Antimicrobial Agents ( 10% ) Flashcards
acyclovir
- is commonly given in doses of 10-20mg tds
- is used to treat CMV
- is a guanosine analogue
- acts to inhibit viral entry into cells
- is only available IV
- is commonly given in doses of 400-800mg 5x daily (poor bioavailability, T 1/2 = 2 hours)
- is used to treat HSV and VZV (10x more potent against HSV than VZV)
- Ganciclovir is used to treat CMV as it is 100x more potent than aciclovir
- is a guanosine analogue (as is ganciclovir)
- acts to inhibit viral DNA synthesis by irreversible binding to viral DNA polymerase, being incorperated into the viral DNA, resulting in termination of the DNA chain
- First needs to be phosphorylated by viral kinase (gives specificity for virally-infected cells but is also a route of resistence)
- is only available IV - can be given orally, IV, or topically
Zidovudine (AZT)
- Has a short half life
- Inhibits viral thymidine kinase.
- Has no activity against retroviruses.
- Has a short half life
- Does not Inhibits viral thymidine kinase, as it is Used in combination with other HIV agents, which need this enzyme to be activated
- Has activity against retroviruses, is Anti-HIV
HIV Treatment:
- NRTIs (Nucleotide/side reverse transcriptase inhibitors - competitively inhibit RT, same mechanism of action as aciclovir etc
- eg abacavir, lamivudine, AZT
- Non-NRTIs - inhibit RT by binding to a seperate site on the enzyme
- Protease inhibitors
- Entry inhibitors
- Integrase strand transfer inhibitors
- A lot of drugs in each class, hopefully not expected to know them
The antiviral drug that acts on reverse transcriptase is
- Acyclovir
- Zidovudine
- Gancyclovir
- Vidarubine
- All of the above
Zidovudine
‘All of the above’ given as initial answer, but aciclovir, gancyclovir, and vidarubine are guanosine-analogues which interfere with DNA transcriptase
Which is a live virus vaccine
- Typhoid
- Tetanus
- Hepatitis B
- Rabies
- Measles
Measles
Amantadine
- Is an antiviral drug
- Produces insomnia not sedation
- Causes acute psychosis
- Potentiates DAergic function
- All of the above
All of the above
Old anti-influenza drug
With regard to antivirals
- Delavirdine is a nucleoside reverse transcriptase inhibitor (NRTI)
- Zidovudine (AZT) is a nonnucleoside reverse transcriptase inhibitor (NNRTI)
- NRTIs activate HIV-1 reverse transcriptase
- NRTIs require intracytoplasmic activation to the triphosphate form
- Abacavir is a protease inhibitor
- Delavirdine is a non nucleoside reverse transcriptase inhibitor (NNRTI)
- Zidovudine (AZT) is a nucleoside reverse transcriptase inhibitor (NRTI)
- NRTIs antagonise HIV-1 reverse transcriptase
- NRTIs require intracytoplasmic activation to the triphosphate form
- Abacavir is a NRTI
acyclovir is active against all except
- HSV
- CMV
- Herpes zoster
- Varicella
- None of the above
Nick says CMV
(as does iMeducate)
Ganciclovir is the agent of choice for CMV as it has 100x the potency of aciclovir against it. This would imply there is some action there, allbeit rather poor.
In vitro testing shows some weak activity (of aciclovir) against CMV, EBV and HHV-6.
