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Flashcards in Pharmacology Deck (101):
1

When should Pneumovax vaccine be administered in splenectomy patient

One month before surgery

The vaccine should be given a minimum of two weeks before elective splenectomy in order to ensure an optimal antibody response.

In emergency splenectomy the patient should be immunised as soon as possible after recovery from the operation and before discharge from hospital.

Unvaccinated patients splenectomised some time earlier should be vaccinated at the first opportunity.

Vaccination is delayed for at least six months after immunosuppressive chemotherapy or radiotherapy during which time prophylactic antibiotics should be given.

2

One of the surgical wards in your hospital notes an outbreak of Methicillin-resistant Staphylococcus aureus (MRSA) infections.
What is the best mechanism for reducing further transmission of this infection on the ward?

Encourage regular hand washing by ward staff

Cross-infection via hands of medical and nursing staff is a very important vehicle of transmission of MRSA. Hand washing before and after contact with patients is the single most effective measure to control hospital spread of this organism.

Screening of ward staff is appropriate only in certain situations and should not be carried out unless recommended by the hospital infection control team.

Vancomycin should never be used for MRSA decolonization.

The hospital infection control policy should outline which patients should be screened and when decolonization should be attempted.

3

A 5-year-old boy presents to the Emergency department complaining of acute pain over his upper tibia. He is febrile and he refuses to move his leg.
A diagnosis of osteomyelitis is suspected.
What is the likely infecting organism?

Staph aureus

The commonest infecting organism in acute osteomyelitis in children over the age of 4 years is Staphylococcus aureus.

With immunisation, cases of haematogenous osteomyelitis due to Haemophilus influenzae have almost been eradicated.

Salmonella is the characteristic organism in sickle cell anaemia.

Pseudomonas infection is a common organism in haemodialysis patients and intravenous drug addicts.

4

A patient with Crohn's disease undergoes a small bowel resection. Post-operatively the patient develops a fistula through the wound. The nurses note the presence of blue/green discolouration on the wound swabs when they are changing the patient's dressings.

Pseudomonas aeruginosa
Patients with Crohn's disease are prone to development of fistulae. Common gut organisms are Gram negative bacilli and anaerobes but the characteristic blue/green discolouration is pathognomonic of Pseudomonas aeruginosa.

5

A 29-year-old man is involved in a car accident and and undergoes an emergency splenectomy. Three years later the patient is admitted to hospital acutely unwell with a cough. He has a fever of 39°C and a white cell count of 19 ×109/L. Within 12 hours he develops septicaemic shock.

Pneumococcus
Post-splenectomy patients are at increased risk of infections by an encapsulated organism. This gentleman has respiratory symptoms and signs of septicaemia as evidenced by the temperature of 39°C. The most likely organism is Pneumococcus.

6

A 64-year-old arteriopath undergoes a PTFE femoro-popliteal bypass graft. The graft fails and the patient requires a below knee amputation. Recovery is protracted and on the 20th post-operative day a purulent discharging sinus develops in the groin at the site of his original surgery. There has been no response to penicillin based therapy.

Methicillin resistant Staphyloccocus aureus (MRSA)
This gentleman is an arteriopath and therefore has poor perfusion of his tissues and is at increased risk of developing infection. He has had two operations including a failed graft followed by an amputation. He develops a post-operative wound discharge 20 days post-operatively. This is not an acute infection and a chronic problem. He has unfortunately developed an MRSA infection of the graft which probably contributed to the initial failure and is now the cause of the purulent discharging sinus.

7

An 80-year-old lady undergoes an emergency open cholecystectomy. She has a five day course of intravenous antibiotics. On the eighth post operative day she develops severe watery diarrhoea.

Clostridium difficile
This lady has been taking intravenous antibiotics for five days. Unfortunately she has therefore developed a bacterial overgrowth of Clostridium difficile which will give her profuse diarrhoea.

8

A 60-year-old man is out gardening when he stabs his foot with a gardening fork. Two days later he presents to casualty with a fever, malaise and severe pain in the left leg. Examination reveals he is very unwell and has crepitus in the muscles of the calf and thigh.

Clostridium welchii/perfringens
This patient has pierced his foot with his gardening fork. He develops localised pain in his leg, associated fever and signs of septicaemia. This is due to gas forming organisms, Clostridium welchii.

This is not due to Clostridium tetani as this has a longer incubation period of three weeks to three months and is associated with muscle spasms.

9

Staph aureus

Colonies appear distinctly yellow/gold on an agar plate.

The capacity to produce coagulase is quite closely correlated to pathogenicity.

Staph. aureus is found in the anterior nasal mucosa of 40-50% of healthy adults.

Staphylococci are Gram positive, spherical in diameter, and arranged in clusters.

10

Notification of infectious disease

Notification of infectious disease is obligatory under the 1968 Public Health Act.

Notifiable diseases include:

Food poisoning
Meningitis
Rubella
Mumps
Measles
Chicken pox is not a notifiable disease.

11

Zoonoses

Zoonoses include:

Anthrax (cattle, goats)
Listeriosis (pets)
Leptospirosis (rats)
Toxocara (cats)
Toxoplasmosis (dogs)
Tapeworms (dogs)
Brucella (sheep)
TB (cattle).
Cholera is an infectious gastroenteritis caused by eating food or drinking water contaminated with cholera vibrios.

12

The germination of tetanus spores in a wound is enhanced by which of the following?

Hypoxia

Germination occurs in contaminated, damaged tissue where poor blood supply has reduced the supply of oxygen. Early careful debridement of devitalised tissue and removal of foreign bodies is a useful preventative measure.

Antitoxin should be promptly administered in all cases of suspected tetanus. It is ineffective when the toxin is already fixed in the central nervous system.

Because spores of C. tetani are so widely distributed, the only effective way to control tetanus is by prophylactic immunisation with tetanus toxoid.

13

Campylobacter jejuni

Causes colitis

Campylobacter jejuni most commonly affects young adults and children. It is transmitted to humans by milk or water infected by wild and domestic animals and poultry.

Proctocolitis and enterocolitis may be due to sexually transmitted agents such as Campylobacter, Shigella, Entamoeba and Giardia, and may be clinically indistinguishable from non-infective causes.

14

Vancomycin side effects

Includes irreversible vestibular damage
Tinnitus is usually the first manifestation of ototoxicity. Irreversible vestibular damage results from the ototoxicity. It is excreted renally and liver impairment does not affect its elimination.

Oral vancomycin is absorbed systemically producing side effects after multiple doses or in inflammatory bowel disease. Side effects are more common in elderly subjects due to the reduced volumes of distribution and reduced renal reserve.

Auditory and renal function should be monitored regularly in the elderly.

15

Osteomyelitis

Infection usually involves the metaphysis of long bones

Osteomyelitis is usually due to Staphylococcus aureus infection.

Streptococcus pyogenes, Haemophilis influenzae and Gram negative organisms can also infect bone.

In children the infection is usually acquired by haematogenous spread to the metaphysis of long bones.

The dead bone within the medullary canal is the sequestrum.

New subperiosteal bone formation is the involucrum.

16

HIV infection

Can be transmitted vertically

Twenty five percent of patients with HIV/AIDs will undergo a surgical procedure. The most common procedure is the insertion of an indwelling catheter to administer foscarnet for cytomegalovirus (CMV) retinitis.

