BNF - Chapter 9 - Blood and nutrition Flashcards
Before initiating treatment for anaemia it is essential to determine what?
To determine which type of anaemia is present - iron salts may be harmful if given to patients with anaemias other than those due to iron deficiency
What is sickle-cell disease?
Sickle-cell disease is caused by a structural abnormality of haemoglobin resulting in deformed, less flexible red blood cells
What is sickle-cell crisis?
where infarction of the microvasculature and restricted blood supply to organs results in severe pain.
What does sickle-cell crisis usually require?
Sickle-cell crisis usually requires hospitalisation, fluid replacement, analgesia, and treatment of any concurrent infection
What does haemolytic anaemia require?
Folate supplementation
What does folate supplementation help in sickle cell anaemia?
Helps to make new red blood cells as haemolytic anaemia increases erythropoiesis; this may increase folate requirements and supplementation with folic acid is recommended
Which drug can reduce the frequency of sickle cell crisis?
Hydroxycarbamide can reduce the frequency of crises and the need for blood transfusions in sickle cell disease
However the beneficial effects may not be evident for several months
What is G6PD deficiency?
Glucose 6-phosphate dehydrogenase (G6PD) deficiency is common in individuals originating from Africa, Asia, the Mediterranean region, and the Middle East; it can also occur less frequently in all other individuals.
Is G6PD deficiency more common in male or female?
In Males
What is haemolytic anaemia?
Hemolytic anemia is a disorder in which red blood cells are destroyed faster than they can be made. The destruction of red blood cells is called hemolysis
Individuals with G6PD deficiency are susceptible to developing what if they take a number of common drugs or when they have an infection?
acute haemolytic anaemia
They are also susceptible to developing acute haemolytic anaemia when they eat fava beans (broad beans); this is termed favism.
When prescribing drugs for patients with G6PD deficiency what three points should be kept in mind?
G6PD deficiency is genetically heterogeneous; susceptibility to the haemolytic risk from drugs varies; thus, a drug found to be safe in some G6PD-deficient individuals may not be equally safe in others;
manufacturers do not routinely test drugs for their effects in G6PD-deficient individuals;
the risk and severity of haemolysis is almost always dose-related.
Which drugs have a definitive risk of haemolysis in most G6PD-deficient individuals?
Dapsone and other sulfones Fluoroquinolones (including ciprofloxacin, moxifloxacin, norfloxacin, and ofloxacin) Methylthioninium chloride Nitrofurantoin Primaquine Quinolones Rasburicase Sulfonamides (including co-trimoxazole)
Which drugs have a possible risk of haemolysis in some G6PD-deficient individuals?
Aspirin
Chloroquine
Menadione, water-soluble derivatives (e.g. menadiol sodium phosphate)
Quinine (may be acceptable in acute malaria)
Sulfonylureas
What may be used as a immunosuppressive treatment for aplastic anaemia?
Intravenous horse antithymocyte globulin in combination with ciclosporin
Why is prednisolone used?
Prednisolone is used for the prevention of adverse effects associated with antithymocyte globulin treatment.
When are epoetins (recombinant human erythropoeitins used)
Epoetins (recombinant human erythropoietins) are used to treat anaemia associated with erythropoietin deficiency in chronic renal failure, to increase the yield of autologous blood in normal individuals and to shorten the period of symptomatic anaemia in patients receiving cytotoxic chemotherapy.
Which Epoetin is licensed for the prevention of anaemia in preterm neonates of low-birth weigh?
Epoetin - a therapeutic response may take several weeks
Compare Darbepoetin alfa to epoetin beta?
Darbepoetin alfa is a hyperglycosylated derivative of epoetin; it has a longer half-life and can be administered less frequently than epoetin.
What is Stevens’-Johnson syndrome (SJS)?
is a rare, serious disorder of the skin and mucous membranes. It’s usually a reaction to medication that starts with flu-like symptoms, followed by a painful rash that spreads and blisters. Then the top layer of affected skin dies, sheds and begins to heal after several days
What has been associated in patients treated with erythropoietins?
- rare cases of Steven’s-Johnson syndrome
What should patients be counselled on when on erthropoetin treatment?
Patients and their carers should be advised of the signs and symptoms of severe skin reactions when starting treatment and instructed to stop treatment and seek immediate medical attention if they develop widespread rash and blistering; these rashes often follow fever or flu-like symptoms—discontinue treatment permanently if such reactions occur.