The agents used to treat CMV infections are: Valganciclovir Ganciclovir Foscarnet and Cidofovir
regarding active immunizations
- the measles vaccine is an inactivated virus
- the Hep B vaccine is preferably given by subcutaneous injection
- booster doses for yellow fever are not required
- primary immunization for HiB involves 2 doses given 1/12 apart
- the meningococcal vaccine should be given to all asplenic individuals
the meningococcal vaccine should be given to all asplenic individuals
Which is the least appropriate for Rickettsia infection
- Chloramphenicol
- Tetracycline
- Sulphamethoxazole
- Erythromycin
- Doxycycline
Sulphamethoxazole
Rickettsia is typhus and RMSF
Vector-borne, obligate-intracellular, gram negative rods
Doxycycline is first line treatment
Ricketssia lack the enzyme target of sulfamethoxazole (and some lack the target of trimethoprim, often co-administered with SMX)
The anti TB drug most associated with peripheral neuropathy is
- Isoniazid
- Rifampicin
- Ethambutol
- Pyrazinamide
- Streptomycin
Isoniazid
Causes peripheral neuropathy and hepatitis
Rifampicin is a potent enzyme inducer
Intermediate spectrum (2nd generation) cephalosporins include all of the following except
- Cefoxitin
- Cephradine
- Cefaclor
- Cefamandole
- Cefuroxine
Cephradine
1st gen cephalosporin
Features of 3rd generation cephalosporins include
- Good efficacy against gram positives
- Reliable activity in cases of P aeruginosa meningitis
- Consistent activity against Haemophilis and Neisseria species
- Reliably high oral bioavailability
- Reversible binding to the 50S subunit of the bacterial ribosome
Consistent activity against Haemophilis and Neisseria species
Third gen can cross the BBB, but only ceftazadime has Pseudomonas activity
All cephalosporins have good efficacy against gram positives, but slightly reduces down the generations in exchange for a broader spectrum of activity
Unsure bioavailability but all seem to be given IV
Regarding penicillins, which is false
- Most cross the BBB only when the meninges is inflamed
- They don’t require a dose adjustment in renal failure
- Penicillins inhibit cross linkage of peptidoglycans in cell wall
- Piperacillin is a penicillin against pseudomonas
- Only about 5-10% of people with a past history of penicillin allergy have a reaction on re-exposure
They don’t require a dose adjustment in renal failure
All are renally excreted (10% glomerular filtration, 90% tubular secretion [hence why probenacid works])
I guess e) is wrong because most people dont recall a specific allergy, just ‘when I was a kid I was told that’. You’re 90 now Jean, time to get up to date with the useful abx.
cephalosporins
- excreted in bile
- excreted via the kidneys in the tubules
- drugs that can undergo hepatic metabolism
- are classified on the basis of their antibacterial ability
- all of the above
Nick says e)
excreted via the kidneys in the tubules
Poorly excreted in bile, as per an article in the journal Gut in 1984
?Undergo hepatic metabolism, but can cause cholestasis/liver injury
Classified into generations base on antimicrobial activity (not age of discovery)
Regarding antibiotic resistance
- Beta lactamase production is responsible for penicillin resistance in pneumococci
- Penicillin’s inability to penetrate the organism is more common with gram negative bacteria
- Penicillin resistance is mainly because of alteration in the target’s PBPs.
- Methicillin resistance in Staph is due to beta lactamase production.
- Beta lactamase are identical but produced by different bacteria.
-
Altered PBP is responsible for penicillin resistance in pneumococci
- On a side note, pneumococcus is another term for Strep. pneumoniae. Only just learnt that.
- Penicillin’s inability to penetrate the organism is more common with gram negative bacteria
- Penicillin resistance is mainly because of beta lactamase
- Methicillin resistance in Staph is due to altered PBP (cell wall)
- Beta lactamase are differernt in differnet bacterial species
All are cell wall inhibitors except
- Vancomycin
- Erythromycin
- Penicillin
- Ceftriaxone
- Imipenim
- Vancomycin - inhibits cell wall synthesis in G+ (glycopeptide)
- Erythromycin - Bacterial protein synthesis inhibitors- bacteriostatic and bacteriocidal
- Penicillin - binds PDP (betalactam)
- Ceftriaxone - binds PDP (betalactam)
- Imipenim - binds PDP (betalactam)
The IV drug of choice for diverticulitis is
- Cefazolin
- Cefuroxime
- Cefoxitin
- Ceftriaxone
- Amoxicillin
Ceftriaxone
Due to its better GN cover and anaerobic cover cf the others.
