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Top 100 Drugs (Pre-reg) > Infection > Flashcards

Infection Flashcards

1
Q

What is the primary indication for the use of nitrofurantoin?

A

Uncomplicated lower urinary tract infection (UTI), as a first-line antibiotic (alternatives being amoxicillin and trimethoprim).

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2
Q

Why is nitrofurantoin particularly suited to the treatment of UTI?

A
  1. It is effective against the common causative agents
  2. It reaches therapeutic concentrations in urine through renal excretion
  3. It is most bactericidal in acidic environments such as urine.
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3
Q

How does nitrofurantoin work?

A

It is reduced in bacterial cells by nitrofuran reductase. Its active metabolite damages bacterial DNA and causes cell death.

Nitrofurantoin is active against the gram-ve (e.coli) and gram+ve (s. saprophyticus) that commonly cause UTIs

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4
Q

What are the main side effects of nitrofurantoin?

A 
Red/brown urine. 
GI upset. 
Hypersensitivity. 
Chronic pulmonary reactions.
Hepatitis. 
Peripheral neuropathy. 
Haemolytic anaemia.
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5
Q

Who should not be prescribed nitrofurantoin?

A

Pregnant women towards term.
Babies in the first 3 months of life.
Patients with renal impairment as impaired excretion increases toxicity and reduces efficacy due to lower urinary drug concentrations.

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6
Q

When should nitrofurantoin be taken?

A

With food or milk to minimise GI effects.

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7
Q

Why would nitrofurantoin not be suitable for complicated UTIs or pyelonephritis?

A

Tissue concentrations of nitrofurantoin are very low, a suitable alternative would be co-amoxiclav with gentamicin.

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8
Q

For the treatment of an acute UTI, what is the typical dosage regimen of nitrofurantoin?

A

50-100mg qds for 3 days for women, up to 7 days for men.

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9
Q

What are the 4 indications for metronidazole use?

A
  1. Antibiotic-associated colitid caused by C.diff which is a Gram+ve anaerobe.
  2. Oral infections/aspiration pneumonia caused by Gram-ve anaerobes from the mout.
  3. Surgical and gynaecological infections caused by Gram-ve anaerobes from the colon, for example B. fragilis.
  4. Treatment of protozoal infections including: trichomonal vaginal infection, amoebic dysentery, giardisis.
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10
Q

How does metronidazole work?

A

Metronidazole enters bacterial cells by passive diffusion.

In anaerobic bacteria, reduction of metronidazole generates a nitroso free radical which binds to bacterial DNA, reducing synthesis and causing widespread damage, DNA degradation and cell death.

As aerobic bacteria are not able to reduce metronidazole in this way they are resistant to its use.

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11
Q

What are the important adverse effects with one-off an chronic metronidazole use?

A

One-off: GI upset such as nausea and vomiting and immediate and delayed hypersensitivity reactions.

Chronic: neurological effect such as peripheral and optic neuropathy, seizures and encephalopathy.

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12
Q

In what patients whould metronidazole doses be reduced?

A

Those with severe liver disease as its metabolised by hepatic CYP450 enzymes.

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13
Q

Metronidazole can treat what protozoal infections? (3)

A

Trichomonal vaginal infection
Amoebic dysentery
Giardisis

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14
Q

Why should metronidazole not be used at the same time as alcohol?

A

Metronidazole inhibits the enzyme acetaldehyde dehydrogenase, which is responsible for clearing the intermediate alcohol metabolite acetaldehyde from the body.

A disulfiram-like reaction, including flushing, headache, nausea and vomiting can occur if alcohol and metronidazole are combined.

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15
Q

What is the interaction between warfarin and metronidazole?

A

Metronidazole has some inhibitory effect on cytochrome p450 enzymes, reducing metabolism of warfarin - increasing the risk of bleeds.

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16
Q

What is the interaction between phenytoin and metronidazole?

A

Metronidazole can inhibit the CYP450 metabolsim of phenytoin leading to an increased risk of phenytoin toxicity.

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17
Q

What effect does metronidazole have on lithium?

A

Increased risk of lithium toxicity

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18
Q

When is vancomycin used to treat gram-positive infection, e.g. endocarditis ?

A

When the infection is severe and/or penicillins cannot be used due to resistance (MRSA) or allergy

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19
Q

When is vancomycin used in the treatment of antibiotic associated colitis?

A

When it is caused by C.diff infection and usually only second-line where metronidazole is ineffective or poorly tolerated.

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20
Q

How does vancomycin work?

A

Vancomycin works by inhibiting the growth and cross-linking of peptidoglycan chains, inhibiting synthesis of the cell wall of gram+ve bacteria.

It has specific activity against gram+ve aerobic and anaerobic bacteria and is inactive against most gram-ve bacteria, which have a different (lipopolysaccharide) cell wall structure.

