Antibiotics/pharmacology

Question 1

11687 – The skin is an unsatisfactory environment for many microbes because of its
1: resident microbial flora
2: alkaline pH
3: dryness
4: mucus secretions

Answer 1

TFTF
The skin is normally dry (ie unsuitable for microbial growth) with an acid pH (around 5.5 in places such as the forehead), and in most areas contains a resident microflora of bacteria (eg staphylococci, coryneforms, anaerobes such as Propionibacterium and lipophilic yeasts (eg Malassezia furfur). Most normal flora microbes occur in areas high in humidity and secretions (eg scalp, foot, axilla). None of the secretions (eg sweat, sebaceous) contains mucus; with the presence of fatty acids, lactate, salt (NaCl), and products of keratinisation in secretions
contributing to the ‘acid mantle’ that covers most skin areas. The skin of the feet while moist (sweat) is not covered in oily secretions; hence its ability to harbour Gram-negative bacilli such as Acinetobacter and pseudomonads. All of these properties (dryness of some areas, acidity, resident flora occupying available niches) renders the skin unsuitable as an environment for many microbes. Those that occur as part of the normal flora are adapted in some way to these conditions.

Question 2

25994 – In relation to antibiotics
1: quinolones are well absorbed after oral administration
2: aminoglycosides include vancomycin
3: cephalosporins may induce bleeding problems following some prolonged administration
4: cephalosporins are generally less resistant than the penicillins to staphylococcal beta-lactamases

Answer 2

TFTF
C.S.S. 2nd ed. P.155/156 Update (antibiotics) M14-M20
A feature of the quinolone group of antimicrobials is their good bioavailability and excellent body distribution after oral administration. Newer quinolones also have long half-lifes permitting once daily oral dosing in most cases. The aminoglycosides now commonly used are gentamicin, tobramycin, netilmicin, and amikacin; vancomycin is a cell wall active glycopeptide unrelated to the ribosomalactive aminoglycosides. One of the major problems of prolonged cephalosporin use is a reduction in the body’s vitamin K levels (vitamin K is synthesised by gut microbes) with consequent platelet dysfunction and bleeding (hypoprothrombinaemia). This is particularly a feature of cephalosporins possessing a methyl-thiotetrazole side chain (eg cefamandole, cefotetan), and although uncommon, has been seen in the elderly and/or malnourished surgical patient. It can be treated and/or prevented by vitamin K supplementation. MRSA are resistant to all Β-lactams (including flucloxacillin, coamoxyclav, piperacillin/tazobactam, imipenem) because resistance is associated with a new target site (penicillin binding protein 2a) to which all Β-lactams have low affinity, and not to penicillinase (Β-lactamase) production. However, all of the penicillins listed above are penicillinase-stable and effective against ‘normal’ (methicillin-susceptible) strains of Staphylococcus aureus.

Question 3

11728 – In relation to antibiotics
1: quinolones are well absorbed after oral administration
2: aminoglycosides include vancomycin
3: some cephalosporins may induce bleeding problems following prolonged administration
4: piperacillin/tazobactam is effective therapeutically against MRSA

Answer 3

TFTF
A feature of the quinolone group of antimicrobials is their good bioavailability and excellent body distribution after oral administration. Newer quinolones also have long half-lifes permitting once daily oral dosing in most cases. The aminoglycosides now commonly used are gentamicin, tobramycin, netilmicin, and amikacin; vancomycin is a cell wall active glycopeptide unrelated to the ribosomalactive aminoglycosides. One of the major problems of prolonged cephalosporin use is a reduction in the body’s vitamin K levels (vitamin K is synthesised by gut microbes) with consequent platelet dysfunction and bleeding (hypoprothrombinaemia). This is particularly a feature of cephalosporins possessing a methyl-thiotetrazole side chain (eg cefamandole, cefotetan), and although uncommon, has been seen in the elderly and/or malnourished surgical patient. It can be treated and/or prevented by vitamin K supplementation. MRSA are resistant to all Β-lactams (including flucloxacillin, coamoxyclav, piperacillin/tazobactam, imipenem) because resistance is associated with a new target site (penicillin binding protein 2a) to which all Β-lactams have low affinity, and not to penicillinase (Β-lactamase) production. However, all of the penicillins listed above are penicillinase-stable and effective against ‘normal’ (methicillin-susceptible) strains of Staphylococcus aureus.

Question 4

23784 – In relation to antibiotics
1: vancomycin is active only against Gram positive bacteria
2: alcohol intolerance is an adverse reaction seen with metronidazole
3: tetracyclines should not be used in young children
4: gentamicin is not active against obligate anaerobes

Answer 4

TTTT
Update (antibiotics) pM12-M22

Question 5

23059 – In relation to antibiotics
1: fusidic acid is a useful consideration for infections by Staphylococcus aureus
2: rifampicin is well absorbed from the alimentary tract
3: chloramphenicol penetrates better than most other antibiotics into the CSF
4: vancomycin is well absorbed after oral administration

Answer 5

TTTF
Update (antibiotics) pM18-M21

Question 6

9795 – Examples of cell wall active antibacterials include
1: vancomycin
2: imipenem
3: piperacillin
4: gentamicin

Answer 6

TTTF
Toouli et al, Integrated Basic Surgical Sciences, Ch 37.2

Question 7

10378, 23299 – Antibiotics which can be used effectively in the empiric therapy of intra-abdominal sepsis originating from the pancreas include
1: imipenem alone
2: gentamicin alone
3: a combination of piperacillin and tazobactam (Tazocin)
4: cefotaxime alone

Answer 7

TFTF
Smith & Payne Aust. NZJ Surgery ‘94.
However, in this case upper gastrointestinal surgery raises the distinct possibility of the participation of enterococci, and possibly yeasts. Although it is generally agreed that empiric cover against yeasts is not at present warranted, certainly the potential for yeasts to be involved should be considered, and
requested in specimen cultures. Imipenem-type drugs, and piperacillin/tazobactam have proved to be superior to most antimicrobials in this situation apparently covering all important aerobic (eg Gram-negative bacilli, staphylococci, streptococci) and obligate anearobes (eg Bacteriodes fragilis, clostridia). Where patients fail to respond as anticipated to one of these drugs, the participation of yeasts such as Candida albicans should be seriously considered. Aminoglycosides such as gentamicin, or third generation cephalosporins like cefotaxine fail to cover obligate anaerobes and bacteria such as Enterococcus faecalis.

Question 8

22609 – Antibiotics/combinations which are adequate prophylaxis for biliary surgery include
1: Augmentin (co-amoxyclav)
2: penicillin
3: amoxycillin plus gentamicin
4: flucloxacillin plus metronidazole

Answer 8

TFTF
Antibiotic Update: Page: AM27.

