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).