HIV can be passed on from mother to child (vertical transmission). Maternal HIV antibody is still present in an infant (up to 12 months, occasionally longer) but this does not mean the infant is infected.

HIV is not transmitted by airborne spread.

Most patients will not have detectable antibodies until three months post infection.

17

Mycobacterium TB

Does not form spores

MTB is one of many aerobic, rod shaped, immotile Mycobacterium (avium, leprae, bovis) that are acid fast.

Mycobacterium species, along with members of a related genus Nocardia, are classified as acid-fast bacteria due to their impermeability by certain dyes and stains. They are typically stained by the Ziehl-Neelsen stain.

Infection produces both humoral and cell mediated (mostly) immunity.

18

A DNA damaging alkylating agent which uses free radicals to perform its task.

Cyclophosphamide
Cyclophosphamide is a DNA damaging alkylating agent. It is commonly used in the treatment of lymphocytic leukaemia and also rheumatoid arthritis. Haemorrhagic cystitis is a rare but dangerous complication.

19

An agent which is a platinum compound that causes DNA damage by causing cross-links and has recently transformed the treatment of testicular cancer.

Cisplatin
Cisplatin is a platinum compound used in the treatment of lung, bladder, ovary and testicular cancer.

20

A folic acid antagonist.

Methotrexate is a folic acid antagonist. It is often used as a treatment for rheumatoid arthritis.

21

An antimetabolite that acts as a pyrimidine antagonist.

5-fluorouracil
Prevents DNA repair by acting as a topoisomerase II inhibitor.

22

Prevents DNA repair by acting as a topoisomerase II inhibitor.

Doxorubicin
Doxorubicin prevents DNA repair in cells. It is also known as cytotoxic antibody and is used in acute leukaemias, lymphomas and a variety of solid tumours.

23

An 80-year-old lady is admitted on the emergency intake and is noted to have facial flushing which she says is long term and related to her "heart tablets".

Nifedipine
ß-blocking agents cause vasoconstriction as they allow unopposed a-activity.

Drugs such as

Calcium channel blockers
Nicotinic acid
Tamoxifen
Opiates
Luteinising hormone-releasing hormone (LHRH) analogues
Glyceryl trinitrate (GTN)
all produce flushing.

24

A 65-year-old man has locally advanced pancreatic cancer and has been paying privately for treatment with erlotinib (Tarceva) for the past nine months. It has worked effectively for that period but a recent CT scan showed further growth in the tumour.
Which of the following mechanisms best explains this resistance to treatment with erlotinib?

Development of antibodies to erlotinib
Lack of autophosphorylation at binding site
Malabsorption
Mutation in the ATP binding pocket of the EGFR kinase domain
Reduced expression of EGFR

Mutation in the ATP binding pocket of the EGFR kinase domain

Erlotinib specifically targets the epidermal growth factor receptor (EGFR) tyrosine kinase (which is required for the conformational change) and binds in a reversible fashion to the adenosine triphosphate binding site.

For the signal to be transmitted, two members of the EGFR family need to come together to form a homodimer. These then use the molecule of adenosine triphosphate (ATP) to autophosphorylate each other, which causes a conformational change in their intracellular structure, exposing a further binding site for binding proteins that cause a signal cascade to the nucleus. By inhibiting the ATP, autophosphorylation is not possible and the signal is stopped.

A key issue with EGFR-directed treatments is that after a period of 8-12 months, the cancer cells become resistant to the treatment. This most commonly occurs due to a mutation in the ATP binding pocket of the EGFR kinase domain. This prevents the binding of erlotinib (Tarceva).

Some IGR-1R inhibitors are in various stages of development (based either around tyrphostins such as AG1024 or AG538 or pyrrolo[2,3-d]-pyrimidine derivatives such as NVP-AEW541).

25

A 65-year-old lady with a history of recurrent DVT has been weaned off her warfarin and started on intravenous heparin prior to cardiac bypass for ischaemic heart disease.
She seems to require very high doses of heparin to achieve adequate anticoagulation especially during surgery.
Which of the following conditions would explain her thrombophilia and her heparin resistance?

Antithrombin III deficiency
Heparin resistance is seen in upto 22% of patients undergoing cardiopulmonary bypass surgery.

Several mechanisms resulting in heparin resistance have been identified, including antithrombin deficiency, increased heparin clearance, elevated heparin-binding proteins, and elevated factor VIII and fibrinogen levels.

For cardiopulmonary bypass in particular, rapid neutralisation of thrombin is required. In order for heparin to be successful in this, it requires antithrombin III which is an alpha2-globulin. It is therefore thought that antitthrombin III deficiency is the underlying problem which is seen in patients resistant to heparin during cardiopulmonary bypass.

The other four answers describe conditions where there is an increased risk of thrombosis, but they are not specifically associated with resistance to Antheparin.

26

A 39-year-old male is receiving cisplatin based chemotherapy as therapy for lymphoma.
Which of the following is a typical side effect of cisplatin?
(Please select 1 option)
Cerebellar ataxia
Haemorrhagic cystitis
Optic neuritis
Ototoxicity
Rhabdomyolysis

PC MONA

Ototoxicity
Typical side effects of cisplatin include

Marrow toxicity
Ototoxicity
Peripheral neuropathy
Nephrotoxicity
Alopecia
Changes in taste.

Although optic neuritis is described it is not a typical side effect.

27

An 85-year-old man weighing 80 kg is admitted as an emergency with lower abdominal pain and fever. He is delirious, has a temperature of 39.0°C and has a blood pressure of 80/40 mmHg.
Urinalysis is strongly positive for blood protein and nitrates. The microbiologist recommends the prescription of gentamicin.
Which of the following is the most appropriate dose of gentamicin to initiate for this man?
(Please select 1 option)
40 mg once daily
40 mg single dose
80 mg 8 hourly
80 mg 12 hourly
320 mg single dose

320mg single dose
The therapeutic dose of gentamicin is 4-7mg/kg, with dosing interval depending on 6-12 plasma level.

28

A 25-year-old shop attendant presents to the local emergency department with left loin pain, which radiates into his groin. He is clearly in some discomfort.
Upon being informed that he has renal colic, the patient expresses an urgent desire for some analgesia.
Which of the following is the most appropriate medication to prescribe in the circumstances?
(Please select 1 option)
Gabapentin
Intramuscular diclofenac CorrectCorrect
Oral amitriptyline
Oral morphine
Oral paracetamol

Non-steroidal anti-inflammatory drugs (NSAIDs), either intramuscularly or by suppository, are the first line treatment for renal colic.

Strong opiates are regarded as appropriate second line therapy.

29

A 68-year-old female with terminal bowel cancer is receiving optimal doses of morphine sulphate therapy.
Which of the following effects may be expected with the addition of a partial opioid agonist?
(Please select 1 option)
Increased analgesia
Increased respiratory depression
Increased sedation
No change
Reduced analgesia CorrectCorrect

Partial opioid agonists (for example, buprenorphine), when used in association with morphine, may produce a reduction in the analgesic effect due to partial antagonism.

This is an aspect of pain management that needs to be considered when using combination therapies.