cefuroxime used if with metronidazole for anaerobics
amoxil and gent used in place of cefuroxime for more specialised GPC and GN cover
ceftriaxone is least effective for which infection
- penicillin resistant Pneumococcal meningitis
- Meningococcal meningitis
- H. influenzae meningitis
- Penicillin resistant gonococcus
- Listeria monocytogenes meningitis
Listeria monocytogenes meningitis
Ceftriaxone is good against betalactamase producing Haemophillus and Neiserria (?and strep)
Meningococcal is Neiserria meningitidus
Listeria is a gram positive coccus, aerobic
Cephalosporins DO NOT have activity against Listeria, but penicillins do (and amoxicillin would probably be 1st line +/- gent)
Which of the following is a 2nd generation cephalosporin
- Cephalothin
- Cephradine
- Cephalexin
- Cephapirin
- Cefamandole
Cefamandole
Which is a 2nd generation cephalosporin
- Cefaclor
- Ceftazidime
- Cephalexin
- Cefotaxime
- Cephalothin
Cefaclor
Ceftazidime - 3rd
Cephalexin - 1st
Cefotaxime - 3rd
Cephalothin - 1st
Which can cause hypoprothrombinaemia
- Cefuroxime
- Cefotetan
- Cefazolin
- Cefaclor
- Ceftriaxone
Cefotetan
??relevance of this question
resistance to β lactams
- can be due to an efflux pump
- is most commonly due to modification of the targets PBPs
- does not involve impaired penetration of drug to target PBPs
- infers resistance only to penicillins
- can involve up to 5 different β lactamases
- can be due to an efflux pump eg pseudomonas
- is most commonly due to betalactamases, but can also be due to modification of the targets PBPs
- can does not involve impaired penetration of drug to target PBPs, eg due to a biofilm
- infers resistance to penicillins, some cephalosporins (penams usually not resistant)
- most bacterial species have their own unique beta lactam
with regard to penicillin
- penicillins inhibit protein synthesis.
- it inhibits cell membrane function
- probenacid is a uricosuric drug that increases penicillin excretion.
- penicillin G is a semi-synthetic penicillin
- penicillamine is a metabolite of penicillin
- penicillins inhibit Peptidoglycan cross-linking (cell wall synthesis)
- it inhibits cell membrane function
- probenacid is a uricosuric drug that decreases penicillin excretion, by inhibiting tubular secretion.
- penicillin G is a natural penicillin
- penicillamine is a chelating agent used in the treatment of Wilsons disease, and is structurally unrelated to penicillin (but was first identified in the urine of patients who had taken penicillin)
flucloxacillin
- is not effective against Strep
- is active against enterococci and anaerobes
- blocks transpeptidation and inhibits peptidoglycan synthesis
- is poorly absorbed orally
- has excellent penetration into CNS and prostate
- is effective against staph/Strep only
- is not active against enterococci and anaerobes
-
blocks transpeptidation and inhibits peptidoglycan synthesis
- along with all beta lactams
- is well absorbed orally, but not if taken with food (binds to food proteins and is broken down by acid)
- has poor penetration into CNS and prostate
- (penicillin used in meningitis only because when inflamed it can get through leaky meninges)
cephalosporins
- are less stable than penicillins
- are active against enterococci and Listeria monocytogenes
- intrinsic antimicrobial activity is high
- belonging to the 1st generation have better activity against gram +
- are active against methicillin resistant strains of Staph
- ??are less stable than penicillins
- are active against enterococci and Listeria monocytogenes
- Have NO action on listeria (penicillin does)
- ??intrinsic antimicrobial activity is high
- belonging to the 1st generation have better activity against gram +
- are active against methicillin resistant strains of Staph