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21
Q

What is the spectrum of activity of vancomycin?

A

Works against gram+ve aerobic and anaerobic bacteria and is inactive against most gram-ve bacteria due to different cell wall structures.

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22
Q

What is the most common adverse effect of vancomycin administration?

A

Pain and inflammation of the vein, thrombophlebitis, at the infusion site.

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23
Q

What is red man syndrome?

A

If vancomycin is infused rapidly, it can cause anaphylactoid reactions described as ‘red man syndrome’ .

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24
Q

Other than red man syndrome, what else can IV vancomycin cause?

A
  1. renal failure/nephrotoxicity
  2. ototoxicty - with tinnitus and hearing loss
  3. blood disorders - neutropenia and thrombocytopenia.
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25
Q

There is an increased risk of ototoxicty and.or nephrotoxicity when vancomycin is prescribed with what?

A
  1. Aminoglycosides
  2. Loop diuretics
  3. Ciclosporin
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26
Q

Antibiotic treatment with vancomycin may be required for several weeks for patients with severe or deep-seated infection e.g. what? (2)

A

Endocarditis
OR
Osteomyelitis

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27
Q

For C. difficile colitis, vancomycin must be given via what route?

A

Oral, typically 125mg 6-hourly for 10-14 days.

28
Q

For C. difficile colitis, vancomycin is given orally for how long?

A

Oraly, typically 125mg 6-hourly for 10-14 days

29
Q

Why should patients takint vancomycin be advised to report any ringing in the ears or change in hearing during treatment.

A

ototoxicity

Which is reversible only if treatment is stopped promptly.

30
Q

Vancomycin plasma concentrations should be above what level to be therapeutic?

A

10mg/L to be therapeutic but below 15mg/L to minimise toxicity.

31
Q

Vancomycin plasma concentrations should be kept below what level to reduce toxicity?

A

10mg/L to be therapeutic but below 15mg/L to minimise toxicity.

32
Q

What are the common indications for aminoglycoside antibiotics?

A

Severe infections, particularly those caused by Gram-negative aerobes (including P. aeruginosa).

  1. Severe sepsis, including where the source is unidentified.
  2. Pyelonephritis and complicated urinary tract infection.
  3. Biliary and other intra-abdominal sepsis.
  4. Endocarditis

Aminoglycosides lack activity against streptococci and anaerobes so should be combined with penicillin and/or metronidazole when the organism is unknown.

33
Q

Why should aminoglycosides be combined with penicillin and/or metronidazole when treating severe infections where the causative agent is unknown?

A

Aminoglycosides lack activity against streptococci and anaerobes so should be combined with penicillin and/or metronidazole when the organism is unknown.

34
Q

How do aminoglycosides work?

A

They bind irrerversibly to bacterial ribosomes (30s subunit) and inhibit protein synthesis.

They are bactericidal (kill bacteria).

35
Q

Why do streptococci and anaerobic bacteria have innate aminoglycoside resistance?

A

Aminoglycosides enter bacterial cells via an oxygen-dependent transport system. Streptococci and anaerobic bacteria do not have this transport system.

36
Q

How can the addition of penicillin to aminoglycoside therapy result in more uptake of aminoglycosides into bacterial cells?

A

Penicillins weaken bacterial cell walls.

37
Q

What are the most important adverse effects of aminoglycosides?

A
  1. Nephrotoxicity

2. Ototoxicity

38
Q

Apart from nephrotoxicity and ototoxicty, what are the less important adverse effects of aminoglycosides?

A

Amioglycosides accumulate in renal tubular epithelial cells and cochlear and vestibular hair cells where they trigger apoptosis and cell death.

Alopecia.

39
Q

As aminoglycosides can impair neuromuscular transmission they should not be given to what patient group unless absolutely necessary?

A

Myasthenia Gravis

40
Q

Ototoxicity is more likely with aminoglycosides if they are co-prescribed with what drugs?

A

Loop diuretics: furosemide.

Vancomycin.

41
Q

Nephrotoxicty is more likely if aminoglycosides are co-prescribed with what drugs? (4)

A
  1. Ciclosporin
  2. Platinum
  3. Cephalosporins
  4. Vancomycin
42
Q

Why are aminoglycosides such as gentamicin and amikacin not given orally?

A

They are highly polarised molecules and do not cross lipid membranes.

In severe infections, parenteral aminoglycosides are usually given as a once daily IV infusion.

43
Q

The dose of aminoglycosides to be used is calculated how?

A

Using the patients ideal weight if obese and renal function.

44
Q

For aminoglycoside therapy, the plasma drug concentration is usually measured how long after the first dose?

A

18-24 hours

45
Q

The safe plasma concentraion of gentamicin is what?

A

<1mg/ml

46
Q

Why are quinolones usually reserved as second or third-line treatment options?