Question 9

23309 – The following are therapeutically useful microbe/antimicrobial agent combinations in the surgical patient
1: candida albicans/fluconazole
2: bacteroides fragilis/amoxycillin
3: staphylococcus aureus/benzyl penicillin
4: enterococcus faecalis/metronidazole

Answer 9

TFFF
Smith & Payne Aust. NZJ Surgery ‘94

Question 10

15568 – The following are therapeutically useful microbe/drug combinations
1: methicillin-resistant Staphylococcus aureus/imipenem
2: Bacteroides fragilis/benzyl penicillin
3: Clostridium difficile/metronidazole
4: Escherichia coli/gentamicin

Answer 10

FFTT
Refer to Aust NZJ Surgery, 1994; STEM Module: Surgical Infections and Antimicrobials.

Question 11

10393, 23694 – Therapeutically useful microbe/antimicrobial agent combinations include
1: Bacteroides fragilis/metronidazole
2: Staphylococcus aureus/piperacillin
3: Enterococcus faecalis/gentamicin
4: Mycoplasma pneumoniae/imipenem

Answer 11

TFFF
Smith & Payne Aust. N.Z. Journal Surgery ‘94.
Bacteroides fragilis has remained universally
susceptible to metronidazole and imipenem or meropenem (and also chloramphenicol). Increasing resistance to clindamycin and cefoxitin is common, while the likes of piperacillin/tazobactam and coamoxyclav are still acceptable second line alternatives to metronidazole or the glycopeptides (eg imipenem). Over 80% of Staphylococcus aureus strains now elaborate penicillinases, which destroy the activity of most penicillins (eg penicillin G, amoxycillin, piperacillin, ticarcillin) other than the so-called penicillinase-stable group eg flucloxacillin, dicloxacillin. Addition of a beta-lactamase inhibitor (eg clavulanic acid, tazobactam, sulbactam) restores the activity of penicillinase-labile penicillins (eg amoxycillin, piperacillin) against S. aureus (eg amoxycillin plus clavulanic acid or co-amoxyclav). Enterococci reveal inherent decreased susceptibility or resistance to aminoglycosides and penicillin G. However, combinations of gentamicin plus penicillin reveal synergy against enterococci and this combination is a useful therapeutic consideration. Ampicillin (or amoxycillin) is more active naturally than penicillin G against enterococci this also reveals increased activity when combined with gentamicin. The usual therapy for enterococcal infections is ampicillin plus gentamicin. Piperacillin is somewhat similar to ampicillin. In addition some of the newer quinolones, eg clinafloxacin, show useful activity against enterococci. Mycoplasmas do not possess a cell wall, and are unaffected by cell wall active antimicrobials such as beta-lactams and vancomycin. Imipenem is a beta-lactam. The usual therapeutic option for infections involving mycoplasmas is a macrolide (eg erythromycin,
clarithromycin).

Question 12

23909 – Aminoglycosides
1: are well absorbed after oral administration
2: are synergistic with penicillins
3: have a high therapeutic index
4: are ineffective against Staphylococcus auerus

Answer 12

FTFF
C.S.S. PAGE: 155, 159 Update pM16
3: narrow therapeutic index - high risk of toxicity

Question 13

11718 – Aminoglycosides
1: have activity against Gram-negative bacilli
2: reveal synergy with penicillins
3: tend to accumulate in renal tissues
4: are well absorbed after oral administration

Answer 13

TTTF
Aminoglycosides are generally safe drugs with known adverse effects, which can be administered by intravenous or intramuscular push or infusion over 15-20 minutes, and which show excellent activity against many Gram-negative bacilli. They also have often unappreciated anti-Staphylococcus aureus activity (including some MRSA), but are devoid of therapeutic anti-anaerobe activity. Although ineffective by themselves against enterococci and streptococci, they reveal synergy with penicillins against these two groups of bacteria. Older regimens of 8-12 hourly dosing, have in many cases been replaced by 24 hourly schedules. This is because aminoglycosides display concentration-dependent bacterial killing (unlike the Β-lactams), and a pronounced post-antibiotic effect (PAE) against many bacteria. In addition, complete ‘wash out’ of the previous dose before administering the next dose results in enhanced cidal activity of the second dose (bacteria exhibit what has been termed adaptive resistance in the presence of low levels of the drug), while once a day dosing is clearly less toxic (to kidney and ear) than multiple daily doses. The most feared complications of aminoglycoside use are nephrotoxicity and ototoxicity. These both result from excessive local accumulation of drug in the presence of poor or deteriorating renal function. Monitoring of trough levels is essential in all patients receiving more than a couple of days of aminoglycoside therapy, especially in the elderly or where renal function is deteriorating. Renal toxicity is reversible, although ototoxicity is not. Some evidence is available that susceptibility to ototoxicity is related to a defect (mutation) in a mitochondrial gene. Aminoglycosides are not absorbed from the alimentary tract, and cannot be given orally if systemic distribution is required.

Question 14

15182 – Gentamicin
1: reveals concentration dependant bacterial killing
2: can be used successfully once daily in many surgical situations
3: is effective against the gram-negative Bacteroides fragilis
4: cannot be administered by intramuscular injection

Answer 14

TTFF
Refer to updates of Aust. NZ Journal of Surgery
3: gent not effective against anaerobes - metronidazole works!

Question 15

11713 – Cephalosporins
1: are active therapeutically against enterococci
2: are associated with greater allergic problems than penicillins
3: have no action against Staphylococcus aureus
4: are generally more resistant to beta-lactamases than the penicillins

Answer 15

FFFT
Cephalosporins can be divided into four generations - reflecting to some extent their date of discovery and increasing spectrum of activity against Gram-negative bacteria (from first to third generation). While activity against some Gram-positive cocci (eg Staphylococcus aureus) decreases slightly from first to third generation, the latter generations, including fourth, have excellent activity against most
streptococci. Second generation compounds, such as cefuroxime, are excellent anti-S. aureus drugs. Most cephalosporins are parenteral-only drugs, although oral formulations are gradually being produced. All cephalosporins show no therapeutic activity against enterococci. Indeed, the widespread use of cephalosporins for prophylaxis, and in some countries (eg USA) for therapy, is thought to be one of the main reasons enterococci have emerged as increasingly significant hospital pathogens. Apart from a few cephamycins (7-methoxycephalosporins) often referred to as second generation cephalosporins (eg cefoxitin, cefotetan), none of the cephalosporins has useful therapeutic activity against obligate anaerobes. Resistance to the likes of cefoxitin (the most active agent) is also now increasing in important anaerobes such as Bacteroides fragilis; cefoxitin and cefotetan are really
only second-line anti-anaerobe agents, although they have found a role in large bowel prophylaxis. Compared to penicillins, cephalosporins have always been significantly more resistant to Β-lactamase inactivation (eg first and second generation compounds have excellent activity against Staphylococcus aureus), and clearly are less likely to induce allergic/hypersensitive states. Cephalosporins can be used with reasonable safety in patients with mild allergy (eg skin rash) to penicillins, although should be avoided where anaphylaxis or similar serious event is likely. The degree of cross reactivity of cephalosporins in patients with penicillin allergy is around 10% or less.