What should the haemoglobin concentration be maintained within when on erythropoietin treatment?
10-12g/100ml
Haemoglobin concentrations higher than 12g/100ml should be avoided
What route should iron salts be given for iron deficiency anaemia?
By mouth unless there are good reasons for using another route
Is haemoglobin regeneration rate affected by the type of iron salt used?
It is little affected by the type of salt used provided sufficient iron is given, and in most patients the speed of response is not critical
what is the choice of preparations of iron salts decided by?
- side effects and cost
List the different iron salts and their content of ferrous iron?
Iron salt/amount Content of ferrous iron
ferrous fumarate 200 mg 65 mg
ferrous gluconate 300 mg 35 mg
ferrous sulfate 300 mg 60 mg
ferrous sulfate, dried 200 mg 65 mg
What should be noted about the folic acid content in iron preparations listed above?
It is important to note that the small doses of folic acid contained in these preparations are inadequate for the treatment of megaloblastic anaemias.
How daily administration are modified release preparations of iron tablets licensed for?
One-daily administration
What may the lower side effects with modified release preparations be associated with?
the low incidence of side-effects may reflect the small amounts of iron available for absorption as the iron is carried past the first part of the duodenum into an area of the gut where absorption may be poor.
What can iron be administered parentally as?
Iron can be administered parenterally as iron dextran, iron sucrose, ferric carboxymaltose, or ferric derisomaltose.
Does parenteral iron produce a faster haemoglobin response than oral iron?
With the exception of patients with severe renal failure receiving haemodialysis, parenteral iron does not produce a faster haemoglobin response than oral iron provided that the oral iron preparation is taken reliably and is absorbed adequately
Is parenteral iron given as a total dose or in divided doses?
Depending on the preparation used, parenteral iron is given as a total dose or in divided doses.
What should further treatment of parenteral iron be guided by?
Further treatment should be guided by monitoring haemoglobin and serum iron concentrations
What have been reported (serious side effects) with parenteral iron use?
Serious hypersensitivity reactions, including life-threatening and fatal anaphylactic reactions
These reactions can occur even when a previous administration has been tolerated (including a negative test dose).
Are test doses of parenteral iron recommended?
No longer recommended and caution is needed with every dose of IV iron
Can intravenous iron be used in pregnancy?
Intravenous iron should be avoided in the first trimester of pregnancy and used in the second or third trimesters only if the benefit outweighs the potential risks for both mother and fetus.
What has ferric carboxymaltose (IV iron) been associated with
The risk of persistent hypophosphatemia
For elderly, oral iron doses above what mg has no evidence of enhanced iron absorption?
Prescription potentially inappropriate (STOPP criteria) at oral doses greater than 200 mg elemental iron daily (no evidence of enhanced iron absorption above these doses).
What are some common side effects of oral iron?
Constipation; diarrhoea; gastrointestinal discomfort; nausea
What therapeutic levels should be aimed for with oral iron use?
The haemoglobin concentration should rise by about 100–200 mg/ 100 mL (1–2 g/litre) per day or 2 g/100 mL (20 g/litre) over 3–4 weeks.
When the haemoglobin is within the normal range, treatment should be continued for how many more months?
A further 3 months to replenish the iron stores
Can iron supplements change the colour of your stools?
yes - to a greenish or grayish black colour - this is normal
What is megaloblastic anaemia?
Megaloblastic anemia is a condition in which the bone marrow produces unusually large, structurally abnormal, immature red blood cells (megaloblasts).
what do most megaloblastic anaemia result from?
From a lack of vitamin B12 or folate and it is essential to establish in every case which deficiency is present and the underlying cause
what may you do in emergencies in megaloblastic anaemia?
In emergencies, when delay might be dangerous, it is sometimes necessary to administer both substances after the bone marrow test while plasma assay results are awaited.
What is one cause of megaloblastic anaemia in the UK?
One cause of megaloblastic anaemia in the UK is pernicious anaemia in which lack of gastric intrinsic factor resulting from an autoimmune gastritis causes malabsorption of vitamin B12.
When else is vitamin B12 also needed in the treatment of megaloblastosis?
in the treatment of megaloblastosis caused by prolonged nitrous oxide anaesthesia, which inactivates the vitamin, and in the rare syndrome of congenital transcobalamin II deficiency.
Which B12 therapy is used more commonly now?