30

A clinical trial assessing a new lipid-lowering therapy for stroke allocates 1000 patients to active treatment and another 1000 patients to placebo.
Results demonstrate that number needed to treat (NNT) is 20 for the prevention of the primary end-point.
Which of the following best describes the results?
(Please select 1 option)
20 patients in the treatment group were protected from stroke
20 extra patients in the placebo group had a stroke
For 1000 patients treated with active therapy, there would be 20 fewer strokes
For 1000 patients treated with active therapy, there would be 50 fewer strokes
For every 1000 patients treated with active therapy there would be 100 fewer strokes

For 1000 patients treated with active therapy, there would be 50 fewer strokes
This prevention study for stroke reveals that 20 patients need to be treated to prevent one event.

Thus if you treat a 1000 patients then you will expect to have 50 fewer strokes.

31

A firm 2-3 cm mass is palpable in the upper outer quadrant of the right breast of a 52-year-old woman. There are no palpable axillary lymph nodes.
A lumpectomy with axillary node dissection is performed and the breast lesion is found to have positive immunohistochemical staining for HER2/neu (c-erb B2). Staining for oestrogen and progesterone receptors is negative.
Which of the following additional treatment options is most appropriate, based upon these findings?
(Please select 1 option)
Radical mastectomy
St John's wort
Tamoxifen
Trastuzumab
Vancomycin

Trastuzumab
This is an infiltrating ductal carcinoma.

The lack of oestrogen receptor staining suggests a poor response to hormonal therapy with tamoxifen.

The positive C-erb B2 (HER2/neu) staining suggests that trastuzumab (Herceptin) may be effective.

32

In a chronic disease which has no known effective treatment, a new treatment is known to be effective in animal models and shows promise in short term studies in patients.
There are some theoretical concerns about toxicity involving liver and bone marrow although no cases have been observed in studies so far.
What is the most appropriate next step in the drug's development?
(Please select 1 option)
Case-control study
No further studies should be done and drug development should be stopped
Open study
Randomised double blind placebo controlled study
Randomised single blind placebo controlled study

RCT double blind study

The story that is described is of an early drug development that has gone through phase I trials (normal volunteers) and phase II studies (more normal volunteers but it also mentions 'studies in patients').

The next step in the development of this drug is a phase III study - where the drug's efficacy and safety should be tested against a placebo.

Broadly, the development of a new drug can be divided into pre-clinical and clinical trials.

Pre-clinical development first involves identifying the target thought to be important in disease. Drug candidates are then identified, and their properties optimised. Pre-clinical safety studies are then conducted to determine dosage, ensure safety and study pharmacokinetic properties. These involve both computer and animal models. All information gathered from pre-clinical testing is submitted to the regulatory authorities, prior to moving to the clinical phase of drug development.

Clinical trials have a number of phases:

In phase I the drug is usually given to healthy volunteers to determine its safety and pharmacokinetic properties in humans.
In phase II a small group of patients (typically 100-250) are given the drug to evaluate its efficacy, optimum dose, safety and side effects (as these may be different in patients compared to healthy volunteers). If these trials are successful larger clinical trials can be planned.
Phase III trials typically involve more than 1000 patients, and are used to determine efficacy and side effects. If successful the drug must be registered by the authorities prior to being released to the market.
It is important to note the majority of drugs identified in early pre-clinical trials will never make it to market, as they are not shown to have a significant effect or they are associated with significant toxicity.

Post-marketing studies then continue to determine the long term and chronic toxicities. UK practitioners are requested to report any side effects via the yellow card scheme.

33

A 55-year-old male presents with acutely painful, red and swollen left great toe. He was recently started on an antihypertensive by his GP.

Thiazide diuretic
The 55-year-old male with symptoms suggestive of acute gout is likely to have been commenced on a thiazide diuretic which has the side effect of producing hyperuricaemia. Other side effects of thiazides include hyperglycaemia, rash and dyslipidaemia.

34

A 55-year-old female presents with a troublesome cough which she has noticed since her GP commenced her on an antihypertensive.

ACEi
The 55-year-old female has a persistent cough associated with the introduction of an antihypertensive. This suggests ACE inhibitors as these agents may produce an irritating cough in approximately 30% of users and is due to accumulation of histamine/bradykinin, etc, within mast cells. Cough is not a feature of AT blockers.

35

A 62-year-old male presents with a deterioration in walking distance due to intermittent claudication. He has peripheral vascular disease and his GP recently started him on an antihypertensive following persistently elevated blood pressure recordings at the clinic.

Beta blockers
The 62-year-old male has a deterioration in his intermittent claudication since commencing an antihypertensive. Beta blockers may exacerbate these symptoms as it may inhibit the beta2-mediated vasodilatation of the skeletal muscle vessels.

36

Associated with an allergic 'red man syndrome' characterised by exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and vasculitis.

Vancomycin
Other side effects include ototoxicity and nephrotoxicity, and thus serum levels should be monitored.

37

Associated with an experimental arthropathy in growing animals and therefore contraindicated in patients under 16 years.

Ciprofloxacin
Other side effects include gastrointestinal disturbances, photosensitive rashes and occasional neurotoxicity can occur.

38

Has a very narrow therapeutic index, and is associated with the development of ototoxicity and nephrotoxicity.

Gentamicin
Toxicity is dose-related and blood levels must be checked. Ototoxicity occurs more frequently with some diuretics.

39

Causes brown discolouration of growing teeth and thus should not be given to children or pregnant women.

Tetracycline
Tetracyclines are generally safe drugs, but side effects include causing a brown discolouration of the teeth, renal failure, and photosensitive rashes.

40

Causes a metallic taste. Rarely can cause a peripheral neuropathy.

Metronidazole
Other recognised side effects of metronidazole include polyneuropathy and they are tumourigenic in animals although carcinogenicity has not been described in humans.

41

Used in the treatment of diffuse oesophageal spasm.

Nifedipine, a calcium channel blocker, which inhibits smooth muscle contraction, provides symptomatic relief in this disorder.

42

An antimuscarinic agent that provides symptomatic relief of gastrointestinal disorders characterised by smooth muscle spasm.

Hyoscine butylbromide
Hyoscine butylbromide, an antimuscarinic, reduces intestinal motility. It is used in the management of irritable bowel syndrome and diverticular disease.

43

A 5-aminosalicylic acid derivative that can induce a remission in mild attacks of ulcerative colitis and colonic Crohn's disease.

Mesalazine; in lower doses it is useful as a maintenance treatment to reduce the number of relapses.

44

An anti-TNF-á antibody that is given as a single infusion, which can produce clinical improvement in 60% of patients with steroid-resistant Crohn's disease.

Infliximab;further infusions may be given at eight weekly intervals to maintain remission though the optimal duration of treatment is unclear at present.

45


An agent that inhibits the gastric hydrogen-potassium-ATPase and blocks the luminal secretion of gastric acid.

Omeprazole inhibits gastric acid by blocking the hydrogen-potassium-ATPase enzyme system of the gastric parietal cell.

46

A primary prevention study of stroke compares the effect of a new drug with an established treatment. Only the organising authority knows the coding for the randomisation of therapies.

Double blind study
The most typical form of study is the double blind placebo controlled study where potential bias is averted through randomisation of patients to drug or placebo without either doctor or patient knowing which agent is being used.

As a variation of this theme patients can be randomised to receive either the new drug or an established therapy.

47


A study reports on the cardiovascular side effects of a new therapy in the treatment of prostate cancer based on randomised controlled trials reported thus far in the medical literature.

Meta-analysis


A frequent way of assessing the effect of treatment or the potential risks of treatment is to review all the data published in the medical literature - a meta-analysis.