- No, MRSA has an altered PBP so no betalactams are active against them
Penicillin reach high concentrations in
- Vitreous humour
- CSF with normal meninges
- Proximal tubulular fluid of the kidney
Proximal tubulular fluid of the kidney
Due to their mechanism of excretion
90% tubular secretion
10% glomerular filtration
A patient with impetigo is most likely going to respond to
- Phenoxymethylpenicllin
- Streptomycin
- Cephalexin
- Kanamycin
- Metronidazole
Cephalexin
The β lactam ring is present in all of the following classes of antibiotics except
- Penicillins
- Monobactams
- Fluoroquinolones
- Carbapenems
- Cephalosporins
Fluoroquinolones
The cephalosporin with the highest activity against Gram +ve is
- Cefuroxime
- Cefotaxime
- Cefaclor
- Cefepime
- Cephalothin
Cephalothin - 1st gen
- Cefuroxime and cefaclor - 2nd gen*
- Cefotaxime - 3rd gen*
- Cefepime - 4th gen*
Gentamicin
- Can be mixed in the same administration set as penicillin
- Most streptococci are sensitive to gentamicin
- If organisms are resistant to gentamicin they will also be resistant to tobramycin
- Purulent exudates do not affect the activity of topical Abs
- Ototoxicity manifests itself mainly as vestibular dysfunction
Ototoxicity manifests itself mainly as vestibular dysfunction
aminoglycosides
- have a β lactam ring
- are DNA gyrase inhibitors
- have good oral absorption but high first pass metabolism
- normally reach high CSF concentrations
- can produce neuromuscular blockade
- have a β lactam ring - no.
- irreverisbly bind the 30s ribosome subunit and prevent protein synthesis
- have shite oral absorption and no metabolism (excreted unchanged)
- normally reach low CSF concentrations
-
can produce neuromuscular blockade
- can prolong it
- ?due to antagonising Ca and impairing ACh release at the NMJ
drug that is most vestibulotoxic
- tobramycin
- gentamicin
- neomycin
- kanamycin
- amikacin
gentamicin
gentamicin (2 CORRECT)
- is not nephrotoxic
- increases the effect of neuromuscular junction blocking drugs
- may be given orally
- enters cells by an oxygen dependent influx
- has a large therapeutic index
increases the effect of neuromuscular junction blocking drugs
enters cells by an oxygen dependent influx
Is nephrotoxic, must be given parenterally or topically, and has a low TI (hence regular concentration checks)
macrolide antibiotics
- are usually active against Neisseria spp
- are bacteristatic but not bactericidal
- bind at the 30S ribosomal subunit
- are unaffected by plasmid mediated resistance
- enhance metabolism by cytochrome P450 pathways
are usually active against Neisseria spp
Azithromycin is first line for gonorrhoea
- are bactericidal at high doses
- bind at the 50S ribosomal subunit
- Gentamicin binds the 30s
- Resistence is usually plasmid mediated:
- Reduced influx or increased efflux via pumps
- Esterase production that hydrolyses macrolides
- Modification of the ribosomal binding site
-
Most inhibit metabolism by cytochrome P450 pathways
- Although azithromycin does not have CYP450 action
Erythromycin
- Is effective against campylobacter jejuni
Is effective against campylobacter jejuni
Chlamydia in children is best treated with
- Ceftriaxone
- Chloramphenicol.
- Doxycycline
- Erythromycin
- Tetracycline
Erythromycin
- Chloramphenicol has a risk of aplastic anaemia
- Doxycycline may cause tooth staining
Ribosomal resistance occurs with
- Sulphonamides
- Penicillin
- Macrolides
- Fluroquinolones
- Trimethoprim
Macrolides
(also gentamicin)
Penicillin targets bacterial PDP
Fluoroquinolones -
Trimethoprim -
Sulphonamides-
Macrolides
- Have enhanced activity at acidic pH.
- Have little activity against legionella
- Have half lives that increase with anuria
- Induce cytochrome p450.
