Pharmacology Flashcards
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
A folic acid antagonist.
Methotrexate is a folic acid antagonist. It is often used as a treatment for rheumatoid arthritis.
An antimetabolite that acts as a pyrimidine antagonist.
5-fluorouracil
Prevents DNA repair by acting as a topoisomerase II inhibitor.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