Question 16

23564 – The broad spectrum antibiotic amoxicillin
1: is effective in prevention of Clostridium difficile diarrhoea
2: is resistant to staphylococcal penicillinases
3: is cell wall active
4: is effective in meningitis

Answer 16

FFTF
C.S.S. 2nd ed. Page: 154-155 Update (antibiotic) M12-14

Question 17

11708, 25986 – Augmentin (co-amoxiclav)
1: is a useful oral anti-staphylococcal agent
2: is effective against mycoplasma
3: has anaerobe activity
4: is not stable to penicillinase

Answer 17

TFTF
Coamoxyclav (‘Augmentin’ - although the generic name is now out of patent and may change eg ‘Synermox’, ‘Alpha-amoxyclav’), is a combination of two Β-lactams, amoxycillin and clavulanic acid. The latter is highly resistant to the activity of some Β-lactamases (eg staphylococcal penicillinases) and has high affinity for them. When administered together with the Β-lactamase labile amoxycillin, any Β-lactamase elaborated by the bacterial pathogen is attracted (and bound) to the clavulanic acid
leaving the amoxycillin ‘free’ to carry out its antibacterial activity. The activity of coamoxyclav relies on the two components (which are not physically bound) having similar body distribution and other pharmacokinetic properties. Coamoxyclav is available as an oral (as well as parenteral) formulation, although the clavulanate portion often has unpleasant gastrointestinal activity eg nausea, diarrhoea.
This cell wall active B-lactam combination is ineffective against mycoplasmas which do not possess a cell wall, but has excellent activity against many significant anaerobes including clostridia and Bacteroides fragilis, and against Staphylococcus aureus - the latter two bacteria elaborate Blactamase susceptible to inactivation by clavulanic acid.
Update - Microbiology Basic Principles PAGE:p M14

Question 18

19432 – The antimicrobial of choice for sepsis involving Bacteroides fragilis is
A. penicillin G
B. clindamycin
C. metronidazole
D. cefoxitin
E. coamoxyclav (Augmentin)

Answer 18

C
As with most other obligate anaerobes, the most useful and potent therapeutic agent is metronidazole.

Question 19

11723, 22058 – Antibiotics effective against Bacteroides fragilis include
1: penicillin G
2: coamoxyclav (Augmentin)
3: metronidazole
4: gentamicin

Answer 19

FTTF
C.S.S. 2ND ED. CHAPTER: 8 PAGE: 154-159 165.
Bacteroides fragilis is an encapsulated Gram-negative obligate anaerobe, frequently associated with intra-abdominal sepsis. It produces Blactamases capable of inactivating most penicillins (eg penicillin G, amoxycillin), but susceptible to clavulanic acid inactivation. Clavulanic acid thus renders coamoxyclav (amoxycillin plus clavulanic acid) a useful agent against B. fragilis. Aminoglycosides (eg gentamicin) have no predictable therapeutic activity against any obligate anaerobes including B. fragilis. As with most other obligate anaerobes, the most useful and potent therapeutic agent is metronidazole.

Question 20

23874 – Antibiotics effective therapeutically against Bacteroides fragilis include
1: penicillin (benzyl penicillin)
2: coamoxyclav (Augmentin)
3: ceftriaxone
4: imipenem

Answer 20

FTFT
Aust. NZJ Surgery

Question 21

23054 – Penicillins resistant to penicillinases (beta-lactamases) of Staphylococcus aureus include
1: penicillin V (phenoxy methyl penicillin)
2: amoxycillin
3: piperacillin
4: flucloxacillin

Answer 21

FFFT
C.S.S. 2ND. ED. PAGE: 155 Update pM14

Question 22

14818 – Resistance in Staphylococcus aureus to β-lactam antibiotics may be mediated by
1: changes in the penicillin binding proteins
2: decreased permeability of the cell wall outer membrane
3: enzymatic destruction of the drug
4: mutation in the gyrase A gene

Answer 22

TFTF
Refer to Microbiology Update, Aust & NZ Journal Surgery 1994

Question 23

11738 – Regarding the treatment of infections by methicillin-resistant Staphylococcus aureus
1: vancomycin is the only reliable empiric therapy
2: coamoxyclav is useful for some strains
3: imipenem is useful for some strains
4: an antibiotic such as fusidic acid maybe useful for some strains

Answer 23

TFFT
Methicillin-resistant Staphylococcus aureus (MRSA) elaborate a new penicillin-binding protein (PBP), PBP2a, which has low affinity for all B-lactam drugs, and permits growth of cells in the presence of Blactams. MRSA strains are resistant to all B-lactams (eg penicillin, flucloxacillin, coamoxyclav, cefuroxime, and imipenem), because of this new target PBP. Since the late 1950s, most (around 80% plus) strains of S. aureus have been resistant to many penicillins (eg benzylpenicillin, amoxicillin, piperacillin) because of the production of penicillinases (B-lactamases) which destroy the biological activity of the drug. Penicillinase-stable penicillins (eg flucloxacillin, coamoxyclav) must be used for the empiric treatment of S. aureus infections. MRSA strains, which only became common around the early 1990s, are resistant to these classical antistaphylococcal (ie penicillinase-stable) penicillins. The only antibiotic to which 100% of MRSA strains are consistently susceptible is vancomycin; although MRSA strains with reduced susceptibility to vancomycin are slowly appearing world-wide. In countries such as New Zealand and Australia, MRSA strains are community (cMRSA) as well as hospital based. While most hospital MRSA strains are multiresistant - ie also resistant to a variety of non Blactam antistaphylococcal agents - most cMRSA are not, and are susceptible to agents such as cotrimoxazole, fusidic acid, rifampicin, gentamicin and ciprofloxacin. Treatment of cMRSA infections usually relies on a combination of two of these drugs.