Many of the guidelines are published through meta-analysis.


48

An alkylating agent resulting in haemorrhagic cystitis.

Cylcophosphamide

All cytotoxic agents have adverse effects. General side-effects include nausea, vomiting and bone marrow suppression, alopecia and stomatitis. More specific side-effects are listed in the questions above. Alkylating agents such as Cyclophosphamide may cause a haemorrhagic cystitis. Asparaginase results in a dose related Pancreatitis.





49

A drug inhibiting protein synthesis may result in a dose related Pancreatitis.

Asparaginase

Bleomycin is the main drug resulting in lung damage and occurs in up to 10% of patients. The damage is dose related.

50


An anthracycline with a serious risk of cardio-toxicity.

The anthracyclines e.g. Doxorubicin and Daunorubicin are cardiotoxic, which is often very difficult to detect. Monitoring with echocardiograms is advised.

Vincristine is an alkaloid agent and results in sensory motor neuropathy with long-term use. It also has an affect on the autonomic system resulting in severe constipation and paralytic ileus. It may also result in sensory changes with parathesis progressing to loss of tendon reflexes.

51

A drug disrupting microtubule leading to loss of deep tendon reflexes.

Vincristine

All cytotoxic agents have adverse effects. General side-effects include:

nausea
vomiting
bone marrow suppression
alopecia, and
stomatitis.

More specific side-effects are listed in the questions above. Alkylating agents such as Cyclophosphamide may cause a haemorrhagic cystitis. Asparaginase results in a dose related Pancreatitis.

52

A drug inhibiting initiation of DNA synthesis resulting in conjunctivitis and cerebellar toxicity.

Cytosine arabinoside

The anthracyclines e.g. Doxorubicin and Daunorubicin are cardiotoxic, which is often very difficult to detect. Monitoring with echocardiograms is advised. Vincristine is an alkaloid agent and results in sensory motor neuropathy with long-term use. It also has an affect on the autonomic system resulting in severe constipation and paralytic ileus. It may also result in sensory changes with parathesis progressing to loss of tendon reflexes.

53

A drug resulting in dose related lung damage.

Bleomycin

Bleomycin is the main drug resulting in lung damage and occurs in up to 10% of patients. The damage is dose related

54

A 31-year-old female is receiving warfarin for a left lower limb deep vein thrombosis after a cholecystectomy. She has been on warfarin 5 mg daily for the last six weeks and her INR has been maintained between 2 and 2.5. However, she recently used some medication she bought over the counter at her pharmacy and her INR is now above 5.

Cimetidine

Drugs that cause prolongation of the INR include erythromycin, ciprofloxacin and esomeprazole. However, cimetidine is the only over-the-counter drug on this list that would prolong INR.

55


A 54-year-old diabetic male is treated for atrial fibrillation with warfarin. He has had stable INR of between 2 and 2.5 on a dose of 3mg of warfarin daily. However, he recently received a treatment for painful dysaethesia in his feet that has resulted in his INR falling to 1.4.

Carbamazepam

Carbamazepine is a cytochrome P450 inducer and would stimulate the metabolism of warfarin thus lowering INR. Oestrogens may reduce INR but this does not apply to this patient. Aspirin, paracetamol or codeine phosphate do not affect INR (although regular, prolonged use of paracetamol may "possibly" affect INR according to the BNF, Cimetidine remains the better choice for Question 1).

56

A study compares the effect of low molecular weight heparin versus aspirin in the prevention of DVT amongst post-operative orthopaedic patients. Patients are randomised to receive one or other treatment as either an injection or a tablet.

Open study
This study assessing DVT post-operatively, is an open study as patients and investigators will know which treatment they are receiving as it is either an injection or a tablet. If, however, they wished to create a double blind study then patients could be randomised to receive either injection+placebo tablet or aspirin+placebo injection.

57

A study compares the effect of no treatment with a new agent for irritable bowel syndrome. Subjects are randomised to receive either a placebo or the drug and, as this is a new agent, only the nurse administering the study in each centre knows which treatment the patient is receiving.

Single blind study
In a single blind study, information that could introduce bias or otherwise skew the result is withheld from the patients, but the experimenter will be in full possession of the facts.

As the nurse is aware which patient is receiving which treatment in this study, it is termed a single blind study (and in this case incorporates a placebo).

58

A double blind placebo control study reports on the reduced risk of stroke associated with the addition of statin therapy to standard therapy in patients with a previous history of stroke.

Secondary prevention trials

These are well recognised types of trials.

The reduction of stroke in patients with previous history of stroke would be classed as a prevention study; in this case secondary prevention as you are trying to prevent the disease occurring again rather than prevent it occurring at all.

59

A study reports on the measurement of serum fibrinogen degradation products (FDPs) in the detection of deep vein thrombosis (DVT) in post-operative patients, compared with the criterion method of Doppler ultrasound.

Diagnostic trials

Measuring FDPs to detect venous thromboembolism (VTE) would be classed as diagnostic as you are endeavouring to diagnose a condition against a standard (in this case ultrasoun

60

A double blind placebo control study reports on changes in the short form 36 (SF-36) questionnaire following treatment with a topical healing agent in patients with chronic leg ulceration.

Quality of life trials
These seek patient views about benefits or changes resulting from treatments. Short form (SF) health surveys are the most widely used tools in the world for measuring patient-reported outcomes. There are several different versions, the short form 36 being one. It records patient assessed scores for eight domains, including general health, physical, mental and emotional health, and social well-being.

61

A study reports on the ability of a new serum oncogenic marker to detect bowel cancer amongst an asymptomatic middle aged population.

Screening trials
Screening trials study the efficacy and acceptability of new screening tests.

Primary prevention trials study the efficacy of a treatment or intervention in preventing people without a disease from getting it.

Secondary prevention trials study the efficacy of a treatment or intervention in preventing a complication or progression of disease in patients who already have a disease.

Treatment trials study the effect of new treatments.

The short form 36 provides an index of well being and thus the study looking at the changes in SF-36 with treatment would be classed as a quality of life trial.

The use of a marker in the detection of a disease in the general population is classed as screening.

62

A 72-year-woman has undergone a major small and large bowel resection for acute mesenteric ischaemia. As a result she requires lifelong total parenteral nutrition (TPN).
Which of the following metabolic side effects of TPN is she unlikely to develop?
(Please select 1 option)
Fatty acid deficiency
Hypercarbia
Hyperglycaemia
Hypoglycaemia
Metabolic alkalosis

Metabolic alkalosis
The side effects of total parenteral nutrition (TPN) are numerous and include catheter-related sepsis and metabolic abnormalities resulting from the administered nutrients.

Fatty acid deficiency may develop during prolonged TPN, though administering 3% of the total caloric input as linoleic acid prevents or corrects this deficiency.

Hyperchloraemic metabolic acidosis may occur because of the liberation of hydrochloric acid during the metabolism of amino acids in the TPN.

Hypercarbia occurs from the increased production of carbon dioxide resulting from the metabolism of large amounts of glucose. A requirement for ventilatory support or weaning difficulties may subsequently occur.

Hyperglycaemia is a potential problem until endogenous insulin production increases, requiring frequent glucose monitoring.

Hypovolaemia due to an osmotic diuresis and a non-ketotic hyperosmolar hyperglycaemic coma are both potential complications of TPN, which may necessitate the addition of insulin to the TPN solutions.