- Are contraindicated in neonates
Nick thinks C), i think e)
- Have reduced activity at acidic pH (give on an empty stomach)
- Have good activity against legionella
- Atypical organism - give roxi in pneumonia to cover this
- c) Have half lives that increase with anuria
- 95% excreted in bile, only 5% in urine
- Risk of ototoxicity if severe renal impairment
-
Inhibit cytochrome p450.
- Excpet azithromycin
-
e) Are contraindicated in neonates
- NZF states risk of hypertrophic pyloric stenosis if given under 2 weeks of age
Regarding erythromycin
- It has a large cross reactivity with penicillin.
- It is bacteriostatic only
- It is ineffective against gram positive organisms
- It is inactivated by β lactamases.
- It binds the 50S subunit on the bacterial ribosome
- It has a low cross reactivity with penicillin
- It is Bactericidal in high doses
- It is effective against gram positive organisms, and can be Used for skin infections if penicillin allergic
- It is not inactivated by β lactamases, as it is not a beta lactam
- It binds the 50S subunit on the bacterial ribosome
A man aged 24 is admitted to hospital with fever, a dry cough and an CXR consistent with an atypical pneumonia, which is the appropriate AB
- Amoxicillin
- Trimethoprim
- Ceftriaxone
- Penicillin
- Doxycycline
Doxycycline
Macrolide or a tetracycline to cover atypicals
The mechanism of resistance most important with tetracyclines is
- Efflux pump
- β lactamases
- change in ribosomal proteins
- impaired penetration
- enzyme inactivation
Efflux pump
Mechanisms of resistence to tetracyclines:
- Impaired influx or increased efflux by a protein pump
- Eg Tet(AE), expressed by gram negatives
- Newer drugs (eg tigecycline) are less susceptible to this mechanism
- However proteus and pseudomonas express different efflux pumps, so are resistant
- Ribosome protection by proteins that bind to the ABx
- Expressed by gram positives
- However they have low affinity for tigecycline
- Enzymatic inactivation (less important)
The following is bacteriostatic
- Penicillin
- Gentamicin
- Isoniazid
- Tetracycline
- Metronidazole
Tetracycline
Others are bactericidal
Other bacteriostatic abx are vancomycin, macrolides at low doses,
doxycycline
- acts to inhibit nucleic acid synthesis
- may cause photosensitivity
may cause photosensitivity
inhibits protein synthesis by reversibly binding to 30s subunit ribosome
Bacteriostatic
Which tetracycline requires dose adjustment in renal failure
- Minocycline
- Doxycycline
- Tetracycline
- Methacycline
- All of the above
No answer given
As per NZF:
Doxy - ‘avoid high doses in RF’, but is 100% excreted in bile
Tetra - ‘avoid in RF as can exacerbate’
Mino - ‘caution mild-mod; avoid severe’
metha - not on NZF
trimethoprim
- activates dihydrofolic acid reductase
- is a weak base
- has limited activity in the prostate.
- does not distribute into the CSF
- is harmless in pregnancy.
- inhibits dihydrofolic acid reductase.
- is a weak base
- has high activity in the prostate.
- does distribute into the CSF, crosses the BBB
- is teratogenic in pregnancy, due to its anti-folate effects
Which is the least appropriate for Rickettsia infection
- Chloramphenicol
- Tetracycline
- Sulphamethoxazole
- Erythromycin
- Doxycycline
Ricketssia is typhus and RMSF
Vector-borne, obligate intracellular, gram negative bacilli
Doxycycline / tetracycline are first line treatment
Sulphamethoxazole noted to be ineffective against Rickettsia
Regarding trimethoprim, which is false
- It is useful in the treatment of UTI
- It is bactericidal
- It is an antifolate, anti-metabolite drug
It is bactericidal
Bacteriostatic as monotherapy
Bactericidal when used in combination with sulfamethoxazole (ie cotrimoxazole)
all of the following inhibit nucleic acid synthesis except
- norfloxacin
- trimethoprim
- rifampicin
- sulfasalazine
- chloramphenicol
- norfloxacin - inhibits DNA synthesis by inhibiting topoisomerase
- trimethoprim - inhibits folate synthesis -> inhibits nucleic acid synthesis
- rifampicin - inhibits bacterial RNA synthesis
- sulfasalazine - inhibits folate synthesis -> inhibits nucleic acid synthesis
- chloramphenicol - binds 50s subunit of ribosome -> inhibits protein synthesis
ciprofloxacin
- is a de-fluorinated analogue of nalidixic acid.