Question 24

19707 – In a hospital where methicillin-resistant Staphylococcus aureus (MRSA) is absent, the empiric therapy for septicaemia involving
Staphylococcus aureus should be
A. Augmentin (co-amoxyclav)
B. ciprofloxacin
C. metronidadole
D. flucloxacillin
E. vancomycin

Answer 24

D
Aust. NZJ Surgery; Update

Question 25

11753 – In hospitals where MRSA are absent, acceptable antibiotics for hip replacement surgery prophylaxis include
1: cephazolin alone
2: vancomycin alone
3: metronidazole plus amoxycillin
4: penicillin G plus flucloxacillin

Answer 25

TFFF
Hip replacement surgery, like open-heart surgery, is an area of ‘clean surgery’ where antimicrobial prophylaxis is clearly warranted and cost effective. The major potential pathogens to be covered are staphylococci - both Staphylococcus aureus and coagulase-negative species such as Staphylococcus epidermidis which have the ability to form biofilms and adhere to foreign materials eg screws, prostheses. First or second generation cephalosporins have ideal antibacterial spectra for this situation - cefamandole possibly has better overall antistaphylococcal activity than cephazolin, although the latter has a longer half life and better bone penetration and is favoured by many institutions. Vancomycin should not be used unless MRSA are a major consideration, and even then it is apparent that the glycopeptide teicoplanin is a better alternative (easier to administer, less potential toxicity and adverse reactions). In general, glycopeptides such as vancomycin and teicoplanin should be reserved for situations where no other antibiotic choice is available. Metronidazole plus amoxicillin is devoid of staphylococcal activity (metronidazole is effective only against obligate anaerobes, and amoxycillin against the likes of streptococci but not staphylococci which elaborate penicillinases). Penicillin G has minimal activity against S. aureus (less than 10% strains), and while flucloxacillin is active against methicillin-susceptible S. aureus, it has poor activity against many (around 50%) strains of coagulase-negative staphylococci. This combination (penicillin + flucloxacillin) is not adequate prophylaxis for hip replacement surgery.

Question 26

8727 – Antibiotics effective therapeutically against methicillin susceptible Staphylococcus aureus include
1: cephalexin
2: coamoxyclav (Augmentin)
3: flucloxacillin
4: cefuroxime

Answer 26

TTTT
Smith, Payne, Berne, Surgeon’s Guide to Antimicrobial Chemotherapy, Ch 1; Smith & Payne, Integrated Basic Surgical Sciences, Ch 37.2

Question 27

24329 – Features of vancomycin include
1: therapeutically active against methicillin resistant staphylococci, e.g. MRSA
2: no therapeutic activity against the obligate anaerobe Clostridium perfringens
3: no therapeutic activity against gram-negative bacilli
4: inhibits cell wall synthesis in susceptible bacteria

Answer 27

TFTT
Antibiotic Update Aust. NZJ Surgery Paper IBSS, Ch 37.2, p782-793 Module: Surgical Infections

Question 28

11733 – Antifungals therapeutically useful for Candida fungaemia in the post surgery patient include
1: amphotericin B
2: griseofulvin
3: fluconazole
4: nystatin

Answer 28

TFTF
Antifungals target some part of the fungal cell absent or sufficiently different to the similar structure found in mammalian cells. As fungal and human cells are both eukaryotic in structure, finding antifungals which are sufficiently toxic for fungi without unduly harming the human cell is not easy. One obvious target is the fungal cell wall - a structure composed of various polysaccharides (eg chitin, cellulose, glucans) of which the glucans appear to provide the structural backbone akin to the peptidoglycan of bacterial cell walls. A few cell wall active antifungals have been developed (eg echinocandins, pneumocandins), and while appearing extremely promising in the laboratory (in vitro) have in general failed to be acceptable in clinical trials because of toxicity problems. Other potential targets are the ribosomes (eg elongation factor 2 which occurs in yeasts and not human cells), DNA/RNA synthesis or function, and the cell membrane. Flucytosine (5-fluorocytosine) and griseofulvin have as their target nucleic acids; these agents have found some clinical use (eg 5FC for yeast infections, griseofulvin for ringworm), but because they have some effects on human nucleic acids, are unsuitable where rapid cell growth and division is found (eg pregnancy). Most of the antifungals currently in clinical use are membrane-active compounds, inhibiting in some way the production of the sterol ergosterol in the cell membrane. Specificity for fungal rather than mammalian cells resides in the fact that ergosterol is a major component of fungal but not human cell membranes, (cholesterol is the major sterol found in mammalian cell membranes). The azole group of antifungals (eg fluconazole) inhibit the cytochrome P450 activity of an enzyme in the ergosterol pathway, while the polyenes (eg amphotericin B) inhibit in some way the amount of ergosterol in the membrane.
Cells lacking in sufficient ergosterol in the membrane ‘leak’ and die. Unfortunately amphotericin B does have some effects on the membranes of human cells, and has a well-documented toxicity profile. Azoles may interact with other drugs (eg cyclosporin) where the conserved cytochrome P450 is also significant in some way. Fluconazole and amphotericin are suitable for treating yeast (eg Candida) infections in surgical patients. In most cases, oral fluconazole (rather than intravenous amphotericin B) is the agent of choice, with amphotericin B being reserved for situation where WBC numbers or function is impaired (eg neutropenia). Fluconazole is much easier to administer and far less toxic than amphotericin B. Nystatin (a polyene) is presently only available as a cream/ointment for topical use, or as lozenges or ovules for lesions involving the mouth or vagina. It is not absorbed
from the gut following oral administration. Griseofulvin is only active against the dermatophytes (ringworm fungi).

Question 29

24259 – Characteristics of the anti-fungal agent, fluconazole include
1: can be administered intravenously
2: has potential interaction with cytochrome P450 metabolised drugs
3: is a useful agent against Candida albicans
4: is less nephrotoxic than amphotericin B

Answer 29

TTTT
Aust. NZJ Surgery.

Question 30

14116 – S: Amphotericin B and fluconazole are both active against the yeast Candida albicans because R: they inhibit glucan synthesis in the yeast cell wall

Answer 30

S is true and R is false
Refer to MCQ Book: Buzzard & Bandanayake; The Surgeon’s Guide to Antimicrobials & Chemotherapy, Smith, Payne & Berne

They act on ergosterol in cell membrane

Question 31

13457 – S: Amphotericin B, ketoconazole and 5-fluorocytosine are all antifungal agents because R: antifungal agents prevent cell wall synthesis
in fungi

Answer 31

Answer: S is true and R is false
Like mammalian cells, fungal cells are eukaryotic in nature. The most important antifungal agents currently available are amphotericin B, 5-fluorocytosine and the azoles: eg imidazoles such as ketoconazole and miconazole; triazoles such as fluconazole and itraconazole (S true). Activity of these agents is directed against membrane (eg cytoplasmic) functions and DNA synthesis/function. Similar structures occur in mammalian cells; hence the general toxicity to man of many of the antifungal agents. As yet antifungal agents with activity against the cell wall (a structure unique to fungi and not present in mammalian cells) are unavailable (R false).

Question 32

11677 – Bacterial plasmids
1: may be associated with virulence
2: are incapable of integration with the bacterial chromosome
3: are important in the transfer of drug resistance
4: can only be transferred amongst strains of the same species

Answer 32

TFTF
Plasmids are extra chromosomal fragments of DNA, usually circular, which are readily transmissible between related and unrelated bacterial strains, and which often carry genes responsible for virulence and antibiotic resistance (eg resistance or R plasmids). While these self-replicating (unlike transposons) DNA elements usually remain separate in the cytoplasm of cells, whole plasmids or fragments from them may incorporate into the chromosomal DNA. Acquisition of antibiotic resistance by DNA (gene) transfer between cells is often plasmid mediated.