Accidental or sudden discontinuation of the TPN infusion may cause hypoglycaemia. The pancreatic insulin response may persist despite discontinuing the TPN, resulting in a high plasma insulin concentration.

Consequently intravenous glucose administration may be required, or alternatively a gradual discontinuation of the TPN over 60 to 90 minutes.

63

Hypokalaemia is a recognised side effect in which of the following?
(Please select 1 option)
Amiloride
Amlodipine
Bumetanide
Digoxin
Spironolactone

Bumetanide (Burinex) is loop diuretic, inhibiting reabsorption in the ascending limb of the loop of Henle. Another loop diuretic is furosemide (furosemide; Lasix). These, and thiazide diuretics (bendroflumethiazide; metolazone), may cause hypokalaemia.

Amiloride, like spironolactone, is a potassium sparing diuretic and may cause hyperkalaemia.

Amlodipine induces no change in plasma potassium.

Digoxin toxicity is exacerbated by hypokalaemia but it does not cause hypokalaemia.

64

Which of the following is correct in a double blind placebo control clinical trial?
(Please select 1 option)
All patients receive a placebo
Everybody receives both treatments
Half the patients do not know which treatment they receive
Some of the patients are not treated
The clinician assessing the effects of the treatment does not know which treatment the patient has been given

The clinician assessing the effects of the treatment does not know which treatment the patient has been given
If every patient were to receive both treatments it would be a 'double blind crossover study'.

In a double blind placebo control clinical trial all of the patients are blind to the treatment choice so it would be incorrect to say that only half of the patients do not know which treatment they receive.

If some of the patients are not treated it could clearly not be considered a blind trial since these patients would be aware that they were not being treated.

The correct answer is that the clinician assessing the effects of the treatment does not know which treatment the patient has been given. In a double blind placebo control clinical trial the clinician is blind to the treatment choice.

65

Which of the following regarding iron deficiency anaemia is correct?
(Please select 1 option)
Absorption of iron is increased by ascorbic acid
Ferrous sulphate 200 mg has less elemental iron than the same dose of ferrous gluconate
Iron is absorbed in the distal jejunum
Parenteral iron is indicated when the anaemia responds slowly to oral iron
Sustained release iron is a useful way of giving larger doses

Absorption of oral iron is improved by ascorbic acid.

Ferrous sulphate has more elemental iron by mass.

Iron is absorbed in the upper small intestine.

Parenteral iron acts no faster than oral iron. It is indicated when oral iron cannot be tolerated or is not absorbed.

Sustained release preparations may improve tolerance of oral iron but do not aid absorption.

66

Which of the following can give a biochemical picture indistinguishable from extra-hepatic obstructive jaundice?
(Please select 1 option)
Erythromycin estolate
Halothane
Isoniazid
Lidocaine
Vancomycin

Erythromycin estolate

Extra-hepatic would suggest raised bilirubin with raised alkaline phosphatase and gamma-glutamyl transpeptidase (GGT).

67

What abx is staph aureus not sensitive to

Cefuroxime
Flucloxacillin
Methicillin
Metronidazole
Vancomycin

S. aureus is sensitive to vancomycin, as are most other Gram positive organisms. Vancomycin is also used in the treatment of pseudomembranous colitis if metronidazole is contraindicated.

Cefuroxime is broad-spectrum and also has good Gram negative activity. It is very useful in surgery for prophylaxis and post-operative infections.

Flucloxacillin is used in the treatment of Gram positive (-lactamase) producers, such as S. aureus.

Metronidazole has activity against anaerobic bacteria only. S. aureus is sensitive to methicillin. However, methicillin-resistant S. aureus were detected in 1961 soon after methicillin was introduced.

68

Which of the following are potassium sparing diuretics?
(Please select 1 option)
Bendroflumethiazide
Captopril
Doxazosin
Furosemide
Triamterene

Potassium sparing diuretics include spironolactone, triamterene and amiloride. They act on the distal convoluted tubule inhibiting, through various mechanisms, the loss of potassium in exchange for sodium.

Captopril is not a diuretic but an angiotensin-converting enzyme (ACE) inhibitor.

Doxazosin is an alpha blocker.

Furosemide is a loop diuretic, and bendroflumethiazide a thiazide diuretic.

69

Which of the following produce severe hyperkalaemia in combination?
(Please select 1 option)
Aspirin and allopurinol
Furosemide and amiloride
Lisinopril and furosemide
Losartan and amiloride
Propranolol and verapamil

Losartan and amiloride

The combination of angiotensin-converting enzyme (ACE) inhibitors/angiotensin blockers with potassium sparing diuretics such as spironolactone and amiloride may produce dangerous hyperkalaemia.

Amiloride is often given with furosemide (co-amilofruse) to replete potassium stores.

Propranolol is not given with verapamil due to the induction of severe bradycardia.

70

Regarding sildenafil (Viagra), which of the following statements is correct?
(Please select 1 option)
Increases libido
Is associated with nasal congestion as a recognised side effect This is the correct answerThis is the correct answer
Is associated with red visual discolouration as a recognised side effect
Is contraindicated in patients with ischaemic heart disease IncorrectIncorrect answer selected
Is of no use in patients who have developed impotence following prostate surgery

Sildenafil is a well established treatment for impotence and works through the inhibition of phosphodiesterase type 5, producing cavernous venodilation and erections in appropriately stimulated patients.

It does not increase sex drive/libido.

It is contraindicated in subjects taking nitrates, as it may produce hypotension but it is not contraindicated in patients with ischaemic heart disease per se.

Side effects include flushing which develops in the majority, but it is also associated with nasal congestion and blue visual discolouration.

71

Which agent interferes with viral multiplication?
(Please select 1 option)
Amantadine
Amphotericin B
Fluconazole
Infliximab
Metronidazole

Amantadine is an antiviral drug. It is used in the treatment of certain RNA viruses and influenza viruses.

Amphotericin and fluconazole are antifungal drugs, and metronidazole can be used as an antiprotozan drug.

Infliximab blocks the action of TNFα by preventing it from binding to its receptor in the cell and is only licensed

72

Which is true, following an aspirin overdose?
(Please select 1 option)
A metabolic acidosis develops more commonly and rapidly in children
Fat metabolism is decreased
Hyperkalaemia is common
Initially a respiratory acidosis is seen
Urinary pH is initially acidic

A metabolic acidosis develops more commonly and rapidly in children

Aspirin (salicylates) directly stimulate the respiratory centre, causing an initial respiratory alkalosis.

The excretion of bicarbonate, potassium and water is increased which results in

hypokalaemia (not hyperkalaemia)
dehydration
a metabolic acidosis.
The metabolic acidosis occurs later and is due to uncoupling of oxidative phosphorylation, increased fat metabolism and inhibition of the tricarboxylic acid cycle. The metabolic acidosis tends to occur more rapidly and more commonly in children under the age of 12.

The urinary pH in aspirin overdosage is initially alkaline and then becomes acidic.

73

Which one of the following has direct agonist action at opioid receptors?
(Please select 1 option)
Buprenorphine
Diamorphine
Naloxone
Naltrexone
Diclofenac

Buprenorphine

Buprenorphine is the only drug listed which is an opioid receptor agonist. It is a partial agonist (it also has antagonist properties).

Diamorphine (diacetylmorphine) is an inactive prodrug, which acts via its active derivatives, morphine and 6-0-acetylmorphine.