- inhibits tropoisomerase II and III.
- has no gram positive cover.
- has a bioavailability of 30%.
- may cause an arthropathy
- is a fluorinated analogue of nalidixic acid
- inhibits tropoisomerase II and IV.
- has some gram positive cover
- MSSA but not MRSA, limited strep and enterococci
- has a bioavailability of 70%.
- Given orally, so unlikely to have poor bioavailability
- may cause an arthropathy, tendonitis, QT prolongation, cartilage growth mishaps
metronidazole, which is false
- it is useful against trichomonis
- it is used to treat gardnerella
- causes a metallic taste in the mouth
- inhibits alcohol dehydrogenase.
- it is used to treat giardiasis
- it is useful against trichomonis
- it is used to treat gardnerella
- causes a metallic taste in the mouth
- inhibits Aldehyde dehydrogenase.
- it is used to treat giardiasis
metronidazole
- inhibits alcohol dehydrogenase
- is effective for vaginal trichomoniasis
- does not cause a metallic taste in the mouth
- turns urine green
- inhibits aldehyde dehydrogenase
- is effective for vaginal trichomoniasis
- Can cause a metallic taste in the mouth
- turns urine green - ??
- All of the following are true regarding penicillins EXCEPT
- Most penicillins only cross the blood brain barrier when the meninges are inflamed.
- Penicillins don’t require dosage adjustment in renal failure
- Penicillins inhibit cross linkage of peptidoglycans in the cell wall
- Piperacillin is a penicillin active against pseudomonas
- Only about 5 to 10% of people with a past history of penicillin allergy have a reaction on re exposure
Penicillins don’t require dosage adjustment in renal failure
90% tubular excretion, 10% glomerular filtration
Ciprofloxacin
- Is a defluorinated analogue of nalidixic acid
- Inhibits tropoisomerases 2 and 3
- Has no gram positive cover
- Has a bioavailability of 30%
- May cause an arthropathy
- Is a fluorinated analogue of nalidixic acid
- Inhibits tropoisomerases 2 and 4
- Has moderate gram positive cover, excellent gram negative cover
- Has a bioavailability of ?60-70% (well absorbed orally)
- May cause an arthropathy
Resistance to B lactams
- Can be due to an efflux pump
- Is most commonly due to modification of the target PBPs
- Does not involve penetration of drug to target PBPs
- Infers resistance only to penicillinc
- Can involve up to 5 different B lactamases
Can be due to an efflux pump
Can involve one of hundreds of identified different B lactamases
Macrolides
- Have enhanced activity at acidic pH
- Have little activity against legionella
- Have half lives which increase in patients with anuria
- Induce cytochrome p450 enzymes
- Are contraindicated in neonates
Have half lives which increase in patients with anuria
Destroyed by acid
Effective against atypical organisms
INHIBIT CYP 450
Flucloxacillin
- a. Is ineffective against streptococci
- b. Is active against enterococci and anaerobes
- c. Blocks transpeptidation and inhibits peptidoglycan synthesis
- d. Is poorly absorbed orally
- e. Has excellent penetration into CNS and prostate
c. Blocks transpeptidation and inhibits peptidoglycan synthesis
All of the following inhibit nucleic acid synthesis EXCEPT
- a. Norfloxacin
- b. Chloramphenicol
- c. Trimethoprim
- d. Rifampicin
- e. Sulfasalazine
- a. Norfloxacin - inhibits isotopomerase II+IV
- b. Chloramphenicol - 50s (inhibits protein synthesis)
- c. Trimethoprim - anti folate
- d. Rifampicin - blocks RNA production
- e. Sulfasalazine - anti-folate
Which of the following is a second generation cephalosporin?