A

Due to the emergence of rapid resistance and an associated with c.diff infection.

47
Q

What are quinolones used for?

A

Normally second or third-line options for:

  1. UTI
  2. Severe GI infection such as Shigella, Campylobacter.
  3. LRTI (moxifloxacin, levofloxacin).
  4. Ciprofloxacin is the only oral antibiotic in common use with against P. aeruginosa. Moxifloxacin and levofloxacin do not have this property.
48
Q

How do quinolones work?

A

They kill bacteria by inhibiting DNA synthesis.
Particularly active against aerobic Gram-negative bacteria, which explains their utilit in treatment of urinary and gastrointestinal infections.

49
Q

Which quinolones are better against Gram-positive organisms?

A

Moxifloxacin and levofloxacin are newer quinolones with enhanced activity against Gram-positive organisms.

They can therefore be used to treat LRTI, which may be caused by either Gram-positive or Gram-negative organisms.

50
Q

What are the side effects associated with quinlones? (4)

A
  1. Neurological effects: lowered seizure threshold, hallucinations.
  2. Inflammation and rupture of muscle tendons.
  3. Quinolones (particularly moxifloxacin) prolong the QT interval and therefore increase the risk of arrhythmias.
  4. They promote C.diff colitis.
51
Q

Quinolones should not be taken at the same time as what?

A

Antacids, calcium etc due to chelation with them

52
Q

Ciprofloxacin inhibits certain CYP450 enzymes, increasing the risk of toxicity with some drugs. What is one notable example?

A

Theophylline.

53
Q

Co-prescription of what drug class increases the risk of seizures with quinolones?

A

NSAIDs

54
Q

Co-prescription of what drug with quinolone increases the risk of tendon rupture?

A

Prednisolone

55
Q

Quinolones should be prescribed with caution in patients taking other drugs that prolong the QT interval such as what? (5)

A
  1. Amiodarone
  2. Antipyschotics
  3. Quinine
  4. Macrolide antibiotics
  5. SSRIs
56
Q

What are the three common indications for a macrolide antibiotic?

A
  1. In the treatment of respiratory and skin and soft tissue infections as an alternative to a penicillin when this is contrainidicated by an allergy.
  2. In severe pneumonia, added to a penicillin to cover atypical organsims including Legionella pneumophilia and Mycoplasma pneumoniae.
  3. Eradication of Helicobacter pylori in combination with a proton pump inhibitor and either amoxicillin or metronidazole.

(also azithromycin for chlamydia)

57
Q

Macrolides are used in the eradication of H.pylori in combination with what other drugs?

A

A PPI and amoxicillin/metronidazole

58
Q

How do macrolides work?

A

They inhibit bacterial protein synthesis by binding to the 50S subunit of the bacterial ribosome and block translocation.

They are bacteriostatic not bactericidal meaning they stop bacteria growth but do not kill bacterial populations.

59
Q

Which macrolides have increased activity against Gram-negative bacteria, particularly Haemophilus influenzae?

A

The newer synthetic macrolides like azithromycin and clarithyromycin have better Gram-negative activity than the original erythromycin.

60
Q

Adverse reactions are more common to what macrolide antibiotic?

A

Erythro.
Macrolides are irritant causing nausea, vomting, abdo pain and diarrhoea when taken orally and thrombophlebitis when given IV.

61
Q

What adverse reactions can occur with macrolide use?

Other than the usual N+V, abdominal pain, diarrhoea etc

A
  1. Antibiotic-associted colitis
  2. Cholestatic jaundice (liver abnormalities)
  3. Prolongation of the QT interval (predisposing to arrythmias)
  4. Ototoxicity (at high doses)
62
Q

Which macrolides inhibit CYP450 enzymes and which dont?

A

Clarithyro and erythro do, azithro doesnt.

63
Q

Because of the effect of the macrolides Clarithyromycin and Erythromycin to inhibit CYP450 enzymes, interactions with with common drugs are possible? (2)

A
  1. Increased anticoagulation due to inhibiting the breakdown/metabolism of warfarin.
  2. Increases risk of myopathy when given with statins.
64
Q

Macrolides should be prescribed with caution in patients taking other drugs that prolong the QT interval such as what? (5)

A
  1. Amiodarone
  2. Antipsychotics
  3. Quinine
  4. Quinolone antibiotics
  5. SSRIs
65
Q

In patients with lower respiratory tract infections (LRTI), macrolides should generally only be added to penicillin treatment when?

A

If there is evidence of pneumonia e.g. consolidation on the chest X-ray.

Macrolides are required to cover penicillin-resistant atypical organisms. e.g. Legionella pneumophila and mycoplasma pneuomonia that cause pneumonia but do not cause other LRTI such as COPD exacerbations.

Top 100 Drugs (Pre-reg) (9 decks)

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