Hydroxocobalamin has completely replaced cyanocobalamin as the form of vitamin B12 of choice for therapy;
Which is retained in the body for longer - hydroxocobalamin or cyanocobalamin?
Hydroxycobalamin is is retained in the body longer than cyanocobalamin and thus for maintenance therapy can be given at intervals of up to 3 months.
How is treatment with hydroxocobalamin initiated?
reatment is generally initiated with frequent administration of intramuscular injections to replenish the depleted body stores. Thereafter, maintenance treatment, which is usually for life, can be instituted. There is no evidence that doses larger than those recommended provide any additional benefit in vitamin B12 neuropathy.
For megaloblastic anaemia is folic acid given long term?
Folic acid has few indications for long-term therapy since most causes of folate deficiency are self-limiting or will yield to a short course of treatment.
It should not be used in undiagnosed megaloblastic anaemia unless vitamin B12 is administered concurrently otherwise neuropathy may be precipitated.
In folate-deficient megaloblastic anaemia (e.g. because of poor nutrition, pregnancy, or antiepileptic drugs), daily folic acid supplementation for how many months replenishes body stores?
daily folic acid supplementation for 4 months brings about haematological remission and replenishes body stores.
What is aplastic aneamia?
it is a condition which occurs when your body stops producing enough new blood cells. The condition leaves you fatigued and more prone to infections and uncontrolled bleeding. A rare and serious condition, aplastic anemia can develop at any age.
in which types of anaemias may tissue iron overload occur in?
in aplastic and other refractory anaemias, mainly as the result of repeated blood transfusions
What can iron overload associated with haemochromatosis be treated with?
Haemochromatosis - Haemochromatosis is an inherited condition where iron levels in the body slowly build up over many years.
Venesection
Venesection may also be used for patients who have received multiple transfusions and whose bone marrow has recovered
Venesection is a procedure where a trained nurse or doctor removes approximately 450mls of blood from your circulation
What if venesection is contra-indicated?
the long-term administration of the iron chelating compound desferrioxamine mesilate is useful
How much desferrioxamine mesilate may also be given at the time of blood transfusion?
Desferrioxamine mesilate (up to 2 g per unit of blood) may also be given at the time of blood transfusion, provided that the desferrioxamine mesilate is not added to the blood and is not given through the same line as the blood (but the two may be given through the same cannula).
Iron excretion induced by desferrioxamine mesilate is enhanced by daily administration of which compound?
Enhanced by administration of ascorbic acid (vitamin C) daily by mouth
Why should ascorbic acid be given separately from food?
Because it also enhances iron absoprtion
In which patients should ascorbic acid not be given to?
Ascorbic acid should not be given to patients with cardiac dysfunction; in patients with normal cardiac function ascorbic acid should be introduced 1 month after starting desferrioxamine mesilate.
What can desferrioxamine mesilate infusion be used to treated in dialysis patients?
can be used to treat aluminium overload in dialysis patients; theoretically 100 mg of desferrioxamine binds with 4.1 mg of aluminium.
What is neutropenia characterised by?
Neutropenia is characterised by a low neutrophil count (absolute neutrophil count less than 1.5 x 109/litre).
What can be sued to stimulate production of neutrophils and may reduce the duration of chemotherapy-induced neutropenia?
Recombinant human granulocyte-colony stimulating factor (rhG-CSF)
List some examples of granulocyte-colony stimulating factors?
‘grastim’
filgrastim, lenograstim, pegfilgrastim and lipegfilgrastim.
Which are longer acting?
Pegfilgrastim and lipegfilgrastim are polyethylene glycol-conjugated (‘pegylated’) derivatives of filgrastim, which are longer-acting forms of filgrastim due to decreased renal clearance.
What is immune thrombocytopenia purpura (ITP)?
Immune thrombocytopenic purpura (ITP) is a blood disorder characterized by a decrease in the number of platelets in the blood. Platelets are cells in the blood that help stop bleeding. A decrease in platelets can cause easy bruising, bleeding gums, and internal bleeding.
In adults with immune thrombocytopenia purpura, what is the initial treatment with?
A corticosteroid (such as prednisolone)
In patients with immune thrombocytopenic purpura who are bleeding or at high-risk of bleeding, who require a surgical procedure, or who are unresponsive to corticosteroids. what may be used?
Intravenous normal immunoglobulin
Immunoglobulin preparations may also be considered where a temporary rapid rise in platelets is needed, for example in pregnancy.
When can splenectomy be considered?