Question 33

12959 – Genes for antibiotic resistance
1: are often found in plasmids
2: may be incorporated into cosmids
3: often occur in circular DNA molecules
4: are useful markers in recombinant DNA technology

Answer 33

TTTT
Genes for antibiotic resistance are widely used as markers in recombinant DNA technology (D true). They are usually incorporated close to the gene under investigation, and are easily identified in culture. Genes for antibiotic resistance are often found in plasmids, whose DNA is circular (A and C true). Cosmids are plasmids/phage hybrids used in recombinant DNA technology (B true).

Question 34

23304 – With successful antimicrobial prophylaxis for surgery involving the colon
1: the antimicrobial used need only cover microbes released from the bowel
2: antimicrobials are effective if commenced one hour post incision
3: post operative wound sepsis may only become apparent weeks after surgery
4: wound infection rates increase with the duration of the operation

Answer 34

FFTT
Smith & Payne Aust. NZJ Surgery ‘94

Question 35

10373 – Antibiotics useful for peritonitis in a 78 year old patient following large bowel surgery, who had been hospitalised for 6 weeks preoperatively include
1: imipenem alone
2: coamoxyclav (Augmentin)
3: cefuroxime plus metronidazole
4: piperacillin/ tazobactam (Tazocin)

Answer 35

TFFT
Peritonitis associated with previous intestinal surgery is a biphasic process an initial local infection often leading to a bacteraemic phase, involving primarily enteric Gram-negative coliforms (eg E. coli) or transient Gram-negative bacilli such as Pseudomonas aeruginosa; followed in those who survive by a second polymicrobial abscess phase in which obligate anaerobes such as Bacteroides fragilis and more aerotolerant gut bacteria (eg coliforms) participate. Empiric antimicrobial regimens must
take this proven sequence of events into consideration. Another important consideration, is that in a patient following prolonged preoperative hospitalisation or following re-operation, more resistant microbes maybe implicated in the peritonitis, eg resistant Gram-negative bacilli, enterococci, yeasts (eg Candida albicans). It must also be remembered that yeasts and enterococci increase in potential
significance with surgery, or leakage, involving the stomach or small intestine. In a 78-year-old
following previous hospitalisation, monotherapy with the likes of imipenem, meropenem or piperacillin/ tazobactam is adequate. This covers the important Gram-negative bacilli and obligate anaerobes. Coamoxyclav lacks sufficient activity against Gram-negative bacilli and probably obligate anaerobes in this situation (really only a second line anti-anaerobe drug), while cefuroxime plus metronidazole lacks appropriate Gram-negative bacillus activity (metronidazole is fine for the obligate anaerobes).

Question 36

9800 – The following antibiotic regimen is considered adequate as prophylaxis for large bowel surgery
1: cephazolin alone
2: cefoxitin alone
3: flucloxacillin plus metronidazole
4: coamoxyclav (Augmentin) alone

Answer 36

FTFT
Toouli et al, Integrated Basic Surgical Sciences, Ch 37.1

Question 37

11743 – Adequate antibiotic prophylaxis for surgery involving the large bowel includes
1: amoxycillin plus metronidazole (both parenterally)
2: cefotetan alone (parenterally)
3: flucloxacillin plus metronidazole (both parenterally)
4: tobramycin alone (parenterally)

Answer 37

FTFF
With large bowel surgery, the significant microbes which are associated with infection in patients who do not receive prophylaxis or where prophylaxis fails, are enteric coliforms such as Escherichia coli, the obligate anaerobe Bacteroides fragilis and of course Staphylococcus aureus (the latter is an important skin wound pathogen in all invasive surgical settings). Acceptable prophylaxis for large bowel surgery must cover these 3 microbes. The combination of amoxycillin plus metronidazole, while adequately covering B. fragilis (metronidazole), is devoid of cover against E. coli (at least 50% of E. coli strains are resistant to amoxycillin by B-lactamase production), or S. aureus (over 80% elaborate
penicillinases which inactivate amoxycillin). The ‘second generation’ cephalosporin cefotetan (in fact a 7-methoxy cephalosporin or cephamycin), provides adequate prophylactic cover against all 3 bacteria, although being only of doubtful use for established and ongoing intraabnormal sepsis. The combination of flucloxacillin plus metronidazole is devoid of any cover against E. coli-like coliforms, although adequate for S. aureus (flucloxacillin) and B. fragilis (metronidazole). Tobramycin alone is devoid of any obligate anaerobe activity, although being excellent for E. coli and probably S. aureus. In addition, anaesthetic agents may potentiate the neuromuscular blocking effects of aminoglycosides. For this reason they are probably best avoided in prophylactic regimens.

Question 38

14823 – Antibiotics acceptable for the empiric treatment of intra-abdominal sepsis following rupture of the appendix include
1: ciprofloxacin alone
2: metronidazole plus cephalothin
3: metronidazole plus amoxycillin
4: imipenem alone

Answer 38

FFFT
Refer to Smith & Payne, ANZ Journal Surgery

Question 39

19797 – Which one of the following antibiotic combinations is appropriate for treating peritonitis associated with a ruptured large bowel
A. cefuroxime plus gentamicin
B. penicillin plus gentamicin plus ampicillin
C. metronidazole plus ampicillin
D. metronidazole plus ciprofloxacin
E. cefuroxime plus gentamicin plus penicillin

Answer 39

D
Syllabus Update - Microbiology Antibiotics in Surgery PAGE: m8 AUST. NZJ Surgery

Question 40

911 – In sepsis following surgery for colon cancer
1: anaerobes are almost invariably involved in abscess formation.
2: benzyl penicillin (penicillin G) is an adequate therapeutic regimen.
3: the most common participating anaerobe is Clostridium perfringens.
4: early onset bacteraemias commonly involve Escherichia coli.

Answer 40

TFFT
Sepsis following surgery for colonic cancer is often associated with anastomotic leakage and can present early with abdominal signs or bacteraemia, or later with abscess formation. Sepsis is commonly due to a mixture of organisms. Early onset bacteraemias commonly involve E.coli (4 correct). Anaerobes are almost always involved in later abscess formation (1 correct), together with other enteric bacteria. The most common participating anaerobes are obligate anaerobes such as B fragilis (3 false). Penicillin G, although very effective against Clostridium perfringens, is not an adequate therapeutic agent in treating sepsis associated with colonic cancer (2 false); it is ineffective against the most significant anaerobe B fragilis, which elaborates a B-lactamase (penicillinase).
Agents with a wide spectrum covering acultative enteric bacteria (E. coli etc) as well as obligate
anaerobes, are required.