Naloxone and naltrexone are opioid antagonists, and the former has a much shorter duration of action.

Diclofenac is a NSAID. These reduces the production of prostaglandins by inhibiting the enzyme cyclo-oxygenase.



74

Which of the following is true regarding morphine?
(Please select 1 option)
Causes direct myocardial depression
Decreases the production of antidiuretic hormone (ADH)
Has a lower affinity for the opioid receptor than diamorphine
Is a phenylpiperidine
May cause bronchospasm

Bronchospasm

Morphine does not causes direct myocardial depression, although it may cause a bradycardia.

The hypotension associated with its use is because of a decrease in the systemic vascular resistance (SVR) which is due, in part, to histamine release. The histamine release may also cause bronchospasm. The production of antidiuretic hormone (ADH) is also increased by morphine.

Diamorphine has almost no affinity for the opioid receptor and is a prodrug of morphine.

Phenylpiperidines include pethidine and fentanyl, whereas morphine is a phenanthrene.

75

Which of the following is true regarding heparin?
(Please select 1 option)
Enhances antithrombin III activity
Has no effect on platelet aggregation
Induces thrombocytopaenia in 20% of patients
Is a strongly acidic protein
Readily crosses the placenta

Enhances antithrombin III activity

Heparin is a strongly acidic mucopolysaccharide (not protein), and as the name heparin implies, it is derived from the liver.

Heparin has many actions, but principally it enhances antithrombin III activity, which in turn inhibits activated factors XII, XI, X, IX and thrombin.

Heparin also activates lipoprotein lipase in plasma, lowering the plasma triglycerides and inhibiting platelet aggregation by fibrin.

A side effect in up to 5% of patients (not 20%) is heparin induced thrombocytopaenia (HIT).

As heparin is so strongly acidic, it binds avidly to proteins and so it crosses the placenta and other membranes poorly. Pregnant women requiring anticoagulation with warfarin are converted to heparin, as this has a much lower risk of teratogenicity.

76

Which one of the following is NOT true of atropine?
(Please select 1 option)
Causes agitation and hallucination, particularly in the elderly
Causes drowsiness and somnolence in the elderly
Is a bronchodilator
Is a non-competitive nicotinic antagonist
May cause a bradycardia

Is a non-competitive nicotinic antagonist

Atropine and its derivative, ipratropium bromide (atrovent), are bronchodilators, due to competitive inhibition of bronchial muscarinic receptors. Atropine is a tertiary amine (i.e. uncharged) and it crosses the blood brain barrier readily.

Central anticholinergic syndrome is seen, particularly in the elderly and the symptoms include

agitation
hallucination
drowsiness
somnolence
amnesia
dysarthria
ataxia (although the stimulatory effects are more common with atropine).
An initial bradycardia may occasionally follow atropine administration, and this is called the Bezold-Jarisch reflex. It is thought to be due to stimulation of the muscarinic type 2 (M2) receptors, before the muscarinic type 1 (M1) effect supervenes.

Atropine is a competitive muscarinic antagonist (not non-competitive), although there may be nicotinic effects at very high doses, this remains competitive antagonism.

77

Which one of the following pharmacological changes does not occur in a burned patient?
(Please select 1 option)
The clearance of cimetidine is increased
The clearance of gentamicin is reduced
The proportion of alfentanil bound to alpha-1-acidglycoprotein is increased
The proportion of diazepam bound to albumin is reduced
There is resistance to non-depolarising muscle relaxants

Clearance of gentamicin in reduced

The pharmacokinetic and pharmacodynamic profiles of many drugs are altered in burned patients. These changes include altered

Cardiovascular dynamics
Protein binding (reduced albumin and increased alpha-1-acid glycoprotein binding)
Volume of distribution
Drug clearance.
The clearance of both gentamicin and cimetidine (during the hyperdynamic phase of the burn injury) is increased, and monitoring the serum levels is necessary to guide dosage.

Diazepam and drugs predominantly bound to albumin have a higher unbound fraction, whereas alfentanil and drugs mainly bound to alpha-1-acidglycoprotein have a lower unbound fraction.

Resistance to non-depolarising muscle relaxants occurs, and may be due to an increase in density of the nicotinic acetylcholine receptors.

78

Which of the following is true regarding metoclopramide?
(Please select 1 option)
Causes side effects which are treated with anticholinergic drugs
Decreases barrier pressure
Increases pyloric tone
Is an agonist at the 5-hydroxytryptamine (5-HT) receptor
May cause drowsiness

Drowsiness

Although it primarily has an antagonistic action at dopamine receptors, metoclopramide is a 5-hydroxytryptamine (5-HT) antagonist at higher doses. Its extrapyramidal side-effects can be treated with procyclidine which has antimuscarinic properties.

Metoclopramide is relatively free of side-effects, apart from oculogyric crises (an extrapyramidal effect) and drowsiness.

The peripheral effects of metoclopramide inhibiting the action of dopamine are illustrated by its enhancement of antral and fundal contractility and relaxation of the pylorus. The net effect is to increase the rate of gastric emptying.

The lower oesophageal sphincter pressure is, however, increased and this leads to an increase in barrier pressure.

79

Which of the following is true regarding antibiotics?
(Please select 1 option)
Amphotericin B is not significantly protein bound
Clarithromycin is the most suitable antibiotic in a patient with severe cellultis who is allergic to penicillin
Lipid formulations of amphotericin B are more nephrotoxic than conventional amphotericin B
Penicillin is a suitable antibiotic in treating infections due to Pseudomonas aeruginosa
The quinolones are RNA gyrase inhibitors

Clarithromycin

Amphotericin B is highly protein bound and penetrates body tissues poorly. The nephrotoxicity is reduced in lipid formulations of amphotericin B.

Ciprofloxacin and norfloxacin are both quinolones which prevent bacterial DNA supercoiling by their action on DNA gyrase. They are suitable antibiotics in treating infections due to Pseudomonas aeruginosa.

For severe cellulitis in a patient allergic to penicillin (so you cannot give the standard treatment of flucloxacillin 1g IV qds and benzyl penicillin 1.2g IV qds) clarithromycin 500 mg IV bd is the best choice.

80

Which of the following is correct about anastrozole?
(Please select 1 option)
A selective oestrogen receptor modulator
Associated with endometrial hyperplasia
Associated with improved outcomes in early breast cancer compared with tamoxifen
Associated with relative hypoadrenalism
Contraindicated in patients with ischaemic heart disease

Associated with improved outcomes in early breast cancer compared with tamoxifen

Unlike the selective oestrogen receptor modulator (SERM) tamoxifen, anastrozole is an aromatase inhibitor, blocking the aromatisation of adrenal androgens to oestrogens. It is orally active and taken daily, and unlike the earlier unselective aromatase inhibitor, aminoglutethimide, it does not inhibit cortisol production.

Used in advanced breast cancer, studies also suggest that anastrozole is superior to tamoxifen in tolerability and also in time to recurrence in the adjuvant therapy of post menopausal women with early breast cancer.

Side effects include exacerbation of sweats and vaginal dryness, and as it is not associated with any SERM-like effects, it is not associated with endometrial hyperplasia.

81

Which one of the following antibiotics acts on bacterial walls?
(Please select 1 option)
Ceftazidime
Clindamycin
Gentamicin
Metronidazole
Trimethoprim

Ceftazidime
The mode of action of antibiotics can be classified as below.