Splenectomy can be considered as a treatment option only if drug therapy has failed; the patients age and co-morbidities should also be taken into account
What is a good dietary source of folic acid?
Broccoli
Which drugs can cause agranulocytosis, neutropenia, other bone-marrow suppression or dyscrasis?
- Carbimazole
- Clozapine
- Co-trimoxazole
- Sulfasalazine
What are the normal levels sodium in the body?
142mmol/L
What is the normal plasma level of potassium?
4.5mmol/L
What is the normal plasma level of bicarbonate?
26mmol/L
What is the normal plasma level of chloride?
103mmol/L
What is the normal plasma level of calcium?
2.5mmol/L
When is compensation for potassium loss especially necessary?
- in those taking digoxin or anti-arryhthmic drugs, where potassium depletion may induce arrhythmias
- in patients in whom secondary hyperaldosteronism occurs, e.g. renal artery stenosis, cirrhosis of the liver, the nephrotic syndrome, and severe heart failure;
- in patients with excessive losses of potassium in the faeces, e.g. chronic diarrhoea associated with intestinal malabsorption or laxative abuse.
Measures may also be required during long-term administration of drugs known to induce potassium loss - give an example of a drug that causes hypokalaemia?
Corticosteroids
When small doses of diuretics are used to treat hypertension what is used to replace potassium?
Potassium supplements
to prevent hypokalaemia due to diuretics such as furosemide or the thiazides when these are given to eliminate oedema, what is preferred to be used for replacing potassium?
Potassium-sparing diuretics (rather than potassium supplements)
If potassium salts are used for the prevention of hypokalaemia then how are the doses given?
- doses of potassium chloride daily (in divided doses) by mouth are suitable in patients taking a normal diet.
Smaller doses must be used if there is renal insufficiency (common in the elderly) to reduce the risk of hyperkalaemia
What limits the use of potassium salts?
They cause nausea and vomiting and poor compliance is a major limitation to their effectiveness; when appropriate, potassium-sparing diuretics are preferable
The depletion of potassium is frequently associated with depletion of which other electrolyte?
Associated with chloride depletion and with metabolic alkalosis, and these disorders require correction
What potassium concentration is classed as acute severe hyperkalaemia?
Plasma potassium concentration 6.5mmol/L or greater or in the presence of ECG changes
What is the urgent treatment for acute severe hyperkalaemia?
- Calcium chloride 10% (unlicensed)
or - Calcium gluconate 10% (unlicensed)
to temporarily protect against myocardial excitability
What’s is a licensed treatment of acute severe hyperkalaemia?
An intravenous injection of soluble insulin (5–10 units) with 50 mL glucose 50% given over 5-15 minutes, reduces serum-potassium concentration; this is repeated if necessary or a continuous infusion instituted.
Can salbutamol be used to treat hyperkalaemia?
Salbutamol [unlicensed indication], by nebulisation or slow intravenous injection may also reduce plasma-potassium concentration; it should be used with caution in patients with cardiovascular disease.
The correction of casual or compounding acidosis should be corrected with what?
Sodium bicarbonate
What must be noted about preparation of sodium bicarbonate and calcium salts?
Sodium bicarbonate and calcium salts should not be administered in the same line - risk of precipitation
What is indicated in states of sodium depletion (hyponatraemia) and usually need to be given intravenously?
Sodium chloride
In chronic conditions associated with mild or moderate degrees of sodium depletion, e.g. in salt-losing bowel or renal disease, oral supplements of sodium chloride or sodium bicarbonate, according to the acid-base status of the patient, may be sufficient.
As a worldwide problem what is by far the most important indication for fluid and electrolyte replacement?
Diarrhoea
Intestinal absorption of sodium and water is enhanced by what?
Enhanced by glucose (and other carbohydrates)
Therefore replacement of fluid and electrolytes lost through diarrhoea can therefore be achieved by giving solutions containing what?
Containing sodium, potassium, and glucose or another carbohydrate such as rice starch
What key concepts should oral rehydration solutions have to be succesfull?
Oral rehydration solutions should:
enhance the absorption of water and electrolytes;
replace the electrolyte deficit adequately and safely;
contain an alkalinising agent to counter acidosis;
be slightly hypo-osmolar (about 250 mmol/litre) to prevent the possible induction of osmotic diarrhoea;
be simple to use in hospital and at home;
be palatable and acceptable, especially to children;
be readily available
What is the difference between WHO’s recommendation of oral rehydration solution contents and of that used in the UK?