- a. Cefaclor
- b. Ceftazidime
- c. Cephalexin
- d. Cefotaxime
- e. Cephalothin
a. Cefaclor
Regarding the pharmacokinetics of the tetracyclines
- Tetracyclines are 40 to 80 % bound by serum proteins
- Absorption is enhanced by coadministration of antacids
- Tetracyclines cross the blood brain barrier easily
- Doxycycline is excreted predominantly by the kidney
- Demeclocyline is a short acting tetracycline drug
- Tetracyclines are 40 to 80 % bound by serum proteins
- Absorption is ??? by coadministration of antacids
- Tetracyclines cross the placenta but not the blood brain barrier
- Doxycycline is excreted 100% in bile
- Demeclocyline is a short acting tetracycline drug
- T 1/2 10-17 hours
- All of the following are recognized adverse effects of isoniazid EXCEPT:
- Hepatitis
- Peripheral neuropathy
- Retrobulbar neuritis
- Decreased phenytoin metabolism – increased phenytoin blood levels / toxicity
- CNS toxicity
Retrobulbar neuritis
- Vancomycin
- 90% of vancomycin is excreted by glomerular filtration
- Inhibits proteinsynthesis in bacteria
- Is bactericidal against gram negative bacilli
- Is well absorbed from the GIT
- One adverse reaction to infusions of vancomycin is the “blue man” syndrome
- 90% of vancomycin is excreted by glomerular filtration
- Inhibits cell-wall building in bacteria
- Is bactericidal against gram positive bacilli
- Is poorly absorbed from the GIT
- One adverse reaction to infusions of vancomycin is the “Redvman” syndrome
- This syndrome, usually appearing within 4 to 10 min after the commencement or soon after the completion of an infusion, is characterized by flushing and/or an erythematous rash that affects the face, neck, and upper torso
- Regarding mechanisms of antiviral drug action
- blockage of viral uncoating is caused by rifampicin
- Zidovudine is a protease inhibitor
- Amantidine blocks viral DNA packaging and assembly
- Indinavir is a reverse transcriptase inhibitor
- Acyclovir inhibits viral DNA synthesis
Acyclovir inhibits viral DNA synthesis
Guanosine analogue
AZT is a reverse transcriptase inhibitor
Amantadine inhibits viral uncoating of RNA
- Regarding toxicity of antibiotics
- Enamel dysplasia is common with aminoglycosides
- Gray baby syndrome occurs with rifampicin use
- Haemolytic anaemias can occur with sulphonamide use
- Nephritis is the most common adverse reaction with isoniazid
- Disulfiram like reaction can occur with macrolides
- Enamel dysplasia is common with tetracyclines
- Gray baby syndrome occurs with chloramphenicol use
- Haemolytic anaemias can occur with sulphonamide use
- Hepatitis is the most common adverse reaction with isoniazid
- Disulfiram like reaction can occur with metronidazole
- Chloramphenicol
- Does not penetrate the blood brain barrier
- Must be administered parenterally
- Can be safely used in premature infants
- Can cause depression of bone marrow function
- Can cause discoloration of developing teeth when given to children
-
Does penetrate the blood brain barrier
- Can be used for meningococcal meningitis with pencillin allergy
- Can be used if you want to kill premature infants
- Causes Gray Baby Syndrome -> circulatory collapse
-
Can cause depression of bone marrow function
- ADRS: N/V/D, reversible bone marrow suppression or aplastic anaemia, grey baby syndrome
All of the following antibiotics bind to the 50S subunit of the ribosome thereby inhibiting proteinsynthesis EXCEPT
- Chloramphenicol
- Erythromycin
- Linezolid
- Doxycycline
- Clindamycin
Doxycycline - 30s
Pharmacokinetics of doxycycline
- 20% bound by serum proteins
- 60-70% absorption after oral administration
- Absorption is impaired by divalent cations, Al3+, and antacids
- Widely distributed especially into the CSF
- Is eliminated via renal mechanisms
Absorption is impaired by divalent cations, Al3+, and antacids
Doxy 100% absorbed, 50% protein bound, not into CSF, 100% bile excretion
Which of the following inhibits DNA gyrase?