Inhibition of nucleic acid synthesis: metronidazole.
Inhibition of protein synthesis: clindamycin, gentamicin.
Action on cell membrane: polymyxin.
Interference with enzyme system (anti-metabolites): trimethoprim.
Action on cell wall: penicillins and cephalosporins.

82

Which one of the following does not have an anti-emetic action?
(Please select 1 option)
Chlorpropamide
Hyoscine hydrobromide
Morphine sulphate
Perphenazine
Promethazine hydrochloride

Morphine sulphate

Hyoscine is an alkaloid
Promethazine is an antihistamine
Perphenazine is an antipsychotic
and all three have anti-emetic properties.

The sulphonylurea chlorpropamide may have anti-emetic properties and has thus been marked as true.

Morphine has an emetic action.

83

Which of the following is true of benzyl penicillin:
(Please select 1 option)
Can be administered orally
Is an effective treatment for cellulites
Is an effective treatment for spontaneous bacterial peritonitis (SBP)
Is ineffective against Clostridium tetani
Undergoes first pass hepatic metabolism

Good for cellulites

Benzyl penicillin (penicillin G) is inactivated by gastric acid and so must be given parenterally (unlike penicillin V).

It is an effective treatment for Strep. infections, for example, cellulitis and is also effective for tetanus.

It is not appropriate for SBP where third generation cephalosporins are advocated.

84

Which of the following is true of gentamicin therapy?
(Please select 1 option)
Does not require monitoring of plasma concentrations
Is associated with neurotoxicity
Is well absorbed orally
May produce ventilatory failure in sensitive patients
Undergoes hepatic excretion

May produce ventilatory failure in sensitive patients

Side effects of the aminoglycosides include oto and renal toxicity (excretion principally by the kidney) and drug concentrations need to be carefully monitored during treatment.

A rare side effect is ventilatory failure associated with impaired neuromuscular junction conduction and it should not be given to patients with myasthenia gravis.

It is given IV and is denatured orally.

85

Which of the following is a side effect of ciprofloxacin?
(Please select 1 option)
Convulsions
Discolouration of the urine
Ischaemic colitis
Nephrotoxicity
Ototoxicity

Convulsions

Ciprofloxacin is an ofloxacin and is generally well tolerated.

Side effects include rashes, pseudomembranous colitis as it is a broad spectrum antibiotic and rarely cholestasis.

Convulsions are rarely associated with ciprofloxacin.

Red discolouration of the urine is typical of rifampicin and ototoxicity is typical of gentamicin.

86

Which of the following is correct regarding the pharmacokinetics of antibiotics?
(Please select 1 option)
Aminoglycosides are absorbed well by the gut
Intramuscular preparation should be avoided in hypoperfusion states
Most antibiotics are better absorbed with food
Oral antibiotics are absorbed principally from the terminal ileum
Topical antibiotics are rapidly absorbed through the skin

Intramuscular preparation should be avoided in hypoperfusion states

Oral antibiotics are absorbed principally in the stomach and proximal small bowel.

Tissue absorption when given by the intramuscular route is unreliable and is reduced further in poor tissue perfusion.

Aminoglycosides are not absorbed by the oral route and require intravenous administration.

Topical antibiotics are poorly absorbed and therefore tend to be used less often.

Most antibiotics are best absorbed on an empty stomach, however, there are some exceptions, for example, doxycycline.

87

Which of the following is true with regard to evidence based medicine?
(Please select 1 option)
It involves the application of clinical expertise and the best available clinical evidence to give sound advice for health decision-making
It provides a blueprint for clinical decision making
Only evidence obtained by prospective randomised clinical trials (RCTs) should be used
The evidence used should be anecdotal
The treatment must be inexpensive

It involves the application of clinical expertise and the best available clinical evidence to give sound advice for health decision-making

RCTs are not the only trials which contribute to evidence based medicine.

Prospective trials, observational and cross-sectional studies all provide vital information which guides our daily decision making.

Evidence based medicine is a guide only and we should not assume that all patients should be treated according to the results of clinical trials - each patient is an individual, and we should never forget this.

Often an RCT will be conducted to assess the benefits or risks associated with a new, expensive treatment.

88

Which of the following is a cytotoxic alkylating agent?
(Please select 1 option)
Azathioprine
Chlorambucil
Fluorouracil
Mercaptopurine
Methotrexate

Chlorambucil

Alkylating agents exert their effects via transfer of their alkyl group to DNA and cytotosolic elements.

They include drugs like

Chlorambucil/cyclophosphamide
Nitrosureas (mustiness)
Busulphan and
Carbazines.

89

Which of the following is true of aminoglycosides?
(Please select 1 option)
Act on the bacterial cell wall
Are inactive against Streptococcus
Are useful against anaerobes
Damage the cochlear nerve
Should not be used in patients with renal failure

Damage cochlear nerve

These antibiotics are derived from Streptomyces spp. and are active against streptococcal species.

They interrupt bacterial protein synthesis by inhibiting ribosomal function.

Anaerobes produce phosphorylating adenylating or acetylating enzymes that inactivate aminoglycoside antibiotics.

Aminoglycosides are nephrotoxic but this is a dose-related effect.

Blood levels must be checked and caution taken with other nephrotoxic agents.

Aminoglycosides are ototoxic (vestibular and auditory) particularly in the elderly.

90

Which of the following antibiotics do not inhibit cell wall synthesis?
(Please select 1 option)
Benzylpenicillin
Cefuroxime
Co-amoxiclav
Erythromycin
Vancomycin

Erythromycin
Like penicillins, cephalosporins inhibit bacterial cell wall synthesis.

Erythromycin inhibits protein synthesis by interrupting ribosomal function.

Vancomycin is a complex and unusual glycopeptide active against Gram positive bacteria and inhibits cell wall synthesis.

Sulphonamides block thymidine and purine synthesis by inhibiting microbial folic acid synthesis.

Penicillins block the terminal cross-linking reaction between alanine and glycine of bacterial cell wall mucopeptide formation.

91

A 68-year-old woman admitted for a total hip replacement develops signs of a urinary tract infection on the third post operative day.
Microscopy confirms the presence of Escherichia coli.
Which of the following antibiotics is unlikely to be effective for this nosocomial acquired infection?
(Please select 1 option)
Ampicillin
Cefuroxime
Ciprofloxacin
Co-amoxiclav
Gentamicin

Ampicillin

Escherichia coli is a Gram negative bacillus which produces penicillinases, but it remains sensitive to numerous antibiotics.

Bacterial resistance to antibiotics is a major problem and where possible sensitivities should be checked before blind treatment of infections is commenced.

Ampicillin and amoxicillin are broad spectrum antibiotics active against non-beta lactamase producing Gram positive and Gram negative organisms. They are inactivated by penicillinases and since up to 50% of Escherichia coli strains are now resistant they would be an unsuitable choice.

Co-amoxiclav consists of amoxicillin and the beta-lactamase inhibitor clavulanic acid. Thus it is active against beta-lactamase producing bacteria that are resistant to amoxicillin, including strains of Escherichia coli.

Cefuroxime is a cephalosporin that is resistant to inactivation by bacterial beta-lactamases and so may be used against Escherichia coli.

Ciprofloxacin has a 6-fluoro substituent which confers enhanced antibacterial potency against both Gram positive and Gram negative organisms, including Escherichia coli.