Question 41

25620 – For surgery involving insertion of an artificial hip
1: antibiotic prophylaxis is not required
2: the principal infecting microbes are staphylococci
3: enteric Gram-negative coliforms occasionally result in significant post operative infection
4: the incidence of infective complications is low (generally less than 1%)

Answer 41

FTTT
C.S.S. 2ND ED. PAGE: 162

Question 42

8722 – Common pathogens found in intravenous catheter-associated sepsis include
1: Streptococcus pyogenes
2: Staphylococcus epidermidis
3: Bacteroides fragilis
4: Candida species

Answer 42

FTFT
Smith, Payne, Berne, Surgeon’s Guide to Antimicrobial Chemotherapy, Ch 11; Smith & Payne, Integrated Basic Surgical Sciences, Ch 37.2

Question 43

11748 – With antimicrobial prophylaxis for coronary artery graft surgery
1: parenteral antibiotics should be commenced 24 hours prior to surgery
2: cefamandole is an acceptable choice
3: the antibiotic(s) used, must cover obligate anaerobes
4: cover against coagulase-negative staphylococci must be included in the antibiotic(s) chosen

Answer 43

FTFT
Coronary artery graft surgery is one of the recognised areas of ‘clean’ surgery where antibiotic prophylaxis is warranted and proven. The most significant potential post-operative pathogens are staphylococci, both coagulase-negative (eg Staphylococcus epidermidis) and coagulase-positive (eg Staphylococcus aureus) species. Of more minor but still significant risk are Gram-negative coliforms, eg Escherichia coli, which may adhere to any foreign material/implants. This group of microbes is more significant in valve replacement rather than artery graft surgery. The antibiotic(s) to be used must therefore cover all types of staphylococci plus or minus Gram-negative coliforms. Second generation cephalosporins adequately fill this role (eg cefamandole, cefuroxime), although most consider the first generation cephazolin (slightly less coliform activity than second generation compounds) also acceptable in artery graft procedures. While most surgical antibiotic prophylaxis is now given parenterally at the induction of anaesthesia (ie around 20 minutes before incision) some ninstitutions favour oral administration (which is clearly cheaper). However, the timing of any orally administered drug is critical, as maximum levels of drug must be present in the tissues to be involved (ie skin, heart, and arteries) at the time of incision. Clearly parenteral regimens offer more control on this aspect of prophylaxis, and as demonstrated in the classical studies of Burke, must be given within the 2-hour period proceeding operation. Significantly elevated levels of surgical-site sepsis are seen when intravenous antibiotics are given more than two hours before incision, or after commencement of the operation.

Question 44

13463 – S: In the prophylaxis of infection in patients having above-knee amputations for ischaemia metronidazole is the drug of choice
because R: the most serious infection occurring after above-knee amputations is caused by anaerobic organisms

Answer 44

S is false and R is true
Infections associated with above-knee amputations commonly involve bacteria acquired from the skin in the perianal region. Important examples are Staphylococcus aureus and bowel commensals such as the anaerobe Clostridium perfringens ; the latter becomes especially important where devitalised and necrotic tissue is involved (eg trauma) and is the most serious infective consequence reported (R true). Such operations are a proven area for prophylaxis which should be with augmentin or flucloxacillin which will cover both the S. aureus and clostridia. While benzyl penicillin alone could be used, it does not cover possible S. aureus contamination although it is the drug of choice for clostridia. The role of the anaerobic agent metronidazole in lower limb prophylaxis is as yet unknown; however, it does not have effective staphylococcal activity. Better choices are available (S false). The use of benzyl penicillin with flucloxacillin (to cover clostridia and S. aureus respectively) is unwarranted as flucloxacillin has adequate clostridial cover. Some texts may still (falsely) recommend such a combination or even benzyl pencillin alone, which is inadequate cover against staphylococci. Problems associated with infection by S. aureus should not be underestimated. Controversy still exists over which pencillin(s) should be used.

Question 45

13451 – S: Alteration of the intestinal flora by some broad spectrum antibiotics may increase the effect of anticoagulants because R: antibiotics inhibit the synthesis of vitamin D absorbed from the gut

Answer 45

Answer: S is true & R is false
Prolonged use of some broad spectrum antibiotics can undoubtedly change and reduce the numbers of bacteria, eg Bacteroides fragilis found in the intestines. These anaerobes are normally responsible for the synthesis of Vitamin K (S true), not Vitamin D which is formed exogenously (R false). Vitamin K is used by the body in such processes as blood clotting. In some cases, additional dietary Vitamin K as to be given to patients on long term antibiotics if bleeding problems are to be averted.

Question 46

24129 – Features of antibiotic associated diarrhoea include that
1: it has been associated with almost all antibiotics
2: it should be treated with intravenous vancomycin in severe cases
3: anticholinergic drugs should be avoided
4: it is due to overgrowth of Clostridium sporogenes

Answer 46

TFTF
C.S.S. 2nd ed. PAGE: 165,166

Question 47

23689 – Antibiotics useful in the treatment of antibiotic associated diarrhoea include
1: vancomycin
2: co-amoxyclav (augmentin)
3: metronidazole
4: ciprofloxacin

Answer 47

TFTF
C.S.S. 2nd ed. p 155/156, 166 Update pM27.

Question 48

18249 – Which one of the following statements concerning overwhelming postsplenectomy sepsis is most correct:
A. pneumococci and meningococci are the most common pathogens
B. it is seen in more than one fifth of patients who undergo splenectomy
C. the majority of cases occur in the second year after splenectomy
D. it can be prevented by leaving small parts of the spleen to regenerate
E. adults are more prone to the syndrome than children

Answer 48

A
The most common pathogens are pneumococci and meningococci (A). All the other responses are incorrect.

Question 49

22003 – Azathioprine
1: metabolism is inhibited by allopurinol
2: can be hepato-toxic
3: suppresses the bone marrow
4: is a folic acid antagonist

Answer 49

TTTF
Pharmacology Textbook 4th ed. Rang, Dale & Ritter Page: 243

Question 50

20763 – S. Cyclosporin A suppresses the activity of some T helper and cytotoxic lymphocytes BECAUSE R. Cyclosporin A blocks the synthesis of nucleic acids by its antimetabolite actions

Answer 50

S is true and R is false
Syllabus Extension & Update ACP1 - ACP39

Question 51

14004 – Which of the following chemotherapeutic agents may result in a fatal pulmonary reaction?
A. cis-platinum
B. bleomycin
C. nitrogen mustard
D. 5-fluoruracil
E. doxorubicin

Answer 51

B
Refer to Robbins, 6th Ed, Ch 16, page 740. Pending review. Jan 2003

Question 52

8597 – Which of the following chemotherapeutic agents has cardiotoxicity as one of its important side effects?
A. doxorubicin
B. bleomycin
C. cis-platinum
D. methotrexate
E. 5-fluorouracil

Answer 52

A
Robbins, 6th ed, Ch 13

Question 53

25544 – Topical antibacterial agents for the treatment of burn wound infections include
1: mupirocin (Bactroban)
2: silver nitrate
3: mafenide (sulphamylon cream)
4: silver sulphadiazine