- Penicillin
- Trimethoprim
- Chloramphenicol
- Ciprofloxacin
- Gentamicin
Ciprofloxacin
Resistance to Penicillin and other β lactams is due to
- Modification of target PBPs
- Impaired penetration of drug to target PBPs
- Presence of an efflux pump
- Inactivation of antibiotics by β lactamase
- e. All of the above
e. All of the above
- All of the following are recognised adverse effects of isoniazid EXCEPT
- Hepatitis
- Peripheral neuropathy
- Retrobulbar neuritis
- ↓ Phenytoin metabolism → ↑ Phenytoin blood levels and toxicity
- CNS toxicity
Retrobulbar neuritis
Regarding fluoroquinolones
- Ciprofloxacin is ineffective in the treatment of gonococcus
- Norfloxacin and Ciprofloxacin are predominantly faecally excreted
- Norfloxacin and Ciprofloxacin have long half lives (12 hours)
- They have poor oral bioavailability
- May damage growing cartilage in children less than 18 years of age
May damage growing cartilage in children less than 18 years of age
Vancomycin
- Is never orally administered as it is poorly absorbed from the GIT
- Binds to the 30S unit on the ribosome and inhibits protein synthesis
- 60% of vancomycin is excreted by glomerular filtration
- Parenteral vancomycin is commonly used for treatment of infections caused by methicillin susceptible staphylococci
- Adverse reactions to vancomycin are encountered in about 10% of patients
Adverse reactions to vancomycin are encountered in about 10% of patients
- Is never orally administered as it is poorly absorbed from the GIT
- Oral for C. diff infection
- Binds to the terminus of the cell-wall pentopeptide preventing cross linking
- Parenteral vancomycin is commonly used for treatment of infections caused by methicillin resistant staphylococci
Regarding the “azole” group of antifungals
- Fluconazole has low water solubility
- Ketoconazole may be given IV/PO
- Itraconazole undergoes renal elimination
- Clotrimazole is the treatment of choice for systemic candidiasis – given orally
- They work by reduction of ergosterol synthesis by inhibition of fungal cytochrome P450 enzymes
They work by reduction of ergosterol synthesis by inhibition of fungal cytochrome P450 enzymes
Imidazoles (clotrimazole, ketoconazole) less specific for fungal CYP450 and so cause more patient CYP450 inhibition - generally used only topically for this reason
The fluoroquinolones
- May be administered to patients with severe campylobacter infection
- Work by inhibiting dihydrofolate reductase
- Have little effect against gram positive organisms
- Are heavily metabolised in the liver
- Are safe to give to breast feeding mothers
May be administered to patients with severe campylobacter infection
- Work by inhibiting topoisomerase (DNA gyrase)
- Have moderate effect against gram positive organisms
- “Most fluoroquinolones are eliminated by renal mechanisms, either tubular secretion or glomerular filtration”
- Are not safe to give to breast feeding mothers
Clindamycin
- Inhibits bacterial cell wall synthesis
- Is often used for prophylaxis of endocarditis in patients with Valvular disease who are undergoing dental procedures
- Penetrates through BBB into CSF well
- Works well against enterococci and gram negative aerobic organisms
- Is 10% protein bound
Is often used for prophylaxis of endocarditis in patients with Valvular disease who are undergoing dental procedures
- Actions against anaerobic (atypical pneumonia) and aerobic (esp S. Aureus)*
- Can be used for skin infections in case of penicillin allergy*
