains of S pneumoniae.
Injection, tablet and oral suspension (all expensive).
Linezolid therapy reserved for multi-drug resistant infections.
May observe bone marrow suppression and peripheral neuropathy with prolonged therapy.

Question 51

What are the drug interactions of linezolid?

Answer 51

Inhibits monamine oxidase, and may cause serotonin syndrome when combined with other MAOIs, SSRIs, pethidine etc.

Question 52

Describe counselling for linezolid.

Answer 52

Avoid foods rich in tyramine (e.g. mature cheese, soy sauce and yeast extracts) as it may increase BP
Tell doctor immediately about tingling or altered sensation, blurred vision or other difficulty in seeing.