Answer 53

TTTT
Update - Microbiology Basic Principles - PAGE: P M22-23

Question 54

22619 – Neostigmine is an anticholinesterase
1: used to reverse the effect of non-competitive neuromuscular blockers
2: whose side-effects may be prevented by co-administration with atropine
3: whose action would be antagonistic to that of suxamethonium
4: used to improve neuromuscular transmission

Answer 54

FTFT
A.C.P. 1996. Pending review. Jan 2003

Question 55

19414 – Suxamethonium is a neuromuscular blocker which may produce
A. hypothermia
B. tachycardia
C. hyperkalaemia
D. respiratory alkalosis
E. CNS stimulation

Answer 55

C
Syllabus Extension & Update ACP1 - ACP39

Question 56

8747 – Digoxin is more likely to cause symptoms of toxicity in the
1: patient with renal failure
2: elderly patient
3: patient with hypokalaemia
4: patient on amiloride

Answer 56

TTTF
Integrated Basic Surgical Sciences, Ch 37; STEM Module: Pharmacology

Question 57

21798 – The following are results from a patient with worsening cardiac failure
serum creatinine 0.20 mmol/L (reference range 0.05-0.11)
serum potassium 3.0 mmol/L (reference range 3.4 -4.5 )
serum alanine transaminase 100 U/L (reference range < 40 )
serum digoxin (12 hour 1.5 ?g/L (reference range 1.0 -2.0 )post dose)
1: peak serum digoxin concentration would better reflect clinical status
2: the patient may have a bradyarrhythmia
3: clearance of digoxin will be enhanced
4: the patient may be clinically digoxin toxic

Answer 57

FTFT
A.C.P. 1996

Question 58

18213 – You are admitting a 70 year old man for an anterior resection of the rectum for carcinoma. He is otherwise in good health. What is the MOST appropriate DVT prophylaxis?
A. Early mobilisation alone
B. Heparin (unfractionated UFH or low molecular weight MWH) pre-operatively and until fully mobile.
C. Anti-embolus stockings and heparin (UFH or LMWH) pre-operatively and until fully mobile plus pneumatic compression in theatre.
D. Aspirin 100mg bd commencing one week before operation
E. An infusion of 500ml of dextran solution (Macrodex) over the period of surgery

Answer 58

C
This is a high-risk patient (cancer, age 70). Early ambulation, aspirin and Macrodex infusion may be appropriate but each is inadequate as sole prophylaxis. The combination of heparin until mobile, stockings and pneumatic compression (C) gives best protection of those listed.

Question 59

18298 – A 32-year-old woman with gallstones is admitted for an elective cholecystectomy. After the birth of her daughter three years ago she suffered a deep venous thrombosis in her left calf. At operation you plan to use pneumatic calf compression devices. What additional course of action would be most appropriate?
A. Start on warfarin immediately after the operation
B. Give intravenous heparin 1000 units/hr with the premedication and continue until mobile
C. Use anti-embolism stockings and apply from the time of premedication
D. No specific measures need to be taken other than early mobilisation
E. Give a 10 day course of subcutaneous heparin, starting at premedication

Answer 59

C
Any action taken to reduce the risk of post-operative venous thrombo-embolic problems will be related to the presence of any risk factors. The patient described in this scenario has a total number of three risk factors, namely a past history of deep venous thrombosis (weighting 2) and she is about to undergo a laparoscopic procedure (weighting 1). She is classified as low risk and use of antiembolism stockings or a low molecular weight heparin given subcutaneously is sufficient prophylaxis
(C is correct, D is incorrect). The subcutaneous heparin would only need to be continued until the patient was mobile (E is incorrect). Intravenous heparin would be more suitable for a high risk patient, particularly one who had been on warfarin before the operation. The dose mentioned is in any event therapeutic rather than prophylactic (B is incorrect). There would be few circumstances where warfarin would be commenced immediately after an operation. If a patient had been on warfarin immediately prior to surgery, it would almost certainly have been stopped and the anticoagulation maintained in the interim with heparin. It is easier to reverse the effects of heparin than warfarin (A is incorrect).

Question 60

22098 – The side effects of prednisolone include
1: cataract formation
2: peptic ulceration
3: growth retardation
4: skin striae

Answer 60

TTTT
ACP 1996

Question 61

19162 – The side effects of prednisolone include
A. osteopetrosis
B. hypernatremia
C. diabetes insipidus
D. hyperkalaemia
E. cerebral calcification

Answer 61

B
ACP 1-39

Question 62

23259 – The side effects of prednisolone include
1: diabetes insipidus
2: pancreatitis
3: hypotension
4: necrosis of the head of the femur

Answer 62

FTFT
ACP 1996

Question 63

21868 – Lignocaine is a local anaesthetic
1: which is pharmacologically active as the cation
2: which is hydrolysed by plasma cholinesterase
3: whose duration of effect is terminated by metabolism
4: whose efficacy is enhanced by low tissue pH

Answer 63

TFFF
ACP

Question 64

19779 – The following drugs are competitive inhibitors of the named enzyme EXCEPT
A. Warfarin: Vitamin K reductase
B. Simvastatin: HMG-CoA reductase
C. Captopril: Angiotensin converting enzyme
D. Aspirin: Cyclo-oxygenase
E. Neostigmine: Acetyl cholinesterase

Answer 64

D
ACP 1996

Question 65

19713 – A patient who weighs 50 Kg is fitting. Given the following pharmacokinetic parameters of phenytoin, what is the correct loading dose for this patient, in order to give a plasma concentration of 40 micro mol/L
(10 mg/L)? Vol of distribution = 0.65 L/Kg Therapeutic range = 40 - 80 micro mol/L(10 - 20 mg/L)
A. 32.5 mg
B. 65 mg
C. 190 mg
D. 325 mg
E. 650 mg

Answer 65

D
A.C.P.

Question 66

23029 – In a patient who has been receiving gentamicin 80 mg. tds for 5 days, and whose investigation yields the following results
serum creatinine 0.20 mmol/L (reference range 0.05 - 0.11)
serum potassium 5.0 mmol/L (reference range 3.4 - 4.5)
serum HCO3 17 mmol/L (reference range 25 - 35)
serum gentamicin 4.0 mg/L (reference range <2.5)(trough) .
1: a likely clinical diagnosis is acute tubular necrosis secondary to gentamicin toxicity
2: a peak (30 min post dose) gentamicin concentration is necessary to confirm the diagnosis
3: gentamicin dosing of 240 mg. mane is less likely to produce these clinical results
4: administration of intravenous HCO3 is necessary to correct the acidosis

Answer 66

TFTF
A.C.P. 1996 Page: 1-39

Question 67

25936 – Ms SLE (30 years of age) has aseptic necrosis of the head of the right femur. She has been taking prednisone (20 mg/day) for 5 years and has used various NSAIDs (currently she is taking ketoprofen). She was recently commenced on azathioprine, in an attempt to limit her reliance on steroids. On examination the appearances of her skin which would be consistent with long term glucocorticoid use include
1: thin skin
2: bruising
3: acne
4: hirsutism

Answer 67

TTTT
All features are consistent with glucocorticosteroid use and they can all contribute to the major subjective dissatisfaction in some patients. Wound healing could also be delayed in this patient due to steroid use. Other changes in physical appearance which are common with long term and/or high dose glucocorticoid use include the ‘Cushinoid’ appearances of ‘moon facies’, redistribution of adipose tissue (centripetally) to give the ‘buffalo hump’ at the back of the neck, and the thinning of the limbs.