Gentamicin is an aminoglycoside which works by binding to the bacterial 30S ribosomal subunit; this inhibits the translocation of the peptidyl-tRNA from the A-site to the P-site and also causes misreading of mRNA, leaving the bacterium unable to synthesise proteins vital to its growth.

They are bacteriacidal by inhibiting protein synthesis as they bind to the 16S rRNA and by disrupting the integrity of bacterial cell membrane.

92

Which of the following is not true of co-trimoxazole:
(Please select 1 option)
Contains two different drugs
Displaces methotrexate from protein binding sites
Inhibits folic acid synthesis
Is bacteriostatic
Potentiates the action of warfarin

Bacteriostatic

Combination of sulphonamide and trimethorpim, with synergistic bactericidal effect through inhibition of folic acid synthesis. It potentiates the effects of warfarin (like erythromycin, isoniazid) and the sulphonamide component can displace methotrexate from its plasma protein binding site.

93

Which of the following is true regarding total parenteral nutrition (TPN) delivered into a central vein?
(Please select 1 option)
Does not affect liver function tests
Contains typically 14-16 g nitrogen as D-amino acids
Contains typically 50 g glucose
Is a hypo-osmolar solution
Is associated with metabolic disturbances in about 5% patients

Is associated with metabolic disturbances in about 5% patients
TPN is hyperosmolar.

Consequently it is advocated that it is given centrally to reduce the risk of thrombophlebitis.

Each bag typically contains 14-16 g of L-amino acids and 250 grams of glucose.

It can induce derangement of liver function and therefore liver function tests should be performed regularly.

94

Hypokalaemia is a recognised side effect in which of the following?
(Please select 1 option)
Amlodipine
Amiloride
Carbenoxolone
Digoxin
Spironolactone

Carbenoxolone may cause hypokalaemic hypertension like liquorice through inhibition of 11 beta hydroxysteroid dehydrogenase (11bHSD).

Amiloride, like spironolactone is a potassium sparing diuretic and causes hyperkalaemia.

Digoxin toxicity is exacerbated by hypokalaemia but it does not cause hypokalaemia.

Amlodipine induces no change in plasma potassium.

95

Which of the following is true regarding antimicrobial therapy?
(Please select 1 option)
Resistance is increased in high nurse: patient ratios
Resistance is more common in ventilated patients
Should be administered at the maximum dose in patients with multiple organ dysfunction syndrome (MODS)
Should be administered for less than two weeks
Should only be administered intravenously in a septic patient

Resistance is more common in ventilated patients

Intravenous infusion is usually necessary but in certain circumstances other routes are preferable, for example, intrathecal infusions in central nervous system infections. Patients with MODS have usually developed renal or hepatic impairment and require adjustment of drug dosages.

Resistance usually develops after recent antimicrobial therapy and is most common where antimicrobial use is heaviest and patients are subject to multiple invasive procedures. Resistance is increased from cross-infection of attendant staff and is reduced when strict infection protocols are adhered to.

Antimicrobials should be continued for sufficient time to prevent resistance developing in the target organism.

96

Which of the following is true regarding a septic patient?
(Please select 1 option)
Assessment requires identification of the source of infection prior to starting antimicrobial therapy
Assessment requires urgent CT if intra-abdominal sepsis is suspected
History and examination is of little help
In whom peritonitis is suspected, should be transferred to theatre immediately for laparotomy
On the intensive care unit who develop unexplained sepsis requires removal,culture and replacement of all indwelling lines

On the intensive care unit who develop unexplained sepsis requires removal,culture and replacement of all indwelling lines
Definitive management requires identification of the source of infection, however, if the patient is at risk of septic shock broad-spectrum antimicrobial therapy should be started empirically.

History and examination are still important as they provide clues to the source of infection.

The patient should be assessed clinically for signs of peritonitis. Patients with peritonitis require fluid resuscitation before transfer to theatre.

All indwelling lines (for example, urinary catheters, central lines) should be replaced and the tips of the lines should be sent for culture.

97

By which of the following is sterilistion of medical devices achieved?
(Please select 1 option)
Chemical disinfectants
Chlorhexidine
Irradiation
Low-temperature steam

Sterilisation (to render an object free of viable microorganisms) is produced in hospitals by

Autoclaves
Hot air ovens
High-temperature steam and formaldehyde
Gas plasma
Irradiation
Ethylene oxide
Sporicidal chemicals.
Disinfection (a process to reduce the number of viable microorganisms) is produced in hospitals by

Low-temperature steam
Boiling water
Chemical disinfectants.

98

Which one of the following would be an effective treatment for acute epiglottitis due to Haemophilus influenzae?
(Please select 1 option)
Cefotaxime
Clarithromycin
Erythromycin
Flucloxacillin
Tetracycline

Cefotaxime

Nearly all isolates of Haemophilus influenzae are resistant to macrolide antibiotics (for example, erythromycin/clarithromycin) and tetracycline is inappropriate in this emergency setting.

Other agents that may be effective include co-amoxiclav.

99

Which one of the following is not a recognised prophylactic antibiotic for the given condition?
(Please select 1 option)
Cefotaxime - Total hip replacement
Cefuroxime + Metronidazole - Hemiarthroplasty
Ciprofloxacin - ERCP
Gentamicin - TURP
Metronidazole - Appendicectomy

Ciprofloxacin has a broad spectrum of action against Gram negative bacteria commonly found in the biliary tree.

Gentamicin has a broad spectrum of action against Gram negative bacteria found in the urinary tract.

Cefuroxime and metronidazole have a broad spectrum of action against mixed Gram positive and negative found in intra-abdominal pus.

Metronidrazole administered per rectum is an acceptable prophylaxis in early appendicitis.

Cefotaxime has a broad spectrum of action against Gram positive bacteria found in the skin.

100

A man attends the Accident and Emergency department with an acutely ischaemic limb. Your registrar tells you to start medical treatment while he is organising a CT angiogram. He may need to go to surgery.
Which medical therapy should be initiated?
(Please select 1 option)
Aspirin
Clopidogrel
Intravenous heparin infusion
Subcutaneous low molecular weight heparin (LMWH)
Warfarin

IV heparin

This patient requires anticoagulation with heparin to prevent progression of clot. Heparin can also recanalise acutely occluded vessels. Anti-platelet therapy with aspirin or clopidogrel is important in the long-term but not acutely.

This patient has a high likelihood of requiring surgery so requires intravenous heparin, which can be stopped pre-operatively. LMWH has a long half-life so prevent the siting of spinal/epidurals due to the risk of spinal haematoma. Intravenous heparin can be reversed easily and rapidly.

101

In a clinical trial of a new drug treatment for inflammatory bowel disease, the following results are obtained.
Drug Placebo
Improved 46 patients 34 patients
Not Improved 14 patients 26 patients
Which is the following statements concerning these data is correct?
(Please select 1 option)
If the statistical probability that the difference between drug andplacebo is 0.1 then the drug can be introduced into clinical practice
Pearson's coefficient of linear correlation could be used to test significance
The data can be evaluated by computing a chi square test
The data can be evaluated using a Student's t test
The superiority of the drug over placebo is so obvious that formal statistical testing is unnecessary

Chi square test

Although the new drug appears to be superior we do not know without performing appropriate statistical analysis.

Chi square test is most appropriate to assess significance of the results.

A t test would be inappropriate here.

A p value less than 0.05 is usually assumed as significant.