The formulation recommended by the WHO and the United Nations Children’s fund is not commonly used in the UK.
Oral rehydration solutions used in the UK are lower in sodium (50–60 mmol/litre) than the WHO formulation since, in general, patients suffer less severe sodium loss.
Should rehydration occur rapidly or slowly?
Rehydration should be rapid over 3 to 4 hours (except in hypernatraemic dehydration in which case rehydration should occur more slowly over 12 hours).
When is sodium bicarbonate used?
It is given by mouth for chronic acidotic states such as uraemic acidosis or renal tubular acidosis
Is the dose correction of metabolic acidosis predicatable?
No and the the response must be assessed
For severe metabolic acidosis, how can sodium bicarbonate be given?
Intravenously
What other reason may sodium bicarbonate be used (to increase what)?
To increase the pH of the urine; it is also used in dyspepsia
What may sodium supplements increase?
Increase the blood pressure or cause fluid retention and pulmonary oedema in those at risk;
Hypokalaemia may be exacerbated
Where hyperchloraemic acidosis is associated with potassium deficiency, as in some renal tubular and gastrointestinal disorders, it may be appropriate to give which drug orally?
Potassium bicarbonate
Hyperchloraemic acidosis is associated with Hyperchloremic acidosis is a form of metabolic acidosis associated with a normal anion gap, a decrease in plasma bicarbonate concentration, and an increase in plasma chloride concentration
To replace electrolytes and water if intravenous administration is not possible, what can be given by subcutaneous infusion (hypodermoclysis)?
Fluid - Sodium chloride 0.9% or glucose 5%
Which solutions can be given safely into a peripheral vein?
Isotonic solutions may be infused safely into a peripheral vein. Solutions more concentrated than plasma, e.g. 20% glucose, are best given through an indwelling catheter positioned in a large vein.
If sodium chloride is required for acute or chronic hyponatraemia how fast or slow should this be given?
Regardless of the cause - the deficit should eb corrected slowly to avoid the risk of osmotic demyelination syndrome and the risk in plasma-sodium concentration should not exceed 10mmol/L in 24 hours.
In severe hyponatraemia what sodium chloride concentration may be used cautiously?
sodium chloride 1.8% may be used cautiously
What compound may be used instead of sodium chloride solution during or after surgery or in the initial management of the injured or wounded which may reduce the the risk of hyperchloraemic acidosis?
- Compound sodium lactate (Hartman’s solution)
When is sodium chloride with glucose solutions indicated?
When there is combined water and sodium depletion
What are glucose solutions (5%) mainly used to replace?
To replace water deficit
What is the average water requirements in an healthy adult?
1.5 to 2.5litres
Excessive loss of water without loss of electrolytes is uncommon but which situations or conditions can this occur in?
occurring in fevers, hyperthyroidism, and in uncommon water-losing renal states such as diabetes insipidus or hypercalcaemia.
What volume of glucose solution is required to replace deficits of water?
The volume of glucose solution needed to replace deficits varies with the severity of the disorder, but usually lies within the range of 2 to 6 litres.
Other than water, glucose solutions are also used to correct and prevent what?
Hypoglycaemia and to provide a source of energy in those too ill to be fed adequately by mouth; glucose solutions are a key component of parenteral nutrition
What is the initial management for the correction of severe hypokalaemia?
Potassium chloride with sodium chloride intravenous infusion - also when sufficient potassium cannot be taken by mouth
Should the initial potassium replacement therapy involve glucose?
No because glucose may cause a further decrease in the plasma-potassium concentration
Sodium bicarbonate is used to control severe metabolic acidosis for pH less than what??
pH<7.1
particularly that caused by loss of bicarbonate (as in renal tubular acidosis or from excessive gastro-intestinal losses)
Mild metabolic acidosis associated with volume depletion should be first managed by what?
managed by appropriate fluid replacement because acidosis usually resolves as tissue and renal perfusion are restored
Why is sodium lactate intravenous infusion no longer used in metabolic acidosis?
because of the risk of producing lactic acidosis, particularly in seriously ill patients with poor tissue perfusion or impaired hepatic function.
For chronic acidotic states, sodium bicarbonate can be given by which route?
By mouth
What is another name for plasma substitutes?
colloids
what is sodium chloride and glucose known as (Hint - plasma substitute is colloids)
Crystalloids