Question 68

25946 – Ms SLE (30 years of age) has aseptic necrosis of the head of the right femur. She has been taking prednisone (20 mg/day) for 5 years and has used various NSAIDs (currently she is taking ketoprofen). She was recently commenced on azathioprine, in an attempt to limit her reliance on steroids. Important side effects of glucocorticoids include
1: pathological fractures
2: retinal detachment
3: pancreatitis
4: hypertension

Answer 68

TFTT
Pathological fractures are one of the manifestations of the effect of corticosteroids on protein synthesis. Other examples would include the proximal myopathy of the limb girdles, the thinning of the skin (made more apparent by loss of subcutaneous fat in the limbs), cataracts, and delay in healing. Changes in calcium balance associated with steroid use would also contribute to the pathological fractures. The major side-effects of steroids seen in the eye are cataract formation and glaucoma. The underlying pathology of steroids causing pancreatitis is not understood. Not all patients appear to have developed the severe diabetes mellitus or hyperlipidaemia which may predispose to its occurrence.

Question 69

25941 – Ms SLE (30 years of age) has aseptic necrosis of the head of the right femur. She has been taking prednisone (20 mg/day) for 5 years and has used various NSAIDs (currently she is taking ketoprofen). She was recently commenced on azathioprine, in an attempt to limit her reliance on steroids. Laboratory investigations consistent with prednisone use would include
1: polycythaemia
2: hypernatraemia
3: hypoglycaemia
4: hyperbilirubinaemia

Answer 69

TTFF
PATHOLOGY Page 172 of 215
Bone marrow stem cells including those of the erythroid series are stimulated by glucocorticoids, and in bone marrow aplasia for instance high dose steroid therapy may be initiated. Prednisone is metabolised to prednisolone which has substantial agonist properties on the mineralocorticoid receptors of the renal tubules. Although marked hypernatraemia is unusual in these patients it can occur, and one would anticipate there should be a relative hypokalaemia accompanying it. Hyperglycaemia and glucose intolerance due to insulin resistance are common in patients on high dose glucocorticoids. In cases when very high doses are being used, such as part of chemotherapy regimes, it may be necessary to use insulin. Unlike the oestrogenic and androgenic steroids, glucocorticoids per se do not cause hepatic dysfunction.

Question 70

23814 – A woman being assessed for hip replacement has been taking oral prednisone (5-10 mg/day) for 5 years as part of her management for chronic obstructive airways disease. The following clinical and laboratory findings would be consistent with her steroid use
1: hyperkalaemia
2: neutropenia
3: glaucoma
4: hyperglycaemia

Answer 70

FFTT
ACP
2: steroids cause bone marrow stimulation

Question 71

25926 – Mr CC has cryptogenic cirrhosis and is admitted with peritonitis, for which an exploratory laparotomy is necessary. Which of the following drugs would have significantly altered clearance in this patient because of his cirrhosis?
1: Frusemide
2: Paracetamol
3: Aspirin
4: Gentamicin

Answer 71

FTTF
Aspirin (acetylsalicylic acid) is metabolised by plasma esterases to salicylic acid, which in turn is metabolised and conjugated in the liver. It has a saturable metabolism, and the half-life is increased in cirrhosis, particularly if there is significant intra-hepatic shunting. Paracetamol is usually cleared by conjugation in the liver, but if this pathway is saturated, the excess is metabolised by the cytochrome P450 system. In severe liver cirrhosis, with a decrease in liver cell mass the toxicity of paracetamol is significantly increased at doses of paracetamol usually considered to be without significant side effects, and hepatic necrosis can occur at total doses of less than 10 g. Gentamicin is excreted by the kidney, and frusemide also is excreted mainly by the kidney.

Question 72

25921 – Mr CC has cryptogenic cirrhosis and is admitted with peritonitis, for which an exploratory laparotomy is necessary. The use of the following drugs during anaesthesia may lead to prolonged neuromuscular blockade in this man
1: Suxamethonium
2: Atracurium
3: Gallamine
4: Mivacurium

Answer 72

TFFT
Both suxamethonium and mivacurium are metabolised by plasma (pseudo) cholinesterase, the synthesis of which is decreased in liver disease. Atracurium usually has a short duration of action because it undergoes spontaneous nonenzymatic rearrangement (Hoffman reaction) in plasma. Gallamine is excreted almost entirely by the kidney.

Question 73

25931 – Mr CC has cryptogenic cirrhosis and is admitted with peritonitis, for which an exploratory laparotomy is necessary. If this patient developed cardiac failure and dysrhythmias post-operatively what would be the effect on the following drugs?
1: the half-life of digoxin would be increased
2: the clearance of lignocaine would be increased
3: the half-life of vancomycin would be decreased
4: the clearance of metronidazole would be decreased

Answer 73

TFFF
Significant cardiac failure causes decreased perfusion of both the kidney and the liver. Plasma half-life is a pharmacokinetic function dependent upon the rate of clearance of a compound. Whether decreased liver perfusion has an effect upon hepatic clearance depends upon whether the drug has a high liver extraction and flow-dependent clearance (eg diltiazem, lignocaine, imiprimine, midazolam,
morphine, naloxone). For a drug with a high extraction ratio, changes due to enzyme induction or hepatic disease should have little effect. Whilst metronidazole is metabolised in the liver, its clearance is not flow dependent and cardiac failure will not significantly alter its half-life. Likewise changes in plasma protein binding should have little influence on a flow-dependent drug. This can be compared with drugs which have low extraction ratios in the liver, and whose clearance will be significantly affected by changes in intrinsic clearance such as enzyme induction or inhibition, and by protein binding (eg phenytoin, salicylic acid and warfarin).
Digoxin’s clearance is predominantly renal, both glomerular filtration and some active secretion down the pathways for basic compounds. Its half-life is significantly increased by both decreased perfusion of the kidney and by glomerular loss such as occurs with age. Vancomycin’s excretion entirely depends upon glomerular filtration, and with the increase in half-life which would occur in cardiac failure, the risk of toxicity is increased. Plasma level monitoring is therefore important.